JP2018171178A - Constituent concentration measuring device and method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To compensate for acoustic mode dependency of concentration measurement sensitivity to a constituent to be measured.SOLUTION: Two of laser diodes 1-1 to 1-3 perform intensity modulation of light of two waves having different wavelengths by signals having the same frequency and different phases and perform irradiation. A photoacoustic cell 13 becomes a resonator for amplifying a photoacoustic signal generated from an object 12 to be measured. An acoustic sensor 7 detects a photoacoustic signal. An information processor 11 estimates an acoustic mode, based on the amount of change in light intensity obtained from a measurement result of the light intensity when the strength of a measurement signal is minimized in each case of two cases in which the wavelength of light for changing intensity differs, and based on the amount of change in light intensity obtained from a data set, and determines a correction coefficient of concentration measurement sensitivity to a constituent to be measured, based on the acoustic mode, and a known relationship between the concentration measurement sensitivity to a constituent to be measured included in the object 12 to be measured and the acoustic mode.SELECTED DRAWING: Figure 3

Description

  The present invention relates to a component concentration measuring apparatus, and more particularly to a measuring apparatus that uses a blood component such as glucose as a measurement target.

  With the aging of society, dealing with lifestyle-related diseases is becoming a major issue, and attention is being paid to blood components. However, the technology that has been developed so far is to detect one component with a single sensor, such as reacting a collected sample with a reagent or adsorbing it to a dedicated sensor. Attention has been paid. Therefore, there is a method of measuring transmitted or reflected electromagnetic waves by utilizing absorption by a blood component to be measured (for example, glucose molecules in the case of blood glucose level) when irradiated with electromagnetic waves. .

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. Furthermore, since living bodies are scatterers against electromagnetic waves, , Has not been effective enough.
Therefore, a photoacoustic method has been attracting attention, in which a sound wave generated by irradiating an electromagnetic wave and locally heating it to cause thermal expansion is observed.

  There are two types of photoacoustic methods: a pulse method and a continuous-wave (hereinafter referred to as CW) method. However, in the conventional pulse method and CW method, during the measurement of the glucose concentration in plasma several times, there is a high possibility that other plasma parameters other than the glucose concentration (for example, body temperature, concentration of other components, etc.) will also change. Therefore, there is a problem that glucose selectivity is poor and it is difficult to obtain an accurate glucose concentration.

  Therefore, as a method belonging to the CW method, an optical power balance shift (OPPBS) method was developed by S. Camou et al. (See Patent Documents 1-3), and Naganuma (K. Naganuma) Has developed a standardization method (see Patent Document 4).

  A configuration example of a conventional component concentration measuring apparatus for carrying out the OPBS method is shown in FIG. The component concentration measurement apparatus includes laser diodes 1-1 and 1-2 that emit laser light, a laser driver 2 that drives laser diodes 1-1 and 1-2, and laser diodes 1-1 and 1-2. Optical fibers 3-1 and 3-2 that guide the emitted laser light, an optical multiplexer 4 that combines the laser beams emitted from the laser diodes 1-1 and 1-2, and an optical multiplexer 4. An optical fiber 5 that guides the laser beam, a collimator 6 that irradiates the object 12 with the light guided by the optical fiber 5 as parallel light, and a photoacoustic signal generated from the object 12 to be detected by the photoacoustic effect. The acoustic sensor 7 that converts the electrical signal proportional to the sound pressure, the amplifier 8 that amplifies the electrical signal output from the acoustic sensor 7, the function generator 9 that generates the reference signal, and the output signal of the amplifier 8 And a reference signal output from the function generator 9, and a lock-in amplifier 10 for detecting a measurement signal having a desired frequency from the output signal of the amplifier 8, and the function generator 9 and the lock-in amplifier 10 are controlled and locked. The information processing apparatus 11 includes a computer that processes a measurement signal detected by the in-amplifier 10 to derive a specific component concentration.

  In the conventional OPBS method using the component concentration measuring apparatus shown in FIG. 18, first, the laser driver 2 generates a rectangular wave drive current according to the reference signal output from the function generator 9 to the laser diode 1-1 (first The light emitted from the laser diode 1-1 is intensity-modulated. The intensity-modulated light radiated from the laser diode 1-1 is guided by the optical fiber 3-1, and is irradiated to the object to be measured 12 through the optical multiplexer 4, the optical fiber 5, and the collimator 6 (step in FIG. 19). S100).

  The acoustic sensor 7 detects a photoacoustic signal generated from the device under test 12, and the amplifier 8 amplifies the electrical signal output from the acoustic sensor 7. The lock-in amplifier 10 detects a measurement signal having a frequency determined by the reference signal output from the function generator 9 among the signals included in the output of the amplifier 8.

  The information processing device 11 changes the frequency of the reference signal generated by the function generator 9, thereby changing the frequency of the drive current supplied from the laser driver 2 to the laser diode 1-1 and gradually changing the light modulation frequency. At the same time, an optical modulation frequency sweep is performed to gradually change the frequency of the measurement signal detected by the lock-in amplifier 10 (the same frequency as the optical modulation frequency) (step S101 in FIG. 19). In this way, the relationship between the modulation frequency and the amplitude (sound pressure) of the measurement signal is acquired (step S102 in FIG. 19), and the peak modulation frequency that is the modulation frequency with the maximum amplitude of the measurement signal is searched (step S103 in FIG. 19).

  Next, the laser diode 1-1 is operated again to output light (step S104 in FIG. 19), and then the laser diode 1-2 (second light source) is operated to output light (step S105 in FIG. 19). ). The wavelengths of light emitted from the two laser diodes 1-1 and 1-2 are different.

  The information processing apparatus 11 changes the frequency of the drive current supplied from the laser driver 2 to the laser diodes 1-1 and 1-2 by changing the frequency of the two reference signals generated by the function generator 9. The modulation frequency is set to the above peak modulation frequency, and the frequency of the measurement signal detected by the lock-in amplifier 10 is set to the peak modulation frequency. At this time, the laser driver 2 supplies the laser diodes 1-1 and 1-2 with drive currents having the same frequency and an opposite phase, so that the light emitted from the laser diodes 1-1 and 1-2 is the same. Intensity modulation is performed with signals having opposite phases at the frequency (peak modulation frequency) (step S106 in FIG. 19).

  The intensity-modulated lights emitted from the laser diodes 1-1 and 1-2 are respectively guided by the optical fibers 3-1 and 3-2, multiplexed by the optical multiplexer 4, and further guided by the optical fiber 5, and the collimator. After being converted into parallel light by 6, the object to be measured 12 is irradiated. The information processing apparatus 11 fixes the intensity of light emitted from the laser diode 1-1 by setting the magnitude of the drive current supplied from the laser driver 2 to the laser diode 1-1 to a predetermined value (FIG. 19). Step S107), by changing the magnitude of the drive current supplied from the laser driver 2 to the laser diode 1-2, performing a light intensity sweep that gradually changes the intensity of the light emitted from the laser diode 1-2, The intensity of light emitted from the laser diode 1-2 is adjusted so that the amplitude of the measurement signal is minimized (step S108 in FIG. 19).

  Then, after the lapse of a certain time (step S109 in FIG. 19), the laser diodes 1-1 and 1-2 are operated again, the intensity of light emitted from the laser diode 1-1 is fixed (step S110 in FIG. 19), and measurement is performed. The intensity of light emitted from the laser diode 1-2 is adjusted so that the amplitude of the signal is minimized (step S111 in FIG. 19). Then, the information processing apparatus 11 calculates the amount of change in light intensity from the light intensity obtained in step S108 and the light intensity obtained in step S111 (step S112 in FIG. 19).

