JP6606019B2 - Component concentration measuring apparatus and method - Google Patents

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 focused on blood components. However, the technology developed up to now is to detect one component with one 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 has been developed by S. Camou et al. (See Patent Documents 1-3).

  FIG. 18 shows a configuration example of a conventional component concentration measuring apparatus for carrying out this OPBS method. 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 for guiding the laser light emitted, an optical coupler 4 for combining the laser light emitted from the laser diodes 1-1 and 1-2, and a laser combined by the optical coupler 4. An optical fiber 5 that guides light, an acoustic sensor 6 that detects a photoacoustic signal generated from the object 11 to be measured by the photoacoustic effect, and converts it into an electrical signal proportional to sound pressure, and an electrical signal output from the acoustic sensor 6 The amplifier 7 for amplifying the signal, the function generator 8 for generating a reference signal, the output signal of the amplifier 7 and the reference signal output from the function generator 8 as inputs, and the output of the amplifier 7 The lock-in amplifier 9 that detects a measurement signal of a desired frequency from the signal, the function generator 8 and the lock-in amplifier 9 are controlled, and the measurement signal detected by the lock-in amplifier 9 is processed to derive a specific component concentration. And an information processing apparatus 10 including a computer.

  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 8 to the laser diode 1-1 (first The light emitted from the laser diode 1-1 is intensity-modulated. The intensity-modulated light emitted from the laser diode 1-1 is guided by the optical fiber 3-1, and irradiated onto the device under test 11 through the optical coupler 4 and the optical fiber 5 (step S100 in FIG. 19).

  The acoustic sensor 6 detects a photoacoustic signal generated from the device under test 11, and the amplifier 7 amplifies the electrical signal output from the acoustic sensor 8. The lock-in amplifier 9 detects a measurement signal having a frequency determined by the reference signal output from the function generator 8 among the signals included in the output of the amplifier 7.

  The information processing apparatus 10 changes the frequency of the reference signal generated by the function generator 8, 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 9 (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 10 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 8. The modulation frequency is set to the above peak modulation frequency, and the frequency of the measurement signal detected by the lock-in amplifier 9 is set to the peak modulation frequency. At this time, light emitted from the laser diodes 1-1 and 1-2 is supplied from the laser driver 2 to the laser diodes 1-1 and 1-2 by supplying a rectangular-wave drive current of the same frequency and opposite phase. Intensity modulation is performed with signals having the same frequency (peak modulation frequency) and opposite phases (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, combined by the optical coupler 4, and further guided by the optical fiber 5 to be measured. The object 11 is irradiated. The information processing apparatus 10 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 10 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).

JP 2014-50563 A JP 2013-106874 A JP 2012-179212 A

  The change in glucose concentration at the biological level is on the order of several tens of mg / dL, and the change in the light absorption coefficient of glucose due to this change in concentration is as small as 0.001 / mm · (g / L). For this reason, the resolution and stability required for the component concentration measuring apparatus are extremely strict at 40 dB or more. Therefore, it has been necessary to increase the measurement sensitivity with respect to a change in glucose concentration in order to relax the requirements for the component concentration measurement device and improve the measurement accuracy.

  The present invention has been made to solve the above-described problems, and an object of the present invention is to provide a component concentration measuring apparatus and method that can improve the measurement sensitivity to the concentration change of the component to be measured contained in the object to be measured. And

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 by using signals having the same frequency and different phases, and irradiating the object to be measured. Light intensity control means for changing the intensity of at least one of the light, temperature control means for controlling the temperature of the object to be measured, and a photoacoustic signal generated from the object to be measured by light irradiation to detect an electrical signal photoacoustic signal detecting means for outputting a light intensity measuring means for measuring the intensity of light which the light intensity control means is varied, for two when the temperature is different in the object to be measured, the intensity of each of the electrical signal Based on the amount of change in the light intensity obtained from the measurement result of the light intensity measuring means when the value reaches the minimum and the amount of change in the light intensity obtained from a known data set, the resonance mode of the photoacoustic signal is obtained. And an acoustic mode estimation means for estimating the acoustic mode, and a plurality of lights that irradiate the object to be measured until the acoustic mode estimated by the acoustic mode estimation means becomes a prescribed acoustic mode that provides a required concentration measurement sensitivity. The light irradiation means, the light intensity control means, the photoacoustic signal detection means, the light intensity measurement means, and the sound are changed while changing at least one of the modulation frequency and the shape of the resonator that accommodates the object to be measured. Change means for causing the mode estimation means to repeatedly execute the process, and change in light intensity obtained from the measurement result of the light intensity measurement means when the acoustic mode estimated by the acoustic mode estimation means becomes the specified acoustic mode and a density deriving means for deriving the concentration of the component to be measured contained in the object to be measured based on the amount, the light irradiation means, the light of two different wavelengths Simultaneously irradiating the object to be measured, the acoustic mode estimating means 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 intensity of the second wavelength light, and the second wavelength with the intensity of the first wavelength light constant after changing the temperature of the object to be measured by the temperature control means The amount of change in the light intensity obtained from the measurement result of the intensity of the light of the second wavelength when the intensity of the electrical signal becomes the minimum by changing the intensity of the light, and obtained from a known data set The acoustic mode is estimated based on the amount of change in light intensity .

