JP2016010717A - Concentration quantification apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a concentration quantification apparatus, a concentration quantification method, and a program capable of noninvasively and accurately quantifying the concentration of target components in an arbitrary layer by accurately measuring and ensuring a close contact state between an irradiation unit and an observation object.SOLUTION: A concentration quantification apparatus 100 according to the present invention comprises: an irradiation part 106; a light reception part 107; an optical path length distribution storage part 103; an optical path length acquisition part 108; a time resolution waveform storage part 105; a close contact determination part 111 for determining whether or not the irradiation part 106 and an observation object is in a close contact state; a measurement light intensity acquisition part 113 for, when the close contact determination part 111 determined that the irradiation part 106 and the observation object is in a close contact state, acquiring the intensity of the light received by the light reception part 107; a light absorption coefficient calculation part 117 for calculating the light absorption coefficient of target components of an arbitrary layer; and a concentration calculation part 120 for calculating the concentration of the target components of the arbitrary layer on the basis of the light absorption coefficient acquired by the light absorption coefficient calculation part 117.

Description

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

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

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

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

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

On the other hand, for biodiagnosis using near-infrared light, for example, the amount of absorption of near-infrared light in the main component of skin is measured by biological tissue imaging using a time-resolved measurement method, and the main skin is determined based on this absorption amount. Methods are known for determining the proportion of each component, for example, the glucose concentration corresponding to blood sugar.
Since the absorption amount of the skin main component is wavelength-dependent, usually, a plurality of spectra are prepared in advance by varying the variable factors that affect the quantification of the skin main component at a plurality of ratios by multivariate analysis. The method of estimating each ratio of the skin main component by comparing the spectrum of the measurement result of the absorption amount of near infrared light in the skin main component with the above plurality of spectra and selecting a spectrum that matches from these spectra. It is taken.

Japanese Patent No. 3931638 Japanese Patent No. 3994588

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

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

Therefore, a sensing unit including a near-infrared irradiation unit and a light receiving unit, holding means for bringing the sensing unit into contact with the skin at a contact pressure of 100 to 750 gf / cm ² , and a contact pressure between the sensing unit and the skin surface A blood glucose level measuring device including a measuring means for measuring the blood pressure and a notification means for notifying that when the contact pressure becomes an appropriate contact pressure can be considered. Since it is not possible to measure the state of light entering inside and the state of light scattered back from the skin entering the light receiving unit, determine the proper contact state based on the measured light intensity waveform and notify that fact. I can't.

  The present invention was made in order to solve the above-described problem, and by measuring and confirming the close contact state between the irradiation unit and the observation target with high accuracy, the concentration of the target component in any layer can be determined. It is an object of the present invention to provide a concentration quantification apparatus, a concentration quantification method, and a program capable of non-invasively and accurately quantifying.

In order to solve the above problems, the present invention employs the following concentration determination apparatus, concentration determination method, and program.
That is, the concentration quantification device of the present invention is a concentration quantification device for quantifying the concentration of a target component in an arbitrary layer among observation targets composed of a plurality of layers, and irradiates the observation target with short-time pulsed light. An irradiating unit, a light receiving unit that receives light scattered back from the observation target by irradiation of the short-time pulsed light, and each of the plurality of layers of short-time pulsed light irradiated to the observation target An optical path length distribution storage unit that stores a model of an optical path length distribution in the layer; an optical path length acquisition unit that acquires an optical path length of each of the plurality of layers at a predetermined time of the optical path length distribution model; and A time-resolved waveform storage unit that stores a model of a time-resolved waveform of short-time pulsed light that is irradiated to an observation target; and a light intensity model acquisition unit that acquires a light intensity at the predetermined time of the model of the time-resolved waveform An irradiation amount control unit for controlling the irradiation amount of the short-time pulse light irradiated from the irradiation unit to the observation target by performing preliminary irradiation of the short-time pulse light from the irradiation unit to the observation target; and the irradiation amount After the amount of irradiation of the short-time pulsed light is controlled by the control unit, measure the light intensity at each time the light-receiving unit receives light with reference to the start time of incidence of the short-time pulsed light on the observation target, A contact determination unit that determines whether or not the irradiation unit and the observation target are in a close contact state based on a relationship between a time at which the light receiving unit starts detecting backscattered light from the observation target and an intensity; When the determination unit determines that the irradiation unit and the observation target are in close contact with each other, a light intensity acquisition unit that acquires the intensity of the light received by the light receiving unit, and the light intensity acquisition unit acquired Light intensity distribution of light intensity The absorption for calculating the absorption coefficient of the arbitrary layer based on the optical path length of each of the plurality of layers acquired by the optical path length acquisition unit and the light intensity model acquired by the light intensity model acquisition unit A coefficient calculator, and a concentration calculator that calculates the concentration of the target component in the arbitrary layer based on the absorption coefficient calculated by the absorption coefficient calculator.

In the concentration determination apparatus of the present invention, the irradiation amount control unit controls the irradiation amount of the short-time pulse light irradiated from the irradiation unit to the observation target by performing preliminary irradiation of the short-time pulse light from the irradiation unit to the observation target. Then, after the irradiation amount control unit controls the irradiation amount of the short-time pulse light, the light-receiving unit receives the light from the contact determination unit based on the start time of the short-time pulse light output from the irradiation unit to the observation target. Measure the light intensity at each time, and determine whether the irradiation unit and the observation target are in close contact based on the relationship between the intensity and the time when the light receiving unit starts detecting backscattered light from the observation target. When the contact determination unit determines that the irradiation unit and the observation target are in contact, the light intensity acquisition unit acquires the intensity of the backscattered light received by the light receiving unit.
Thereafter, the irradiation amount control unit performs preliminary irradiation of the short-time pulse light from the irradiation unit to the observation target, whereby the irradiation amount of the short-time pulse light irradiated from the irradiation unit to the observation target can be controlled.
In particular, the degree of reduction in the amount of irradiation of the short-time pulse light is set to 1/1000 to 1/10 with respect to the light output irradiated at the time of concentration measurement in consideration of the amount of exposure that the human body receives by irradiation of the short-time pulse light. By setting it within the range, the amount of exposure when the human body is irradiated with short-time pulse light can be reduced, and the short-time pulse light output from the irradiation unit can be kept in close contact with the observation target. In this state, measurement can be performed and measurement accuracy can be improved.
As described above, when the contact determination unit determines whether or not the irradiation unit and the observation target are in a close contact state, and the contact determination unit determines that the irradiation unit and the observation target are in a close contact state, the light intensity By acquiring the intensity of the backscattered light received by the light receiving unit by the acquiring unit, it is possible to quickly and easily confirm the contact state between the irradiation unit and the observation target, and any layer that is a specific part for quantification Thus, the absorption coefficient of the target component, that is, the concentration of the target component can be measured quickly and easily. As a result, the concentration of the target component in any layer can be quantified non-invasively and quickly.

  In the concentration quantification device according to the present invention, the contact determination unit is configured to detect the intensity of direct propagation light propagating on the surface of the observation target and the backscattered light from the observation target as the light intensity at each time received by the light receiving unit. An intensity is selected, and when the intensity of the directly propagated light is 1/10 or less of the intensity of the backscattered light, it is determined that the irradiation unit and the observation target are in close contact with each other.

In the concentration quantification apparatus of the present invention, the intensity of the direct propagation light propagating on the surface of the observation target and the intensity of the backscattered light from the observation target are selected as the light intensity at each time received by the light receiving unit, When the intensity is 1/10 or less of the intensity of the backscattered light, it is determined that the irradiation unit, the light receiving unit, and the observation target are in close contact.
As described above, when the intensity of the directly propagated light is 1/10 or less of the intensity of the backscattered light, it is determined that the irradiation unit and the observation target are in close contact with each other. It is possible to easily and simply determine the close contact state between the irradiation unit and the observation target using the ratio with the intensity of the light.
Therefore, the concentration of the target component can be measured quickly and easily, and as a result, the concentration of the target component in any layer can be quantified non-invasively and quickly.

The concentration determination apparatus of the present invention is characterized in that the contact determination unit includes a notification unit that notifies the result of determining whether or not the irradiation unit and the observation target are in a contact state.
In this concentration determination apparatus, the contact determination unit includes a notification unit for notifying the result of determining whether or not the irradiation unit, the light receiving unit, and the observation target are in a close contact state. It is possible to quickly and easily know whether or not the object is in close contact.

In the concentration determination apparatus of the present invention, the contact determination unit continuously determines whether or not the irradiation unit and the observation target are in a close contact state, and determines that the irradiation unit and the observation target are in a close contact state. When the light intensity acquisition unit acquires the intensity of the light received by the light receiving unit, and the irradiation amount control unit determines that the irradiation unit and the observation target are not in close contact with each other, By performing preliminary irradiation of short-time pulse light from the irradiation unit to the observation target, the irradiation amount of the short-time pulse light irradiated from the irradiation unit to the observation target is controlled, and the irradiation unit and the observation target are controlled. It is characterized by determining again whether or not is in a close contact state.
In this concentration determination device, the contact determination unit and the dose control unit control the irradiation amount of short-time pulsed light irradiated from the irradiation unit to the observation target, and continuously monitor the contact state between the irradiation unit and the observation target. By doing so, the intensity of the backscattered light from the observation target at the time when the irradiation unit and the observation target are in close contact with each other can be quickly acquired.

  The concentration quantification device of the present invention includes a light intensity distribution of the light intensity acquired by the light intensity acquisition unit, an optical path length of each of the plurality of layers acquired by the optical path length acquisition unit, and the light intensity. Based on the light intensity model acquired by the model acquisition unit, an integration interval calculation unit that calculates an integration interval that is a time range of a region corresponding to the light intensity distribution of the arbitrary layer from the light intensity distribution, The absorption coefficient calculation unit calculates the absorption coefficient of the target component in the arbitrary layer by changing the integration interval calculated by the integration interval calculation unit.

In this concentration quantification apparatus, the integration interval calculation unit includes the light intensity distribution of the light intensity acquired by the light intensity acquisition unit, the optical path length of each of the plurality of layers acquired by the optical path length acquisition unit, and the light intensity model. Based on the light intensity model acquired by the acquisition unit, an integration interval that is a time range of a region corresponding to the light intensity distribution of an arbitrary layer is calculated from the light intensity distribution, and the absorption coefficient calculation unit is an integration interval calculation unit. The absorption coefficient of the target component in an arbitrary layer is calculated by changing the integration interval calculated by.
Thus, based on the integration interval calculated by the integration interval calculation unit, it is a specific part to be quantified by obtaining the light intensity in the time zone corresponding to the integration interval from the light intensity received by the light receiving unit. Light from any layer can be measured separately from light from other layers, and the influence of light from other layers on light from any layer can be reduced. Therefore, the light absorption amount of the target component in any layer, that is, the concentration of the target component can be accurately measured. As a result, the concentration of the target component in any layer is quantified noninvasively and with high accuracy. be able to.

