JP5552819B2 - Concentration measuring device - Google Patents

Description

  The present invention relates to a concentration measuring apparatus and is suitable for measuring hemoglobin concentration, for example.

  2. Description of the Related Art Conventionally, there has been proposed an apparatus that non-invasively measures the concentration of a specific component of a living body by irradiating a test site with a predetermined band of light and analyzing the light reflected from the test site (for example, a patent) Reference 1).

  In this apparatus, a first light source that irradiates light having a wavelength that is absorbed by a biological component that is a measurement target, and a component that is not absorbed by the biological component that is the measurement target and has a larger component amount in the living body than the measurement target And a second light source that emits light having a wavelength that is absorbed by the light source.

  Then, a living body that is a measurement target is obtained by a multiple regression analysis of the scattered light intensity of the wavelength corresponding to the first light source, the scattered light intensity of the wavelength corresponding to the second light source, and the biological component concentration corresponding to them. The component concentration is determined.

JP 2009-273719 A

  By the way, the first and second light sources are preferably LEDs (Light Emitting Diodes) compared to lasers in terms of miniaturization and the like. However, when an LED is applied, the intensity of light emitted from the LED shows a peak at the central wavelength, but a wavelength close to the central wavelength also exhibits a certain intensity. That is, the wavelength of light emitted from the LED is not a single wavelength but has a certain wavelength width.

  Therefore, the absorption characteristics of components other than the biological component that is the measurement target are also reflected, and the reliability of the concentration of the biological component that is the measurement target becomes poor.

  The present invention has been made in consideration of the above points, and intends to propose a concentration measuring apparatus capable of improving measurement accuracy.

In order to solve such a problem, the present invention is a concentration measuring apparatus, which includes light having different central wavelengths of N or more types (N is a natural number of 1 or more) of types of measurement substances to be measured. Multiple light emitting diodes that irradiate sequentially for each central wavelength, transmittance calculation means that calculates the transmittance of light emitted from the light emitting diodes and transmitted through the human body for each central wavelength, and the concentration per unit optical path length of each measured substance A plurality of equations generated by generating, for each central wavelength, an equation that expresses the transmittance by the sum of values obtained by multiplying the unit length concentration of each measurement substance by the absorption coefficient of the measurement substance, with each unit length concentration as a variable. the and a concentration calculation means for calculating a unit length measured concentration of substances respectively by solving the multiple simultaneous equations, the reference light-emitting diodes to be a reference of the light-emitting diodes, As compared to the light-emitting diodes, the linear distance between the particular and the center wavelength of the wavelength variation width of transmittance appears greater for the wavelength for the particular analyte, wavelength at which the intensity of said central wavelength half value of the measured substance, It is set narrower than other light emitting diodes.

In the present invention, successively to irradiate, discrete transmittance is obtained taking the absorption spectrum of the light passing through the human body, multiplied by the absorption coefficient in the unit length density per analyte light a different central wavelengths from each other An equation expressing the transmittance is generated for each central wavelength by adding the obtained values, and these are solved simultaneously. Therefore, it is possible to accurately calculate a plurality of unit length concentrations as compared with the case where the transmittance of light having a wavelength at which the measurement substance exhibits an absorption peak is obtained.
In the present invention also a straight line distance between the wavelength at which half of the intensity in a light-emitting diode for emitting light of the reference center wavelength and narrower than the light-emitting diode for emitting light of another center wavelength.
Therefore, the transmittance reflected by the plurality of substances can be obtained with high resolution, and as a result, the concentration per unit optical path length of the measurement substance can be accurately calculated.

It is the schematic which shows the structure of a density | concentration measuring apparatus. It is the schematic where it uses for description of reflection in a human body epidermis. It is the schematic which shows the structure of a measurement part. It is the schematic which shows the functional structure of CPU in the light absorption coefficient calculation mode. It is a photograph which shows a color sample example. It is a graph with which it uses for description of the transition of the calculation result process in the light absorption coefficient calculation mode. It is the schematic which shows the functional structure of CPU in density | concentration measurement mode. It is a graph with which it uses for description of transition of the calculation result process in density | concentration measurement mode. It is the schematic which shows the example of a density | concentration display screen. It is the schematic where it uses for description of the wavelength characteristic of LED. It is a graph which shows the absorption spectrum of a human body epidermis. It is a graph which shows the error of the measured value according to the wavelength width of irradiation light.