  As described above, in the conventional OPBS method, two light beams having different light wavelengths and a phase difference of 180 ° are irradiated to the object to be measured from the same light output port, and the intensity of the two light beams is increased or decreased. Then, the phase inflection point of the portion where the amplitude of the photoacoustic signal is minimum is searched, and the concentration of the molecule dissolved in the blood is obtained from the result. Specifically, by searching for the light intensity at which the amplitude of the photoacoustic signal is minimized while changing the intensity of one of the two light beams, the specific component in the object to be measured is determined from the amount of change in the light intensity. Make an accurate measurement of the concentration of (eg glucose).

  FIG. 20 shows a resonance mode of a sound wave taking resonance in this cylindrical cavity as an example when the case for accommodating the object to be measured is cylindrical, that is, the space in which the photoacoustic energy is confined is a cylindrical cavity. Where R is the radius of the cylinder, L is the length of the cylinder, j is the number of the radial mode, m is the number of the circumferential mode, and q is the longitudinal mode. Is the number.

  FIG. 21 shows the relationship between the modulation frequency and the sound pressure. In FIG. 21, (101), (200), (102), (300) indicate the resonance mode (jmq). For example, (101) is the radial mode number j, and the circumferential mode. This indicates that the number m is 0 and the mode number q in the longitudinal direction is 1. In this manner, in the cylindrical resonator, the sound wave resonates in various modes, and a sound wave distribution in which they interfere with each other in a complicated manner is generated.

  In the conventional photoacoustic method using CW light, there is a problem that the measurement value greatly changes due to the distribution of the sound wave generated by the light irradiation and the interference of the sound wave of the standing wave. That is, there is a problem that the slope of the calibration curve of the concentration of the target component contained in the object to be measured changes on the order of several times.

JP 2014-50563 A JP 2013-106874 A JP 2012-179212 A US Patent No. 8332006

  The present invention has been made to solve the above problems, and provides a component concentration measuring apparatus and method that can compensate the acoustic mode dependence of the concentration measuring sensitivity for the component to be measured included in the object to be measured. For the purpose.

  The component concentration measuring apparatus according to the present invention includes a light irradiating unit that irradiates a measured object with a plurality of lights having different wavelengths with the same frequency and different phase signals, and irradiates the object to be measured. A light intensity controller that changes the intensity of at least one of the plurality of intensity-modulated light, a resonator that amplifies a photoacoustic signal generated from the object to be measured by light irradiation, and the resonator amplified by the resonator The photoacoustic signal detection unit that detects the photoacoustic signal and outputs an electrical signal, the light intensity measurement unit that measures the intensity of the light changed by the light intensity control unit, and the wavelength of the light whose intensity is changed are different 2 Change in the light intensity obtained from the measurement result of the light intensity measurement unit when the intensity of the electrical signal is the lowest in each case for two cases or two cases where the temperatures of the measured objects are different An acoustic mode estimation unit that estimates an acoustic mode that is a resonance mode of the photoacoustic signal based on a change amount of light intensity obtained from a known data set, an acoustic mode estimated by the acoustic mode estimation unit, and A correction coefficient determination unit that determines a correction coefficient of the concentration measurement sensitivity for the measurement target component based on a known relationship between the concentration measurement sensitivity for the measurement target component included in the object to be measured and the acoustic mode; and the light intensity And a concentration deriving unit for deriving the concentration of the component to be measured based on the amount of change in light intensity obtained from the measurement result of the measuring unit and the correction coefficient.

Moreover, in one structural example of the component concentration measuring apparatus of this invention, the said light irradiation part irradiates the said to-be-measured object light of two different wavelengths simultaneously, and the said acoustic mode estimation part is light of 1st wavelength. The measurement result of the light intensity of the second wavelength when the intensity of the electric signal becomes the minimum by changing the intensity of the light of the second wavelength while keeping the intensity of The intensity of light obtained from the measurement result of the intensity of the light of the third wavelength when the intensity of the electric signal is minimized by changing the intensity of the light of the third wavelength while keeping the intensity of light constant. The acoustic mode is estimated based on the amount of change and the amount of change in light intensity obtained from a known data set.
Moreover, in one structural example of the component concentration measuring apparatus of this invention, it further has the temperature control part which controls the temperature of the said to-be-measured object, The said light irradiation part simultaneously has the light of two different wavelengths to the to-be-measured object. And the acoustic mode estimation unit changes the intensity of the light of the second wavelength while keeping the intensity of the light of the first wavelength constant, and the intensity of the electric signal becomes the minimum. The measurement result of the light intensity of the wavelength and the intensity of the light of the second wavelength are changed with the intensity of the light of the first wavelength constant after changing the temperature of the object to be measured by the temperature control unit. The change amount of the light intensity obtained from the measurement result of the light intensity of the second wavelength when the intensity of the electric signal becomes the minimum, and the change amount of the light intensity obtained from the known data set. The acoustic mode is estimated based on .

Further, in one configuration example of the component concentration measuring apparatus of the present invention, the resonator has a variable resonator length, and further includes a resonator length control unit that controls the resonator length, and the light irradiation unit includes: Before simultaneously irradiating the object to be measured with light of two different wavelengths, the object to be measured is irradiated with only the light of the first wavelength, and the resonator length control unit is configured to emit light of the first wavelength. The resonator length is set so that the intensity of the electric signal obtained when the object to be measured is irradiated only on the object is maximized.
Moreover, in one structural example of the component concentration measuring apparatus of this invention, the some light irradiated to the said to-be-measured object is components other than the component of the measuring object contained in the to-be-measured object with respect to the wavelength of these some light Are characterized in that their light absorption coefficients are substantially equal.
Moreover, in one structural example of the component concentration measuring apparatus of this invention, the said light irradiation part irradiates the substantially same area | region of the said to-be-measured object coaxially by making several light of a different wavelength into parallel light, respectively, The plurality of light beams have substantially the same beam diameter.
Moreover, in one structural example of the component concentration measuring apparatus of this invention, the said resonator has two surfaces substantially orthogonal to the optical axis of the light irradiated from the said light irradiation part, and these surfaces are mutually parallel. It is a flat surface.

  The component concentration measuring method according to the present invention includes a first step of irradiating a device under test with a plurality of light beams having different wavelengths, each having an intensity modulated with signals having the same frequency and different phase, and the device under test. A second step of changing the intensity of at least one of a plurality of intensity-modulated lights irradiated to the light, and detecting a photoacoustic signal generated from the object to be measured by the light irradiation and amplified by a resonator to detect an electric signal The third step of outputting the light, the fourth step of measuring the intensity of the light changed in the second step, and two cases where the wavelengths of the light changing the intensity are different, or the temperature of the object to be measured is For two different cases, the amount of change in light intensity obtained from the measurement result of the fourth step when the intensity of the electrical signal is the lowest in each case, and a known data set A fifth step of estimating an acoustic mode, which is a resonance mode of the photoacoustic signal, based on the amount of change in the light intensity, the acoustic mode estimated in the fifth step, and a measurement included in the object to be measured Based on the known relationship between the concentration measurement sensitivity for the target component and the acoustic mode, a sixth step for determining a correction coefficient for the concentration measurement sensitivity for the target component and the measurement result obtained in the fourth step. And a seventh step of deriving the concentration of the component to be measured based on the amount of change in light intensity and the correction coefficient.

  According to the present invention, a plurality of lights having different wavelengths are modulated in intensity by signals having the same frequency and different phases, and the object to be measured is irradiated, and the intensity of at least one of the plurality of intensity-modulated lights is set. The photoacoustic signal generated from the object to be measured by light irradiation is amplified by the resonator and detected by the photoacoustic signal detector, and the temperature of the object to be measured is different in two cases where the wavelengths of the light whose intensity changes are different. For two different cases, the amount of change in light intensity obtained from the measurement result of the light intensity measurement unit when the intensity of the electric signal is the lowest in each case, and the amount of change in light intensity obtained from a known data set Based on a known relationship between the acoustic mode and the concentration measurement sensitivity and acoustic mode for the component to be measured contained in the object to be measured. By determining the correction factor for the measurement sensitivity and deriving the concentration of the component to be measured based on the amount of change in the light intensity obtained from the measurement result of the light intensity measurement unit and the correction factor, the measurement target in the measurement object is measured. It is possible to compensate for the change in the concentration measurement sensitivity with respect to the component due to the acoustic mode, and to improve the measurement sensitivity.