から任意の層の吸収係数を算出する、ことを特徴とする。 In the concentration determination apparatus of the present invention, the light intensity acquisition unit acquires light intensities at a plurality of times t _{1 to} t _m where the number of layers to be observed is n or more (where n is a natural number of 1 or more, m is a natural number greater than or equal to n), the absorption coefficient calculating unit is ln (·) indicating a natural logarithm, I (t) indicating the light intensity received by the light receiving unit at time t, and time resolution of the short-time pulsed light N (t) indicating the light intensity at time t of the waveform model, Li (t) indicating the optical path length of the i-th layer at time t of the optical path length distribution model, and μ _i indicating the absorption coefficient of the i-th layer. make use of,

From the above, the absorption coefficient of an arbitrary layer is calculated.

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

から任意の層の吸収係数を算出する、ことを特徴とする。 In the concentration quantification device of the present invention, the light intensity acquisition unit acquires the light intensity from a predetermined time to at least a predetermined time τ, and the absorption coefficient calculation unit includes ln (·) indicating the natural logarithm, I (t) indicating the light intensity received by the light receiving unit at time t, N (t) indicating the light intensity at time t of the time-resolved waveform model of the short-time pulse light, and time t of the model of the optical path length distribution Li (t) indicating the optical path length of the i-th layer, n indicating the number of layers to be observed, and μi indicating the absorption coefficient of the i-th layer,

From the above, the absorption coefficient of an arbitrary layer is calculated.

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

から前記任意の層における前記目的成分の濃度を算出する、ことを特徴とする。 In the concentration quantification device of the present invention, the irradiation unit irradiates light having a plurality of wavelengths 1 to q, and the absorption coefficient calculation unit calculates the absorption coefficient in the arbitrary layer for each of the plurality of wavelengths irradiated by the irradiation unit. The concentration calculation unit calculates μa (i) indicating the absorption coefficient of the wavelength i in the a-th layer which is the arbitrary layer, gj indicating the molar concentration of the j-th component forming the observation target, and jth Ε _{j (i)} indicating the absorption coefficient for the wavelength i of the component, p indicating the number of main components forming the observation object, q indicating the number of types of wavelengths irradiated by the irradiation unit,

From the above, the concentration of the target component in the arbitrary layer is calculated.

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

  The concentration quantification method of the present invention includes an irradiation unit that irradiates an observation target composed of a plurality of layers with a short-time pulsed light, and a light receiving unit that receives light scattered back from the observation target by the irradiation of the short-time pulsed light. An optical path length distribution storage unit for storing a model of an optical path length distribution in each of the plurality of layers of short-time pulse light irradiated to the observation target, and a short irradiation to the observation target A time-resolved waveform storage unit that stores a time-resolved waveform model of time-pulsed light, and a concentration quantification method using a concentration quantification device that quantifies the concentration of a target component in any layer of the observation target, The irradiation unit irradiates the observation target with short-time pulsed light, the light receiving unit receives light scattered back from the observation target by the irradiation of the short-time pulsed light, and the irradiation amount control unit The preliminary irradiation of the short-time pulse light from the irradiation unit to the observation target is performed, the irradiation amount of the short-time pulse light irradiated from the irradiation unit to the observation target is controlled, and the short-time pulse is controlled by the irradiation amount control unit After the irradiation amount of light is controlled, whether the irradiation unit and the observation target are in close contact based on the relationship between the time when the light receiving unit starts detecting the backscattered light and the intensity by the contact determination unit And when the light intensity acquisition unit determines that the irradiation unit and the observation target are in a close contact state, the light intensity acquisition unit acquires the intensity of the light received by the light receiving unit, An optical path length acquisition unit acquires an optical path length of each of the plurality of layers at a predetermined time of the optical path length distribution model, and a light intensity model acquisition unit acquires the short path from the time-resolved waveform storage unit. Time-resolved wave of time pulse light The light intensity at the predetermined time of the model is acquired, and the light intensity acquired by the light intensity acquisition unit and the optical path length of each of the plurality of layers acquired by the optical path length acquisition unit by the absorption coefficient calculation unit And the light intensity model acquired by the light intensity model acquisition unit, the absorption coefficient of the target component in the arbitrary layer is calculated, and based on the absorption coefficient calculated by the absorption coefficient calculation unit by the concentration calculation unit The concentration of the target component in the arbitrary layer is calculated.

In the concentration determination method of the present invention, the irradiation amount control unit performs preliminary irradiation of short-time pulse light from the irradiation unit to the observation target, and the irradiation amount of short-time pulse light irradiated from the irradiation unit to the observation target. After the irradiation amount control unit controls the irradiation amount of the short-time pulsed light, the contact determination unit receives the short-time pulsed light output from the irradiation unit with respect to the observation start time as a reference. Measuring the light intensity at each time the unit receives light, and determining whether the irradiation unit and the observation target are in close contact based on the relationship between the intensity and the time at which the light receiving unit starts detecting backscattered light, When the contact determination unit determines that the irradiation unit and the observation target are in contact, the light intensity acquisition unit acquires the intensity of the backscattered light received by the light receiving unit.
As described above, the irradiation amount control unit controls the irradiation amount of the short-time pulse light emitted from the irradiation unit to the observation target, and the contact determination unit determines whether the irradiation unit and the observation target are in a close contact state. When the contact determination unit determines that the irradiation unit and the observation target are in contact with each other, the light intensity acquisition unit obtains the intensity of the backscattered light received by the light receiving unit, and performs the quantification. It is possible to quickly and easily measure the absorption coefficient of the target component in any layer that is the site, that is, the concentration of the target component. As a result, the concentration of the target component in any layer can be determined non-invasively and quickly. can do.

  The program of the present invention includes an irradiation unit that irradiates an observation target composed of a plurality of layers with a short-time pulsed light, and a light-receiving unit that receives light backscattered from the observation target due to the irradiation of the short-time pulsed light. An optical path length distribution storage unit for storing a model of an optical path length distribution in each of the plurality of layers of the short-time pulse light applied to the observation target; and a short-time pulse applied to the observation target A time-resolved waveform storage unit that stores a model of a time-resolved waveform of light, and a computer for a concentration quantification device that quantifies the concentration of a target component in an arbitrary layer of the observation target; An irradiation procedure for irradiating light, a light receiving procedure for receiving light scattered back from the observation target by irradiation with the short-time pulse light, and a short-time pulse light from the irradiation unit to the observation target By performing pre-irradiation, the irradiation amount control procedure for controlling the irradiation amount of the short-time pulse light irradiated to the observation object from the irradiation unit, the irradiation amount of the short-time pulse light is controlled by the irradiation amount control procedure. After that, the contact determination procedure for determining whether or not the irradiation unit and the observation target are in close contact based on the relationship between the intensity and the time when the backscattering light from the observation target starts to be detected by the light receiving procedure. , A light intensity acquisition procedure for acquiring the intensity of the light received by the light receiving procedure when it is determined by the contact determination procedure that the irradiation unit and the observation target are in a close contact state, the optical path length distribution storage An optical path length acquisition procedure for acquiring an optical path length of each of the plurality of layers at a predetermined time of the optical path length distribution model from the unit, and from the time-resolved waveform storage unit, A light intensity model acquisition procedure for acquiring the light intensity at the predetermined time of the model of the decomposition waveform, the light intensity distribution acquired by the light intensity acquisition procedure, and the plurality of layers acquired by the optical path length acquisition means Based on the optical path length of each layer and the light intensity acquired by the light intensity model acquisition procedure, the absorption coefficient calculation procedure for calculating the absorption coefficient of the arbitrary layer, calculated by the absorption coefficient calculation procedure A concentration calculation procedure for calculating the concentration of the target component in the arbitrary layer is executed based on an absorption coefficient.

  In the program of the present invention, an irradiation procedure for irradiating the observation target with the short-time pulse light on the computer of the concentration quantification apparatus, a light-receiving procedure for receiving the light scattered back from the observation target by the irradiation of the short-time pulse light, from the irradiation unit Dose control procedure for controlling the irradiation amount of short-time pulse light irradiated from the irradiation unit to the observation object by performing preliminary irradiation of the short-time pulse light on the observation object, and start of incidence of the short-time pulse light on the observation object The light intensity at each time received by the light receiving procedure is measured with respect to the time, and the irradiation unit and the observation target are in close contact based on the relationship between the time and intensity at which the backscattered light from the observation target starts to be detected by the light receiving procedure. After performing the adhesion determination procedure for determining whether or not it is in the state, the light intensity distribution acquired by the light intensity acquisition procedure and each of the plurality of layers acquired by the optical path length acquisition means Based on the optical path length and the light intensity acquired by the light intensity model acquisition procedure, the absorption coefficient calculation procedure for calculating the absorption coefficient of an arbitrary layer, based on the absorption coefficient calculated by the absorption coefficient calculation procedure, The concentration calculation procedure for calculating the concentration of the target component in the layer is sequentially executed.

  In this way, the light intensity at each time received by the light receiving procedure is measured based on the start time of incidence of the short-time pulse light on the observation target, and the short-time pulse light is transmitted from the irradiation unit to the observation target by the dose control procedure. The amount of short-time pulsed light emitted from the irradiation unit to the observation target is controlled by performing preliminary irradiation, and based on the relationship between the time when the backscattering light from the observation target is detected by the light receiving procedure and the intensity. By performing the contact determination procedure for determining whether or not the irradiation unit and the observation target are in close contact with each other, the contact state between the irradiation unit and the observation target can be quickly and easily confirmed and quantified. The absorption coefficient of the target component, that is, the concentration of the target component in an arbitrary layer that is a specific site can be measured quickly and easily. As a result, the concentration of the target component in any layer can be quantified non-invasively and rapidly.