Hereinafter, modes for carrying out the invention will be described. The description will be in the following order.
<1. Embodiment>
[1-1. Configuration of concentration measuring device]
[1-2. Configuration of measurement unit]
[1-3. Absorption coefficient calculation mode]
[1-4. Concentration measurement mode]
[1-5. Measurement accuracy improvement measures]
[1-6. Effect]
<2. Other embodiments>

<1. Embodiment>
[1-1. Configuration of concentration measuring device]
FIG. 1 shows a concentration measuring apparatus 1 according to this embodiment. The concentration measuring apparatus 1 includes an irradiation unit 10, a light receiving unit 20, and a measurement unit 30.

  The irradiating unit 10 includes five light emitting diodes (hereinafter also referred to as LEDs) that irradiate light having different wavelengths as central wavelengths as light sources. The irradiation unit 10 irradiates light emitted from these light sources from an incident direction that is oblique to the irradiation surface IF.

  In this embodiment, glycated hemoglobin is selected as one of the substances whose concentration is to be measured. It was confirmed by the present inventors that the wavelength that markedly shows the difference in extinction coefficient between this glycated hemoglobin and other hemoglobins (oxygenated hemoglobin and reduced hemoglobin) is 580 [nm] or several wavelengths in the vicinity thereof. . Therefore, the center wavelength of one of the five LEDs in the irradiation unit 10 is 580 [nm], and the center wavelengths of the other LEDs are around 500 [nm] and 540 [nm], which are around 580 [nm]. , 620 [nm] and 660 [nm].

  When light in the visible region is irradiated obliquely with respect to the irradiation surface IF, as shown in FIG. 2, it enters the human body surface and is regularly reflected at the interface between the basal layer and dermis layer of the epidermis (squamous epithelium), It passes through the human epidermis (between the basal layer and the human body surface) and exits from the human body surface.

  The light receiving unit 20 receives light transmitted through the human body surface from the interface between the base layer and the dermis layer (hereinafter also referred to as epidermal transmitted light), and sends the light reception result to the measurement unit 30.

  The measuring unit 30 uses Lambert-Beer law. The Lambert-Beer law is that the absorbance is A, the concentration per unit optical path length [mol / L · cm] (hereinafter referred to as unit length concentration) is cl, and the molar extinction coefficient (hereinafter simply referred to as the extinction coefficient). Where ε is

  A = ε · cl (1)

Represented as:

  Absorbance A is expressed by the following equation, where transmittance is t.

  A = log (1 / t) (2)

Since it can be expressed by the common logarithm of the transmittance t as shown in FIG.

  log (1 / t) = ε · cl (3)

The relationship is established.

  The measurement unit 30 has a mode for calculating an extinction coefficient of a substance (hereinafter also referred to as an extinction coefficient calculation mode) and a mode for measuring the concentration of the substance (hereinafter also referred to as a concentration measurement mode).

  When executing the extinction coefficient calculation mode, the measurement unit 30 calculates the extinction coefficient of the substance using the equation (3), and registers the extinction coefficient.

  On the other hand, when the concentration measurement mode is executed, the measurement unit 30 calculates the concentrations of a plurality of substances including glycated hemoglobin using the extinction coefficient calculated in the extinction coefficient calculation mode and the equation (3). And the measurement part 30 memorize | stores these density | concentrations, and shows the transition of the said density | concentration as needed.

[1-2. Configuration of measurement unit]
As shown in FIG. 3, the measurement unit 30 is configured by connecting various hardware to a CPU (Central Processing Unit) 41 that controls the control.

  Specifically, a ROM (Read Only Memory) 42, a RAM (Random Access Memory) 43 serving as a work memory of the CPU 41, an operation input unit 44 for inputting a command according to a user operation, an interface unit 45, a display unit 46, and a storage The unit 47 is connected via the bus 48.

  The ROM 42 stores a program for executing an extinction coefficient calculation mode (hereinafter also referred to as a coefficient calculation program) and a program for executing a concentration measurement mode (hereinafter also referred to as a concentration measurement program). The The interface unit 45 is connected to the irradiation unit 10 and the light receiving unit 20 via a dedicated transmission path, and can be connected to other devices via a wired or wireless transmission path.

  A liquid crystal display, an EL (Electro Luminescence) display, or the like is applied to the display unit 46. For the storage unit 47, a magnetic disk represented by HD (Hard Disk), a semiconductor memory, an optical disk, or the like is applied. A removable memory (portable memory) such as a USB (Universal Serial Bus) memory or a CF (Compact Flash) memory may be applied.

  The CPU 41 expands, in the RAM 43, a program corresponding to a command given from the operation input unit 44 among the plurality of programs stored in the ROM 42, and the interface unit 45, the display unit 46, or the storage unit 47 is loaded according to the expanded program. Control as appropriate.