FIG. 1 is a diagram showing response characteristics of glucose concentration. FIG. 2 is a diagram showing the relationship between the resonator length and the sound wave intensity. FIG. 3 is a block diagram showing the configuration of the component concentration measuring apparatus according to the first embodiment of the present invention. FIG. 4 is a block diagram showing the configuration of the information processing apparatus of the component concentration measuring apparatus according to the first embodiment of the present invention. FIG. 5 is a flowchart for explaining the operation of the component concentration measuring apparatus according to the first embodiment of the present invention. FIG. 6 is a diagram showing an example of the relationship between the resonator length and the sound wave intensity in the first embodiment of the present invention. FIG. 7 is a diagram showing an example of light intensity change in the first embodiment of the present invention. FIG. 8 is a diagram showing an example of the relationship between the acoustic mode and the ratio of the change in light intensity in the first embodiment of the present invention. FIG. 9 is a diagram showing an example of the relationship between the glucose concentration sensitivity and the acoustic mode in the first embodiment of the present invention. FIG. 10 is a block diagram showing another configuration of the component concentration measuring apparatus according to the first embodiment of the present invention. FIG. 11 is a block diagram showing the configuration of the component concentration measuring apparatus according to the second embodiment of the present invention. FIG. 12 is a block diagram showing the configuration of the information processing apparatus of the component concentration measuring apparatus according to the second embodiment of the present invention. FIG. 13 is a flowchart for explaining the operation of the component concentration measuring apparatus according to the second embodiment of the present invention. FIG. 14 is a diagram showing an example of light intensity change in the second embodiment of the present invention. FIG. 15 is a diagram showing an example of the relationship between the acoustic mode and the ratio of the change in light intensity in the second embodiment of the present invention. FIG. 16 is a block diagram showing another configuration of the component concentration measuring apparatus according to the second embodiment of the present invention. FIG. 17 is a diagram showing the relationship between the reflectance of sound waves and the acoustic impedance. FIG. 18 is a block diagram showing a configuration of a conventional component concentration measuring apparatus. FIG. 19 is a flowchart for explaining a conventional optical power balance shift method. FIG. 20 is a diagram for explaining a resonance mode of a sound wave in a cylindrical cavity. FIG. 21 is a diagram illustrating an example of the relationship between the modulation frequency and the sound pressure.

[Principle of the Invention]
In the present invention, the influence of sound wave interference is reduced by using collimated light. When the shape of the object to be measured can be freely changed, an effect equivalent to that of collimated light can be obtained by using the object to be measured having a cylindrical shape whose diameter is smaller than half the wavelength of the sound wave. The collimated light can be expressed as the following expression (1) as an intensity distribution.

  Moreover, the magnitude | size S of the sound wave produced by a photoacoustic effect can be represented like the following formula | equation (2).

In equations (1) and (2), C is a constant, α is the light absorption coefficient of the object to be measured for light of a specific wavelength, q is the acoustic mode, and F (α, q) is the light absorption coefficient α and the acoustic mode. A function of q, ω is a modulation frequency, w is a light beam diameter, z is a depth from the surface of the object to be measured, r is a distance in the radial direction from the optical axis, and I is a light intensity.
The light absorption coefficient α can be described as in equation (3).

In Expression (3), ΔC is the concentration of the specific component in the object to be measured, ΔT is the temperature of the object to be measured, β is the molar absorbance of the specific component, and γ is the temperature absorbance of the object to be measured. Α ₀ represents the light absorption coefficient of the object to be measured in the initial state.

  For example, in a cylindrical resonator, the acoustic wave mode is given by the following equations (4) and (5). Acoustic wave modes include longitudinal, circumferential, and radial modes.

In equations (4) and (5), c is the speed of sound in the object to be measured, q is the acoustic mode in the optical axis direction, R is the radius of the cylinder, L is the length of the cylinder, and α _{m, n} is the object to be measured. This is the nth-order root that satisfies the boundary condition that the change in sound pressure in the radial direction on the wall surface is zero.

  For example, when the object to be measured is irradiated with collimated light, q corresponds to the standing wave mode in the cylindrical axis direction (FIG. 20). In this case, the function F can be described approximately as shown in the equation (6), and thus takes a discrete value for each mode.

The light absorption coefficient α _i and _{i of} the function F _i are subscripts corresponding to the wavelength of light. The resonance of the sound wave between the parallel plates can be handled in the same manner as the resonance of the sound wave in the cylinder. Here, the magnitude S of the sound wave generated when the object to be measured is irradiated with two lights having different wavelengths and having a phase difference of 180 ° is expressed as the superposition of the sound waves generated by the respective lights as follows. Can do.

S ₁ and S ₂ are the magnitudes of two sound waves. In the OPBS method, S ₁ = S ₂ because it is equivalent to considering a state where the signal intensity of the sound wave is minimum, that is, ideally zero.
Assuming that a specific component in the object to be measured changes in concentration by ΔC, the following equation (8) is established.

I ₁ is the intensity of the first light, I ₂ is the intensity of the second light, and ΔI ₂ is the amount of change in the intensity of the second light when the concentration of the specific component in the object to be measured changes by ΔC. From the equation (8), the relationship between the component concentration change and the light intensity change can be approximated as in the equations (9) and (10).

  If the acoustic mode q and the background light absorption are known from the equations (9) and (10), the sensitivity of density change can be obtained. FIG. 1 shows an example of response characteristics when the measurement object is almost water and the glucose concentration changes. FIG. 1 shows that the light intensity changes in proportion to the glucose concentration and that the sensitivity changes depending on the acoustic mode q. It can also be seen that the sensitivity changes greatly when the acoustic mode q changes.

  Therefore, it is necessary to correct the acoustic mode. This correction can be realized by preparing a data set of an absorption spectrum with respect to light having a third wavelength different from the light having a wavelength used for measurement or temperature, and performing numerical correction on actually measured data. Two methods of the present invention for correcting the interference error of the resonance mode of the sound wave using the equations (9) and (10) and the known absorption coefficient difference will be described.

[First correction method]
By irradiating the object to be measured with light of the first wavelength and sweeping the resonator length L in an arbitrary range, the relationship between the resonator length L and the sound pressure as shown in FIG. 2 is acquired. The resonator length L of the sound wave in the object to be measured can be selected from the peak of FIG.

Next, as described above, two light beams having different light wavelengths and a phase difference of 180 ° are irradiated to the object to be measured from the same light output port. The resonator length at this time is the resonator length L selected above. The intensity I ₀ of the second wavelength light is measured while the intensity of the generated sound wave is minimized while the intensity of the first wavelength light is fixed and the intensity of the second wavelength light is increased or decreased.

Next, the sound wave generated while switching the light of the second wavelength to the light of the third wavelength whose light absorption coefficient for the object to be measured is known and increasing or decreasing the intensity of the light of the third wavelength in the same manner as described above. The intensity I ₁ of the light of the third wavelength at which the intensity is minimized is measured. The ratio ΔI / I of the change amount (I ₁ −I ₀ ) of the light intensity with respect to the light intensity I ₀ from the obtained light intensity I ₀ , I ₁ is expressed by the equation (11).

  Here, when sufficiently collimated light is used, the relationship of the above equation is given by the following equation for each acoustic mode q.

The function F _i and _{i of} the light absorption coefficient α _i are subscripts corresponding to the wavelength of light. F ₁ is a function of light absorption coefficient α and acoustic mode q for light of the first wavelength, F ₂ is a function of light absorption coefficient α and acoustic mode q for light of the second wavelength, and F ₁ ′ is a third wavelength. Is a function of the light absorption coefficient α and the acoustic mode q for the first wavelength light, F ₂ ′ is a function of the light absorption coefficient α and the acoustic mode q for the third wavelength light, and α ₂ is the second function. It is a light absorption coefficient of the object to be measured with respect to light of a wavelength.