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.
Further, in one configuration example of the component concentration measuring apparatus of the present invention, the light irradiating means irradiates a plurality of lights having different wavelengths as parallel lights, coaxially irradiating substantially the same region of the object to be measured, and having different wavelengths. The plurality of light beams have substantially the same beam diameter.
Further, one configuration example of the component concentration measuring apparatus of the present invention is characterized by further comprising a resonator for accommodating the object to be measured and amplifying the photoacoustic signal.
Moreover, in one configuration example of the component concentration measuring apparatus of the present invention, the resonator has two surfaces substantially orthogonal to the optical axis of the light emitted from the light irradiation means, and these surfaces are parallel to each other. It is a flat surface.

The component concentration measurement method of the present invention includes a light irradiation step of irradiating a measured object with a plurality of lights having different wavelengths by using signals having the same frequency and different phases, and the plurality of intensity modulations. A light intensity control step for changing the intensity of at least one of the light; a photoacoustic signal detection step for detecting a photoacoustic signal generated from the object to be measured by light irradiation and outputting an electrical signal; and the light intensity. a light intensity measuring step of measuring the intensity of light is changed in the control step, said the two when the temperature is different of the object to be measured, the light intensity measuring step when the intensity of each of the electrical signal becomes minimum Based on the change amount of the light intensity obtained from the measurement result and the change amount of the light intensity obtained from the known data set, the acoustic mode which is the resonance mode of the photoacoustic signal is obtained. An acoustic mode estimation step for estimating a measurement mode, and modulation frequencies of a plurality of lights irradiated on the object to be measured until the acoustic mode estimated in the acoustic mode estimation step becomes a prescribed acoustic mode for obtaining a required concentration measurement sensitivity The light irradiation step, the light intensity control step, the photoacoustic signal detection step, the light intensity measurement step, and the acoustic mode estimation step while changing at least one of the shapes of the resonators that accommodate the object to be measured And the step of repeatedly executing the step, and the amount of change in light intensity obtained from the measurement result of the light intensity measurement step when the acoustic mode estimated in the acoustic mode estimation step becomes the specified acoustic mode. look containing a concentration derivation step of deriving the concentration of the component to be measured contained in the object to be measured, the light irradiation step Includes the step of simultaneously irradiating the object to be measured with light of two different wavelengths, and the acoustic mode estimating step changes the intensity of the light of the second wavelength while keeping the intensity of the light of the first wavelength constant. The measurement result of the intensity of the light of the second wavelength when the intensity of the electrical signal becomes the minimum, and the light of the first wavelength after changing the temperature of the object to be measured by the temperature control means The intensity of light obtained from the measurement result of the intensity of the light 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 light constant. The method includes a step of estimating the acoustic mode based on a change amount and a change amount of light intensity obtained from a known data set .

According to the present invention, the light irradiating means for irradiating the object to be measured by intensity-modulating a plurality of lights having different wavelengths with signals having the same frequency and different phases, and at least one of the plurality of intensity-modulated lights. Light intensity control means for changing the intensity of light, temperature control means for controlling the temperature of the object to be measured, and photoacoustic signal detection for detecting a photoacoustic signal generated from the object to be measured by light irradiation and outputting an electrical signal Light intensity measurement means for measuring the intensity of the light changed by the light intensity control means, and light intensity measurement when the intensity of the electric signal is the lowest at each of two time points at which the temperature of the object to be measured is different. An acoustic mode estimator 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 measurement results of the means and the amount of change in light intensity obtained from a known data set. Until the acoustic mode estimated by the acoustic mode estimation means becomes a prescribed acoustic mode that provides the required concentration measurement sensitivity, and the modulation frequency of the plurality of lights irradiated to the object to be measured and the resonator that accommodates the object to be measured By changing at least one of the shapes while providing a changing means for repeatedly executing the light irradiating means, the light intensity controlling means, the photoacoustic signal detecting means, the light intensity measuring means, and the acoustic mode estimating means, The mode can be controlled, and the measurement sensitivity to the concentration change of the component to be measured included in the object to be measured can be improved.

  In the present invention, the intensity of the light 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 light of the first wavelength constant. After the measurement result and the temperature of the object to be measured are changed by the temperature control means, the intensity of the light of the first wavelength is made constant by changing the intensity of the light of the second wavelength, and the intensity of the electric signal becomes the minimum. The acoustic mode can be estimated based on the change amount of the light intensity obtained from the measurement result of the light intensity of the second wavelength at that time and the change amount of the light intensity obtained from the known data set.