[1-3. Absorption coefficient calculation mode]
When the CPU 41 expands the coefficient calculation program corresponding to the command for calculating the extinction coefficient from the operation input unit 44 in the RAM 43, as shown in FIG. 4, the substance determination unit 51, the drive control unit 52, and the reflectance calculation unit 53. , Function as a unit length concentration difference acquisition unit 54 and an extinction coefficient calculation unit 55.

  The substance determining unit 51 determines a substance that is set in advance or designated as a measurement target from the operation input unit 44 as a substance whose extinction coefficient is to be calculated. In this embodiment, three types of hemoglobin (oxygenated hemoglobin, reduced hemoglobin, and glycated hemoglobin) are designated as measurement targets and melanin is set as a substance whose extinction coefficient is to be calculated.

  The drive control unit 52 drives the irradiation unit 10 to sequentially drive the five LEDs for each predetermined irradiation period, and drives the light receiving unit 20 to acquire light received during the irradiation period as data. .

  The reflectance calculation unit 53 includes a color sample (hereinafter also referred to as a target color sample) associated with a substance determined to calculate an extinction coefficient, and a color sample that serves as a reference for the color sample (hereinafter also referred to as a reference color sample). The reflectance is calculated.

  For example, as shown in FIG. 5, the reference color sample and the target color sample are prepared as a comparison table between colors and identifiers such as substance names and numbers. The target color sample is a sample of a color that is exhibited when the unit length concentration of the substance whose extinction coefficient is to be calculated is different from the reference color sample.

  In the following, the target color sample corresponding to the unit length density difference between the oxygenated hemoglobin and the reference color sample is referred to as an OxyHb color sample, and the target corresponding to the unit length density difference between the reduced hemoglobin and the reference color sample. The color sample is called an Hb color sample. The target color sample corresponding to the unit length density difference between the glycated hemoglobin and the reference color sample is called an HbA1c color sample, and the target color sample corresponding to the unit length density difference between the melanin and the reference color sample is melanin. Called a color sample.

  Here, a specific method for obtaining the reflectance is given as an example. As a first step, the reflectance calculation unit 53 determines a color sample to be acquired from among a reference color sample, an OxyHb color sample, an Hb color sample, an HbA1c color sample, and a melanin color sample.

  As a second step, the reflectance calculation unit 53 notifies the irradiation surface IF of the irradiation unit 10 that the color sample to be acquired should be arranged using, for example, the display unit 46 and the light reception unit 20 receives the light. Start getting results.

  As a third stage, the reflectance calculation unit 53 calculates the ratio of the amount of received light to the amount of irradiation light (the reflectance of the color sample) in units of the LED irradiation period (FIG. 6A).

  In this way, the processes from the first stage to the third stage are performed until all the spectra in the reference color sample, the OxyHb color sample, the Hb color sample, the HbA1c color sample, and the melanin color sample are acquired. Incidentally, in FIG. 7, for convenience, a part of the melanin sample is omitted.

  The unit length concentration acquisition unit 54 is a unit length between the reference color sample in the color sample (OxyHb color sample, Hb color sample, HbA1c color sample, melanin color sample) associated with the substance determined by the substance determination unit 51. Get the density difference.

  The unit length density difference from the reference color sample corresponds to “cl” on the right side of the equation (3). As a specific method for obtaining the unit length density difference, for example, the unit length density difference between the reference color sample in the color sample associated with the substance determined by the substance determination unit 51 from the operation input unit 44 is calculated. There is a method to input.

  As another example, a server holding a substance and a unit length density difference control database is accessed, and a unit length density difference between a color sample associated with the substance determined by the substance determination unit 51 and a reference color sample is downloaded. There is a technique to do.

  In addition, the storage unit 47 stores a reference database of the substance and unit length concentration difference, and from the storage unit 47 to the reference color sample in the color sample associated with the substance determined by the substance determination unit 51. There is a method of reading the unit length density difference.

  However, the method for obtaining the unit length density difference from the reference color sample is not limited to these exemplified methods, and methods other than the exemplified methods can be widely adopted.

  The extinction coefficient calculation unit 55 acquires the reflectance of all the color samples associated with the substance determined to calculate the extinction coefficient, and acquires the unit length density difference between the color sample and the reference color sample. In such a case, the extinction coefficient is calculated using these.

  Here, a specific method for calculating the extinction coefficient is given as an example. As a first stage, the extinction coefficient calculation unit 55 calculates the logarithm of the reciprocal of each of the reflectances at five wavelengths (the central wavelengths of the five LEDs in the irradiation unit 10) (FIG. 6B). The logarithm of the reciprocal of this reflectance corresponds to “log (1 / t)” on the left side of equation (3).

