JP2018013417A - Component concentration measuring device and method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To improve accuracy of measuring concentration of an object component.SOLUTION: A wavelength λ1 of light of a light source 101 is set to be a wavelength in which an object component 110G shows characteristic absorption, a wavelength λ2 of light of a light source 102 is set to be a wavelength in which the object component 110G does not show characteristic absorption and the wavelength λ1 of light of the light source 101 and the wavelength λ2 of light of the light source 102 are set to be a wavelength in which temperature dependency of a background component 110W in a measurement target object 110 is equal to each other. For example, the wavelength λ1 is set to be 1608 nm and the wavelength λ2 is set to be 1312 nm. Photoacoustic signals A1 and A2 from the measurement target object 110, generated by light from the light sources 101 and 102 in which power is set to be equal to each other are obtained to determine inclination (proportional multiplier) of a photoacoustic signal with respect to absorbance of the measurement target object 110 on the basis of intensity of the obtained photoacoustic signals A1 and A2.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a component concentration measuring apparatus and component concentration measuring method for a target component in a measured object using a photoacoustic method, and in particular, a non-invasive component concentration measuring apparatus and a component concentration measuring method in which the measured object is a human or an animal. Regarding the method.

  With the aging of society, dealing with adult diseases is becoming a major issue. In particular, in blood glucose level tests and the like, blood collection is necessary, which is a heavy burden on the patient. For this reason, a non-invasive component concentration measuring apparatus that does not collect blood has attracted attention.

  A photoacoustic method has been proposed as a noninvasive component concentration measuring apparatus. The photoacoustic method irradiates the skin with electromagnetic waves, causes the blood component to be measured, for example, glucose molecules to absorb the electromagnetic waves, and causes local thermal expansion due to the radiation of heat from the glucose molecules, resulting in thermal expansion. Observe sound waves generated from the body. 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.

  FIG. 11 is a configuration example of a component concentration measuring apparatus 200 using a conventional photoacoustic method (see, for example, Patent Document 1). This component concentration measuring apparatus 200 measures the concentration of a target component in a solution (measurement object) in which a background component and a target component are mixed using a light source that is continuously intensity-modulated.

  In FIG. 11, 201 is a first light source, 202 is a second light source, 203 is a first drive circuit, 204 is a second drive circuit, 205 is an oscillator, 206 is a delay adjuster, 207 is an optical multiplexer, 208 is an optical fiber, 209 is a light emitting part, 210 is an object to be measured (a solution in which the target component 210G and the background component 210W are mixed), 211 is a sound wave detector (acoustic sensor), 212 is an amplifier, 213 is waveform observation , 214 is a recorder.

  In the component concentration measurement apparatus 200, the first light source 201 generates measurement light having a wavelength λ1. The second light source 202 generates reference light having a wavelength λ2. The oscillator 205 outputs a modulation signal for intensity-modulating the light output from the first light source 201 and the second light source 202. The delay adjuster 206 inverts one of the modulation signals from the oscillator 205 and outputs the result.

  The first drive circuit 203 drives the first light source 201. The second drive circuit 204 drives the second light source 202 based on the modulation signal inverted by the delay adjuster 206. The first light source 201 modulates the intensity of the measurement light having the wavelength λ 1 with the signal from the first drive circuit 203 and outputs the measurement light. The second light source 202 modulates the intensity of the reference light having the wavelength λ 2 with the signal from the second drive circuit 204 and outputs the reference light. As a result, the first light source 201 and the second light source 202 output light of different wavelengths λ1 and λ2 that is electrically intensity-modulated by signals having the same frequency and opposite phases.

  The light of wavelength λ 1 from the first light source 201 and the light of wavelength λ 2 from the second light source 202 are combined by the optical multiplexer 207 and guided to the light emitting unit 209 by the optical fiber 208. The light emitting unit 209 emits the light combined by the optical multiplexer 207 (measurement combined light) toward the object to be measured 210. In response to the measurement combined light from the optical multiplexer 207, the DUT 210 generates sound waves.