  Further, in the present invention, the light irradiating means converts a plurality of lights having different wavelengths into parallel light and irradiates substantially the same region of the object to be measured coaxially, thereby reducing the influence of the interference of the sound wave.

It is a figure explaining the resonance mode of the sound wave in a cylindrical cavity. It is a figure which shows one example of the relationship between a light modulation frequency and a sound pressure. It is a figure which shows the response characteristic of glucose concentration. It is a figure which shows the relationship between a light modulation frequency and a sound wave intensity. It is a block diagram which shows the structure of the component concentration measuring apparatus which concerns on the reference example of this invention. It is a block diagram which shows the structure of the information processing apparatus of the component density | concentration measuring apparatus which concerns on the reference example of this invention. It is a flowchart explaining operation | movement of the component concentration measuring apparatus which concerns on the reference example of this invention. It is a figure which shows one example of the relationship between the light modulation frequency and sound wave intensity in the reference example of this invention. It is a figure which shows the example of the light intensity change in the reference example of this invention. It is a figure which shows one example of the relationship between the acoustic mode in the reference example of this invention, and the ratio of the variation | change_quantity of light intensity. It is a figure which shows one example of the relationship between the glucose concentration sensitivity and acoustic mode in the reference example of this invention. It is a block diagram which shows the structure of the component concentration measuring apparatus which concerns on embodiment of this invention. It is a block diagram which shows the structure of the information processing apparatus of the component concentration measuring apparatus which concerns on embodiment of this invention. It is a flowchart explaining operation | movement of the component concentration measuring apparatus which concerns on embodiment of this invention. It is a figure which shows the example of the light intensity change in embodiment of this invention. It is a figure which shows one example of the relationship between the acoustic mode in embodiment of this invention, and ratio of the variation | change_quantity of light intensity. It is a figure which shows the relationship between the reflectance of a sound wave, and acoustic impedance. It is a block diagram which shows the structure of the conventional component density | concentration measuring apparatus. It is a flowchart explaining the conventional optical power balance shift method.

[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.

  FIG. 1 shows a resonance mode of a sound wave taking a resonance in this cylindrical cavity as an example when the case 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.

  The relationship between the modulation frequency and the sound pressure is shown in FIG. 2, (101), (200), (102), (300) indicate the resonance mode (jmq). For example, (101) is the mode number j in the radial direction, and the mode in the circumferential direction. This indicates that the number m is 0 and the mode number q in the longitudinal direction is 1. Thus, 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.

  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. 1). 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.

Here, 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. 3 shows an example of response characteristics when the measured object is almost water and the glucose concentration changes. FIG. 3 shows that the light intensity changes in proportion to the glucose concentration, and that the measurement sensitivity changes depending on the acoustic mode q. In addition, by using the acoustic mode q, the measurement sensitivity can be greatly improved. In the case of a glucose aqueous solution system, especially when the even-order acoustic mode is used, it is five times the case of the zero-order acoustic mode. A degree of measurement sensitivity improvement is expected.

Two methods, the method of the reference example described later and the method of the present invention, will be described as methods for improving the measurement sensitivity using Equation (9).

[ Reference Example Method ]
The relationship between the modulation frequency and the sound pressure as shown in FIG. 4 is acquired by irradiating the object to be measured with light of the first wavelength and sweeping the modulation frequency of the light in an arbitrary range. The resonance frequency of the sound wave in the object to be measured can be selected from the peak in 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 light modulation frequency at this time is the modulation frequency 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, by 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, the sound wave intensity generated while increasing or decreasing the intensity of the light of the third wavelength in the same manner as described above. Measure the intensity I ₁ of the light of the third wavelength that minimizes. 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.

  By comparing the equations (11) and (12), the acoustic mode q can be estimated by searching for a response with the closest density measurement sensitivity. If the estimated acoustic mode q is a prescribed acoustic mode that provides the required concentration measurement sensitivity, measurement is performed using the current light modulation frequency. When the estimated acoustic mode q is different from the prescribed acoustic mode that provides the required concentration measurement sensitivity, the above procedure is performed while changing to the modulation frequency of another peak in FIG. 4 until the prescribed acoustic mode is obtained. .

[ Method of the present invention ]
Similar to the method of the reference example, the relationship between the modulation frequency and the sound pressure as shown in FIG. 4 is obtained by irradiating the object to be measured with light of the first wavelength and sweeping the modulation frequency of the light in an arbitrary range. get. The resonance frequency of the sound wave in the object to be measured can be selected from the peak in 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 modulation frequency at this time is the modulation frequency 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 intensity I ₀ , I ₁ is expressed by the following equation (14).

  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.

  By comparing the equations (14) and (15), the acoustic mode q can be estimated by looking for a response with the closest concentration measurement sensitivity. If the estimated acoustic mode q is a prescribed acoustic mode that provides the required concentration measurement sensitivity, measurement is performed using the current light modulation frequency. When the estimated acoustic mode q is different from the prescribed acoustic mode that provides the required concentration measurement sensitivity, the above procedure is performed while changing to the modulation frequency of another peak in FIG. 4 until the prescribed acoustic mode is obtained. .