  As a second stage, the extinction coefficient calculation unit 55 calculates the logarithm of the reciprocal of the reflectance for the five wavelengths in the reference color sample and the reflectance for the five wavelengths in the OxyHb color sample, the Hb color sample, the HbA1c color sample, and the melanin color sample. The difference between the reciprocal number and the logarithm is calculated (FIG. 6C).

  As a third stage, the extinction coefficient calculation unit 55 calculates the difference and the unit length density difference between the reference color sample acquired by the unit length density acquisition unit 54 by substituting into the equation (3). As a result, as shown in FIG. 6D, the extinction coefficients of oxyhemoglobin, reduced hemoglobin, glycated hemoglobin, and melanin determined by the substance determination unit 51 are calculated.

  When the extinction coefficient calculation unit 55 calculates the extinction coefficients of oxyhemoglobin, reduced hemoglobin, glycated hemoglobin, and melanin, the extinction coefficient is registered in the storage unit 47 and recorded.

[1-4. Concentration measurement mode]
On the other hand, when the CPU 41 develops in the RAM 43 a concentration measurement program corresponding to a command whose concentration should be measured from the operation input unit 44, as shown in FIG. 7, the drive control unit 52, the transmittance acquisition unit 61, and the extinction coefficient reading. Functions as a unit 62, an epidermis transmission characteristic analysis unit 63, a concentration calculation unit 64, and a graph presentation unit 65.

  As described above, the drive control unit 52 drives the irradiation unit 10 to sequentially drive the five LEDs for each predetermined irradiation period, and causes the light receiving unit 20 to receive light received during the irradiation period as data. Drive to get.

  The transmittance acquisition unit 61 acquires the transmittance of light (see FIG. 2) that passes through the human epidermis (the layer between the basal layer and the human body surface) disposed on the irradiation surface IF of the irradiation unit 10.

  Here, a specific method for obtaining the transmittance is given as an example. As a first step, the transmittance acquisition unit 61 notifies that the living body part should be arranged with respect to the irradiation surface IF of the irradiation unit 10 using, for example, the display unit 46 and acquires the light reception result in the light receiving unit 20. Is started. In this embodiment, the living body portion to be disposed on the irradiation surface IF is the finger pad surface of the finger.

  The skin transmitted light corresponding to each LED in the irradiation unit 10 enters the light receiving unit 20 for each irradiation period of the LED.

  As a second stage, the transmittance acquisition unit 61 calculates the ratio of the amount of received light to the amount of irradiation light (skin transmission light rate) in units of LED irradiation periods (FIG. 8A).

  The extinction coefficient reading unit 62 reads out extinction coefficients of melanin, reduced hemoglobin, oxidized hemoglobin, and glycated hemoglobin registered in the extinction coefficient calculation mode from the storage unit 47 (FIGS. 8B to 8E).

  The skin transmission characteristic analysis unit 63 calculates the extinction coefficient in the extinction coefficient calculation mode using the epidermal transmission light rate acquired by the transmitted light rate calculation unit 61 and the extinction coefficient read by the extinction coefficient reading unit 62. The unit length concentration of the obtained substance and the reflectance at the interface between the basal layer and the dermis layer are calculated.

  In the human epidermis, melanin having a unit length concentration larger than the unit length concentration of the three types of hemoglobin specified as the measurement target is interposed. In the human epidermis, the visible light irradiated from the irradiation unit 10 is reflected before reaching the interface between the basal layer and the dermis layer. Specifically, as shown in FIG. 2, there are reflection on the surface of the human body and irregular reflection on the human body skin. For this reason, the epidermal transmitted light (the light that specularly reflects the interface between the basal layer and the dermis layer and passes through the human epidermis) is reflected at the interface between the basal layer and the dermis layer (hereinafter referred to as the human body interface). (Also called reflectance) is greatly involved.

  Therefore, in the epidermal transmission characteristic analysis unit 63, in addition to the unit length concentrations of the three types of hemoglobin designated as the measurement target, the unit length concentration of melanin larger than the unit length concentration of the hemoglobin, the basal layer and the dermis layer The reflectance at the interface is the calculation target.

  Specifically, the absorbance of the human epidermis is LogS, the unit length extinction coefficient of melanin is Mn, the unit length extinction coefficient of reduced hemoglobin is Hb, the unit length extinction coefficient of oxyhemoglobin is HbO2, and the unit length of glycated hemoglobin Assuming that the extinction coefficient is HbA1c and the human body interface reflectance is D, the equation (3) can be expressed by the following equation:

Mn · ε1 + Hb · ε2 + HbO2 · ε3 + HbA1c · ε4 + D
= -LogS (4)

It becomes.

