JP2009213563A - Component concentration measuring apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To achieve the identification of component concentration of a target component when a background component and an article to be measured are in the state of a mixed composition in a component concentration measuring apparatus using a photoacoustic method. <P>SOLUTION: The component concentration measuring apparatus 91 using the photoacoustic method includes a wavelength sweeping light source 11 for sweeping a wavelength of a light emitted to the article to be measured 101. Specifically, the component concentration measuring apparatus is equipped with a reference light source 10 and a wavelength varying light source 11 as two light generating parts for measurement, the reference light source 10, the wavelength varying light source 11, driving circuits 12a, 12b, a delay adjustment device 13, and an oscillator 14 as a light modulating part, a multiplexer 15, a light emitting part 16, a sound wave detecting part 17, a preamplifier 18, a phase detection amplifier 19, and a photoacoustic signal output terminal 20. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a component concentration measuring device for a target component using a photoacoustic method, and more particularly to a non-invasive component concentration measuring device in which an object to be measured is a human or an animal.

  With the aging of society, dealing with adult diseases is becoming a major issue. Since blood collection is necessary for examinations such as blood sugar levels, it is a heavy burden on the patient. Therefore, a non-invasive component concentration measurement apparatus that does not collect blood has attracted attention.

  The photoacoustic method has attracted attention as a noninvasive component concentration measuring apparatus developed so far. The photoacoustic method irradiates the skin with electromagnetic waves, absorbs the blood component to be measured, for example, glucose molecules, causes local thermal expansion by the radiation of heat from the glucose molecules, and from the living body by thermal expansion. Observe the generated sound wave. However, the interaction between glucose and electromagnetic waves is small, and there is a limit to the intensity of electromagnetic waves that can be safely irradiated to a living body.

6 and 7 are configuration examples showing a conventional component concentration measuring apparatus using a photoacoustic method. Blood glucose in the blood to be measured 101, that is, glucose is used as a target component.
The first conventional example shown in FIG. 6 uses light pulses as electromagnetic waves (see, for example, Non-Patent Document 1). In FIG. 6, the driving power supply 102 supplies the excitation current on the pulse to the pulse light source 103, and the pulse light source 103 generates an optical pulse having a sub-microsecond duration. The generated light pulse is applied to the object to be measured 101. The light pulse generates a sound wave called a pulsed photoacoustic signal inside the object to be measured 101, and the generated sound wave is detected by the ultrasonic detector 104 and further converted into an electric signal proportional to the sound pressure.

The waveform of the converted electric signal is observed by the waveform observer 105. The waveform observer 105 is triggered by a signal synchronized with the excitation current, and the converted electric signal is displayed at a certain position on the tube surface of the waveform observer 105. The amplitude of the converted electric signal is analyzed, and the amount of glucose in the blood existing in the device under test 101 is measured.
In the case of the example shown in FIG. 6, an optical pulse having a sub-microsecond pulse width is repeatedly generated at a maximum of 1 kHz and the electric signal is measured, but sufficient accuracy is not obtained.

  Therefore, a second conventional example has been disclosed for the purpose of improving accuracy (see, for example, Patent Document 2). The second conventional example shown in FIG. 7 uses a light source that is continuously intensity modulated. In this example as well, blood sugar is the main measurement target, and high accuracy is attempted using a plurality of light sources having different wavelengths. In order to avoid complicated explanation, the operation when the number of light sources is 2 will be described with reference to FIG. In FIG. 7, light sources having different wavelengths, that is, a first light source 201 and a second light source 202 are driven by a driving power source 203 and a driving power source 204, respectively, and output continuous light.

  The light output from the first light source 201 and the second light source 202 is intermittently driven by a chopper plate 213 that is driven by a motor 214 and rotates at a constant rotational speed. Here, the chopper plate 213 is formed of an opaque material, and a relatively small number of openings are formed on the circumference through which the light of the first light source 201 and the second light source 202 passes with the axis of the motor 214 as the center. Is formed.

  With the above-described configuration, the light output from each of the first light source 201 and the second light source 202 is intensity-modulated with the prime modulation frequency f1 and the modulation frequency f2, and then multiplexed by the multiplexer 211. The object to be measured 101 is irradiated as a light beam.