  An example in which the glucose concentration measurement sensitivity of the aqueous glucose solution is improved using the acoustic resonance mode of the photoacoustic method will be described below.

[ Reference example ]
Hereinafter, reference examples of the present invention will be described with reference to the drawings. FIG. 5 is a block diagram showing a configuration of a component concentration measuring apparatus according to a reference example of the present invention. The component concentration measuring apparatus of this reference example includes laser diodes 1-1, 1-2, 1-3 that emit laser light, and a laser driver 2 that drives the laser diodes 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 coupler 4 for combining the laser light emitted from the optical fiber 5, an optical fiber 5 for guiding the laser light combined by the optical coupler 4, and a photoacoustic signal generated from the object to be measured 11 by the photoacoustic effect; An acoustic sensor 6 serving as a photoacoustic signal detection means for converting an electrical signal proportional to the sound pressure, an amplifier 7 for amplifying the electrical signal output from the acoustic sensor 6, a function generator 8 for generating a reference signal, and an amplifier 7 Output signals and The lock-in amplifier 9 that detects a measurement signal of a desired frequency from the output signal of the amplifier 7, the laser driver 2, the function generator 8, and the lock-in amplifier 9 is controlled using the reference signal output from the motion generator 8 as an input. In addition, the information processing apparatus 10 includes a computer that processes a measurement signal detected by the lock-in amplifier 9 to derive a specific component concentration.

  The laser diodes 1-1, 1-2, 1-3, the laser driver 2, and the function generator 8 constitute light irradiation means. The information processing apparatus 10 and the function generator 8 constitute light intensity control means.

Examples of the laser diodes 1-1, 1-2, and 1-3 include, for example, a distributed feedback semiconductor laser (DFB-LD). An example of the acoustic sensor 6 is a microphone using a piezoelectric sensor.
The object to be measured 11 is introduced into, for example, a cylindrical photoacoustic cell (not shown), and laser light is irradiated through a glass optical window provided in the photoacoustic cell.

  FIG. 6 is a block diagram illustrating a configuration of the information processing apparatus 10. The information processing apparatus 10 is radiated from the generator control unit 100 that controls the function generator 8, the light intensity control unit 101 that controls the intensity of light via the function generator 8, and the laser diodes 1-1 to 1-3. The intensity of the measurement signal at each of the light intensity measuring unit 102 serving as a light intensity measuring means for measuring the light intensity and two time points at which the wavelength of the light whose intensity is changed are different or two time points at which the temperature of the object to be measured 11 is different. Of the light intensity change amount calculation unit 103 for calculating the change amount of the light intensity obtained from the measurement result of the light intensity when the light intensity becomes the minimum, and two time points at which the wavelengths of the light whose intensity changes are different or the measurement object 11 For two time points with different temperatures, 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, 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 the light intensity obtained from the data set, and the acoustic mode estimated by the acoustic mode estimation unit 104 is the required concentration measurement. The peak modulation frequency changing unit 105 that changes the modulation frequency of a plurality of lights irradiated to the object to be measured 11 and the concentration of a specific component in the object to be measured 11 are derived so that the specified acoustic mode can be obtained. It has a density deriving unit 106 and a storage unit 107 for storing information.

Next, the operation of the component concentration measuring apparatus of this reference example 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 rectangular-wave 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 emitted from the laser diode 1-1 is guided by the optical fiber 3-1, and irradiated onto the device under test 11 through the optical coupler 4 and the optical fiber 5 (step S200 in FIG. 7).

  The acoustic sensor 6 detects a photoacoustic signal generated from the device under test 11, and the amplifier 7 amplifies the electrical signal output from the acoustic sensor 8. The lock-in amplifier 9 detects a measurement signal having a frequency determined by the reference signal output from the function generator 8 among the signals included in the output of the amplifier 7.

  The generator control unit 100 of the information processing apparatus 10 changes the frequency of the reference current generated by the function generator 8 to change the frequency of the drive current supplied from the laser driver 2 to the laser diode 1-1, thereby performing optical modulation. The optical modulation frequency sweep is performed to gradually change the frequency and gradually change the frequency of the measurement signal detected by the lock-in amplifier 11 (the same frequency as the optical modulation frequency) (step S201 in FIG. 7).

Thus, the relationship between the optical modulation frequency and the amplitude (sound pressure) of the measurement signal is acquired (step S202 in FIG. 7), and the peak modulation frequency that is the optical modulation frequency with the maximum amplitude of the measurement signal is searched (step S203 in FIG. 7). ). FIG. 8 shows the relationship between the light modulation frequency and the sound wave intensity obtained in this reference example .