  Therefore, the skin transmission characteristic analysis unit 63 calculates the skin transmission light rate acquired by the transmission light rate calculation unit 61 and the extinction coefficient read by the extinction coefficient reading unit 62 for each wavelength with respect to the equation (4). And a five-way simultaneous equation is generated as shown in FIG.

  The skin permeation characteristic analysis unit 63 solves the five-way simultaneous equations to obtain the unit length concentration of the substance for which the extinction coefficient is calculated in the extinction coefficient calculation mode and the reflectance at the interface between the base layer and the dermis layer. Is calculated.

  Incidentally, in the quinary simultaneous equation shown in FIG. 8F, the unit length extinction coefficient Mn of melanin is 1.47E-5 [mol / L · cm], and the unit length extinction coefficient Hb of reduced hemoglobin is 1.47E-5 [ mol / L · cm]. In addition, the unit length extinction coefficient HbO2 of oxyhemoglobin is 2.52E-5 [mol / L · cm], the unit length extinction coefficient HbA1c of glycated hemoglobin is 0.18E-5 [mol / L · cm], and reflection in the human body interface The rate D is 0.3.

  The concentration calculation unit 64 uses the unit length concentration of the substance calculated by the epidermis permeation characteristic analysis unit 63 to determine the substance (melanin, oxygenated hemoglobin, reduced hemoglobin, glycated hemoglobin) determined as a calculation target in the extinction coefficient calculation mode. Calculate the concentration.

  Specifically, the concentration of melanin is calculated using the unit length concentration of melanin and the average of the distance between the basal layer in the human body and the surface of the human body, for example.

  On the other hand, using the unit length concentrations of the three types of hemoglobin and the average of the distances between the basal layer and the human body surface in the human body, the hemoglobin concentration is calculated. Incidentally, in the human epidermis, capillaries including hemoglobin are in the vicinity of the basal layer, and the basal layer is approximately constant from the surface of the human body.

  When the concentrations of melanin, oxyhemoglobin, reduced hemoglobin, and glycated hemoglobin are calculated, the concentration calculation unit 64 stores these concentrations in the storage unit 47 in association with the date and time of the calculation.

  When the concentration is calculated by the concentration calculation unit 64 or when there is an instruction to present the concentration from the operation input unit 44, the graph presentation unit 65 associates the concentration stored in the storage unit 47 with the concentration. For example, the display screen shown in FIGS. 9A to 9D is displayed on the display unit 46 using the recorded date.

  On this display screen, a graph (hereinafter referred to as a concentration transition graph) PGF with the vertical axis as the density at the center of the screen and the horizontal axis as the date and time (hereinafter referred to as a concentration transition graph) is displayed for each type. The upper and lower limits of the range to be shown are shown, and the concentration trend is plotted.

  A comment CM for the overall trend state in the concentration is attached immediately above the concentration transition graph PGF, and when the plot indicating the trend of the concentration is above or below the normal range, the plot position Is marked with a warning mark WM indicating that it is abnormal.

  In this way, the graph presentation unit 65 displays the concentration trend for a plurality of substances in the biological epidermis together with the corresponding normal range as the concentration transition graph PGF, and attaches the warning mark WM to the plot position outside the normal range, The overall trend status is attached as a comment CM.

  Therefore, the user can intuitively grasp the change, quality, measurement frequency, etc. of the substance concentration contained in his / her biological epidermis from the concentration transition graph PGF, the warning mark WM, and the comment CM.

[1-5. Measurement accuracy improvement measures]
In this embodiment, measures for accurately obtaining unit length concentrations for three types of hemoglobin (glycated hemoglobin, oxidized hemoglobin, and reduced hemoglobin) that are measurement substances are taken for the LEDs in the irradiation unit 10.

  Specifically, with respect to an LED having a central wavelength at a wavelength (580 [nm] or several nearby wavelengths) that significantly shows the difference in extinction coefficient between glycated hemoglobin and other hemoglobins, A linear distance between wavelengths (hereinafter also referred to as a wavelength width) W (FIG. 10) is set narrower than other LEDs.

  More specifically, the wavelength width W for an LED having a central wavelength of 580 [nm] is 10 [nm] or less, and the wavelength width W for other LEDs is 20-40 [nm].

  By the way, the absorption spectrum of visible light (skin-transmitted light) transmitted through the human body surface from the interface between the basal layer and the dermis layer of the human body has a wavelength region in which it changes sharply as compared with other wavelength regions as shown in FIG. The wavelength becomes AR, and the wavelength range includes a wavelength (580 [nm] or several nearby wavelengths) that significantly shows a difference in extinction coefficient between glycated hemoglobin and other hemoglobin.