  Therefore, the acoustic mode q can be obtained by comparing the responses of the equations (11) and (12) and searching for the response with the closest density measurement sensitivity. Using the acoustic mode q, the concentration measurement sensitivity Gq at the current resonator length L can be estimated from the equation (9). When the constant coefficient A is determined so that the density measurement sensitivity Gq is the same as the density measurement sensitivity G0 when the acoustic mode q = 0, the relationship with the compensated density is expressed by the following equation.

[Second correction method]
Similar to the first correction method, the light having the first wavelength is irradiated onto the object to be measured, and the resonator length L and the sound pressure as shown in FIG. Get the relationship. The resonator length L of the sound wave in the object to be measured can be selected from the peak of FIG.

Next, as described above, two light beams having different light wavelengths and a phase difference of 180 ° are irradiated to the object to be measured from the same light output port. The resonator length at this time is the resonator length L selected above. The intensity I ₀ of the second wavelength light is measured while the intensity of the generated sound wave is minimized while the intensity of the first wavelength light is fixed and the intensity of the second wavelength light is increased or decreased.

Next, the temperature of the object to be measured is changed by ΔT using a temperature controller, and the intensity of the generated sound wave is minimized while increasing or decreasing the intensity of the second wavelength light in the same manner as described above. The light intensity I ₁ is measured. The ratio ΔI / I of the change amount (I ₁ −I ₀ ) of the light intensity with respect to the light intensity I ₀ from the obtained light intensities I ₀ and I ₁ is expressed by the following equation (15).

  When the change in the light absorption coefficient with respect to the temperature change of the object to be measured is given by the temperature dependence γ of the light absorption coefficient from the spectral data set, the response characteristic with respect to temperature is given by

γ ₁ is the temperature dependence of the light absorption coefficient α ₁ of the object to be measured with respect to the first wavelength light, and γ ₂ is the temperature dependence of the light absorption coefficient α ₂ of the object to be measured with respect to the light of the second wavelength.

  Therefore, the acoustic mode q can be obtained by comparing the responses of the equations (15) and (16) and searching for the response with the closest sensitivity. Using the acoustic mode q, the concentration measurement sensitivity Gq at the current resonator length L can be estimated from the equation (9). When the constant coefficient A is determined so that the density measurement sensitivity Gq is the same as the density measurement sensitivity G0 when the acoustic mode q = 0, the relationship with the compensated density is expressed by the following equation.

  A method for compensating the acoustic resonance mode of the photoacoustic method will be described below using a glucose aqueous solution as an example.

[First embodiment]
Hereinafter, embodiments of the present invention will be described with reference to the drawings. FIG. 3 is a block diagram showing the configuration of the component concentration measuring apparatus according to the first embodiment of the present invention. The component concentration measuring apparatus of the present embodiment includes a laser diode 1-1, 1-2, 1-3 that emits laser light, and a laser driver 2 that drives the laser diode 1-1, 1-2, 1-3. , Optical fibers 3-1, 3-2 and 3-3 for guiding laser light emitted from the laser diodes 1-1, 1-2 and 1-3, and laser diodes 1-1, 1-2 and 1-3. An optical multiplexer 4 that combines the laser light emitted from the optical fiber 5, an optical fiber 5 that guides the laser light combined by the optical multiplexer 4, and parallel light that is guided by the optical fiber 5. A photoacoustic signal detector that detects a photoacoustic signal generated from the object to be measured 12 by the photoacoustic effect and converts it into an electrical signal proportional to the sound pressure, and an acoustic sensor 7. Amplifier that amplifies the electrical signal output from And a function generator 9 for generating a reference signal, and a lock-in amplifier for detecting a measurement signal of a desired frequency from the output signal of the amplifier 8 with the output signal of the amplifier 8 and the reference signal output from the function generator 9 as inputs. 10, an information processing apparatus 11 including a computer that controls the laser driver 2, the function generator 9, and the lock-in amplifier 10, and processes a measurement signal detected by the lock-in amplifier 10 to derive a specific component concentration; It comprises a photoacoustic cell 13 that houses a device under test 12 and serves as a resonator that amplifies a photoacoustic signal.

  The laser diodes 1-1, 1-2, 1-3, the laser driver 2, the function generator 9, the optical fibers 3-1, 3-2, 3-3, 5, the optical multiplexer 4 and the collimator 6 are irradiated with light. Part. The information processing apparatus 11 and the function generator 9 constitute a light intensity control unit.

Examples of the laser diodes 1-1, 1-2, and 1-3 include, for example, a distributed feedback semiconductor laser (DFB-LD). As an example of the acoustic sensor 7, there is a microphone using a piezoelectric sensor.
In the present embodiment, the object to be measured 12 is introduced into, for example, a cylindrical photoacoustic cell 13, and laser light is irradiated through a glass optical window provided in the photoacoustic cell 13.

  FIG. 4 is a block diagram showing the configuration of the information processing apparatus 11. The information processing apparatus 11 is radiated from the generator control unit 100 that controls the function generator 9, the light intensity control unit 101 that controls the intensity of light via the function generator 9, and the laser diodes 1-1 to 1-3. The intensity of the measurement signal is the lowest in each case for the light intensity measuring unit 102 that measures the intensity of the light and the two cases where the wavelengths of the light that changes the intensity are different or two cases where the temperatures of the measured object 12 are different. The light intensity change amount calculation unit 103 that calculates the change amount of the light intensity obtained from the measurement result of the light intensity when the light intensity changes, and the temperature of the object to be measured 12 is different in two cases where the wavelengths of the light that changes the intensity are different. For the two cases, the amount of change in the light intensity obtained from the measurement result of the light intensity when the intensity of the measurement signal is the lowest in each case, and the known The acoustic mode estimation unit 104 that estimates the acoustic mode that is the resonance mode of the photoacoustic signal based on the amount of change in light intensity obtained from the data set, the acoustic mode estimated by the acoustic mode estimation unit 104, and the object to be measured 12 A correction coefficient determination unit 105 that determines a correction coefficient of the concentration measurement sensitivity for the specific component based on a known relationship between the concentration measurement sensitivity for the specific component (for example, glucose) and the acoustic mode; It has a concentration deriving unit 106 for deriving component concentrations, a storage unit 107 for storing information, and a resonator length control unit 108 for controlling the resonator length.

  Next, the operation of the component concentration measuring apparatus of the present embodiment will be described with reference to the flowchart of FIG. First, only the laser diode 1-1 (first light source) is operated. When a drive current is supplied from the laser driver 2, the laser diode 1-1 emits laser light (continuous light). At this time, when a drive current is supplied from the laser driver 2, the laser diode 1-1 emits intensity-modulated light. The wavelength (first wavelength) of the light emitted from the laser diode 1-1 is, for example, 1382 nm. The intensity-modulated light radiated from the laser diode 1-1 is guided by the optical fiber 3-1, and is irradiated to the object to be measured 12 through the optical multiplexer 4, the optical fiber 5, and the collimator 6 (step in FIG. 5). S200).

  At this time, the generator control unit 100 of the information processing apparatus 11 changes the frequency of the drive current supplied from the laser driver 2 to the laser diode 1-1 by changing the reference signal generated by the function generator 9, thereby The modulation frequency is set to a specific frequency, and the frequency of the measurement signal detected by the lock-in amplifier 10 is set to the same value as the optical modulation frequency.

  The acoustic sensor 7 detects a photoacoustic signal generated from the device under test 12, and the amplifier 8 amplifies the electrical signal output from the acoustic sensor 8. The lock-in amplifier 10 detects a measurement signal having a frequency determined by the reference signal output from the function generator 9 among the signals included in the output of the amplifier 8.