  Next, the laser diode 1-1 is operated again to output continuous light (step S204 in FIG. 7), and then the laser diode 1-2 (second light source) is operated to output continuous light (FIG. 7). Step S205). 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 apparatus 10 changes the frequency of the two reference signals generated by the function generator 8 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 peak modulation frequency, and the frequency of the measurement signal detected by the lock-in amplifier 9 is set to the peak modulation frequency. At this time, light emitted from the laser diodes 1-1 and 1-2 is supplied from the laser driver 2 to the laser diodes 1-1 and 1-2 by supplying a rectangular-wave drive current of the same frequency and opposite phase. Intensity modulation is performed with signals having the same frequency (peak modulation frequency) and opposite phases (step S206 in FIG. 7). Therefore, in the present reference example , 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, combined by the optical coupler 4, and further guided by the optical fiber 5 to be measured. The object 11 is irradiated.

  The light intensity control unit 101 of the information processing apparatus 10 controls the function generator 8 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 S207 in FIG. 7).

  Further, the light intensity control unit 101 of the information processing apparatus 10 controls the function generator 8 to change the voltage of the reference signal for driving the laser diode 1-2, so that the laser driver 2 changes the laser diode 1-. The intensity of the measurement signal output from the lock-in amplifier 9 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 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. 7).

The light intensity measurement unit 102 of the information processing apparatus 10 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 8. The storage unit 107 of the information processing apparatus 10 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. 7).

  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. 7). 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 apparatus 10 changes the frequency of the two reference signals generated by the function generator 8 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 peak modulation frequency, and the frequency of the measurement signal detected by the lock-in amplifier 9 is set to the peak modulation frequency. At this time, light emitted from the laser diodes 1-1 and 1-3 is supplied from the laser driver 2 to the laser diodes 1-1 and 1-3 by supplying a rectangular-wave drive current having the same frequency and opposite phase. Intensity modulation is performed using signals having the same frequency (peak modulation frequency) and opposite phases (step S211 in FIG. 7).

  The light intensity control unit 101 of the information processing apparatus 10 controls the function generator 8 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 9 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 1-3. In this way, the intensity of light emitted from the laser diode 1-3 is adjusted (step S212 in FIG. 7). 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 10 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 8. Similarly to the above, the storage unit 107 of the information processing apparatus 10 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. 7).

The light intensity change amount calculation unit 103 of the information processing apparatus 10 compares the light intensity change amount ΔI = (I ₁ −I ₀ ) with respect to the light intensity I _{0 based} on 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. 7). An example of the light intensity change ratio ΔI / I in this reference example is shown in FIG.

Next, the acoustic mode estimation unit 104 of the information processing apparatus 10 uses the 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. 7). 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 . The length L of the DUT 11 is a known value.

From the result of the calculation in step S215, the relationship between the acoustic mode q and the light intensity change ratio ΔI ₂ / I ₂ as shown in FIG. 10 is obtained. The acoustic mode estimation unit 104 of the information processing apparatus 10 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 peak modulation frequency (step S216 in FIG. 7).

  When the acoustic mode q estimated by the acoustic mode estimation unit 104 is not the prescribed acoustic mode q that provides the required concentration measurement sensitivity (NO in step S217 in FIG. 7), the peak modulation frequency changing unit 105 of the information processing apparatus 10 Returning to the process of step S203, in the relationship between the optical modulation frequency acquired in step S202 and the amplitude of the measurement signal, the acoustic mode determination process immediately before the peak modulation frequency that is the optical modulation frequency with the maximum amplitude of the measurement signal. The generator control unit 100 is made to select a peak modulation frequency different from the peak modulation frequency selected in (Steps S203 to S216). In this way, the processing of steps S203 to S217 is repeatedly executed while changing the peak modulation frequency until the acoustic mode q estimated by the acoustic mode estimation unit 104 becomes the prescribed acoustic mode q that provides the required concentration measurement sensitivity.

Here, when the known relationship between the concentration measurement sensitivity G of the specific component (glucose in the example of the present reference example ) in the DUT 11 and the acoustic mode q is as shown in FIG. The prescribed acoustic mode in which the density measurement sensitivity is obtained refers to, for example, the acoustic mode q in which the maximum density measurement sensitivity G is obtained (q = 2 in the example of FIG. 11).

  When the acoustic mode q estimated by the acoustic mode estimation unit 104 becomes the prescribed acoustic mode q that provides the required concentration measurement sensitivity (YES in step S217), the concentration deriving unit 106 of the information processing apparatus 10 performs the previous step. Based on the ratio ΔI / I of the change amount of the light intensity calculated in the process of S214, the change amount ΔC [%] of the concentration of the specific component in the DUT 11 at an arbitrary time after the start of measurement. Is calculated (step S218 in FIG. 7).

  At this time, the concentration deriving unit 106 determines the ratio G0 / Gq of the density measurement sensitivity G0 when the acoustic mode q = 0 to the density measurement sensitivity Gq when the specified acoustic mode q is the correction coefficient A, and this correction coefficient Based on the ratio ΔI / I of the change amount of the light intensity calculated in the process of A and the immediately preceding step S214, the change amount ΔC [%] of the concentration of the specific component in the DUT 11 is calculated by the equation (17). To do. For example, if the specified acoustic mode q is q = 2, 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. A = 1/5.