  The sound wave detector 211 detects a sound wave generated from the object to be measured 210 and converts it into an electric signal (photoacoustic signal) having a strength proportional to the sound pressure. The converted photoacoustic signal is amplified by the amplifier 212 and then sent to the waveform observer 213. The waveform observer 213 observes the photoacoustic signal sent from the sound wave detector 211 via the amplifier 212 and sends the observation result to the recorder 214. The recorder 214 calculates the concentration of the target component 210G in the DUT 210 based on the observation result of the photoacoustic signal sent from the waveform observer 213.

  In this component concentration measuring apparatus 200, the two wavelengths λ1 and λ2 are wavelengths in which the difference in absorption exhibited by the target component 210G is greater than the difference in absorption exhibited by the background component 210W. The wavelength λ1 is set to a wavelength at which the target component 210G exhibits characteristic absorption. The wavelength λ2 is set to a wavelength at which the target component 210G does not exhibit characteristic absorption. The wavelengths λ1 and λ2 may be two wavelengths in which the difference in absorption exhibited by the target component 210G is greater than the difference in absorption exhibited by other components. Thereby, the influence of absorption by components other than water and the component to be measured can be reduced, and the measurement accuracy of the component concentration measuring apparatus 200 can be improved.

  Further, in this component concentration measuring apparatus 200, the frequency for electrically intensity-modulating each of the two wavelengths λ1 and λ2 is set to the same frequency as the resonance frequency related to the detection of the sound wave generated by the object to be measured 210. Measure the sound wave for the light of two wavelengths selected in consideration of the nonlinearity related to the absorption coefficient in the measured value of the sound wave, and normalize the sound wave of one wavelength from the sound wave of the difference of the two wavelengths to keep it constant It is possible to detect the sound wave generated in the measured object 210 with high accuracy by eliminating the influence of many difficult parameters.

  In this component concentration measuring apparatus 200, the waveform observer 213 has a photoacoustic signal intensity generated by light of wavelength λ1 as A1, and a photoacoustic signal intensity generated by light of wavelength λ2 as A2. The difference value (A1-A2) between the photoacoustic signals A1 and A2 is measured (FIG. 12: Step S301). Then, the photoacoustic signal An generated by the light from the first light source 201 or the second light source 202 is measured (step S302), and the difference value (A1-A2) between the measured photoacoustic signals A1 and A2 and The photoacoustic signal An is sent to the recorder 214 as an observation result of the photoacoustic signal. In this example, the photoacoustic signal A2 generated by the light having the wavelength λ2 from the second light source 201 is measured as the photoacoustic signal An.

  Note that when a constant voltage current source (not shown) supplies a voltage to the first drive circuit 203 and the second drive circuit 204, the measurement composite light (λ1 + λ2) is irradiated onto the device under test 210. By detecting the measurement sound wave generated by the measurement combined light, the waveform observer 213 can observe the difference value (A1-A2) between the photoacoustic signals A1 and A2. Further, when the constant voltage current source does not supply a voltage to the first drive circuit 203 and the constant voltage current source supplies a voltage only to the second drive circuit 204, the reference light is irradiated to the object 210 to be measured. Therefore, the photoacoustic signal An can be observed by the waveform observer 213 by detecting the normalization sound wave generated by the reference light.

  The recorder 214 divides the difference value (A1−A2) between the photoacoustic signals A1 and A2 by An, normalizes the proportional multiplier C, and absorbs α (α = C · (A1−A2)) of the target component 210G. Is calculated (step S303). Then, the molar concentration M (M = α / αg) of the target component 210G is calculated from the calculated absorbance α of the target component 210G and the known molar absorbance αg of the target component 210G (step S304). Thereby, when the target component 210G is glucose in blood, the molar concentration M of glucose in blood can be measured.

  In the component concentration measuring apparatus 200, the wavelength λ1 of light from the first light source 201 is 1608 nm, and the wavelength λ2 of light from the second light source 202 is 1380 nm. As for these two wavelengths λ1 (1608 nm) and λ2 (1380 nm), as shown in the graph of water absorbance temperature dependency in FIG. 13, the temperature dependence coefficient of water has a positive or negative tendency at each wavelength.