It is a schematic block diagram which shows the structure of the blood glucose level measuring apparatus of the 1st Embodiment of this invention. It is a schematic diagram which shows the cross-sectional structure of skin. It is a figure which shows the relationship between the wavelength of light, and the penetration depth to skin. It is a figure which shows the optical path length distribution of each layer which the simulation part computed. It is a figure which shows the time-resolved waveform of the light intensity at the time of non-absorption obtained in the simulation part. It is a graph which shows the absorption spectrum of the main component of skin. It is a figure which shows the procedure which measures a blood glucose level using the blood glucose level measuring apparatus of the 1st Embodiment of this invention. It is a figure which shows the procedure which measures a blood glucose level using the blood glucose level measuring apparatus of the 1st Embodiment of this invention. It is a figure which shows the measurement timing in case an irradiation part is a non-contact state with the surface of skin. It is a figure which shows the measurement timing in case an irradiation part is in the state of adhesion | attachment inadequate with the surface of skin. It is a figure which shows the measurement timing in case an irradiation part is a close contact state with the surface of skin. It is a figure which shows the detected light intensity waveform in the case where an irradiation part and skin are in a close contact | adherence state. It is a figure which shows the relationship between the absorption coefficient in a dermis layer, and an integration area. It is a figure which shows the procedure which measures a blood glucose level using the blood glucose level measuring apparatus of the 2nd Embodiment of this invention. It is a figure which shows the procedure which measures a blood glucose level using the blood glucose level measuring apparatus of the 2nd Embodiment of this invention.

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

[First Embodiment]
FIG. 1 is a schematic block diagram showing a configuration of a blood sugar level measuring apparatus according to the first embodiment of the present invention.
This blood glucose level measuring device 100 is a device that non-invasively quantifies the concentration of glucose (target component) contained in a dermis layer (arbitrary layer) of a plurality of layers constituting skin (observation target) such as a palm. Yes, a simulation unit 101, an optical path length distribution calculation unit 102, an optical path length distribution storage unit 103, a time-resolved waveform calculation unit 104, a time-resolved waveform storage unit 105, an irradiation unit 106, a light receiving unit 107, and an optical path Length acquisition unit 108, non-absorption light intensity acquisition unit (light intensity model acquisition unit) 109, measurement timing calculation unit 110, adhesion determination unit 111, notification unit 112, measurement light intensity acquisition unit (light intensity acquisition unit) ) 113, measurement time-resolved waveform storage unit 114, measurement non-absorption light intensity acquisition unit 115, integration interval calculation unit 116, absorption coefficient calculation unit 117, absorption coefficient distribution storage unit 118, and absorption unit An acquiring unit 119, and a concentration calculator 120, and a dose controller 121.

The simulation part 101 performs the simulation which irradiates light with respect to the skin model whose absorption coefficient is zero.
The optical path length distribution calculation unit 102 calculates a model of the optical path length distribution in each layer constituting the skin of the short-time pulse light irradiated to the skin. Here, the optical path length distribution of the skin model with zero absorption coefficient is calculated.
The optical path length distribution storage unit 103 stores a model of the optical path length distribution in each layer constituting the skin calculated by the optical path length distribution calculation unit 102. Here, the optical path length distribution of the skin model having zero absorption coefficient is stored.

Here, the short-time pulsed light is pulsed light whose pulse width is shorter than the time during which light travels directly from the irradiation unit 106 to the light receiving unit 107 in the air. 0.1 ps to 10 ps refers to pulsed light having a time interval of 1 ps to 100 ps between two pulsed lights.
Further, the optical path length distribution is a distribution function representing the length (optical path length) of the moving path of light (photon) based on the time until the light (photon) reaches the light receiving unit 107.

The time-resolved waveform calculation unit 104 calculates a model of a time-resolved waveform of short-time pulse light that is applied to the skin. Here, the time-resolved waveform of the skin model with zero absorption coefficient is calculated.
The time-resolved waveform storage unit 105 stores a model of the time-resolved waveform of the short-time pulse light calculated by the time-resolved waveform calculation unit 104. Here, the time-resolved waveform of the skin model having zero absorption coefficient is stored.

The irradiation unit 106 irradiates the skin with pulsed light for a short time. The plurality of short-time pulse lights emitted by the irradiation unit 106 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 107 receives light obtained by back-scattering the short-time pulse light by the skin. The light receiving unit 107 includes an internal memory (not shown) that records the light reception intensity. The internal memory may be replaced with an external memory that is electrically connected to the light receiving unit 107.

Here, the structure of the human skin tissue to be observed will be described.
FIG. 2 is a schematic diagram showing a cross section of a human skin tissue. The skin 31 is composed of three layers of an epidermis layer 32, a dermis layer (arbitrary layer) 33, and a subcutaneous tissue 34.
The epidermis layer 32 is an outermost thin layer having a thickness of 0.2 mm to 0.3 mm, and is a layer containing about 60% of water, protein, lipid and glucose, and includes a stratum corneum, a granular layer, and a spiny layer. , Including bottom layer.

The dermis layer 33 is a layer formed under the epidermis layer 32 and having a thickness of 0.5 mm to 2 mm. The dermis layer 33 is a layer containing approximately 60% of water, protein, lipid, and glucose. , Hair roots, sebaceous glands, sweat glands, hair follicles, blood vessels, lymphatic vessels, and the like.
The subcutaneous tissue 34 is a layer having a thickness of 1 to 3 mm formed under the dermis layer 33. The subcutaneous tissue 34 is mostly made of subcutaneous fat containing approximately 90% or more of lipids and the balance being water.
Capillaries and the like are developed in the dermis layer 33, mass transfer according to blood glucose occurs rapidly, and the glucose concentration in the dermis layer 33 follows the blood glucose concentration (blood glucose level). It is thought to change.

  In this blood glucose level measuring apparatus 100, the irradiation unit 106 and the light receiving unit 107 are brought into close contact with the surface of the skin 31 with a predetermined input / output distance W, and light R is emitted from the irradiation unit 106 to the surface of the skin 31 in this close contact state. Irradiate. The irradiated light R is scattered by the tissue in the skin 31 and diffuses into the skin 31. A part of the diffused light R reaches the light receiving unit 107 (backscattered light). The path through which the backscattered light that has reached the light receiving unit 107 has propagated in the skin 31 is a banana-shaped three-dimensional shape, a so-called banana-shaped path.

  There is a certain relationship between the distance W between the incident part 106 and the light receiving part 107 and the penetration depth of the light R entering the skin 31. Therefore, the penetration depth of the light R that penetrates into the skin 31 is uniquely determined by defining the distance W between the emission and emission between the irradiation unit 106 and the light receiving unit 107. For example, if the distance W between incident and outgoing is 10 mm, the penetration depth of the light R is 10 mm, and if the distance W between incoming and outgoing is 0.8 mm, the penetration depth of the light R is 0.8 mm.

FIG. 3 is a diagram showing the relationship between the wavelength of light and the penetration depth into the skin. In the figure, “Nd-YAG” is the wavelength of the laser beam output from the Nd-YAG laser, “Xe” is the wavelength of the laser beam output from the Xe laser, and “Cs” is the wavelength of the laser beam output from the Cs laser. “CO” represents the wavelength of the laser beam output from the carbon monoxide laser, and “CO ₂ ” represents the wavelength of the laser beam output from the carbon dioxide laser.
According to FIG. 3, it can be seen that the laser light output from the Nd-YAG laser is suitable as the light sufficient to penetrate the dermis layer 33.

The optical path length acquisition unit 108 acquires, from the optical path length distribution storage unit 103, the optical path length of each layer of the skin at a predetermined time of the optical path length distribution model. Here, the optical path length at a certain time is acquired from the optical path length distribution storage unit 103.
The non-absorption light intensity acquisition unit 109 acquires the non-absorption light intensity at a predetermined time of the time-resolved waveform model of the short-time pulsed light from the time-resolved waveform storage unit 105. Here, the non-absorption light intensity at a certain time is acquired from the time-resolved waveform storage unit 105.

The measurement timing calculation unit 110 calculates a measurement timing that is a time difference between the time of the trigger signal when the irradiation unit 106 irradiates the short-time pulse light and the time of the measurement light intensity output from the light receiving unit 107.
The irradiation amount control unit 121 controls the irradiation amount of the short time pulse light irradiated from the irradiation unit 106 to the observation target by performing preliminary irradiation of the short time pulse light from the irradiation unit 106 to the observation target.
In the irradiation amount control unit 121, in particular, the degree of reduction of the irradiation amount of the short-time pulse light is determined with respect to the light output irradiated at the time of concentration measurement in consideration of the exposure amount received by the human body by the irradiation of the short-time pulse light. To within a range of 1/1000 to 1/10. Thereby, the amount of exposure when the human body is irradiated with the short-time pulse light is reduced, and the measurement is performed in a stable state in which the human body is in close contact with the observation target of the short-time pulse light output from the irradiation unit 106. . As a result, the measurement accuracy can be increased.
After the irradiation amount control unit 121 controls the irradiation amount of the short-time pulsed light, the contact determination unit 111 causes the irradiation unit 106 to adhere to the skin surface based on the measurement timing output from the measurement timing calculation unit 110. It is determined whether or not.
Here, it is determined whether the measurement timing output from the measurement timing calculation unit 110 corresponds to any one of (1) to (3) stored in the contact state storage unit built in the contact determination unit 111.

(1) the time of a trigger signal at which the irradiation unit 106 in a “non-contact state” irradiates a pulsed light for a short time with respect to the skin surface receiving light reflected by the skin surface by propagating air; A measurement timing that is a time difference from the time of the measurement light intensity output from the light receiving unit 107.
(2) The irradiation unit 106 in the “insufficient contact state” for a short time pulsed against the surface of the skin receiving both the light propagated through the air and reflected at the skin surface and the light propagated through the skin. A measurement timing that is a time difference between the time of the trigger signal for irradiating light and the time of the measurement light intensity output from the light receiving unit 107.
(3) Time of a trigger signal when the irradiation unit 106 emits pulsed light for a short time to the surface of the skin receiving only the light propagated through the skin and the measurement output from the light receiving unit 107 Measurement timing, which is the time difference from the time of light intensity.

  The contact determination unit 111 is provided with a notification unit 112 that notifies the determination result of the contact determination unit 111. This notification unit 112 is a sound device such as a speaker that notifies the determination result by voice, a display device such as a liquid crystal display that displays the determination result as an image, a sound device such as a speaker, and a light emitting device such as an LED. One or two or more of notification devices, etc. to be notified are provided. These can be selected and used as required.