  Inside the DUT 101, a photoacoustic signal having a modulation frequency f1 is generated by the light from the first light source 201, and a photoacoustic signal having a modulation frequency f2 is generated by the light from the second light source 202. The acoustic signal is detected by the acoustic sensor 212 and converted into an electrical signal proportional to the sound pressure, and the frequency spectrum is observed by the frequency analyzer 215. In this example, the wavelengths of the plurality of light sources are all set to the glucose absorption wavelength, and the intensity of the photoacoustic signal corresponding to each wavelength is measured as an electrical signal corresponding to the amount of glucose contained in the blood. The

Here, the relationship between the intensity of the measured value of the photoacoustic signal and the value obtained by measuring the glucose concentration by separately collected blood is stored, and the amount of glucose is measured from the measured value of the photoacoustic signal. Yes.
JP-A-10-189 University of Oulu (University of Oulu, Finland) thesis “Pulse photoacoustic techniques and glucodesistion in human blood and tissue” (IBS 951-42-6690-0, 2001/95.

  In practical use, the background component and the object to be measured are mostly mixed compositions. When the background component and the object to be measured have a mixed composition, it is difficult to quantify only the target component from the mixed composition with the conventional photoacoustic method, unless the target component significantly absorbs the single wavelength. Met.

  Therefore, an object of the present invention is to make it possible to identify the component concentration of a target component in a component concentration measurement device using a photoacoustic method even when the background component and the object to be measured are in a mixed composition state. .

  In order to achieve the above object, a component concentration measuring apparatus according to the present invention is characterized in that, in a component concentration measuring apparatus using a photoacoustic method, the wavelength of light irradiated on a measurement object is swept.

  Specifically, the component concentration measuring apparatus according to the present invention generates and outputs two light beams having different wavelengths with the same absorption of the background component in the object to be measured in which the background component and the target component are mixed. From the measurement light generation unit, the light modulation unit for modulating the intensity of light from the two measurement light generation units at a predetermined frequency in opposite phases to each other, and the two measurement light generation units The measurement synthesized light obtained by synthesizing the intensity-modulated light is generated from the measured object by the light emitting part that emits the measured light toward the measured object in which the solution exists and the measured synthetic light emitted by the light emitting part. A sound wave detection unit that detects a measurement sound wave, and a wavelength sweep unit that sweeps light from one of the two measurement light generation units in a certain wavelength range.

  In a component concentration measurement apparatus using a photoacoustic method including two measurement light generation units, a light modulation unit, a light emission unit, and a sound wave detection unit, the wavelength variable light from one of the measurement light generation units is a component of the target component It is used for density identification, and the reference light from the other of the measurement light generator is used to remove a difference from the photoacoustic signal generated from the background component. If the wavelength of the tunable light is swept within a certain wavelength range where the characteristic absorption peak of the target component exists, the transition of the amplitude of the photoacoustic signal obtained from the measurement sound wave has a shape of the characteristic absorption peak of the target component. Therefore, even when the amount of absorption other than the target component has changed, the amount of absorption by the target component can be specified by performing multivariate analysis. Thereby, in the component concentration measuring apparatus using the photoacoustic method, it is possible to identify the component concentration of the target component even when the background component and the measured object are in a mixed composition state.

In the component concentration measuring apparatus according to the present invention, it is preferable that the wavelength range swept by the wavelength sweeping unit includes a wavelength at which the absorption exhibited by the target component is maximized.
Since the wavelength of tunable light is swept within a certain wavelength range where the characteristic component has an absorption peak, the component concentration of the target component can be identified even when the background component and the measured object are in a mixed composition state. Can be.

In the component concentration measuring apparatus according to the present invention, it is preferable that the apparatus further includes a temperature detecting unit that detects the temperature of the object to be measured.
The temperature shift amount of the absorbance of the background component or the target component can be estimated from the temperature of the object to be measured. Since the difference between the wavelength of the reference light and the photoacoustic signal generated from the liquid can be accurately removed, the amount of absorption by the target component can be accurately specified.

The component concentration measurement apparatus according to the present invention may further include a first phase-locked detection unit that detects the measurement sound wave detected by the sound wave detection unit so as to be synchronized with a period of intensity modulation by the light modulation unit. preferable.
By synchronizing the detection of the measurement sound wave with the pulse period of the measurement combined light, noise other than the measurement sound wave can be eliminated.