  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. 7). The reference concentration can be obtained by performing a standard blood glucose measurement method on the object to be measured 11. 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 a peak modulation frequency.

As described above, in this reference example, it is possible to improve the measurement sensitivity with respect to the concentration change of the specific component contained in the DUT 11.

[ Embodiment ]
Next, an embodiment of the present invention will be described. FIG. 12 is a block diagram showing the configuration of the component concentration measuring apparatus according to the embodiment of the present invention. The same components as those in FIG. 5 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 coupler 4, an optical fiber 5, and an acoustic sensor. 6, an amplifier 7, a function generator 8, a lock-in amplifier 9, an information processing device 10 a, and a temperature controller 12 that changes the temperature of the DUT 11.

  FIG. 13 is a block diagram showing the configuration of the information processing apparatus 10a of this embodiment. The information processing apparatus 10a 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 peak modulation frequency change unit 105, The concentration derivation unit 106, the storage unit 107, and the temperature control unit 108 that controls the temperature of the DUT 11 are provided.

Next, the operation of the component concentration measuring apparatus according to 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 rectangular-wave drive current is supplied from the laser driver 2, the laser diode 1-1 emits intensity-modulated light. Similar to the reference example , the wavelength (first wavelength) of light emitted from the laser diode 1-1 is, for example, 1382 nm. The intensity-modulated light emitted from the laser diode 1-1 is guided by the optical fiber 3-1, and irradiated onto the device under test 11 through the optical coupler 4 and the optical fiber 5 (step S300 in FIG. 14).

  The acoustic sensor 6 detects a photoacoustic signal generated from the device under test 11, and the amplifier 7 amplifies the electrical signal output from the acoustic sensor 8. The lock-in amplifier 9 detects a measurement signal having a frequency determined by the reference signal output from the function generator 8 among the signals included in the output of the amplifier 7.

  The generator control unit 100 of the information processing apparatus 10a changes the frequency of the reference current generated by the function generator 8 to change the frequency of the drive current supplied from the laser driver 2 to the laser diode 1-1, thereby performing optical modulation. The optical modulation frequency sweep is performed to gradually change the frequency and gradually change the frequency of the measurement signal detected by the lock-in amplifier 11 (step S301 in FIG. 14). Thus, the relationship between the light modulation frequency and the amplitude (sound pressure) of the measurement signal is acquired (step S302 in FIG. 14), and the peak modulation frequency that is the light modulation frequency with the maximum amplitude of the measurement signal is searched (step S303 in FIG. 14). ).

  Next, the laser diode 1-1 is operated again to output continuous light (step S304 in FIG. 14), and then the laser diode 1-2 (second light source) is operated to output continuous light (FIG. 14). Step S305). The wavelength of the light emitted from the laser diode 1-1 is, for example, 1382 nm, and the wavelength of the light emitted from the laser diode 1-2 (second wavelength) is, for example, 1610 nm.

  The generator control unit 100 of the information processing apparatus 10a changes the frequency of the two reference signals generated by the function generator 8 to thereby 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 peak modulation frequency, and the frequency of the measurement signal detected by the lock-in amplifier 9 is set to the peak modulation frequency. At this time, light emitted from the laser diodes 1-1 and 1-2 is supplied from the laser driver 2 to the laser diodes 1-1 and 1-2 by supplying a rectangular-wave drive current of the same frequency and opposite phase. Intensity modulation is performed with signals having the same frequency (peak modulation frequency) and opposite phases (step S306 in FIG. 14).

  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, combined by the optical coupler 4, and further guided by the optical fiber 5 to be measured. The object 11 is irradiated.

  The light intensity control unit 101 of the information processing apparatus 10a controls the function generator 8 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 sends 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 S307 in FIG. 14).

  Further, the light intensity controller 101 is supplied from the laser driver 2 to the laser diode 1-2 by controlling the function generator 8 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 9 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. 14).

The light intensity measurement unit 102 of the information processing apparatus 10a measures the intensity of light emitted from the laser diode 1-2, as in the reference example . 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. 14).

  Next, the temperature control unit 108 of the information processing apparatus 10a controls the temperature controller 12 to increase the temperature of the DUT 11 by ΔT (for example, 1 ° C.) (step S310 in FIG. 14).

  The light intensity control unit 101 of the information processing apparatus 10a controls the function generator 8 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 9 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. 14). 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 10a 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. 14).

The light intensity change amount calculation unit 103 of the information processing apparatus 10a 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 (14) (step S313 in FIG. 14). FIG. 15 shows the ratio ΔI / I of the change amount of the light intensity before and after the temperature change when the temperature of the DUT 11 is increased by 1 ° C.