  Therefore, when light with a wide wavelength width having a peak at the center wavelength is irradiated from the LED, the light reflects the absorption characteristics of substances other than glycated hemoglobin, resulting in a measurement error in the measurement unit 30.

  In addition, it is known that glycated hemoglobin has a lower content in blood than oxyhemoglobin or reduced hemoglobin. Specifically, it is about 4-5 [%] of hemoglobin. Therefore, the measurement error for glycated hemoglobin in the measurement unit 30 is larger than that of other substances.

  Here, as an experimental result, the error of the measured value according to the wavelength width of the light irradiated from LED is shown below.

  As is clear from these tables, when the wavelength width of the LED having a central wavelength of 580 [nm] is increased from 10 [nm] to 20 [nm], not only the unit length concentration of glycated hemoglobin but also oxyhemoglobin and deoxyhemoglobin. Even the unit length concentration varies greatly. In particular, the content of glycated hemoglobin in the blood may be smaller than that of oxyhemoglobin or reduced hemoglobin, and the unit length concentration of the glycated hemoglobin becomes impossible to measure when it extends from 10 [nm] to 20 [nm]. .

  On the other hand, the wavelength width of an LED having a wavelength other than 580 [nm] (500 [nm], 540 [nm], 620 [nm], 660 [nm]) as the center wavelength is 10 [nm] to 20 [nm]. ], The fluctuation range of the unit length concentration of various hemoglobins is relatively small and almost the same.

  In this way, by setting the wavelength width W in the LED having the wavelength indicating the absorption characteristic of glycated hemoglobin as the center wavelength, compared with other LEDs, three types of hemoglobin (glycated hemoglobin, oxidized hemoglobin, and reduced hemoglobin) are set. It is possible to accurately measure the unit length concentration.

[1-6. Effect]
In the above configuration, the concentration measuring apparatus 1 sequentially emits light having different center wavelengths from the five LEDs. Then, the concentration measuring device 1 calculates the skin transmittance of each of these lights (FIG. 8 (A)), and calculates unit length concentrations of a plurality of substances using the skin transmittance (FIG. 8 (F)). .

  In this concentration measuring apparatus 1, since five LEDs are used, a transmittance obtained by discretely taking an absorption spectrum of light passing through the human body can be obtained. Therefore, the concentration measuring apparatus 1 can accurately calculate the unit length concentrations of a plurality of substances compared to simply obtaining the transmittance of light having a wavelength at which the measurement substance exhibits an absorption peak.

  As shown in FIG. 11, the center wavelength of the reference LED among the five LEDs is included in a wavelength region AR that changes more rapidly than other wavelength regions in the absorption spectrum of visible light. Further, the linear distance between wavelengths, which is half the intensity at the center wavelength, is set narrower than other LEDs as shown in FIG.

  Therefore, as can be seen from Tables 1 and 2, the concentration measuring apparatus 1 can increase the resolution of hemoglobin in the human epidermis, and as a result, the unit length concentration of the measurement substance can be calculated more accurately.

  In addition, glycated hemoglobin is adopted as one of the calculation targets of the unit length concentration in this embodiment. The change in the wavelength range AR shown in FIG. 11 involves the absorption characteristics of glycated hemoglobin, and the wavelength remarkably showing the difference in the extinction coefficient from other hemoglobins is 580 [nm] or several wavelengths in the vicinity thereof. This has been confirmed by the present inventors.

  Since the LED having the central wavelength of 580 [nm] is used as a reference LED, the glycated hemoglobin whose content in the blood is approximately 4 to 5 [%] in comparison with oxyhemoglobin and deoxyhemoglobin is captured more sensitively. Can do.

  By the way, the concentration measuring apparatus 1 uses a unit length concentration of the measurement substance, a unit length concentration of the substance that is about the content of the measurement target in the human epidermis, and an interface where visible light is regularly reflected in the human body as a solution. An equation is generated and the unit length concentration of the measurement substance is calculated.

  Specifically, the wavelength corresponding to the number to be solved using the spectrum of the user's epidermis transmitted light and the three types of hemoglobin and the molar extinction coefficient of melanin which is equal to or higher than the unit length concentration of those hemoglobins Every one meets Lambert-Beer's law (FIG. 9G).

  Rather than generating simultaneous equations by solving the unit length concentrations of the three types of hemoglobin specified as the measurement target, simultaneous equations are generated by adding other elements to the measurement target. Specifically, not only the unit length concentration of the measurement target, but also the unit length concentration of melanin that is higher than the content of the measurement target in the human epidermis and the interfacial interface reflectivity that is largely involved as light that passes through the human epidermis (Reflectance at the interface between the base layer and the dermis layer) is a calculation target.