The component concentration measurement apparatus according to the present invention further includes a second phase-synchronous detection unit that detects the measurement sound wave detected by the sound wave detection unit so as to be synchronized with a period in which the wavelength sweep unit sweeps the wavelength. Is preferred.
By synchronizing the detection of the sound wave for measurement with the wavelength sweep period, it is possible to extract the component that causes the spectrum change in the wavelength sweep range,

In the component concentration measuring apparatus according to the present invention, it is preferable that the constant wavelength range swept by the wavelength sweeping unit includes a wavelength of light from the other of the measurement light generating unit.
Since the two wavelengths of the wavelength tunable light and the reference light are close to the change in the absorption of the background component caused by the environmental change such as temperature, the absorption of both changes similarly. Even in such a situation, when the wavelength of the reference light is within the wavelength sweep range, the photoacoustic signal generated from the absorption of the background component in the object to be measured can be efficiently removed. As a result, it is possible to extract only components that cause a spectrum change in the wavelength sweep range, and to increase the measurement accuracy of the target component.

  In the component concentration measuring apparatus according to the present invention, the wavelength of the light from the other of the measurement light generation unit is different from the wavelength of the light from the other of the measurement light generation unit in the absorption exhibited by the background component. Among the wavelengths, it is preferable that an absorbance change coefficient with respect to temperature is closest to the wavelength of light from one of the measurement light generation units. In the difference removal from the photoacoustic signal generated from the background component, it can be made less susceptible to the influence of temperature.

  According to the present invention, in the component concentration measuring apparatus using the photoacoustic method, it is possible to identify the component concentration of the target component even when the background component and the object to be measured are in the mixed composition state.

Embodiments of the present invention will be described with reference to the accompanying drawings. The embodiment described below is an example of the configuration of the present invention, and the present invention is not limited to the following embodiment.
FIG. 1 is a schematic configuration diagram illustrating a first example of a component concentration measuring apparatus according to the present embodiment. A component concentration measuring device 91 shown in FIG. 1 detects a photoacoustic signal generated in the device under test 101. A solution exists in the DUT 101. The DUT 101 is, for example, a living body, a measurement sample, or a fruit. The solution is a mixture of background components and target components. The target component is a substance that absorbs light and thermally expands. If the DUT 101 is a living body, the solution is, for example, blood lymph fluid and tears. If the solution is blood, the target component is, for example, cholesterol or glucose in blood.

  The component concentration measuring device 91 according to the present embodiment can measure non-invasively with respect to the measurement object 101, but can also be used to collect blood from a living body and measure a target component. Moreover, if the to-be-measured object 101 is a fruit and the target component is sucrose or fructose, the component concentration measuring device 91 functions as a fruit sugar content meter. Thus, the measurement apparatus according to the present embodiment can be applied to various objects without departing from the spirit of the present embodiment.

  The component concentration measuring apparatus 91 according to this embodiment includes a configuration for detecting a photoacoustic signal generated by the device under test 101. For example, the component concentration measurement apparatus 91 includes two reference light sources 10 and a wavelength variable light source 11 as measurement light generation units, a reference light source 10 as a light modulation unit, a wavelength variable light source 11, drive circuits 12a and 12b, and delay adjustment. And an oscillator 14, a multiplexer 15, a light emitting unit 16, a sound wave detecting unit 17, a preamplifier 18, a phase detection amplifier 19, and a photoacoustic signal output terminal 20. Further, the component concentration measuring device 91 includes a temperature transmission window 21, a temperature detection unit 22, and a temperature signal output terminal 23.

The reference light source 10, the wavelength tunable light source 11, the drive circuits 12a and 12b, the delay adjuster 13 and the oscillator 14 function as light modulators, which reverse the light from the reference light source 10 and the wavelength tunable light source 11 at a predetermined constant frequency. Output the intensity modulated to the phase. Specifically, drive circuits 12 a and 12 b that supply current to the reference light source 10 and the wavelength tunable light source 11 are connected. An oscillator 14 for supplying a voltage is connected to the drive circuits 12a and 12b. The oscillator 14 has a function of generating a pulse train having an arbitrary frequency. Further, the delay adjuster 13 adjusts the delay to approximately half of the cycle in order to drive the reference light source 10 and the variable wavelength light source 11 in opposite phases. The reference light source 10 generates and outputs reference light having a constant wavelength λ ₂ by driving the drive circuit 12a. Variable wavelength light source 11 is provided with the wavelength sweeping unit (not shown), and outputs the wavelength-tunable light wavelength sweep at a constant wavelength range Δλ that includes a wavelength lambda ₁ by the driving of the drive circuit 12b. The starting point of the wavelength sweep may be on either the short wavelength side or the long wavelength side.