  The resonator length control unit 108 of the information processing apparatus 11 performs a resonator length sweep that gradually changes the resonator length L, which is the distance between two parallel planes (mirrors) of the resonator, within a predetermined range (step in FIG. 5). S201).

  As a method for sweeping the resonator length L, for example, two methods are conceivable. As in the present embodiment, when the DUT 12 is accommodated in the photoacoustic cell 13 and the collimator 6 and the acoustic sensor 7 are attached to the photoacoustic cell 13, the size of the photoacoustic cell 13 is changed. Thus, the resonator length L can be changed. For this purpose, a photoacoustic cell 13 capable of moving at least one of two parallel planes, that is, a surface on which the collimator 6 is fixed and a surface on which the acoustic sensor 7 is fixed, and resonator length control A drive mechanism (not shown) that moves at least one of the two parallel planes of the photoacoustic cell 13 in accordance with an instruction from the unit 108 is required.

  As another method for sweeping the resonator length L, there is a method corresponding to the case where the DUT 12 is a deformable solid and the photoacoustic cell 13 is not provided. When the object 12 is held between the first flat plate (mirror) to which the collimator 6 is fixed and the second flat plate (mirror) to which the acoustic sensor 7 is fixed, the first flat plate and the second flat plate are held. By moving at least one of the flat plates, it is possible to change the resonator length L at the same time that the DUT 12 is deformed. For this purpose, a drive mechanism (not shown) that moves at least one of the first flat plate and the second flat plate in accordance with an instruction from the resonator length control unit 108 is required.

  In this way, by performing the resonator length sweep, the relationship between the resonator length L and the amplitude (sound pressure) of the measurement signal is obtained (step S202 in FIG. 5), and the resonator length L at which the amplitude of the measurement signal is maximum is obtained. A certain peak resonator length is searched (step S203 in FIG. 5). FIG. 6 shows the relationship between the resonator length L and the sound wave intensity obtained in this example.

  Next, the laser diode 1-1 is operated again to output continuous light (step S204 in FIG. 5), and then the laser diode 1-2 (second light source) is operated to output continuous light (FIG. 5). Step S205). At this time, the resonator length control unit 108 sets the resonator length L to the peak resonator length. The wavelength of the light emitted from the laser diode 1-1 is, for example, 1382 nm, and the wavelength (second wavelength) of the light emitted from the laser diode 1-2 is, for example, 1610 nm. The two laser diodes 1-1, 1- The wavelengths of light emitted from the two are different.

  The generator control unit 100 of the information processing device 11 changes the frequency of the two reference signals generated by the function generator 9 to change the frequency of the drive current supplied from the laser driver 2 to the laser diodes 1-1 and 1-2. And the optical modulation frequency is set to the above specific frequency, and the frequency of the measurement signal detected by the lock-in amplifier 10 is set to the same value as the optical modulation frequency. By supplying drive currents having the same frequency and opposite phases from the laser driver 2 to the laser diodes 1-1 and 1-2, the light emitted from the laser diodes 1-1 and 1-2 is supplied to the same specific frequency. Then, intensity modulation is performed with the signals of opposite phases (step S206 in FIG. 5). Therefore, in this embodiment, two intensity-modulated lights are generated by intensity-modulating two laser beams having different wavelengths with signals having the same frequency and opposite phases.

  The intensity-modulated lights emitted from the laser diodes 1-1 and 1-2 are respectively guided by the optical fibers 3-1 and 3-2, and are combined by the optical multiplexer 4, and the optical fiber 5 and the collimator 6 are further connected. The object to be measured 12 is irradiated through.

  The light intensity control unit 101 of the information processing apparatus 11 controls the function generator 9 to set the voltage of the reference signal for driving the laser diode 1-1 to a predetermined value, so that the laser driver 1 transmits the laser diode 1 to the laser diode 1. -1 is made constant, and the intensity of light emitted from the laser diode 1-1 is made constant (step S207 in FIG. 5).

  Further, the light intensity control unit 101 of the information processing apparatus 11 controls the function generator 9 to change the voltage of the reference signal for driving the laser diode 1-2, so that the laser driver 1 outputs the laser diode 1-. The intensity of the measurement signal output from the lock-in amplifier 10 is minimized by performing a light intensity sweep that changes the intensity of the drive current supplied to 2 and gradually changes the intensity of the light emitted from the laser diode 1-2. The intensity of light emitted from the laser diode 1-2 is adjusted so as to become (step S208 in FIG. 5).

The light intensity measurement unit 102 of the information processing apparatus 11 measures the intensity of light emitted from the laser diode 1-2. The light intensity measurement unit 102 acquires the voltage of the reference signal for driving the laser diode 1-2 output from the function generator 9. The storage unit 107 of the information processing apparatus 11 stores in advance calibration data indicating the relationship between the voltage of the reference signal and the intensity of light emitted from the laser diode 1-2. Calibration data can be obtained in advance by actual measurement of voltage and intensity. The light intensity measurement unit 102 refers to such calibration data, and converts the voltage of the acquired reference signal into the intensity of light emitted from the laser diode 1-2. The light intensity measurement unit 102 stores the intensity I ₀ of the light emitted from the laser diode 1-2 when the amplitude of the measurement signal is minimum in the storage unit 107 (step S209 in FIG. 5).

  Next, the operation of the laser diode 1-2 is stopped, and the laser diode 1-3 (third light source) is operated to output continuous light (step S210 in FIG. 5). The resonator length control unit 108 sets the resonator length L to the above-described peak resonator length. The wavelength of light emitted from the laser diode 1-3 (third wavelength) is, for example, 1650 nm, and the wavelengths of light emitted from the two laser diodes 1-1 and 1-3 are different.

  The generator control unit 100 of the information processing device 11 changes the frequency of the two reference signals generated by the function generator 9 to change the frequency of the drive current supplied from the laser driver 2 to the laser diodes 1-1 and 1-3. And the optical modulation frequency is set to the above specific frequency, and the frequency of the measurement signal detected by the lock-in amplifier 10 is set to the same value as the optical modulation frequency. By supplying drive currents having the same frequency and an opposite phase waveform from the laser driver 2 to the laser diodes 1-1 and 1-3, the light emitted from the laser diodes 1-1 and 1-3 has the same specific frequency. Then, intensity modulation is performed with the signals of opposite phases (step S211 in FIG. 5).

  The light intensity control unit 101 of the information processing apparatus 11 controls the function generator 9 to change the voltage of the reference signal for driving the laser diode 1-3 to change the laser driver 2 to the laser diode 1-3. The intensity of the measurement signal output from the lock-in amplifier 10 is minimized by performing a light intensity sweep that changes the magnitude of the supplied drive current and gradually changes the intensity of the light emitted from the laser diode 1-3. In this way, the intensity of light emitted from the laser diode 1-3 is adjusted (step S212 in FIG. 5). As described above, the intensity of light emitted from the laser diode 1-1 is constant.

The light intensity measurement unit 102 of the information processing apparatus 11 measures the intensity of light emitted from the laser diode 1-3. The light intensity measurement unit 102 acquires the voltage of the reference signal for driving the laser diode 1-3 output from the function generator 9. Similarly to the above, the storage unit 107 of the information processing apparatus 11 stores in advance calibration data indicating the relationship between the voltage of the reference signal and the intensity of light emitted from the laser diode 1-3. The light intensity measurement unit 102 refers to such calibration data, and converts the voltage of the acquired reference signal into the intensity of light emitted from the laser diode 1-3. The light intensity measurement unit 102 stores the intensity I ₁ of the light emitted from the laser diode 1-3 when the amplitude of the measurement signal is minimum in the storage unit 107 (step S213 in FIG. 5).

The light intensity change amount calculation unit 103 of the information processing apparatus 11 calculates the ratio of the light intensity change amount ΔI = (I ₁ −I ₀ ) with respect to the light intensity I ₀ from the light intensities I ₀ and I ₁ obtained in steps S209 and S213. ΔI / I is calculated by equation (11) (step S214 in FIG. 5).