The measurement light intensity acquisition unit 113 acquires the light intensity at a certain time of the light received by the light receiving unit 107 when the contact determination unit 111 determines that “the irradiation unit 106 is in close contact with the surface of the skin”.
The measurement time-resolved waveform storage unit 114 stores a model of the time-resolved waveform of the short-time pulse light acquired by the measurement light intensity acquisition unit 113. Here, the time-resolved waveform of the skin model when the absorption coefficient is zero, that is, no absorption is stored.
The measurement non-absorption light intensity acquisition unit 115 acquires the non-absorption light intensity from the time-resolved waveform of the short-time pulse light stored in the measurement time-resolved waveform storage unit 114.

  The integration interval calculation unit 116 calculates the optical path length of each layer of the model skin of the optical path length distribution acquired by the optical path length acquisition unit 108 and the time-resolved waveform of the short-time pulse light acquired by the non-absorption light intensity acquisition unit 109. Based on the non-absorbing light intensity of the model and the light intensity distribution received by the light receiving unit 107 acquired by the measurement light intensity acquisition unit 113, the time of the region corresponding to the light intensity of an arbitrary layer from the light intensity distribution The range of is calculated.

Here, the integration interval is a time width of a region corresponding to the light intensity of an arbitrary layer in the light intensity distribution, and can be determined by the start time, the end time, and the increment time.
For example, (1) the light intensity output from the light receiving unit 107 that receives the backscattered light is detected with a light intensity equal to the minimum detection sensitivity from the time when the light intensity output exceeds the minimum detection sensitivity of the measurement light intensity acquisition unit 113. Time to time, (2) time characteristics of non-absorbing light intensity acquired from the time-resolved waveform storage unit 105 storing the non-absorbing light intensity obtained by the simulation unit 101, and (3) a light receiving unit 107 in contact with the skin surface And (4) the start time of the integration interval using the size and optical characteristics (scattering coefficient, absorption coefficient, anisotropic parameter, or refractive index) of the skin model given to the simulation unit 101, Determine the end time and increment time.

The absorption coefficient calculation unit 117 is based on the time range of the region corresponding to the light intensity of the arbitrary layer calculated by the integration interval calculation unit 116, for example, the arbitrary layer of the skin based on the start time, end time, and increment time of the integration interval. The absorption coefficient is calculated.
Here, the absorption coefficient and estimated error rate of an arbitrary layer in the integration interval determined by the integration interval calculation unit 116 are obtained, and the distribution of the absorption coefficient and estimated error rate of the arbitrary layer with respect to the integration interval is calculated.
In this absorption coefficient calculation unit 117, the absorption coefficient of an arbitrary layer in the skin is calculated from the following equation (4).

Where ln (A) is the natural logarithm of A, I (t) is the light intensity received by the light receiving unit 107 at time t, and N (t) is a model of a time-resolved waveform of short-time pulsed light with a specific wavelength λk. The light intensity at time t, Li (t) represents the optical path length of the i-th layer at time t in the model of the optical path length distribution in each layer of the skin, and μi represents the absorption coefficient of the i-th layer.
Here, the first layer is the epidermis layer, the second layer is the dermis layer, the third layer is the subcutaneous tissue, μ ₁ is the epidermal layer absorption coefficient, μ ₂ is the dermal layer absorption coefficient, and μ ₃ is the subcutaneous tissue. Absorption coefficient is shown.

The absorption coefficient distribution storage unit 118 stores the absorption coefficient and estimated error rate distribution of an arbitrary layer for the integration interval calculated by the absorption coefficient calculation unit 117.
The absorption coefficient acquisition unit 119 uses the distribution of the absorption coefficient and estimated error rate of an arbitrary layer with respect to the integration interval acquired from the absorption coefficient distribution storage unit 118, and the standard such as the range of the absorption coefficient fluctuation rate with respect to the change of the integration interval. Thus, an absorption coefficient based on the glucose concentration corresponding to blood glucose in the skin main component of the layer at a specific depth from the skin surface is obtained.

The concentration calculation unit 120 calculates the concentration of glucose contained in the layer at the specific depth from the absorption coefficient based on the glucose concentration corresponding to blood glucose in the skin main component of the layer at the specific depth from the skin surface acquired by the absorption coefficient acquisition unit 19. Calculate the concentration.
The concentration calculator 20 calculates the glucose concentration in an arbitrary layer of the skin from the following equation (5).

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

  In this blood glucose level measuring apparatus 100, the irradiation unit 106 irradiates the skin with short-time pulse light, the light-receiving unit 107 receives light back-scattered by the short-time pulse light by the skin, and the measurement timing calculation unit 110 The irradiation unit 106 calculates a measurement timing that is a time difference between the time of the trigger signal that irradiates the short-time pulse light and the time of the measurement light intensity output from the light receiving unit 107, and the contact determination unit 111 calculates the measurement timing. Based on the measurement timing output from 110, it is determined whether or not the irradiation unit 106 is in close contact with the surface of the skin.

Here, when it is determined that the irradiation unit 106 is in close contact with the surface of the skin, the notification unit 112 notifies the determination result, and the measurement light intensity acquisition unit 113 receives the rear light received by the light receiving unit 107 at time t. Obtain the light intensity of the scattered light.
On the other hand, when it is determined that the irradiation unit 106 is not in close contact with the skin surface, the notification unit 112 notifies the determination result, and the contact determination unit 111 “the irradiation unit 106 is in close contact with the skin surface”. Until the determination is made, the irradiation unit 106 is slid on the surface of the skin, and the contact determination unit 111 repeatedly performs an operation of “determining whether or not the irradiation unit 106 is in close contact with the surface of the skin”.

  Next, the optical path length acquisition unit 108 acquires the optical path length of each layer of the skin at time t of the optical path length distribution in the skin model from the optical path length distribution storage unit 103, and the non-absorption light intensity acquisition unit 109 stores the time-resolved waveform storage From the unit 105, 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 integration interval calculation unit 116 calculates the optical path length of each skin layer of the optical path length distribution model acquired by the optical path length acquisition unit 108, for example, the optical path length acquired from the optical path length distribution storage unit 103, and the non-absorbing light. The light intensity in the time-resolved waveform model of the short-time pulse light acquired by the intensity acquisition unit 109, for example, the light intensity acquired from the time-resolved waveform storage unit 105, and the light receiving unit 107 acquired by the measurement light intensity acquisition unit 113 receive light. Based on the light intensity distribution, an integration interval of a region corresponding to the light intensity of an arbitrary layer is calculated from the light intensity distribution.

  For example, (1) the light intensity output from the light receiving unit 107 that receives the backscattered light is detected with a light intensity equal to the minimum detection sensitivity from the time when the light intensity output exceeds the minimum detection sensitivity of the measurement light intensity acquisition unit 113. Time to time, (2) time characteristics of non-absorbing light intensity acquired from the time-resolved waveform storage unit 105 storing the non-absorbing light intensity obtained by the simulation unit 101, and (3) a light receiving unit 107 in contact with the skin surface And (4) the start time of the integration interval using the size and optical characteristics (scattering coefficient, absorption coefficient, anisotropic parameter, or refractive index) of the skin model given to the simulation unit 101, Determine the end time and increment time.

Next, the absorption coefficient calculation unit 117 obtains the absorption coefficient and estimated error rate of an arbitrary layer in the integration interval determined by the integration interval calculation unit 116, and calculates the distribution of the absorption coefficient and estimated error rate of the arbitrary layer with respect to the integration interval. calculate.
Next, the absorption coefficient distribution storage unit 118 stores the distribution of the absorption coefficient and estimated error rate of an arbitrary layer for the integration interval calculated by the absorption coefficient calculation unit 117.
Next, the absorption coefficient acquisition unit 119 includes a distribution of an absorption coefficient and an estimated error rate of an arbitrary layer with respect to the integration interval acquired from the absorption coefficient distribution storage unit 118, and a reference such as a range of the absorption coefficient variation rate with respect to a change in the integration interval. Is used to obtain an absorption coefficient based on the glucose concentration corresponding to blood glucose in the skin main component of the layer at a specific depth from the surface of the skin.

Next, the concentration calculation unit 120 identifies the skin surface based on the absorption coefficient based on the glucose concentration corresponding to blood glucose in the skin main component of the layer at the specific depth from the skin surface acquired by the absorption coefficient acquisition unit 119. The concentration of glucose contained in the layer at the depth is calculated based on the above equation (5).
Thereby, the influence of the noise by layers other than the layer of specific depth can be reduced, and the concentration of glucose contained in the layer of specific depth can be calculated.

  In this blood sugar level measuring apparatus 100, the measurement timing calculation unit 110 measures a time difference between the time of the trigger signal when the irradiation unit 106 irradiates the pulsed light for a short time and the time of the measurement light intensity output from the light receiving unit 107. The timing is calculated, and the contact determination unit 111 determines whether or not the irradiation unit 106 is in close contact with the skin surface based on the measurement timing output from the measurement timing calculation unit 110. The amount of light absorbed in the layer having a specific depth, that is, the concentration of glucose can be measured noninvasively with high accuracy.

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

Here, a method for calculating the optical path length distribution and time-resolved waveform of the skin model will be described.
First, the simulation unit 101 generates a skin model. The skin model is generated by determining the light scattering coefficient, absorption coefficient, and thickness of each layer of the skin. Here, 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 32 is approximately 0.3 mm, the thickness of the dermis layer 33 is approximately 1.2 mm, and the thickness of the subcutaneous tissue 34 is approximately 3.0 mm.
The absorption coefficient of the skin model used here is zero. The reason is that the amount of light absorption is calculated using this skin model.

  When the simulation unit 101 generates a skin model, the simulation unit 101 performs a simulation of irradiating the skin model with light. At this time, it is necessary to determine the distance between the position of the irradiation unit 106 and the position of the light receiving unit 107. 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 uses a model of light to be irradiated as a photon (light beam), and performs calculation to irradiate the skin model with the photon. Photons irradiated to the skin model move in the skin model. At this time, the photon determines the distance L and the direction θ to the next advancing point by the random number R. The simulation unit 101 calculates the distance L to the point at which the photon advances next using Equation (6).

Here, ln (A) represents the natural logarithm of A, and μs represents the scattering coefficient of the s-th layer (any one of the epidermis layer, dermis layer, and subcutaneous tissue layer) of the skin model.
In addition, the simulation unit 101 calculates the direction θ up to the point where the photon advances next by Expression (7).

However, g shows the anisotropic parameter which is the average of cosine (cos) of a scattering angle, and the anisotropic parameter of skin is about 0.9.
The simulation unit 101 can calculate the movement path of photons from the irradiation unit 106 to the light receiving unit 107 by repeating the calculations of the above formulas (6) and (7) every unit time. The simulation unit 101 calculates a movement distance for a plurality of photons. For example, the simulation unit 101 calculates the movement distance for 10 ⁸ photons.