  The wavelength tunable light source 11 is a laser light source such as a dye laser, a titanium sapphire laser, an Er-doped fiber laser, or a semiconductor laser, or a broadband white light source. The wavelength sweep unit (not shown) is, for example, a wavelength sweep circuit or a wavelength tunable filter. In the case of a semiconductor laser, variable wavelength light can be generated by performing direct modulation using a wavelength sweep circuit. If it is a broadband white light source, the wavelength tunable light can be generated by transmitting the generated light through the wavelength tunable filter.

  The light generated by the reference light source 10 and the wavelength tunable light source 11 is connected to the optical input terminal of the optical multiplexer 15 by an optical fiber that is a light transmission means. The combined light for measurement output from the light output terminal of the optical multiplexer 15 is transmitted to the light emitting part 16 to the device under test 101 by an optical fiber which is a light transmission means. The light emitting unit 16 may adhere any of a right-angle prism, a fiber collimator, and a ferrule to the tip of the optical fiber according to the shape of the device under test 101.

The light emitting unit 16 emits the measurement combined light obtained by combining the intensity-modulated light from the reference light source 10 and the variable wavelength light source 11 toward the object to be measured 101. The synthetic light for measurement from the light emitting part 16 reaches the device under test 101 through the heat conduction window 21. The sound wave detection unit 17 detects the measurement sound wave generated from the measurement object 101 by the measurement combined light emitted from the light emission unit 16. The photoacoustic signal (s ₁ -s ₂ ) obtained by converting the measurement sound wave into an electrical signal is amplified by the preamplifier 18 and is amplified by the phase detection amplifier 19 with the amplitude of the same frequency component as the modulation frequency of the drive circuits 12a and 12b. The phase is extracted and output to the acoustic signal output 20.

Furthermore, constituent concentration measuring device 91, the reference light from the reference light source 10 alone by irradiating the target subject 101, to measure the photoacoustic signal s ₂ by the reference beam. The measured photoacoustic signal s ₂ is output to the acoustic signal output 20.
The component concentration measuring device 91 can measure the concentration of the target component in the object to be measured by measuring the photoacoustic signal (s ₁ -s ₂ ) and the photoacoustic signal s ₂ .

  Here, the phase detection amplifier 19 has a function as a first phase-locked detection unit. That is, the phase detection amplifier 19 detects the measurement sound wave detected by the sound wave detection unit 17 so as to be synchronized with the phase whose intensity is modulated by the drive circuits 12a and 12b. The phase at which the drive circuits 12 a and 12 b modulate the intensity can be obtained from the output signal of the oscillator 14. Since the photoacoustic signal is generated in the pulse cycle of the synthetic light for measurement, the measurement sound wave can be extracted.

  In addition, the component concentration measuring device 91 preferably further includes a temperature detection unit 22 that detects the temperature of the object 101 to be measured. For example, heat generated by photothermal conversion in the DUT 101 is conducted through the temperature transmission window 21 and detected by the temperature detection unit 22 and output to the temperature signal output terminal 23.

Next, a second example of the component concentration measuring apparatus according to this embodiment will be described. FIG. 2 is a schematic configuration diagram illustrating a second example of the component concentration measuring apparatus according to the present embodiment. The component concentration measuring apparatus 92 shown in FIG. 2 includes a phase detection amplifier 24 at the subsequent stage of the phase detection amplifier 19 shown in FIG.
The phase detection amplifier 24 has a function as a second phase-locked detection unit. That is, the phase detection amplifier 24 detects the measurement sound wave detected by the sound wave detection unit 17 so as to be synchronized with the phase in which the wavelength is swept by the wavelength variable light source 11. The amplitude and phase of the same frequency component are extracted and output to the photoacoustic signal output terminal 20.