Next, the acoustic mode estimation unit 104 of the information processing apparatus 10a uses the predetermined data set as shown in Table 2 to calculate the light intensity change amount ratio ΔI ₂ / I ₂ using the equations (15) and (16). Is calculated for each acoustic mode q (step S314 in FIG. 14). The data set represents the relationship between the first, second, and third 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. The length L of the DUT 11 is a known value.

The relationship between the acoustic mode q and the light intensity change ratio ΔI ₂ / I ₂ as shown in FIG. 16 is obtained from the calculation result of step S314. The acoustic mode estimation unit 104 of the information processing apparatus 10a 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 peak modulation frequency (step S315 in FIG. 14).

  When the acoustic mode q estimated by the acoustic mode estimation unit 104 is not the prescribed acoustic mode q that provides the required concentration measurement sensitivity (NO in step S316 in FIG. 14), the peak modulation frequency changing unit 105 of the information processing device 10a Returning to the process of step S303, in the relationship between the optical modulation frequency acquired in step S302 and the amplitude of the measurement signal, the acoustic mode determination process immediately before the peak modulation frequency that is the optical modulation frequency with the maximum amplitude of the measurement signal. The generator control unit 100 is made to select a peak modulation frequency different from the peak modulation frequency selected in (Steps S303 to S315). In this way, the processing of steps S303 to S316 is repeatedly executed while changing the peak modulation frequency until the acoustic mode q estimated by the acoustic mode estimation unit 104 becomes the prescribed acoustic mode q that provides the required concentration measurement sensitivity.

  When the acoustic mode q estimated by the acoustic mode estimation unit 104 becomes the prescribed acoustic mode q that provides the required concentration measurement sensitivity (YES in step S316), the concentration deriving unit 106 of the information processing device 10a performs the previous step. Based on the ratio ΔI / I of the change amount of the light intensity calculated in the process of S313, the change amount ΔC [%] of the concentration of the specific component in the measurement object 11 at an arbitrary time point after the start of measurement. Is calculated (step S317 in FIG. 14). At this time, the concentration deriving unit 106 determines the ratio G0 / Gq of the density measurement sensitivity G0 when the acoustic mode q = 0 to the density measurement sensitivity Gq when the specified acoustic mode q is the correction coefficient A, and this correction coefficient Based on the ratio ΔI / I of the change amount of the light intensity calculated in the process of A and the immediately preceding step S313, the change amount ΔC [%] of the concentration of the specific component in the DUT 11 is calculated by the equation (17). To do.

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. 14).
Thus, in the present embodiment, the same effect as the above-described reference example can be obtained.

  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 Expression (20).

  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 between the DUT 11 and the resonator material interface being 0.8 or more is a necessary condition for functioning as a resonator (a photoacoustic cell accommodating the DUT 11). Examples of materials that satisfy this condition include various metals such as glass, iron, and copper. The frequency of the sound wave generated by the irradiating light can be described as in Expression (21). It is preferable that the resonator has two planes substantially orthogonal to the optical axis of the irradiated light, and these two planes are parallel to each other.

  λ is the wavelength of the sound wave, C is the speed of sound in the DUT 11, and f is the modulation frequency of the light. In the measurement method using the photoacoustic of the present invention, when the modulation frequency of light is 100 kHz-1 MHz, the wavelength of the sound wave at this time is less than 1 mm to 12 mm. For example, in order to obtain a secondary mode in the axial direction, the resonance length needs to be set to about the wavelength.

In the reference example and the embodiment , the plurality of lights irradiated on the object to be measured 11 have light absorption coefficients of components other than the component to be measured included in the object to be measured 11 with respect to the wavelengths of the plurality of lights. It is preferable that they are substantially equal.

Further, in the reference example and the embodiment , it is preferable that a plurality of light beams having different wavelengths are converted into parallel light beams by an optical system (not shown) and irradiated on the substantially same region of the DUT 11 coaxially. At this time, it is preferable that the beam diameters of a plurality of lights having different wavelengths are substantially equal.

Further, in the reference example and the embodiment , the peak modulation frequency changing unit 105 is provided as the changing unit so that the acoustic mode q estimated by the acoustic mode estimating unit 104 becomes the prescribed acoustic mode q that provides the required concentration measurement sensitivity. However, the present invention is not limited to this, and a mechanism that can change the shape of the resonator that accommodates the DUT 11 during measurement is provided as a changing means, and the acoustic mode estimation unit 104 estimates the frequency. The shape of the resonator (that is, the shape of the DUT 11) may be changed so that the acoustic mode q that has been obtained becomes the specified acoustic mode q. In this case, steps S204 to S217 (in S304 to S316) are performed while changing the shape of the resonator until the peak modulation frequency is constant and the acoustic mode q estimated by the acoustic mode estimation unit 104 becomes the specified acoustic mode q. The above process may be repeated. Further, both the peak modulation frequency and the shape of the resonator may be changed so that the acoustic mode q estimated by the acoustic mode estimation unit 104 becomes the prescribed acoustic mode q.