FIG. 4 is a diagram illustrating the optical path length distribution of each layer calculated by the simulation unit.
In FIG. 4, the horizontal axis represents the elapsed time from the photon irradiation, and the vertical axis represents the logarithm of the optical path length.
The simulation unit 101 classifies each movement path of photons that have reached the light receiving unit 107 for each layer through which the movement path passes. And the simulation part 101 calculates the optical path length distribution of each layer of skin as shown in FIG. 4 by calculating the average length of the movement path | route of the photon which arrived for every unit time for every classified layer.

Moreover, the simulation part 101 calculates the time-resolved waveform of a skin model as shown in FIG. 5 by calculating the number of photons that have reached the light-receiving part 107 every unit time.
FIG. 5 is a diagram showing a time-resolved waveform of the non-absorbing light intensity (equal to the number of received photons) N (t) obtained by the simulation unit 101. In FIG. 5, the horizontal axis represents the elapsed time from photon irradiation, and the vertical axis represents the number of photons detected by the light receiving unit 107.

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

FIG. 6 is a graph showing the absorption spectrum of the main component of the skin. In FIG. 6, the horizontal axis represents the wavelength of light to be irradiated, and the vertical axis represents the absorption coefficient.
According to FIG. 6, it can be seen that the absorption coefficient of glucose is maximized when the wavelength is 1600 nm, and the absorption coefficient of water is maximized when the wavelength is 1450 nm.
Therefore, the simulation unit 101 may calculate the optical path length distribution and the time-resolved waveform for wavelengths having a large difference in the absorption spectrum of the main component of the skin, such as 1400 nm, 1450 nm, 1500 nm, 1600 nm, 1680 nm, 1720 nm, and 1740 nm.

  When the simulation unit 101 calculates the optical path length distribution and time-resolved waveform of the skin model for a plurality of wavelengths, the optical path length distribution storage unit 103 stores information on the calculated optical path length distribution, and the time-resolved waveform storage unit 105 Information on the calculated time-resolved waveform is stored.

Next, a procedure for measuring a blood sugar level using the blood sugar level measuring apparatus 100 will be described with reference to FIGS.
First, the person to be measured places the blood glucose level measuring device 100 on the skin such as the wrist and operates the blood glucose level measuring device 100 by pressing a measurement start switch (not shown) or the like. Irradiation with λk short-time pulse light is performed (step S1).
As the wavelength λ _k , for example, one of a plurality of wavelengths for which the simulation unit 101 has calculated the optical path length distribution and the time-resolved waveform is preferable.
For example, among the main components that make up the skin, light having a wavelength at which the absorption coefficient of a specific component in one main component is greater than the absorption coefficient of another component, that is, the minimum value of the absorption coefficient of a specific component is absorbed by the other component It is preferable to calculate the optical path length distribution and the time-resolved waveform for light having a wavelength significantly different from the minimum value of the coefficient.

When the irradiation unit 106 irradiates the short pulse light having a wavelength lambda _k, the light receiving portion 107 receives the light backscattered by the skin is irradiated from the irradiation unit 106 (step S2).
At this time, the light receiving unit 107 records the received light intensity for each unit time from the start of irradiation (for example, times t _{1 to} t _m every 1 picosecond) in an internal memory (not shown).

Next, the irradiation amount control unit 121 performs preliminary irradiation of short-time pulse light from the irradiation unit 106 to the observation target, so that the human body reduces the irradiation amount of the short-time pulse light irradiated from the irradiation unit 106 to the observation target. In consideration of the exposure amount received by the time pulse light irradiation, the light output irradiated at the time of concentration measurement is controlled within a range of 1/1000 to 1/10 (step S3).
Here, when the irradiation amount of the short-time pulse light is not set within the range of 1/1000 to 1/10 with respect to the light output irradiated at the concentration measurement, the irradiation unit 106 again applies to the skin. Irradiation with short-time pulsed light of wavelength λk (step S1) and subsequent steps are performed.
Next, it is determined whether or not the irradiation unit 106 is in close contact with the surface of the skin (step S4).
That is, the measurement timing calculation unit 110 calculates the measurement timing that is the time difference between the time of the trigger signal when the irradiation unit 106 irradiates the short-time pulse light and the time of the measurement light intensity output from the light receiving unit 107, The determination unit 111 determines whether or not the irradiation unit 106 is in close contact with the surface of the skin based on the measurement timing output from the measurement timing calculation unit 110.
Here, it is determined whether the measurement timing output from the measurement timing calculation unit 110 corresponds to any one of (1) to (3) stored in the contact state storage unit built in the contact determination unit 111.

(1) the time of a trigger signal at which the irradiation unit 106 in a “non-contact state” irradiates a pulsed light for a short time with respect to the skin surface receiving light reflected by the skin surface by propagating air; A measurement timing that is a time difference from the time of the measurement light intensity output from the light receiving unit 107.
In this non-contact state, as shown in FIG. 9, leak light (directly propagated light) in the skin is observed within t ₁ ps, for example, within 10 ps from the emission time of the irradiation unit 106 that is the starting point of time. No backscattered light from the skin is observed after t ₂ ps.

(2) The irradiation unit 106 in the “insufficient contact state” for a short time pulsed against the surface of the skin receiving both the light propagated through the air and reflected at the skin surface and the light propagated through the skin. A measurement timing that is a time difference between the time of the trigger signal for irradiating light and the time of the measurement light intensity output from the light receiving unit 107.
In this inadequate contact state, as shown in FIG. 10, leak light (direct propagation light) in the skin is observed within t ₁ ps, for example, within 10 ps from the emission time of the irradiation unit 106 that is the starting point of time, Backscattered light from the skin is observed after t ₂ ps from the emission time.

(3) Time of a trigger signal when the irradiation unit 106 emits pulsed light for a short time to the surface of the skin receiving only the light propagated through the skin and the measurement output from the light receiving unit 107 Measurement timing, which is the time difference from the time of light intensity.
In this close contact state, as shown in FIG. 11, backscattered light from the skin is observed after t ₂ ps from the emission time of the irradiation unit 106, which is the starting point of time, and within t ₁ ps, for example, within 10 ps from the emission time. In addition, leak light (direct propagation light) in the skin is not observed.

FIG. 12 shows the detected light intensity waveform received by the light receiving unit 107 when the irradiation unit 106 and the skin are not sufficiently in close contact with each other. The starting point of time is that the irradiation unit 106 irradiates the pulsed light for a short time. It is time.
In FIG. 12, the detected light intensity waveform (A) having a small amplitude is due to the light received by propagating the irradiated light on the skin surface without propagating through the skin, and after this detected light intensity waveform (A). The detected light intensity waveform (B) having a large amplitude is due to the light received by the irradiation light propagating through the skin.

Thus, it can be seen that there is a clear time difference between the light propagated through the skin surface and the light propagated through the skin, so that it can be clearly discriminated by detecting this time difference.
In this case, if the intensity of the light propagated through the skin surface and received is 1/10 or less of the intensity of the light propagated in the skin (back scattered light), the irradiation unit 106 and the skin are in close contact with each other. Therefore, the irradiation unit 106 and the skin are in close contact with each other by comparing the intensity of the light received through the skin surface with the intensity of the light (backscattered light) transmitted through the skin. It is easy to determine whether or not.

Here, when the contact determination unit 111 determines that the irradiation unit 106 is in close contact with the surface of the skin, the notification unit 112 notifies the determination result, and the measurement light intensity acquisition unit 113 receives the light reception unit 107. The light intensity distribution of the backscattered light obtained is acquired. At this time, the light receiving unit 107 records the received light intensity for each unit time from the start of irradiation (for example, times t _{1 to} t _m every 1 picosecond) in the internal memory.
On the other hand, when it is determined that the irradiation unit 106 is not in close contact with the surface of the skin, the notification unit 112 notifies the determination result and again “irradiates the pulsed light for a short time” (step S1) to “the irradiation unit is skin. ”Determine whether or not it is in close contact with the surface” (step S4).

The execution of steps S1 to S4 is repeated until the contact determination unit 111 determines that “the irradiation unit 106 is in close contact with the surface of the skin”.
For example, when the contact determination unit 111 determines that the irradiation unit 106 and the observation target are not in a close contact state, the irradiation amount control unit 121 performs preliminary irradiation of short-time pulse light from the irradiation unit 106 to the observation target. Then, the irradiation amount of the short-time pulse light irradiated to the observation target from the irradiation unit 106 is controlled, and it is determined again whether or not the irradiation unit 106 and the observation target are in a close contact state.
As described above, the contact determination unit 111 and the irradiation amount control unit 121 continuously control the irradiation amount of the short-time pulse light irradiated from the irradiation unit 106 to the observation target and the contact state between the irradiation unit 106 and the observation target. By monitoring the intensity, the intensity of the backscattered light from the observation target at the time when the irradiation unit 106 and the observation target are in close contact with each other can be quickly acquired.
When the contact determination unit 111 determines that the irradiation unit 106 is in close contact with the surface of the skin, the integration interval is changed to calculate the absorption coefficient of the dermis layer (Process A: Step S5).
This process A (step S5) is performed according to the procedure shown in FIG.

  First, the integration interval calculation unit 116 (1) determines the minimum detection sensitivity from the time when the light intensity output from the light receiving unit 107 that receives the backscattered light exceeds the minimum detection sensitivity of the measurement light intensity acquisition unit 113. Time until time detected with equal light intensity, (2) time characteristics of non-absorbing light intensity acquired from the time-resolved waveform storage unit 105 storing the non-absorbing light intensity obtained by the simulation unit 101, (3) Using the distance between the light receiving unit 107 and the irradiation unit 106 in contact with the skin surface, and (4) the size and optical characteristics (scattering coefficient, absorption coefficient, anisotropic parameter, or refractive index) of the skin model given to the simulation unit 101 Then, an integration interval that is a time range of the region corresponding to the light intensity of the dermis layer is calculated. More specifically, the start time, end time, and increment time of the integration interval are calculated (step S11).