  The light absorption coefficient of the device under test 12 for the third wavelength light emitted from the laser diode 1-3 is based on the light absorption coefficient of the device under test 12 for the second wavelength light emitted from the laser diode 1-2. FIG. 7 shows the ratio ΔI / I of the change amount of the light intensity when 0.02 / mm is larger. According to FIG. 7, the result ΔI / I = 4.7% is obtained.

Next, the acoustic mode estimation unit 104 of the information processing apparatus 11 uses a predetermined data set as shown in Table 1 to calculate the light intensity change amount ratio ΔI ₂ / I ₂ using the equations (12) and (13). Is calculated for each acoustic mode q (step S215 in FIG. 5). The data set represents the relationship between the first, second, and third wavelengths and the light absorption coefficient of a specific component (for example, glucose) with respect to light of these wavelengths.

The function F ₁ can be calculated from the light absorption coefficient α ₁ = 0.30 / mm for the first wavelength light and the acoustic mode q, and the function F ₂ is the light absorption coefficient α ₂ = for the second wavelength light. It can be calculated from 0.28 / mm and the acoustic mode q. Δα ₂ is a change amount of the light absorption coefficient α _{2 with} respect to the light absorption coefficient α ₁ . As described above, the resonator length L is set to a known peak resonator length.

The relationship between the acoustic mode q and the light intensity change ratio ΔI ₂ / I ₂ as shown in FIG. 8 is obtained from the calculation result of step S215. The acoustic mode estimation unit 104 of the information processing apparatus 11 has the light intensity change ratio ΔI / I calculated in step S214 equal to the light intensity change ratio ΔI ₂ / I ₂ calculated in step S215. The value of the acoustic mode q is determined as the value of the acoustic mode at the current resonator length (step S216 in FIG. 5). In the example of this embodiment, it can be estimated that q = 2.

  The correction coefficient determination unit 105 of the information processing apparatus 11 measures the concentration of a specific component (glucose in the example of the present embodiment) in the DUT 12 corresponding to the value of the acoustic mode q estimated by the acoustic mode estimation unit 104. The sensitivity Gq is obtained from the known relationship between the density measurement sensitivity and the acoustic mode q (FIG. 9), and the ratio G0 / Gq of the density measurement sensitivity G0 when the acoustic mode q = 0 with respect to the density measurement sensitivity Gq is the correction coefficient A. (Step S217 in FIG. 5).

  According to FIG. 9, the density measurement sensitivity Gq when the acoustic mode q = 2 is approximately five times larger than the density measurement sensitivity G0 when the acoustic mode q = 0, so that the correction coefficient determination unit 105 performs the correction coefficient A = 1 / 5 can be obtained.

The concentration deriving unit 106 of the information processing apparatus 11 calculates the light intensity change ratio ΔI / I (the light intensity change ratio ΔI ₂ / I ₂ when the acoustic mode q = 2) calculated in step S214. Based on the correction coefficient A determined by the correction coefficient determination unit 105, the amount of change ΔC [%] of the concentration of the specific component in the device under test 12 at an arbitrary time after the start of measurement is expressed by equation (14). Calculation is performed (step S218 in FIG. 5).

  Finally, the concentration deriving unit 106 calculates the concentration of the specific component at an arbitrary time point after the elapse of an arbitrary time from the change amount ΔC [%] of the concentration of the specific component calculated in step S218 and the known reference concentration of the specific component. (Step S219 in FIG. 5). The reference concentration can be obtained by performing a standard blood glucose measurement method on the object 12 to be measured. To perform a standard blood glucose measurement method, insert a glucose sensor into the body of the blood glucose meter, set the needle on a dedicated machine (or body), collect blood from a finger, etc., and absorb the blood into the glucose sensor. Let A standard blood glucose measurement method uses a known concentration of glucose solution as a standard calibration solution for machine operation confirmation. It is used to check whether the machine is operating normally during initial operation, or to check whether the blood glucose level is abnormal (ie, whether the machine is operating normally). Such a standard blood glucose measurement method may be performed at the time of starting measurement, for example, when selecting the peak resonator length.

  As described above, in this embodiment, it is possible to compensate for the change in the density measurement sensitivity with respect to the specific component in the DUT 12 due to the acoustic mode, and to improve the measurement sensitivity.

  The wavelength of the sound wave is determined by the following equation depending on the modulation frequency of the irradiated light.

  f is the modulation frequency of light, v is the speed of sound, and λ is the wavelength of sound. If the device under test 12 is thinner than the wavelength λ and the acoustic mode q cannot be defined, it can be solved by providing an acoustic matching layer 14 between the device under test 12 and the acoustic sensor 7 as shown in FIG. When the DUT 12 is a living body, examples of the acoustic matching layer 14 include rubber and a gel for ultrasonic diagnosis. The acoustic matching layer 14 is preferably variable in thickness.

[Second Embodiment]
Next, a second embodiment of the present invention will be described. FIG. 11 is a block diagram showing the configuration of the component concentration measuring apparatus according to the second embodiment of the present invention. The same components as those in FIG. 3 are denoted by the same reference numerals. The component concentration measuring apparatus according to the present embodiment includes laser diodes 1-1 and 1-2, a laser driver 2, optical fibers 3-1 and 3-2, an optical multiplexer 4, an optical fiber 5, and a collimator 6. And an acoustic sensor 7, an amplifier 8, a function generator 9, a lock-in amplifier 10, an information processing device 11 a, and a temperature controller 15 that changes the temperature of the device under test 12.

  FIG. 12 is a block diagram showing the configuration of the information processing apparatus 11a of this embodiment. The information processing apparatus 11a includes a generator control unit 100, a light intensity control unit 101, a light intensity measurement unit 102, a light intensity change amount calculation unit 103, an acoustic mode estimation unit 104, a correction coefficient determination unit 105, a concentration It has a derivation unit 106, a storage unit 107, a resonator length control unit 108, and a temperature control unit 109 that controls the temperature of the DUT 12.

  Next, the operation of the component concentration measuring apparatus of the present embodiment will be described with reference to the flowchart of FIG. First, only the laser diode 1-1 (first light source) is operated. When a drive current is supplied from the laser driver 2, the laser diode 1-1 emits laser light (continuous light). At this time, when a drive current is supplied from the laser driver 2, the laser diode 1-1 emits intensity-modulated light. Similar to the first embodiment, the wavelength of light emitted from the laser diode 1-1 (first wavelength) is, for example, 1382 nm. The intensity-modulated light radiated from the laser diode 1-1 is guided by the optical fiber 3-1, and is irradiated to the object to be measured 12 through the optical multiplexer 4, the optical fiber 5, and the collimator 6 (step in FIG. 13). S300). Similarly to the first embodiment, the generator control unit 100 of the information processing apparatus 11 sets the optical modulation frequency to a specific frequency, and the frequency of the measurement signal detected by the lock-in amplifier 10 is the same as the optical modulation frequency. Set to value.

  The acoustic sensor 7 detects a photoacoustic signal generated from the device under test 12, and the amplifier 8 amplifies the electrical signal output from the acoustic sensor 8. The lock-in amplifier 10 detects a measurement signal having a frequency determined by the reference signal output from the function generator 9 among the signals included in the output of the amplifier 8.

  Similar to the first embodiment, the resonator length control unit 108 of the information processing apparatus 11a performs a resonator length sweep that gradually changes the resonator length L within a predetermined range (step S301 in FIG. 13). Thus, by performing the resonator length sweep, the relationship between the resonator length L and the amplitude (sound pressure) of the measurement signal is acquired (step S302 in FIG. 13), and the resonator length L at which the amplitude of the measurement signal is maximum is obtained. A certain peak resonator length is searched (step S303 in FIG. 13).