  Next, wavelength setting of the reference light source 10 and the wavelength tunable light source 11 in this embodiment will be described with reference to FIG. FIG. 3 is an example of the absorbance of a solution, (a) the absorbance and absorption coefficient of an aqueous glucose solution, and (b) the absorbance difference and specific absorbance of glucose with respect to water. Here, for easy understanding, a case where the solution in which the background component and the target component are mixed is a glucose aqueous solution in which water and glucose are mixed will be described.

First, the constant wavelength range Δλ swept by the wavelength sweeping unit is set so as to include a wavelength at which the absorption exhibited by the target component is maximized. For example, as shown in FIG. 3B, the difference in absorbance or specific absorbance of glucose obtained by subtracting water from an aqueous glucose solution is maximized at a wavelength λ _{1a in the} vicinity of the wavelength 1600 nm and λ _1b in the vicinity of the wavelength 2100 nm. In this case, for example, the wavelength λ _1a is selected as the wavelength that maximizes the absorption exhibited by the target component.

Next, in order to eliminate the difference from the photoacoustic signal generated from the background component, from the water absorption coefficient shown in FIG. 3A, the absorption of the water as the background component is different from the wavelength λ _2a equal to the wavelength λ _1a or One of the wavelengths λ _2b is selected. Here, it is preferable that the absorbance change coefficient with respect to the temperature of the wavelength λ _2a or the wavelength λ _2b is the wavelength closest to the wavelength λ _1a . For example, if the wavelength lambda _2a or wavelength lambda _2b, it is preferable to select a wavelength lambda _2b. Further, if there is a wavelength where the sign of the absorption slope exhibited by water is equal to the wavelength λ _1a , it is preferable to select that wavelength.

Next, the fixed wavelength range Δλ in which the wavelength sweep unit sweeps the wavelength is selected so as to include the wavelength λ _1a or the wavelength λ _{1b in} which the absorption exhibited by the target component is maximized. For example, it is set to 50 nm or more and 100 nm or less from the wavelength λ _1a . Here, the fixed wavelength range Δλ is preferably selected so that the wavelength λ _{1a at} which the absorption exhibited by the target component is maximized even when the temperature of the object to be measured 101 changes is included. Further, it is preferable that the fixed wavelength range Δλ swept by the wavelength tunable light source includes the wavelength λ _2a or the wavelength λ _2b of the reference light so that the influence of the wavelength shift due to the temperature change can be directly measured.

There are two characteristic absorptions of glucose, around 1600 nm and around 2100 nm. For this reason, the reference light source 10 may be used as a wavelength tunable light source, and a fixed wavelength range Δλ for wavelength sweeping may be used in the same manner by using two locations near 1600 nm and 2100 nm simultaneously. In this case, it is preferable to set a fixed wavelength range Δλ that sweeps the wavelength so that the absorption exhibited by water includes the wavelength λ _2b that is equal to the wavelength λ _1a in the first sweep wavelength range. It is preferable to set a certain wavelength range for wavelength sweeping so that the second sweep wavelength range includes a wavelength λ _{2d in} which the absorption exhibited by water is equal to the wavelength λ _1b . Then, the absorbance of glucose is measured for each of the first sweep wavelength range and the second sweep wavelength range. In that case, even if the impurity absorption overlaps the absorption in one sweep wavelength range, the reliability can be ensured by using the absorption in the other sweep wavelength range.

The wavelength shift due to temperature change will be described. FIG. 4 is an explanatory diagram of wavelength shift due to temperature change. A spectrum 31 is an absorbance spectrum of water at the temperature T. In this case, both the photoacoustic signal obtained by the tunable optical and wavelength lambda ₂ of the reference light of the wavelength lambda ₁ has a waveform such as the photoacoustic signal 33, it is possible to eliminate the influence of the background component serving water.
However, when the temperature (T + ΔT) is reached due to the temperature change ΔT, the water absorbance spectrum 32 shifts from the spectrum 31. At this time, while reducing the signal amplitude of the photoacoustic signal 35 obtained by wavelength-tunable optical wavelength lambda _1, since the signal amplitude of the photoacoustic signal 34 obtained by the reference beam wavelength lambda ₂ is increased, the background component The influence of dripping water cannot be removed. For this reason, it is preferable that the wavelength λ ₁ of the wavelength tunable light and the wavelength λ _{2 of the} reference light are included in the constant wavelength range Δλ to be swept. By setting the wavelength λ _{2 of the} reference light within the wavelength sweep range of the wavelength tunable light, the amount of change in the signal amplitude of the photoacoustic signal 35 and the photoacoustic signal 34 can be measured. However, the influence of water as a background component can be removed and only the amount of change in the spectrum can be observed.