FIG. 13 is a diagram showing the relationship between the absorption coefficient and the integration interval in the dermis layer. In FIG. 13, a three-layer skin model of the epidermis layer, the dermis layer, and the subcutaneous tissue is used, and the absorption coefficient of the epidermis layer is changed from 25% to 150% with respect to the absorption coefficient of the dermis layer. In FIG. 15, A indicates 25%, B indicates 50%, C indicates 75%, D indicates 100%, E indicates 125%, and F indicates 150%.
According to FIG. 13, in the range of 14 ps to 34 ps, when the absorption coefficient values of the epidermis layer and the dermis layer approach, a value close to 0.55 / mm which is the value of the true absorption coefficient given in advance is calculated. You can see that. It can also be seen that there is a tendency to increase and have a peak in the range of 34 ps to 54 ps. Thus, it can be seen that the value of the absorption coefficient of the dermis layer converges in a specific range (0.54 to 0.56 / mm in FIG. 15) as the integration interval becomes wider.

Next, the measurement light intensity acquisition unit 113 acquires the received light intensity at a certain time t by the same number as the number of skin layers from the received light intensity recorded in the internal memory (step S12).
For example, when concentration measurement is performed on three layers of skin using four types of wavelengths, received light intensity I (t ₁ ) to I (t ₃ ) at _three different times t _{1 to} t ₃ is acquired. Here, the reason why the received light intensity is obtained in the same number as the number of skin layers is to calculate the absorption coefficient of each skin layer by simultaneous equations in the processing described later.

Also, the times t ₁ to t _{3 at} which the measurement light intensity acquisition unit 113 acquires the light intensity may be a time at which the optical path length distribution of each layer of the skin becomes a peak. That is, the light intensity at the time obtained by adding the time when the optical path length of each layer of the skin in FIG.

When the measurement light intensity acquisition unit 113 acquires the received light intensity I (t ₁ ) to I (t ₃ ), the optical path length acquisition unit 108 calculates the time from the optical path length distribution of the wavelength λ ₁ stored in the optical path length distribution storage unit 103. t ₁ ~t optical path length of each layer of the skin at _{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₎ to get (step S13).
When the measurement light intensity acquisition unit 113 acquires the received light intensities I (t ₁ ) to I (t ₃ ), the non-absorption light intensity acquisition unit 109 performs time resolution of the wavelength λ ₁ stored in the time-resolved waveform storage unit 105. from the waveform, the light intensity at a predetermined time model of time-resolved waveform of the short pulse light, for example, the time _t 1 ~t ₃ in the detection photon number (no absorption at the light _{intensity) N (t 1) ~N (} t 3) Is acquired (step S14).

When the optical path length acquisition unit 108 acquires the optical path length of each layer of the skin, and the non-absorption light intensity acquisition unit 109 acquires the number of detected photons (non-absorption light intensity) N (t ₁ ) to N (t ₃ ), the absorption coefficient The calculation unit 117 calculates the absorption coefficients μ _{1 to} μ ₃ of each skin layer in a certain integration interval calculated by the integration interval calculation unit 116 based on the equation (8) (step S15). Here, the absorption coefficient μ ₁ indicates the absorption coefficient of the epidermis layer, the absorption coefficient μ ₂ indicates the absorption coefficient of the dermis layer, and the absorption coefficient μ ₃ indicates the absorption coefficient of the subcutaneous tissue.

Here, ln (A) represents the natural logarithm of A, and N (t) represents the light intensity at the time t of the model of the time-resolved waveform of the short-time pulsed light with the specific wavelength λk. I _in represents the light intensity of the short-time pulsed light irradiated by the irradiation unit 106. N _in indicates the number of photons for which the simulation unit 101 has simulated irradiation.

When the absorption coefficient calculation unit 117 calculates the absorption coefficient μ _{1 to} μ ₃ of each skin layer in an integration interval, the absorption coefficient distribution storage unit 118 calculates the skin in a certain integration interval calculated by the absorption coefficient calculation unit 117. The absorption coefficients μ _{1 to} μ ₃ of each layer are stored (step S16).

When the absorption coefficient calculation unit 117 calculates the absorption coefficient μ _{1 to} μ ₃ of each skin layer in an integration interval, whether the absorption coefficient calculation unit 117 has calculated the absorption coefficient of the dermis layer 33 in the set integration interval or not. Is determined (step S17).
In this embodiment, blood sugar levels are measured with four main components of skin, water, protein, lipid, and glucose, so that the absorption coefficient calculation unit 117 has absorption coefficients for the _four wavelengths λ _{1 to} λ ₄ . It is determined whether μ _{1 to} μ ₃ are calculated. Here, the wavelengths λ _{1 to} λ ₄ are selected from a plurality of wavelengths calculated by the simulation unit 301 for the optical path length distribution and the time-resolved waveform.

Here, when it is determined that there is an absorption coefficient that has not been calculated in the absorption coefficients μ _{1 to} μ ₃ of the dermis layer 33 in the integration interval set by the absorption coefficient calculation unit 117 (step S17: NO), a certain time again Returning to the acquisition of the received light intensity (step S12), the absorption coefficient of the dermis layer that has not yet been calculated is calculated, and it is determined again whether or not the absorption coefficient of the dermis layer can be calculated in the set integration interval (step S17). Do.
On the other hand, when it is determined that the absorption coefficient μ _{1 to} μ ₃ of the dermis layer in the integration interval set by the absorption coefficient calculation unit 117 is calculated (step S17: YES), the absorption coefficient is acquired from the absorption coefficient distribution of the dermis layer. (Step 18).

The absorption coefficient acquisition unit 119 determines whether or not the absorption coefficient of the number of wavelengths corresponding to the number of types of skin main components has been calculated (step S6).
Here, when it is determined that the absorption coefficient acquisition unit 119 has not calculated the absorption coefficient of the number of wavelengths corresponding to the number of main components of the skin (step S6: NO), irradiation with short-time pulsed light (step S1) Returning to step S6, the absorption coefficient of the number of wavelengths corresponding to the number of types of the main component of the skin that has not yet been calculated is calculated, and it is determined again whether the absorption coefficient can be calculated (step S6).

On the other hand, when it is determined that the absorption coefficient acquisition unit 119 has calculated the absorption coefficient of the number of wavelengths corresponding to the number of types of skin main components (step S6: YES), the concentration calculation unit 120 determines the concentration of glucose contained in the dermis layer. Is calculated (step S7).
The concentration calculation unit 120 calculates the glucose concentration in the dermis layer by the following equation (9).

_{However, μ 2 (1) ~μ 2} (4) shows the absorption coefficient of the wavelength lambda ₁ to [lambda] ₄ in the dermis layer.
Further, g ₁ to g ₄ shows the water respectively in the dermal layer is the main component of skin, proteins, lipids, the molar concentration of glucose. _{Further, ε 1 (1) ~ε 1} (4) shows a molar extinction coefficient of water with respect to the wavelength _{λ 1 ~λ 4, ε 2 (} 1) ~ε 2 (4) is for the wavelength lambda ₁ to [lambda] ₄ Indicates the molar extinction coefficient of the protein, ε _{3 (1) to} ε _{3 ( 4)} indicate the molar extinction coefficient of the lipid for wavelengths λ _{1 to} λ ₄ , and ε _{4 (1) to} ε _{4 (4)} indicate the wavelength The molar extinction coefficient of glucose with respect to λ _{1 to} λ ₄ is shown.
That is, by calculating g ₄ in Equation (9), the molar concentration of glucose contained in the dermis layer can be obtained.

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

The blood glucose level measuring apparatus 100 described above has a built-in computer system, and the processing operation of each step described above is stored in a computer-readable recording medium in the form of a program. Therefore, the computer can read out and execute this program to perform the above processing operation.
Here, examples of the computer-readable recording medium include a magnetic disk, a magneto-optical disk, a CD-ROM, a DVD-ROM, and a semiconductor memory.
Further, the computer program may be distributed to the computer via a communication line, and the computer that has received the distribution may execute the program.

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

  As described above, according to the present embodiment, the measurement timing calculation unit 110 causes the time of the trigger signal when the irradiation unit 106 irradiates the pulsed light for a short time and the time of the measurement light intensity output from the light receiving unit 107. Is calculated, and the irradiation amount control unit 121 controls the irradiation amount of the short-time pulse light emitted from the irradiation unit 106 to the observation target. The irradiation amount control unit 121 controls the irradiation amount of the short-time pulse light. Is controlled by the contact determination unit 111 based on the measurement timing output from the measurement timing calculation unit 110, so that the irradiation unit 106 is in close contact with the skin surface. The state of close contact with the skin can be confirmed quickly and easily, and as a result, the glucose concentration in the dermis layer can be accurately measured.

Further, by the integration interval calculation unit 116, the optical path length of each layer of the skin of the model of the optical path length distribution acquired by the optical path length acquisition unit 108 and the time resolution of the short-time pulse light acquired by the non-absorption light intensity acquisition unit 109 Based on the non-absorption light intensity of the waveform model and the intensity distribution of the light received by the light receiving unit 107 acquired by the measurement light intensity acquisition unit 113, an area corresponding to the light intensity of the dermis layer is calculated from the light intensity distribution. Since the integration interval is calculated, based on the integration interval calculated by the integration interval calculation unit 116, by acquiring the light intensity in the time zone corresponding to the integration interval from the light intensity received by the light receiving unit 107, Light from the dermis layer can be measured separately from light from other layers, and the influence of light from other layers on light from the dermis layer can be reduced. Therefore, the glucose concentration in the dermis layer can be accurately measured, and as a result, the glucose concentration in the dermis layer can be quantified non-invasively and accurately.
Moreover, the measurement accuracy of the glucose concentration in the dermis layer can be increased by varying the integration interval.

In the present embodiment, the simulation unit 101 performs the simulation of irradiating light to the skin model having the zero absorption coefficient. However, the simulation unit 101 performs the simulation for the skin model having the zero absorption coefficient. If the simulation result of irradiating light is stored in the optical path length distribution storage unit 103 and the time-resolved waveform storage unit 105, even if the simulation unit 101 is not provided, the same operations and effects as in this embodiment can be achieved. it can.
In addition, the contact determination unit 111 calculates the time difference between the time of the trigger signal when the irradiation unit 106 output from the measurement timing calculation unit 110 emits short-time pulse light and the time of the measurement light intensity output from the light receiving unit 107. Based on a certain measurement timing, it is determined whether or not the irradiation unit 106 is in close contact with the surface of the skin. By continuously performing the determination by the contact determination unit 111, the irradiation unit 106 is It may be determined whether or not it is in close contact with the surface.