  Next, the laser diode 1-1 is operated again to output continuous light (FIG. 13, step S304), and then the laser diode 1-2 (second light source) is operated to output continuous light (FIG. 13). Step S305). At this time, the resonator length control unit 108 sets the resonator length L to the peak resonator length. The wavelength of the light emitted from the laser diode 1-1 is, for example, 1382 nm, and the wavelength (second wavelength) of the light emitted from the laser diode 1-2 is, for example, 1610 nm. The two laser diodes 1-1, 1- The wavelengths of light emitted from the two are different.

  The generator control unit 100 of the information processing device 11a changes the frequency of the two reference signals generated by the function generator 9, thereby changing the frequency of the drive current supplied from the laser driver 2 to the laser diodes 1-1 and 1-2. And the optical modulation frequency is set to the above specific frequency, and the frequency of the measurement signal detected by the lock-in amplifier 10 is set to the same value as the optical modulation frequency. By supplying drive currents having the same frequency and opposite phases from the laser driver 2 to the laser diodes 1-1 and 1-2, the light emitted from the laser diodes 1-1 and 1-2 is supplied to the same specific frequency. Then, the intensity is modulated by the signals having opposite phases (step S306 in FIG. 13).

  The intensity-modulated lights emitted from the laser diodes 1-1 and 1-2 are respectively guided by the optical fibers 3-1 and 3-2, and are combined by the optical multiplexer 4, and the optical fiber 5 and the collimator 6 are further connected. The object to be measured 12 is irradiated through.

  The light intensity control unit 101 of the information processing apparatus 11a controls the function generator 9 to set the voltage of the reference signal for driving the laser diode 1-1 to a predetermined value. -1 is made constant, and the intensity of light emitted from the laser diode 1-1 is made constant (step S307 in FIG. 13).

  Further, the light intensity controller 101 is supplied from the laser driver 2 to the laser diode 1-2 by controlling the function generator 9 to change the voltage of the reference signal for driving the laser diode 1-2. The intensity of the measurement signal output from the lock-in amplifier 10 is minimized by performing a light intensity sweep that changes the magnitude of the drive current and gradually changes the intensity of the light emitted from the laser diode 1-2. The intensity of light emitted from the diode 1-2 is adjusted (step S308 in FIG. 13).

The light intensity measurement unit 102 of the information processing apparatus 11a measures the intensity of light emitted from the laser diode 1-2, as in the first embodiment. Then, the light intensity measurement unit 102 stores the intensity I ₀ of the light emitted from the laser diode 1-2 when the amplitude of the measurement signal is minimum in the storage unit 107 (step S309 in FIG. 13).

  Next, the temperature controller 109 of the information processing apparatus 11a controls the temperature controller 15 to increase the temperature of the DUT 12 by ΔT (for example, 1 ° C.) (step S310 in FIG. 13).

  The light intensity control unit 101 of the information processing apparatus 11a controls the function generator 9 to change the voltage of the reference signal for driving the laser diode 1-2, thereby changing the laser driver 2 to the laser diode 1-2. The intensity of the measurement signal output from the lock-in amplifier 10 is minimized by changing the magnitude of the supplied drive current and performing a light intensity sweep that gradually changes the intensity of the light emitted from the laser diode 1-2. In this way, the intensity of the light emitted from the laser diode 1-2 is adjusted (step S311 in FIG. 13). As described above, the intensity of light emitted from the laser diode 1-1 is constant.

The light intensity measurement unit 102 of the information processing apparatus 11a measures the intensity of light emitted from the laser diode 1-2 in the same manner as in step S309. Then, the light intensity measurement unit 102 stores the intensity I ₁ of the light emitted from the laser diode 1-2 when the amplitude of the measurement signal is minimum in the storage unit 107 (step S312 in FIG. 13).

The light intensity change amount calculation unit 103 of the information processing apparatus 11a calculates the ratio of the light intensity change amount ΔI = (I ₁ −I ₀ ) to the light intensity I ₀ from the light intensities I ₀ and I ₁ obtained in steps S309 and S312. ΔI / I is calculated by equation (15) (step S313 in FIG. 13). FIG. 14 shows the ratio ΔI / I of the amount of change in light intensity before and after the temperature change when the temperature of the DUT 12 is raised by 1 ° C. According to FIG. 14, a result of ΔI / I = 1.8% is obtained.

Next, the acoustic mode estimation unit 104 of the information processing apparatus 11a uses the predetermined data set as shown in Table 2 to calculate the light intensity change amount ratio ΔI ₂ / I ₂ using Equations (16) and (17). Is calculated for each acoustic mode q (step S314 in FIG. 13). The data set represents the relationship between the first and second wavelengths, the light absorption coefficient of a specific component (for example, glucose) with respect to light of these wavelengths, and the temperature dependence of these light absorption coefficients.

γ ₁ is the temperature dependence of the light absorption coefficient α ₁ of the object to be measured for the first wavelength light (temperature absorbance), and γ ₂ is the temperature dependence of the light absorption coefficient α ₂ of the object to be measured for the second wavelength light. It is sex. The function F ₁ can be calculated from the light absorption coefficient α ₁ = 0.30 / mm for the first wavelength light and the acoustic mode q, and the function F ₂ is the light absorption coefficient α ₂ = for the second wavelength light. It can be calculated from 0.28 / mm and the acoustic mode q. As described above, the resonator length L is set to a known peak resonator length.

From the result of the calculation in step S314, the relationship between the acoustic mode q and the light intensity change ratio ΔI ₂ / I ₂ as shown in FIG. 15 is obtained. The acoustic mode estimation unit 104 of the information processing apparatus 11a has the light intensity change ratio ΔI / I calculated in step S313 equal to the light intensity change ratio ΔI ₂ / I ₂ calculated in step S314. The value of the acoustic mode q is determined as the value of the acoustic mode at the current resonator length (step S315 in FIG. 13). In the example of this embodiment, it can be estimated that q = 1.

  The correction coefficient determination unit 105 of the information processing apparatus 11a measures the concentration of a specific component (glucose in the example of the present embodiment) in the DUT 12 corresponding to the value of the acoustic mode q estimated by the acoustic mode estimation unit 104. The sensitivity Gq is obtained from the known relationship between the density measurement sensitivity and the acoustic mode q (FIG. 9), and the ratio G0 / Gq of the density measurement sensitivity G0 when the acoustic mode q = 0 with respect to the density measurement sensitivity Gq is the correction coefficient A. (Step S316 in FIG. 13).

  According to FIG. 9, since the density measurement sensitivity Gq when the acoustic mode q = 1 is approximately three times larger than the density measurement sensitivity G0 when the acoustic mode q = 0, the correction coefficient determination unit 105 determines that the correction coefficient A = 1 / 3 can be obtained.

The concentration deriving unit 106 of the information processing apparatus 11a calculates the light intensity change amount ratio ΔI / I (the light intensity change amount ratio ΔI ₂ / I ₂ when the acoustic mode q = 1) calculated in step S313. Based on the correction coefficient A determined by the correction coefficient determination unit 105, the change amount ΔC [%] of the concentration of the specific component in the DUT 12 at an arbitrary time after the start of measurement is expressed by the equation (18). Calculation is performed (step S317 in FIG. 13).

Finally, the concentration deriving unit 106 calculates the concentration of the specific component at an arbitrary time point after the elapse of an arbitrary time from the change amount ΔC [%] of the concentration of the specific component calculated in step S317 and the known reference concentration of the specific component. (Step S318 in FIG. 13).
Thus, in this embodiment, the same effect as in the first embodiment can be obtained.

  As described in the first embodiment, also in this embodiment, the acoustic matching layer 14 may be provided between the DUT 12 and the acoustic sensor 7 (FIG. 16).

  The reflected propagation of sound waves can be evaluated using acoustic impedance. For example, the reflectance R and transmittance T at the interface between different materials can be expressed by the following equations.

Z ₁ is the acoustic impedance of the first material, and Z ₂ is the acoustic impedance of the second material in contact with the first material. The acoustic impedance Z can be expressed by Equation (22).