Further, when the wavelength λ _{2 of the} reference light is set to a wavelength λ ₂ shorter than the maximum peak of the spectrum 31, the photoacoustic signal 35 and the photoacoustics are obtained in the spectrum 32 that has become a temperature (T + ΔT) due to the temperature change ΔT. As shown by the signal 34, the differential signal of the photoacoustic signal varies greatly with the temperature ΔT. The change from the photoacoustic signal 33 to the photoacoustic signal 34 is larger than the spectral change within a certain wavelength range Δλ in which the wavelength is swept, as indicated by the photoacoustic signal 33 to the photoacoustic signal 35. For this reason, it is preferable that the wavelength of the reference light has an absorbance change coefficient with respect to temperature that is the closest to the wavelength λ ₁ of the wavelength tunable light among the wavelengths λ _2a and λ _2b of the reference light having the same absorption exhibited by water. . For example, it is preferable to select the wavelength λ _2b located on the longer wavelength side than the wavelength λ ₁ of the wavelength tunable light among the wavelengths λ _2a and λ _2b of the reference light shown in FIG. As for the influence of the temperature change ΔT, a correction curve corresponding to the water temperature is prepared in advance, and the photoacoustic signal can be corrected from the measured water temperature. Thereby, the influence of the temperature change ΔT can be reduced.

FIG. 5 is an example of a time waveform of the photoacoustic signal according to the present embodiment, where (a) is a photoacoustic signal based on reference light, (b) is a photoacoustic signal based on wavelength-tunable light, and (c) is a synthesis for measurement. The photoacoustic signal by light is shown.
The photoacoustic signal by the reference light shown in FIG. 5A is generated at the modulation frequency of the drive circuit 12a shown in FIG. And since the wavelength irradiated to a to-be-measured object is constant, signal intensity is constant.

  The photoacoustic signal by the wavelength tunable light shown in FIG. 5B is generated at the modulation frequency of the drive circuit 12b shown in FIG. Since the wavelength irradiated to the object to be measured changes within a certain wavelength range Δλ, the signal intensity changes in synchronization with the phase of the wavelength sweep. The spectrum change in the wavelength sweep time repeated at a constant period becomes the absorption spectrum of the object to be measured. The change in signal intensity includes a change in absorbance of the background component and a change in absorbance of the target component.

The photoacoustic signal by the synthetic light for measurement shown in FIG. 5C is generated at the modulation frequency of the drive circuits 12a and 12b shown in FIG. Since the reference light and the wavelength tunable light are intensity-modulated in opposite phases, the reference light and the wavelength tunable light are intensity-modulated in opposite phases. Therefore, the background at the wavelength λ ₁ where the absorption exhibited by the target component is maximized. The spectrum due to absorption equal to the absorption exhibited by the component has been eliminated. The photoacoustic signal by the synthetic light for measurement includes an absorption peak of glucose as a target component. Therefore, the concentration of glucose as the target component can be quantified by sequentially performing multivariate analysis on the differential absorption spectrum obtained by the synthetic light for measurement acquired in time series. Alternatively, the concentration may be quantified using glucose calibration from the amount of signal obtained by phase detection of the photoacoustic signal output in synchronization with the wavelength sweep.

  Since the component concentration measurement apparatus 91 according to the present embodiment performs measurement using light having a plurality of wavelengths that give the same absorption coefficient, it can solve the nonlinear absorption coefficient dependency existing in the measurement value of the photoacoustic signal. The principle will be described below.

数式（１）を解いて未知の血液成分濃度Ｍを求める。ここで、Ｃは、変化し制御或は予想困難な係数である。例えば、図１における、音響結合、音波検出部１７の感度、光出射部１６と被測定物１０１の間の距離（以下ｒと定義する）、被測定物１０１の比熱、被測定物１０１の熱膨張係数、被測定物１０１での音速、駆動回路１２ａ、１２ｂの変調周波数、更に、被測定物１０１の吸収係数にも依存する未知乗数である。 For each light of wavelength λ ₁ and wavelength λ ₂ , absorption coefficients α ₁ ^(b) and α ₂ ^{(b) of} the background component and molar absorption α ₁ ⁽⁰⁾ and α ₂ ^{(0 )} Is known, the simultaneous equations including the measured values s ₁ and s ₂ of the photoacoustic signals at the respective wavelengths are expressed as the following formula (1).