The information processing apparatuses 10 and 10a according to the reference example and the embodiment 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. The CPU executes the processing described in the reference example and the embodiment in accordance with a 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 coupler, 6 ... Acoustic sensor, 7 ... Amplifier, 8 ... Function generator, 9 ... Lock-in amplifier, 10, 10a ... Information processing device, 11 ... Object to be measured, 12 ... Temperature controller, 100 ... Generator control unit, 101 ... Light intensity control unit, 102 ... Light intensity measurement unit, 103 ... Light intensity change amount Calculation unit 104 ... acoustic mode estimation unit 105 ... peak modulation frequency changing unit 106 ... concentration deriving unit 107 ... storage unit 108 ... temperature control unit

Claims (6)

A light irradiation means for irradiating the object to be measured by modulating the intensity of a plurality of lights having different wavelengths with signals of the same frequency and different phases,
Light intensity control means for changing the intensity of at least one of the plurality of intensity-modulated lights;
Temperature control means for controlling the temperature of the object to be measured;
Photoacoustic signal detection means for detecting a photoacoustic signal generated from the object to be measured by light irradiation and outputting an electrical signal; and
A light intensity measuring means for measuring the intensity of the light changed by the light intensity control means;
From two points in time at which the temperature of the object to be measured is different, the amount of change in light intensity obtained from the measurement result of the light intensity measuring means when the intensity of the electrical signal is the lowest, and a known data set. Acoustic mode estimation means for estimating an acoustic mode that is a resonance mode of the photoacoustic signal based on the amount of change in light intensity;
A resonator that accommodates the modulation frequencies of a plurality of lights that irradiate the measurement object and the measurement object until the acoustic mode estimated by the acoustic mode estimation means becomes a specified acoustic mode that provides the required concentration measurement sensitivity. Changing means for causing the light irradiation means, the light intensity control means, the photoacoustic signal detection means, the light intensity measurement means, and the acoustic mode estimation means to repeatedly execute processing while changing at least one of the shapes of ,
Based on the amount of change in light intensity obtained from the measurement result of the light intensity measurement means when the acoustic mode estimated by the acoustic mode estimation means becomes the specified acoustic mode, A concentration deriving means for deriving the concentration of the component ,
The light irradiating means simultaneously irradiates the object to be measured with light of two different wavelengths,
The acoustic mode estimation means changes the intensity of the light of the second wavelength while keeping the intensity of the 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 control means, 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 . In the component concentration measuring apparatus according to claim 1 ,
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. The component concentration measuring apparatus according to claim 1 or 2 ,
The light irradiating means 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 3 ,
Furthermore, a component concentration measuring apparatus comprising a resonator for accommodating the object to be measured and amplifying the photoacoustic signal. In the component concentration measuring apparatus according to claim 4 ,
The resonator has two surfaces substantially perpendicular to the optical axis of the light emitted from the light irradiation means, and these surfaces are parallel to each other. A light irradiating step of irradiating the object to be measured with intensity modulation of a plurality of lights having different wavelengths with signals of the same frequency and different phases;
A light intensity control step of changing the intensity of at least one of the plurality of intensity-modulated lights;
A photoacoustic signal detection step for detecting a photoacoustic signal generated from the object to be measured by light irradiation and outputting an electrical signal;
A light intensity measurement step for measuring the intensity of the light changed in the light intensity control step;
From two points in time at which the temperature of the object to be measured is different, the amount of change in light intensity obtained from the measurement result of the light intensity measurement step when the intensity of the electrical signal is the lowest, and the data obtained from a known data set An acoustic mode estimation step for estimating an acoustic mode that is a resonance mode of the photoacoustic signal, based on the amount of change in the light intensity;
Resonators that accommodate modulation frequencies of a plurality of lights that irradiate the measurement object and the measurement object until the acoustic mode estimated in the acoustic mode estimation step becomes a specified acoustic mode that provides a required concentration measurement sensitivity. A change step of repeatedly executing the light irradiation step, the light intensity control step, the photoacoustic signal detection step, the light intensity measurement step, and the acoustic mode estimation step while changing at least one of the shapes of:
Based on the amount of change in light intensity obtained from the measurement result of the light intensity measurement step when the acoustic mode estimated in the acoustic mode estimation step becomes the specified acoustic mode, the measurement target included in the object to be measured only contains a concentration deriving step to derive the concentration of the component,
The light irradiation step includes a step of simultaneously irradiating the object to be measured with light of two different wavelengths,
In the acoustic mode estimation step, the light 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 light of the first wavelength constant. The intensity measurement result and the temperature of the object to be measured by the temperature control means are changed, and then the intensity of the light of the first wavelength is made constant while changing the intensity of the light of the second wavelength. Based on the amount of change in the light intensity obtained from the measurement result of the intensity of the light of the second wavelength when the signal intensity is minimum, and the amount of change in the light intensity obtained from a known data set, A component concentration measurement method comprising the step of estimating an acoustic mode .