  Therefore, the measurement unit 30 can calculate the unit length concentration of the measurement target in the human epidermis more accurately.

  As described above, glycated hemoglobin generally has a lower content in blood than oxyhemoglobin or reduced hemoglobin. Specifically, it is about 4-5 [%] of hemoglobin.

  As shown in FIG. 11, there is a wavelength range AR that changes sharply in the absorption spectrum of visible light compared to other wavelength ranges. This change mainly involves the absorption characteristics of glycated hemoglobin, and its center. The wavelength is 580 [nm].

  Therefore, even when other elements are added to the measurement target and a simultaneous equation is generated, the accuracy of the unit length concentration of glycated hemoglobin to be calculated increases as the distance from the wavelength reflected in the absorption spectrum based on 580 [nm] increases. Will be reduced.

  However, in this embodiment, the wavelength to be noted (the wavelength of each value to be fitted to the simultaneous equations) is selected based on 580 [nm], and therefore the absorption characteristics of glycated hemoglobin are most sensitive. As a result, the unit length concentration can be accurately calculated.

  In addition, the measurement unit 30 calculates the measurement substance to be used in the simultaneous equations and the content thereof from the reflectance of the color sample corresponding to the measurement material and the material that is about the content of the measurement target in the human epidermis. Calculate the molar extinction coefficient of the substance.

  Therefore, the measurement unit 30 can easily increase the types of the measurement substance capable of calculating the unit length concentration in the human epidermis and the substance whose content is about the content or more from the color sample.

<2. Other embodiments>
In the above-described embodiment, five LEDs are employed. However, the number of LEDs is not limited to five. Any number of two or more LEDs that irradiate light having different center wavelengths may be used.

  In the above-described embodiment, the ratio of the amount of light reflected at the interface in the human body and emitted from the human body surface to the amount of incident light is calculated. However, the ratio of the amount of light emitted from the surface facing the incident surface with respect to the amount of incident light may be a calculation target. That is, instead of a form for calculating the human body skin transmittance using the light reflected from the human body, a form for calculating the human body skin transmittance using the light transmitted through the human body may be adopted. However, when this form is adopted, the human body interface reflectance D in the equation (4) is omitted.

  In the above-described embodiment, the center wavelength of the light emitting diode to be used as a reference is 580 [nm]. However, it is not limited to this wavelength. For example, when a substance having a lower content than glycated hemoglobin (for example, bilirubin) is used as one of the measurement substances between the entrance surface or the human body interface and the exit surface, the difference in extinction coefficient between the bilirubin and other hemoglobin Can be set to a wavelength at which absorption peaks of other measurement substances also appear.

  In short, an LED having a central wavelength at a wavelength at which the variation range of the transmittance is larger than that of other light emitting diodes may be used as the reference LED.

  In the above-described embodiment, three kinds of hemoglobin (oxygenated hemoglobin, reduced hemoglobin, and glycated hemoglobin) are designated as the measurement substances to be measured. However, the type of the measurement substance is not limited to hemoglobin. For example, various components in the human body such as collagen and bilirubin can be used as measurement substances.

  Incidentally, it is not an indispensable condition to use all three types of hemoglobin as measurement substances. For example, when only glycated hemoglobin is used as a measurement target, oxyhemoglobin, reduced hemoglobin, and melanin are set as substances that are about the content of the glycated hemoglobin in the human epidermis. As another example, when reduced hemoglobin and glycated hemoglobin are measured, oxyhemoglobin and melanin are set as substances that have a content of about or more than the content of the glycated hemoglobin in the human epidermis.

  In short, in the optical path of the light emitted from the LED in the human body, various substances in the human body can be used as the measurement substance by adding substances that are about the content of the substance specified as the measurement target. can do.

  In addition, the substance which becomes more than the content in the substance designated as the measurement target is set in advance in the above-described embodiment. However, depending on the type of measurement substance specified as the measurement target, the number, type, and all or part of the wavelength to be noticed should be determined. It may be.

  For example, the wavelength of light emitted from the LED, the layer of the interface and the surface of the human body where the light of the wavelength is regularly reflected in the human body, the content of the substance in the layer, and the absorption characteristics of the substance in the layer Are stored in the storage unit 47 as a database. In this way, depending on the type of measurement substance specified as the measurement target, the number and type of substances that are about the content of the measurement substance in the layer or more, and all or part of the wavelength to be noted are determined. can do. Therefore, as a result of reliably selecting a substance having a content level or more in the substance designated as the measurement target, it is possible to improve the measurement accuracy of the unit length concentration of the substance designated as the target.