Equation (1) is solved to determine an unknown blood component concentration M. Here, C is a coefficient that varies and is difficult to control or predict. For example, in FIG. 1, acoustic coupling, sensitivity of the sound wave detection unit 17, distance between the light emitting unit 16 and the object to be measured 101 (hereinafter, defined as r), specific heat of the object to be measured 101, heat of the object to be measured 101. It is an unknown multiplier that depends on the expansion coefficient, the speed of sound at the device under test 101, the modulation frequency of the drive circuits 12a and 12b, and the absorption coefficient of the device under test 101.

If there is a difference between C in the first row and the second row of Equation (1), it can be other than the amount related to the irradiation light, that is, the difference due to the absorption coefficient. Here, if the combination of the wavelength λ ₁ and the wavelength λ ₂ is selected in parentheses in each row of the formula (1), that is, the absorption coefficients are equal to each other, the absorption coefficients become the same, and the first and second lines Are equal. However, strictly doing this is inconvenient because the combination of wavelength λ ₁ and wavelength λ ₂ will depend on the unknown blood component concentration M.

数式（２）の後段の変形にはｓ_１≒ｓ_２という性質を用いている。 Here, the proportion of the absorption coefficient (in each parenthesis) of the formula (1) is a term in which the background component absorption coefficient α _i ^(b) (where i = 1, 2) includes the blood component concentration M. It is significantly larger than (Mα _i ⁽⁰⁾ ). Thus, it is sufficient to make the absorption coefficients of the background, α _i ^(b) equal, instead of making the absorption coefficients of each row exactly equal. That is, the two light beams having different wavelengths λ ₁ and λ ₂ may be selected so that the absorption coefficients α ₁ ^(b) and α ₂ ^(b) of the background components are equal to each other. Thus, if C in the first and second lines can be equal, it is erased as an unknown constant, and the blood component concentration M to be measured is expressed by Equation (2).

The property of s ₁ ≈s ₂ is used for the subsequent deformation of Equation (2).

Here, looking at Equation (2), the difference in the absorption coefficient of the blood component to be measured at the wavelengths λ ₁ and λ ₂ appears in the denominator. When the difference is larger, the difference signal s ₁ -s _{2 of the} photoacoustic signal is larger, and the measurement becomes easier. In order to maximize this difference, the wavelength at which the absorption coefficient α ₁ ⁽⁰⁾ of the component to be measured is maximized is selected as the wavelength λ ₁ and α ₂ ⁽⁰⁾ = 0, that is, the component to be measured is It is preferable to select the wavelength λ ₂ as a wavelength that does not show the absorption characteristics. Here, from the previous condition, the wavelength λ ₂ of this reference light must be α ₂ ^(b) = α ₁ ^(b) , that is, the absorption coefficient of the background component should be equal to the absorption coefficient of the wavelength λ ₁ of the tunable light. I must.

Furthermore, in Equation (2), the photoacoustic signal s ₁ appears only in the form of a difference s ₁ -s _{2 from} the photoacoustic signal s ₂ . Now, taking as an example the glucose as a component to be measured, as described above, the two intensities of the photoacoustic signal s ₁ and the photoacoustic signal s _2, only less than 0.1% difference.

However, it is sufficient that the photoacoustic signal s ₂ in the denominator of the formula (2) has an accuracy of about 5%. Therefore, rather than sequentially measuring the _two photoacoustic signals s ₁ and the photoacoustic signal s ₂ , the difference s ₁ -s ₂ between them is measured, and this measured value is determined by the individually measured photoacoustic signal s ₂ . It is much easier to maintain accuracy. Therefore, in the component concentration measurement apparatus according to the present embodiment, the light of the _two wavelengths λ ₁ and λ ₂ is irradiated with the intensity modulated in opposite phases to each other, so that the photoacoustic signal s ₁ and the light are emitted in vivo. The difference signal s ₁ -s ₂ between the photoacoustic signals generated by superimposing the acoustic signals s ₂ is measured.