  When using light having a wavelength at which the absorbance of water has temperature dependence, the temperature is directly measured for the absorbance change Δαw due to temperature change, or Δαw is obtained from a known absorbance spectrum, or the amount of light absorption The temperature change ΔT is estimated from the change, and Δαw is obtained from the known absorbance spectrum. In this case, it can be described as α = M · αg + Δαw. Therefore, the molar concentration M can be obtained as M = (Δα−Δαw) / αg.

JP 2007-89662 A

  However, in the above-described conventional component concentration measuring apparatus, the estimation accuracy of the temperature change of the target component (glucose) is not sufficient, and the measurement accuracy of the concentration of the target component is lowered due to the temperature dependence of the absorbance of the background component (water). . In addition, since the inclination (proportional multiplier) of the photoacoustic signal with respect to the change in the sound source distribution due to the change in absorbance strongly depends on the absorbance α depending on the resonance mode in the cavity, it is difficult to standardize the proportional multiplier. For this reason, the conventional component concentration measuring apparatus has a problem that an error occurs in the concentration of the target component to be measured.

  The present invention has been made to solve such problems, and an object of the present invention is to provide a component concentration measuring apparatus and a component concentration measuring method capable of improving the measurement accuracy of the concentration of the target component. There is.

  In order to achieve such an object, the present invention irradiates the object to be measured (110) with light, and measures a sound wave from the object to be measured (110) generated by the irradiated light as a photoacoustic signal. In the component concentration measuring apparatus (100) for measuring the concentration of the target component (110G) in the object to be measured (110) from the intensity of the measured photoacoustic signal, the first light source (101) having the same power is set. The slope of the photoacoustic signal with respect to the absorbance of the object to be measured (110) is calculated as a proportional multiplier based on the intensity of the photoacoustic signal from the object to be measured (110) generated by the light from the second light source (102). Proportional multiplier calculating means (114-1) and the first light source (101) and the second light source (102) whose powers are adjusted so that the intensity of the photoacoustic signal from the device under test (110) is equal. ) Driving means (103 to 104) for simultaneously irradiating the object to be measured (110) with light whose intensity is modulated by signals of the opposite phase at the same frequency, and light irradiated by the driving means (103 to 104) The photoacoustic signal acquisition means (113-1) for acquiring the photoacoustic signal from the generated object (110) to be generated, the proportional multiplier calculated by the proportional multiplier calculation means (114-1), and the photoacoustic signal acquisition means ( 113-1) calculates the absorbance of the target component (110G) from the intensity of the photoacoustic signal acquired in step 113-1), and uses the molar absorbance of the target component (110G) obtained as a known value in advance. 110G) and a molar concentration calculation means (114-2) for calculating the molar concentration of the first light source (101), and the wavelength of the light from the second light source (102) as λ2. In this case, the wavelength λ1 of the light from the first light source (101) is set to a wavelength at which the target component (110G) exhibits characteristic absorption, and the wavelength λ2 of the light from the second light source (102) is (110G) is set to a wavelength that does not exhibit characteristic absorption, and the wavelength λ1 of the light from the first light source (101) and the wavelength λ2 of the light from the second light source (102) are the measured object (110) The temperature dependence of the background component in is set to the same wavelength.

  In this invention, the wavelength λ1 of the light from the first light source (101) is set to a wavelength at which the target component (110G) exhibits characteristic absorption, and the wavelength λ2 of the light from the second light source (102) is The wavelength at which the component (110G) does not exhibit characteristic absorption is set, and the wavelength λ1 of the light from the first light source (101) and the wavelength λ2 of the light from the second light source (102) are the measured object (110 The temperature dependence of the background component (110 W) in () is set to the same wavelength. For example, the wavelength λ1 of the light from the first light source (101) is 1608 nm, and the wavelength λ2 of the light from the second light source (102) is 1312 nm. As a result, when the difference value between the photoacoustic signal generated by the light of wavelength λ1 and the photoacoustic signal generated by the light of wavelength λ2 is measured, the temperature dependency of the absorbance of the background component (110 W) is canceled, and the temperature fluctuation A decrease in the measurement accuracy of the concentration of the target component (110G) due to is suppressed.