[Second Embodiment]
FIGS. 14 and 15 are flowcharts showing the operation of the blood sugar level measuring apparatus (concentration quantifying apparatus) according to the second embodiment of the present invention measuring the blood sugar level.
The blood sugar level measuring apparatus of the present embodiment has the same configuration as the blood sugar level measuring apparatus 100 of the first embodiment, and includes an optical path length acquisition unit 108, a non-absorption light intensity acquisition unit 109, a measurement light intensity acquisition unit 113, and an absorption. The operation of the coefficient calculation unit 117 is different.

Next, a procedure for measuring a blood sugar level using the blood sugar level measuring apparatus 100 will be described.
In the present embodiment, the steps from “irradiation unit 106 irradiates pulsed light for a short time” (step S21) to “determining the adhesion between irradiation unit 106 and skin” (step S23) are the same as those in the first embodiment. Since it is completely the same, description is abbreviate | omitted.

In step S23, when the contact determination unit 111 determines that the irradiation unit 106 is in close contact with the surface of the skin, the absorption interval of the dermis layer is calculated by changing the integration interval (process B: step S24).
This process B (step S24) is performed by the operation shown in FIG.

  First, the integration interval calculation unit 116 (1) determines the minimum detection sensitivity from the time when the light intensity output from the light receiving unit 107 that receives the backscattered light exceeds the minimum detection sensitivity of the measurement light intensity acquisition unit 113. Time until time detected with equal light intensity, (2) time characteristics of non-absorbing light intensity acquired from the time-resolved waveform storage unit 105 storing the non-absorbing light intensity obtained by the simulation unit 101, (3) Using the distance between the light receiving unit 107 and the irradiation unit 16 in contact with the skin surface, and (4) the size and optical characteristics (scattering coefficient, absorption coefficient, anisotropic parameter, or refractive index) of the skin model given to the simulation unit 101 Calculate the integration interval. More specifically, the start time, end time, and increment time of the integration interval are calculated (step S31).

Next, when the light receiving unit 107 completes the light reception, the measurement light intensity acquisition unit 113 acquires a time distribution of the light reception intensity from a certain time to time τ from the light reception intensity recorded in the internal memory (step S32). .
For example, when concentration measurement is performed for three layers of skin using four types of wavelengths, time distributions of received light intensity at _three different times τ _{1 to} τ ₃ are acquired.

When the measurement light intensity acquisition unit 113 acquires the time distribution of the received light intensity during the time τ, the optical path length acquisition unit 108 starts from the optical path length distribution of the wavelength λ ₁ stored in the optical path length distribution storage unit 103 from a certain time. The optical path length of each layer of the skin during time τ, for example, optical path lengths L ₁ (t ₁ ) to L ₁ (t ₃ ), L ₂ (t ₁ ) to L ₂ (t ₃ ), L ₃ (t ₁ ) ~L ₃ acquires _{(t 3)} (step S33).
When the measurement light intensity acquisition unit 113 acquires the time distribution of the received light intensity during the time τ, the non-absorption light intensity acquisition unit 109 calculates the time-resolved waveform of the wavelength λ ₁ stored in the time-resolved waveform storage unit 105. The non-absorption light intensity between a certain time and the time τ, for example, the number of detected photons (non-absorption light intensity) N (t ₁ ) to N (t ₃ ) between the certain time and the time τ is acquired (step S34). ).

When the optical path length acquisition unit 108 acquires the optical path length of each layer of the skin, and the non-absorption light intensity acquisition unit 109 acquires the number of detected photons (non-absorption light intensity) N (t ₁ ) to N (t ₃ ), the absorption coefficient The calculation unit 117 calculates the absorption coefficients μ _{1 to} μ ₃ of each layer of the skin in a certain integration interval calculated by the integration interval calculation unit 116 based on the equation (10) (step S35). Here, the absorption coefficient μ ₁ indicates the absorption coefficient of the epidermis layer, the absorption coefficient μ ₂ indicates the absorption coefficient of the dermis layer, and the absorption coefficient μ ₃ indicates the absorption coefficient of the subcutaneous tissue layer.

Here, ln (A) represents the natural logarithm of A. Further, I (t) indicates the light reception intensity of the light receiving unit 107 at time t, and I _in indicates the light intensity of the short-time pulsed light irradiated by the irradiation unit 106. N (t) represents the number of detected photons at time t of the time-resolved waveform, and N _in represents the number of photons on which the simulation unit 301 has simulated the irradiation. L ₁ (t) to L ₃ (t) indicate the optical path length of each layer of the skin at time t.

When the absorption coefficient calculation unit 117 calculates the absorption coefficient μ _{1 to} μ ₃ of each skin layer in an integration interval, the absorption coefficient distribution storage unit 118 calculates the skin in a certain integration interval calculated by the absorption coefficient calculation unit 117. The absorption coefficients μ _{1 to} μ ₃ of each layer are stored (step S36).

When the absorption coefficient calculation unit 117 calculates the absorption coefficient μ _{1 to} μ ₃ of each layer of the skin in an integration interval, whether the absorption coefficient calculation unit 117 has calculated the absorption coefficient of the dermis layer in the set integration interval or not. Is determined (step S37).
In this embodiment, blood sugar levels are measured with four main components of skin, water, protein, lipid, and glucose, so that the absorption coefficient calculation unit 117 has absorption coefficients for the _four wavelengths λ _{1 to} λ ₄ . It is determined whether μ _{1 to} μ ₃ are calculated. Here, the wavelengths λ _{1 to} λ ₄ are selected from a plurality of wavelengths calculated by the simulation unit 101 for the optical path length distribution and the time-resolved waveform.

Here, when it is determined that there is an absorption coefficient that has not been calculated in the absorption coefficient μ _{1 to} μ ₃ of the dermis layer in the integral interval set by the absorption coefficient calculation unit 117 (step S37: NO), again at a certain time. Returning to the acquisition of the received light intensity (step S32), the absorption coefficient of the dermis layer that has not been calculated yet is calculated, and it is determined again whether or not the absorption coefficient of the dermis layer can be calculated in the set integration interval (step S37). .
On the other hand, when it is determined that the absorption coefficient μ _{1 to} μ ₃ of the dermis layer in the integration interval set by the absorption coefficient calculation unit 117 is calculated (step S37: YES), the absorption coefficient is acquired from the absorption coefficient distribution of the dermis layer. (Step 38).

The absorption coefficient acquisition unit 119 determines whether or not the absorption coefficient of the number of wavelengths corresponding to the number of types of the main components of the skin has been calculated (step S25).
Here, when it is determined that the absorption coefficient acquisition unit 119 has not calculated the absorption coefficient of the number of wavelengths corresponding to the number of types of main components of the skin (step S25: NO), irradiation with short-time pulsed light (step S21) Returning to FIG. 5, the absorption coefficient of the number of wavelengths corresponding to the number of types of the main component of the skin that has not been calculated yet is calculated, and it is determined again whether or not the absorption coefficient can be calculated (step S25).

  On the other hand, when it is determined that the absorption coefficient acquisition unit 119 has calculated the absorption coefficient of the number of wavelengths corresponding to the number of types of main components of the skin (step S25: YES), the concentration calculation unit 120 calculates the above equation (9). Based on this, the concentration of glucose contained in the dermis layer is calculated (step S26).

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

As described above, each embodiment of the present invention has been described with reference to the drawings. However, the specific configuration is not limited to the above-described one, and various design changes and the like can be made without departing from the scope of the present invention. Is possible.
For example, in each of the above embodiments, the blood sugar level measuring device is used as the concentration determination device, the skin of a human palm is used as the observation target, glucose is used as the target component, and short-time pulsed light is used as the pulsed light. Although the case of measuring the concentration of glucose contained in the dermal layer of the present invention is not limited to this, the concentration determination method is not limited to this, and the concentration of the target component in an arbitrary layer to be observed formed from a plurality of light scattering medium layers May be used in other devices for quantitative determination, and short-time pulsed light with a specific wavelength may be replaced with continuous light with a specific wavelength.
For example, when it is applied to a portable skin main component concentration measuring apparatus, it can be effectively used for examination, diagnosis and treatment of skin diseases.

DESCRIPTION OF SYMBOLS 100 ... Blood glucose level measuring apparatus (concentration quantification apparatus), 103 ... Optical path length distribution storage part, 105 ... Time-resolved waveform storage part, 106 ... Irradiation part, 107 ... Light receiving part, 108 ... Optical path length acquisition part, 109 ... Non-absorption light Intensity acquisition unit (light intensity model acquisition unit), 113 ... Measurement light intensity acquisition unit (light intensity acquisition unit), 116 ... Integration interval calculation unit, 117 ... Absorption coefficient calculation unit, 118 ... Absorption coefficient distribution storage unit,
120 ... Concentration calculation part, 121 ... Irradiation amount control part, 31 ... Skin (observation object), 33 ... Dermal layer (
Arbitrary layer), S1 to S6, S11 to S18, S21 to S26, S31 to S38 ... step

In order to solve the above problems, the present invention employs the following concentration determination apparatus, concentration determination method, and program.
The concentration quantification device of the present invention is a concentration quantification device for quantifying the concentration of glucose in the skin as an observation target, an irradiation unit for irradiating the observation target with a short-time pulsed light, and the short-time pulsed light A light receiving unit that receives light backscattered from the observation target due to irradiation, and the light receiving unit receives a light intensity that is greater than or equal to a predetermined intensity within a predetermined time from the emission time of the short-time pulsed light to the observation target Whether or not the irradiation unit and the observation target are in a close contact state, a contact determination unit for notifying the determination result of the contact determination unit, and the light receiving unit receiving light And a concentration calculating unit that calculates the concentration of glucose using the intensity of the light.
That is, the concentration quantification device of the present invention is a concentration quantification device for quantifying the concentration of a target component in an arbitrary layer among observation targets composed of a plurality of layers, and irradiates the observation target with short-time pulsed light. An irradiating unit, a light receiving unit that receives light scattered back from the observation target by irradiation of the short-time pulsed light, and each of the plurality of layers of short-time pulsed light irradiated to the observation target An optical path length distribution storage unit that stores a model of an optical path length distribution in the layer; an optical path length acquisition unit that acquires an optical path length of each of the plurality of layers at a predetermined time of the optical path length distribution model; and A time-resolved waveform storage unit that stores a model of a time-resolved waveform of short-time pulsed light that is irradiated to an observation target; and a light intensity model acquisition unit that acquires a light intensity at the predetermined time of the model of the time-resolved waveform An irradiation amount control unit for controlling the irradiation amount of the short-time pulse light irradiated from the irradiation unit to the observation target by performing preliminary irradiation of the short-time pulse light from the irradiation unit to the observation target; and the irradiation amount After the amount of irradiation of the short-time pulsed light is controlled by the control unit, measure the light intensity at each time the light-receiving unit receives light with reference to the start time of incidence of the short-time pulsed light on the observation target, A contact determination unit that determines whether or not the irradiation unit and the observation target are in a close contact state based on a relationship between a time at which the light receiving unit starts detecting backscattered light from the observation target and an intensity; When the determination unit determines that the irradiation unit and the observation target are in close contact with each other, a light intensity acquisition unit that acquires the intensity of the light received by the light receiving unit, and the light intensity acquisition unit acquired Light intensity distribution of light intensity The absorption for calculating the absorption coefficient of the arbitrary layer based on the optical path length of each of the plurality of layers acquired by the optical path length acquisition unit and the light intensity model acquired by the light intensity model acquisition unit A coefficient calculator, and a concentration calculator that calculates the concentration of the target component in the arbitrary layer based on the absorption coefficient calculated by the absorption coefficient calculator.