  As described above, when measuring blood component concentrations, using two waves of different specific wavelengths, the photoacoustic signals generated by the two waves of different specific wavelengths in the living body are individually provided. Rather than measuring, the difference signal of the photoacoustic signal is measured, and further, the predetermined one photoacoustic signal is set to zero, the other photoacoustic signal is measured, and these are calculated by Equation (2), It can be seen that the blood component concentration can be easily measured.

  The present invention relates to a noninvasive component concentration measuring device for a solution existing in a human or an animal, and a component concentration measuring device for a solution collected from a human or an animal.

It is a schematic block diagram which shows the 1st example of the component concentration measuring apparatus which concerns on this embodiment. It is a schematic block diagram which shows the 2nd example of the component concentration measuring apparatus which concerns on this embodiment. It is an example of the light absorbency of a solution, (a) The light absorbency and absorption coefficient of glucose aqueous solution, (b) shows the light absorbency difference of glucose with respect to water, and a specific light absorbency. It is explanatory drawing of the wavelength shift by a temperature change. It is an example of the time waveform of the photoacoustic signal which concerns on this embodiment, (a) is a photoacoustic signal by reference light, (b) is a photoacoustic signal by wavelength-tunable light, (c) is photoacoustic by the synthetic light for a measurement. Signals are shown. It is a structural example which shows the 1st component density | concentration measuring apparatus by the conventional photoacoustic method. It is a structural example which shows the 2nd component density | concentration measuring apparatus by the conventional photoacoustic method.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Reference light source 11 Wavelength variable light source 12a, 12b Drive circuit 13 Delay adjuster 14 Oscillator 15 Multiplexer 16 Light output part 17 Sound wave detection part 18 Preamplifier 19, 24 Phase detection amplifier 20 Photoacoustic signal output terminal 21 Temperature transmission window DESCRIPTION OF SYMBOLS 22 Temperature detection part 23 Temperature signal output terminal 31, 32 Water absorption spectrum 33, 34, 35 Photoacoustic signal 91, 92 Component density | concentration measuring apparatus 101 Measured object 102 Drive power supply 103 Pulse light source 104 Ultrasonic detector 105 Waveform detector DESCRIPTION OF SYMBOLS 201 1st light source 202 2nd light source 203,204 Drive power supply 211 Multiplexer 212 Acoustic sensor 213 Chopper board 214 Motor 215 Frequency analyzer

Claims (7)

Two measurement light generators for generating and outputting light of different wavelengths having the same absorption of the background component in a solution in which the background component and the target component are mixed; and
A light modulation unit for intensity-modulating and outputting light from the two measurement light generation units in a phase opposite to each other at a predetermined constant frequency;
A light emitting unit that emits the synthetic light for measurement, which is obtained by synthesizing the intensity-modulated light from the two measurement light generating units, toward the object to be measured in which the solution exists;
A sound wave detection unit for detecting a measurement sound wave generated from the object to be measured by the synthetic light for measurement emitted from the light emitting unit;
A wavelength sweeping unit that sweeps light from one of the two measurement light generation units in a certain wavelength range;
A component concentration measuring apparatus comprising:   The component concentration measurement apparatus according to claim 1, wherein the constant wavelength range swept by the wavelength sweeping unit includes a wavelength at which absorption of the target component is maximized.   The component concentration measuring apparatus according to claim 1, further comprising a temperature detecting unit that detects a temperature of the object to be measured.   4. The apparatus according to claim 1, further comprising a first phase-locked detection unit that detects the measurement sound wave detected by the sound wave detection unit so as to be synchronized with a phase whose intensity is modulated by the light modulation unit. A component concentration measuring apparatus according to claim 1.   5. The apparatus according to claim 1, further comprising a second phase-locked detection unit that detects the measurement sound wave detected by the sound wave detection unit so as to be synchronized with a phase in which the wavelength sweep unit sweeps the wavelength. The component concentration measuring apparatus in any one.   6. The component concentration measuring apparatus according to claim 1, wherein the fixed wavelength range swept by the wavelength sweeping unit includes a wavelength of light from the other of the measurement light generating unit.   The wavelength of light from the other side of the measurement light generation unit is the closest to the light from one side of the measurement light generation unit with respect to the temperature among the different wavelengths with the same absorption of the background component. The component concentration measuring device according to claim 1, wherein the component concentration measuring device has a wavelength.

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