  In the present invention, the photoacoustic signals (A1, A2) from the object to be measured (110) generated by the light from the first light source (101) and the second light source (102) having the same power are used. Based on the acquired intensity of the photoacoustic signal (A1, A2), the inclination of the photoacoustic signal with respect to the absorbance of the object to be measured (110) is calculated as a proportional multiplier. That is, in the present invention, instead of normalizing the proportional multiplier, the light to be measured (110) is irradiated with light from the first light source (101) and the second light source (102) having the same power. Then, the slope of the photoacoustic signal with respect to the absorbance of the measured object (110) is directly obtained as a proportional multiplier from the photoacoustic signal (A1, A2) generated from the measured object (110). As a result, a proportional multiplier close to the actual value is obtained as the proportional multiplier of the photoacoustic signal with respect to the change in the sound source distribution due to the change in absorbance, and the molar concentration of the target component (110G) is calculated using the proportional multiplier close to the actual value. Thus, the measurement accuracy of the concentration of the target component is improved.

  In the above description, as an example, constituent elements on the drawing corresponding to the constituent elements of the invention are indicated by reference numerals with parentheses.

  As described above, according to the present invention, the temperature dependency of the absorbance of the background component is canceled, and a proportional multiplier close to the actual value is obtained as the proportional multiplier of the photoacoustic signal with respect to the change in the sound source distribution due to the change in absorbance. Thus, the measurement accuracy of the concentration of the target component can be improved.

FIG. 1 is a diagram showing a basic configuration of a component concentration measuring apparatus according to Embodiment 1 of the present invention. FIG. 2 is a diagram showing an absorbance spectrum of an aqueous glucose solution and an absorbance spectrum of water. FIG. 3 is a diagram showing a proportional relationship between the intensity of the photoacoustic signal converted by the sound wave detector and the absorbance. FIG. 4 is a diagram showing a differential spectrum (glucose differential absorption spectrum) obtained by subtracting the absorbance spectrum of water from the absorbance spectrum of an aqueous glucose solution. FIG. 5 is a diagram showing the temperature dependence of the water absorbance spectrum. FIG. 6 is a flowchart showing the process until the molar concentration of the target component is obtained in the component concentration measuring apparatus according to the first embodiment. FIG. 7 is a diagram showing the slope (proportional multiplier) C ′ of the photoacoustic signal obtained in the component concentration measuring apparatus of the first embodiment. FIG. 8 is a diagram showing a basic configuration of a component concentration measuring apparatus according to Embodiment 2 of the present invention. FIG. 9 is a flowchart showing the process until the molar concentration of the target component is obtained in the component concentration measuring apparatus according to the second embodiment. FIG. 10 is a diagram showing the relationship between the absorbance measured while sweeping the frequency of the oscillator and the photoacoustic signal. FIG. 11 is a diagram illustrating a configuration example of a component concentration measuring apparatus using a conventional photoacoustic method. FIG. 12 is a flowchart showing the process until the molar concentration of the target component is obtained in the conventional component concentration measuring apparatus. FIG. 13 is a diagram showing the absorbance temperature dependency of water.

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

[Embodiment 1]
FIG. 1 is a diagram showing a basic configuration of a component concentration measuring apparatus 100 according to Embodiment 1 of the present invention. The configuration of the component concentration measuring apparatus 100 cancels the temperature dependence of the water absorbance and calibrates the proportional multiplier of the photoacoustic signal with respect to the change in the sound source distribution due to the change in absorbance.

  In FIG. 1, 101 is a first light source, 102 is a second light source, 103 is a first drive circuit, 104 is a second drive circuit, 105 is an oscillator, 106 is a delay adjuster, 107 is an optical multiplexer, Reference numeral 108 denotes an optical fiber, 109 denotes a light emitting portion, 110 denotes an object to be measured (a solution in which the target component 110G and the background component 110W are mixed), 111 denotes a sound wave detector (acoustic sensor), 112 denotes an amplifier, and 113 denotes waveform observation. , 114 is a recorder.