  In the above-described embodiment, the wavelength range of the light irradiated by the irradiation unit 10 is the visible light range. However, the wavelength range of the light to be irradiated is not limited to the visible light range. Near-infrared light region (780 [nm] to 3 [μm]) may be applied.

  When the near-infrared light region is applied, the near-infrared light mainly passes through the human epidermis, is reflected at the interface between the dermis and the fat layer, and is emitted from the human body surface. Near-infrared light has the property of being particularly absorbed by hemoglobin contained in blood vessels intervening in the dermis. Therefore, the unit length concentration of hemoglobin can be acquired more accurately.

  In addition, the human body interface reflectance D in the equation (4) is the reflectance at the interface between the dermis and the fat layer as described above. In addition, since the dermis contains a large amount of collagen and contains receptors such as patchoni bodies and cell components of fat cells, it is also possible to calculate including the extinction coefficient and unit length concentration of the collagen or fat. .

  In the above-described embodiment, the concentration is calculated from the unit length concentration and the trend of the concentration is presented as necessary. However, it is not an essential condition to calculate the concentration. That is, the unit length density itself may be stored in the storage unit 47 and the trend of the unit length density may be presented.

  In the above-described embodiment, the concentration measurement device 1 that executes the extinction coefficient calculation mode and the concentration measurement mode is applied. However, a system that allows connection between a concentration measurement device that executes only the extinction coefficient calculation mode and a concentration measurement device that executes only the concentration measurement mode through a wired or wireless communication medium such as a local area network or the Internet is applied. May be.

  The present invention can be used in the bio-industry such as genetic experiments, creation of medicines, or patient follow-up.

  DESCRIPTION OF SYMBOLS 1 ... Density measuring apparatus, 10 ... Irradiation part, 20 ... Light receiving part, 30 ... Measurement part, 41 ... CPU, 42 ... ROM, 43 ... RAM, 44 ... Operation input part, 45 ... Interface unit 46... Display unit 47... Storage unit 51 .sub.substance determination unit 52 .. drive control unit 53 .. reflectance calculation unit 54... Unit length concentration difference acquisition unit 55. Absorption coefficient calculation unit, 61... Transmittance acquisition unit, 62... Absorption coefficient reading unit, 63... Epidermal transmission characteristic analysis unit, 64... Concentration calculation unit, 65.

Claims (7)

A plurality of light emitting diodes that sequentially irradiate light having different central wavelengths for each of the central wavelengths of N or more (N is a natural number of 1 or more) types of measurement substances that are substances to be measured ;
A transmittance calculating means for calculating, for each central wavelength, the transmittance of light emitted from the light emitting diode and transmitted through the human body;
The transmittance is represented by the sum of the unit length concentration of each of the measurement substances multiplied by the extinction coefficient of the measurement substance, with the unit length concentration being the concentration per unit optical path length of each of the measurement substances as a variable . An equation for each central wavelength, and concentration calculation means for calculating a unit length concentration of each of the measurement substances by solving the generated equations as a multiple simultaneous equation ,
Among the light emitting diodes, a reference light emitting diode to be used as a reference has a wavelength at which a fluctuation range of transmittance with respect to a wavelength for a specific specific measurement substance among the measurement substances appears larger than that of other light emitting diodes as a central wavelength.
A concentration measuring apparatus , wherein a linear distance between wavelengths which is a half value of intensity at the central wavelength is set narrower than that of the other light emitting diodes. In addition to using the unit concentration length of each of the measurement substances as a variable, the concentration calculation means uses the reflectance at the interface between the basal layer and the dermis layer in the human body as a constant,
The equation represents the transmittance by adding the constant to the sum of the unit length concentration of each of the measurement substances multiplied by the extinction coefficient of the measurement substance,
The number of the central wavelengths is N + 1 or more
The concentration measuring apparatus according to claim 1. One of the measurement substances is melanin intervening in the human epidermis
The concentration measuring apparatus according to claim 1. The center wavelength of the reference light emitting diode is
The absorption spectrum in the layer between the interface where the light incident obliquely on the human body surface is specularly reflected in the human body and the human body surface is included in the wavelength region having a larger fluctuation range than other wavelength regions. The concentration measuring apparatus according to claim 1 . The concentration measuring apparatus according to claim 4, wherein the absorption spectrum is an absorption spectrum in a visible light region. The center wavelength of the light to the reference light-emitting diode is irradiated, glycated hemoglobin, concentration measurement according to claim 4 width shown the difference between the extinction coefficient of oxyhemoglobin and deoxyhemoglobin is larger wavelength than other wavelengths apparatus. The concentration measuring apparatus according to claim 4 , wherein the central wavelength of light emitted from the reference light emitting diode is 580 [nm] or a wavelength in the vicinity thereof.