Claims (10)

A concentration quantification device for quantifying the concentration of a target component in an arbitrary layer among observation targets composed of a plurality of layers,
An irradiation unit for irradiating the observation target with a short-time pulsed light;
A light receiving unit that receives light scattered back from the observation target by irradiation with the short-time pulsed light;
An optical path length distribution storage unit for storing a model of an optical path length distribution in each of the plurality of layers of short-time pulse light irradiated to the observation target;
An optical path length acquisition unit that acquires an optical path length of each of the plurality of layers at a predetermined time of the optical path length distribution model;
A time-resolved waveform storage unit that stores a model of a time-resolved waveform of a short-time pulsed light irradiated to the observation target;
A light intensity model acquisition unit for acquiring light intensity at the predetermined time of the model of the time-resolved waveform;
An irradiation amount control unit that controls the irradiation amount of the short-time pulse light irradiated from the irradiation unit to the observation target by performing preliminary irradiation of the short-time pulse light from the irradiation unit to the observation target;
After the irradiation amount control unit controls the irradiation amount of the short-time pulsed light, the light intensity at each time received by the light-receiving unit is measured with reference to the start time of incidence of the short-time pulsed light on the observation target. A contact determination unit that determines whether or not the irradiation unit and the observation target are in a close contact state based on a relationship between the time when the light receiving unit starts to detect backscattered light from the observation target and the intensity; ,
A light intensity acquisition unit that acquires the intensity of the light received by the light receiving unit when the contact determination unit determines that the irradiation unit and the observation target are in a contact state;
The light intensity distribution of the light intensity acquired by the light intensity acquisition unit, the optical path length of each of the plurality of layers acquired by the optical path length acquisition unit, and the light intensity acquired by the light intensity model acquisition unit An absorption coefficient calculation unit for calculating an absorption coefficient of the arbitrary layer based on the model;
Based on the absorption coefficient calculated by the absorption coefficient calculation unit, a concentration calculation unit that calculates the concentration of the target component in the arbitrary layer;
A concentration quantification apparatus comprising:   The contact determination unit selects the intensity of direct propagation light propagating on the surface of the observation target and the intensity of backscattered light from the observation target as the light intensity at each time received by the light receiving unit, and the direct propagation The concentration quantification apparatus according to claim 1, wherein when the intensity of light is 1/10 or less of the intensity of the backscattered light, the irradiation unit and the observation target are determined to be in a close contact state.   The concentration determination apparatus according to claim 1, wherein the contact determination unit includes a notification unit that notifies a result of determining whether or not the irradiation unit and the observation target are in a contact state. . The contact determination unit continuously determines whether or not the irradiation unit and the observation target are in a close contact state, and obtains the light intensity when the irradiation unit and the observation target are determined to be in a close contact state. Obtains the intensity of the light received by the light receiving unit,
When it is determined that the irradiation unit and the observation target are not in a close contact state, the irradiation amount control unit performs preliminary irradiation of pulsed light from the irradiation unit to the observation target, so that the irradiation unit and the observation target 4. The method according to claim 1, wherein the irradiation amount of the short-time pulse light applied to the observation target is controlled to determine again whether or not the irradiation unit and the observation target are in close contact with each other. 1. The concentration determination apparatus according to item 1. The light intensity distribution of the light intensity acquired by the light intensity acquisition unit, the optical path length of each of the plurality of layers acquired by the optical path length acquisition unit, and the light intensity acquired by the light intensity model acquisition unit An integration interval calculation unit that calculates an integration interval that is a time range of a region corresponding to the light intensity distribution of the arbitrary layer from the light intensity distribution based on the model;
The said absorption coefficient calculation part changes the said integration area calculated by the said integration area calculation part, and calculates the absorption coefficient of the target component in the said arbitrary layers. The concentration determination apparatus described. The light intensity acquisition unit acquires light intensities at a plurality of times t _{1 to} t _{m that} are equal to or greater than the number n of the observation target layers (where n is a natural number of 1 or more, m is a natural number of n or more),
The absorption coefficient calculation unit
Ln (·) indicating the natural logarithm, I (t) indicating the light intensity received by the light receiving unit at time t, and N (t) indicating the light intensity at time t of the time-resolved waveform model of the short-time pulsed light , Li (t) indicating the optical path length of the i-th layer at time t in the model of the optical path length distribution, and μ _i indicating the absorption coefficient of the i-th layer,

Calculate the absorption coefficient of any layer from
The concentration determination apparatus according to any one of claims 1 to 5, wherein the concentration determination apparatus according to any one of claims 1 to 5 is provided. The light intensity acquisition unit acquires a light intensity during a predetermined time τ from a predetermined time,
The absorption coefficient calculation unit
Ln (·) indicating the natural logarithm, I (t) indicating the light intensity received by the light receiving unit at time t, and N (t) indicating the light intensity at time t of the time-resolved waveform model of the short-time pulsed light , Li (t) indicating the optical path length of the i-th layer at time t in the optical path length distribution model, n indicating the number of layers to be observed, and μi indicating the absorption coefficient of the i-th layer,

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

Calculate the concentration of the target component in the arbitrary layer from
8. The concentration quantification apparatus according to claim 1, wherein An irradiating unit that irradiates an observation target composed of a plurality of layers with a short-time pulse light, a light-receiving unit that receives light scattered back from the observation target by the irradiation of the short-time pulse light, and the observation target An optical path length distribution storage unit for storing a model of an optical path length distribution in each of the plurality of layers, and a time-resolved waveform of the short-time pulse light irradiated to the observation target. A time-resolved waveform storage unit that stores a model, and a concentration quantification method using a concentration quantification device that quantifies the concentration of a target component in an arbitrary layer of the observation target,
The irradiation unit irradiates the observation target with short-time pulsed light,
The light receiving unit receives light backscattered from the observation target by irradiation with the short-time pulsed light,
The irradiation amount control unit performs preliminary irradiation of the short-time pulse light from the irradiation unit to the observation target, and controls the irradiation amount of the short-time pulse light irradiated from the irradiation unit to the observation target,
After the irradiation amount control unit controls the irradiation amount of the short-time pulse light, the contact determination unit receives the light reception on the basis of the start time of incidence of the short-time pulse light output from the irradiation unit on the observation target. Whether the irradiation unit and the observation target are in close contact with each other based on the relationship between the intensity and the time when the light receiving unit starts detecting the backscattered light. Determine
The light intensity acquisition unit acquires the intensity of the light received by the light receiving unit when the contact determination unit determines that the irradiation unit and the observation target are in a close contact state,
The optical path length acquisition unit acquires the optical path length of each of the plurality of layers at a predetermined time of the optical path length distribution model,
The light intensity model acquisition unit acquires the light intensity at the predetermined time of the model of the time-resolved waveform of the short-time pulsed light from the time-resolved waveform storage unit,
The light intensity acquired by the light intensity acquisition unit by the absorption coefficient calculation unit, the optical path length of each of the plurality of layers acquired by the optical path length acquisition unit, and the light acquired by the light intensity model acquisition unit Based on the strength, calculate the absorption coefficient of the target component in the arbitrary layer,
Based on the absorption coefficient calculated by the absorption coefficient calculation unit, the concentration calculation unit calculates the concentration of the target component in the arbitrary layer.
Concentration determination method characterized by this. An irradiating unit that irradiates an observation target composed of a plurality of layers with a short-time pulse light, a light-receiving unit that receives light scattered back from the observation target by the irradiation of the short-time pulse light, and the observation target An optical path length distribution storage unit for storing a model of an optical path length distribution in each of the plurality of layers, and a time-resolved waveform of the short-time pulse light irradiated to the observation target. A time-resolved waveform storage unit that stores a model, and a computer of a concentration quantification device that quantifies the concentration of a target component in any layer of the observation target,
An irradiation procedure for irradiating the observation object with the short-time pulsed light,
A light receiving procedure for receiving light backscattered from the observation target by irradiation with the short-time pulsed light,
A dose control procedure for controlling the dose of short-time pulsed light irradiated from the irradiation unit to the observation target by performing preliminary irradiation of the short-time pulsed light from the irradiation unit to the observation target;
After the irradiation amount of the short-time pulse light is controlled by the irradiation amount control procedure, the light intensity at each time received by the light-receiving procedure with reference to the start time of incidence of the short-time pulse light on the observation target is determined. A contact determination procedure for measuring and determining whether or not the irradiation unit and the observation target are in a close contact state based on the relationship between the intensity and the time when the light reception procedure starts detecting backscattered light from the observation target ,
A light intensity acquisition procedure for acquiring the intensity of the light received by the light receiving procedure when it is determined by the contact determination procedure that the irradiation unit and the observation target are in a contact state;
An optical path length acquisition procedure for acquiring an optical path length of each of the plurality of layers at a predetermined time of the optical path length distribution model from the optical path length distribution storage unit;
A light intensity model acquisition procedure for acquiring the light intensity at the predetermined time of the model of the time-resolved waveform of the short-time pulsed light from the time-resolved waveform storage unit;
The light intensity distribution acquired by the light intensity acquisition procedure, the optical path length of each of the plurality of layers acquired by the optical path length acquisition means, and the light intensity acquired by the light intensity model acquisition procedure Based on the above, an absorption coefficient calculation procedure for calculating the absorption coefficient of the arbitrary layer,
A concentration calculation procedure for calculating the concentration of the target component in the arbitrary layer based on the absorption coefficient calculated by the absorption coefficient calculation procedure;
A program characterized by having executed.

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