  ρ is the density of the material, and C is the speed of sound within the material. The sound wave to be reflected and transmitted is determined by the difference in acoustic impedance. FIG. 17 shows the relationship between sound wave reflectance and acoustic impedance. A reflectance of 0.8 or more between the DUT 12 and the resonator material interface is a necessary condition for functioning as a resonator. As a material for the resonator satisfying this condition, there are various metals such as glass, iron and copper. The photoacoustic cell 13 constituting the resonator preferably has two surfaces substantially orthogonal to the optical axis of the irradiated light, and these two surfaces are preferably parallel to each other. Or it is preferable that the 1st, 2nd flat plate which comprises a resonator is arrange | positioned so as to be substantially orthogonal to the optical axis of the irradiated light, and these two flat plates are mutually parallel.

  In the first and second embodiments, the plurality of lights irradiated on the object to be measured 12 is light absorption of components other than the component to be measured included in the object to be measured 12 with respect to the wavelengths of the plurality of lights. It is preferable that the coefficients are substantially equal.

  Further, in the first and second embodiments, a plurality of lights having different wavelengths are converted into parallel lights by the collimator 6 and irradiated on substantially the same region of the object 12 to be measured coaxially. The diameters are preferably substantially equal.

  The information processing apparatuses 11 and 11a of the first and second embodiments can be realized by, for example, a computer having a CPU (Central Processing Unit), a storage device, and an interface, and a program for controlling these hardware resources. In such a computer, the program for realizing the component concentration measurement method of the present invention is provided in a state of being recorded on a recording medium such as a flexible disk, a CD-ROM, a DVD-ROM, or a memory card, and stored in a storage device. Stored. The CPU executes the processing described in the first and second embodiments according to the program stored in the storage device.

  The present invention can be applied to a technique for monitoring the concentration of components such as blood glucose and albumin.

   DESCRIPTION OF SYMBOLS 1-1 to 1-3 ... Laser diode, 2 ... Laser driver, 3-1 to 3-3, 5 ... Optical fiber, 4 ... Optical multiplexer, 6 ... Collimator, 7 ... Acoustic sensor, 8 ... Amplifier, 9 ... Function generator, 10 ... Lock-in amplifier, 11 ... Information processing device, 12 ... Device under test, 13 ... Photoacoustic cell, 14 ... Acoustic matching layer, 15 ... Temperature controller, 100 ... Generator controller, 101 ... Light intensity control , 102 ... Light intensity measurement unit, 103 ... Light intensity change amount calculation unit, 104 ... Acoustic mode estimation unit, 105 ... Correction coefficient determination unit, 106 ... Concentration derivation unit, 107 ... Storage unit, 108 ... Resonator length control unit 109 temperature control unit.

Claims (8)

A light irradiating unit that irradiates an object to be measured by modulating the intensity of a plurality of lights having different wavelengths with signals having the same frequency and different phases; and
A light intensity control unit that changes the intensity of at least one of the plurality of intensity-modulated lights irradiated by the light irradiation unit;
A resonator for amplifying a photoacoustic signal generated from the object to be measured by light irradiation;
A photoacoustic signal detector that detects the photoacoustic signal amplified by the resonator and outputs an electrical signal; and
A light intensity measurement unit that measures the intensity of light changed by the light intensity control unit;
Measurement results of the light intensity measurement unit when the intensity of the electric signal is the lowest in each case for two cases where the wavelengths of light whose intensity is changed are different or two cases where the temperature of the object to be measured is different. An acoustic mode estimation unit that estimates an acoustic mode that is a resonance mode of the photoacoustic signal, based on a variation in light intensity obtained from a variation in light intensity obtained from a known data set;
Based on the known relationship between the acoustic mode estimated by the acoustic mode estimation unit, the concentration measurement sensitivity for the measurement target component included in the object to be measured, and the acoustic mode, the correction of the concentration measurement sensitivity for the measurement target component is performed. A correction coefficient determination unit for determining a coefficient;
A component concentration measuring apparatus comprising: a concentration deriving unit that derives a concentration of a component to be measured based on a change amount of light intensity obtained from a measurement result of the light intensity measuring unit and the correction coefficient. In the component concentration measuring apparatus according to claim 1,
The light irradiation unit simultaneously irradiates the object to be measured with light of two different wavelengths,
The acoustic mode estimation unit changes the intensity of light of the second wavelength while keeping the intensity of light of the first wavelength constant, so that the light of the second wavelength when the intensity of the electrical signal becomes the minimum And the third wavelength when the intensity of the electric signal becomes the minimum by changing the intensity of the light of the third wavelength while keeping the intensity of the light of the first wavelength constant. A component concentration measuring apparatus that estimates the acoustic mode based on a change amount of light intensity obtained from a measurement result of light intensity and a change amount of light intensity obtained from a known data set. In the component concentration measuring apparatus according to claim 1,
A temperature control unit for controlling the temperature of the object to be measured;
The light irradiation unit simultaneously irradiates the object to be measured with light of two different wavelengths,
The acoustic mode estimation unit changes the intensity of light of the second wavelength while keeping the intensity of light of the first wavelength constant, so that the light of the second wavelength when the intensity of the electrical signal becomes the minimum And the intensity of the light of the first wavelength is made constant after changing the temperature of the object to be measured by the temperature controller and the intensity of the light of the second wavelength is changed. Based on the change amount of the light intensity obtained from the measurement result of the light intensity of the second wavelength when the intensity of the electric signal is the lowest, and the change amount of the light intensity obtained from the known data set, A component concentration measuring apparatus for estimating the acoustic mode. The component concentration measuring apparatus according to claim 2 or 3,
The resonator has a variable resonator length,
A resonator length controller for controlling the resonator length;
The light irradiation unit irradiates the object to be measured only with light of the first wavelength before simultaneously irradiating the object to be measured with light of two different wavelengths,
The resonator length control unit sets the resonator length so that the intensity of the electric signal obtained when the object to be measured is irradiated with only light of the first wavelength is maximized. Component concentration measuring device. In the component concentration measuring apparatus according to any one of claims 1 to 4,
The plurality of lights irradiated on the object to be measured have a component concentration measurement characterized in that light absorption coefficients of components other than the component to be measured included in the object to be measured are substantially equal to the wavelengths of the plurality of lights. apparatus. In the component concentration measuring apparatus according to any one of claims 1 to 5,
The light irradiating unit coaxially irradiates substantially the same region of the object to be measured with each of a plurality of lights having different wavelengths as parallel light,
A component concentration measuring apparatus, wherein the beam diameters of a plurality of lights having different wavelengths are substantially equal. In the component concentration measuring apparatus according to any one of claims 1 to 6,
The resonator has two surfaces substantially orthogonal to the optical axis of light emitted from the light irradiation unit, and these surfaces are parallel to each other. A first step of irradiating an object to be measured after intensity-modulating a plurality of lights having different wavelengths with signals having the same frequency and different phases;
A second step of changing the intensity of at least one of a plurality of intensity-modulated lights irradiated to the object to be measured;
A third step of detecting a photoacoustic signal generated from the object to be measured by light irradiation and amplified by a resonator and outputting an electrical signal;
A fourth step of measuring the intensity of the light changed in the second step;
The measurement result of the fourth step when the intensity of the electric signal is the lowest in each case for two cases where the wavelengths of light whose intensity changes are different or two cases where the temperature of the object to be measured is different. A fifth step of estimating an acoustic mode, which is a resonance mode of the photoacoustic signal, based on the amount of change in light intensity obtained from the above and the amount of change in light intensity obtained from a known data set;
Based on the known relationship between the acoustic mode estimated in the fifth step, the concentration measurement sensitivity for the measurement target component included in the object to be measured, and the acoustic mode, the concentration measurement sensitivity correction for the measurement target component is performed. A sixth step of determining coefficients;
A component concentration measuring method comprising: a seventh step of deriving the concentration of the component to be measured based on the amount of change in light intensity obtained from the measurement result of the fourth step and the correction coefficient.