  In the component concentration measuring apparatus 100, the first light source 101 and the second light source 102 are continuously intensity-modulated light sources. For example, a DFB (Distributed Feedback) semiconductor laser, which is a kind of semiconductor laser, can be used. In this case, the laser output is about 10 mW, and the laser intensity stability is about 0.1% / h in the continuous light mode. When the first light source 101 is used as a wavelength tunable laser, there are a method of changing the oscillation frequency by temperature adjustment, a method of using an external resonator, and the like. A solid-state laser can also be used for the light sources 101 and 102. When a predetermined wavelength is extracted from the solid-state laser, a dispersion element such as a prism or a diffraction grating is used.

  In the component concentration measuring apparatus 100, the first light source 101 generates measurement light having a wavelength λ1. The second light source 102 generates reference light having a wavelength λ2. The oscillator 105 outputs a modulation signal for intensity-modulating the light output from the first light source 101 and the second light source 102. The delay adjuster 106 inverts one of the modulation signals from the oscillator 105 and outputs the result.

  The first drive circuit 103 drives the first light source 101. The second drive circuit 104 drives the second light source 102 based on the modulation signal inverted by the delay adjuster 106. The first light source 101 modulates the intensity of the measurement light having the wavelength λ 1 with the signal from the first drive circuit 103 and outputs the measurement light. The second light source 102 modulates the intensity of the reference light having the wavelength λ2 by the signal from the second drive circuit 104 and outputs the reference light. As a result, the first light source 101 and the second light source 102 output lights having different wavelengths λ1 and λ2 that are electrically intensity-modulated by signals having the same frequency and opposite phases.

  The light of wavelength λ 1 from the first light source 101 and the light of wavelength λ 2 from the second light source 102 are combined by the optical multiplexer 107 and guided to the light emitting unit 109 by the optical fiber 108. The light emitting unit 109 emits the light combined by the optical multiplexer 107 (measurement combined light) toward the object to be measured 110. Note that a right-angle prism, fiber collimator, or ferrule may be bonded to the tip of the optical fiber 108 in accordance with the shape of the object to be measured 110. The measurement object 110 generates sound waves by the measurement combined light emitted from the optical multiplexer 107.

  The sound wave detector 111 detects a sound wave generated from the object to be measured 110 and converts it into an electric signal (photoacoustic signal) having a strength proportional to the sound pressure. For example, a microphone or a piezoelectric element can be used for the sound wave detector 111. The converted photoacoustic signal is amplified by the amplifier 112 and then sent to the waveform observer 113. The waveform observer 113 observes the photoacoustic signal sent from the sound wave detector 211 via the amplifier 112 and sends the observation result to the recorder 114. The recorder 114 calculates the concentration of the target component 110G in the DUT 110 based on the observation result of the photoacoustic signal sent from the waveform observer 113.

  In this component concentration measuring apparatus 100, the waveform observer 113 assumes that the photoacoustic signal generated by the light of wavelength λ1 is A1, and the photoacoustic signal generated by the light of wavelength λ2 is A2, the photoacoustic signals A1 and A2 Is measured by the phase detector amplifier (not shown), and the amplitude (A) and phase (φ) of the photoacoustic signal are observed. You may make it do.

  The recorder 114 has a database of water absorbance spectra, absorbance spectra of in vivo components, and absorbance spectra of target components at different concentrations, and a function of calculating the concentration of the target component from the intensity of the acquired photoacoustic signal. have.

  FIG. 2 shows the absorbance spectrum of the aqueous glucose solution (characteristic curve I indicated by a dotted line) and the absorbance spectrum of water (characteristic curve II indicated by a solid line). For example, if the measurement object 110 is a living body and the target component 110G is glucose in blood, the absorption exhibited by the background component 110W can be the absorption exhibited by water.

  In the conventional component concentration measuring apparatus 200 (FIG. 11), the wavelength λ1 of light output from the first light source 201 is 1608 nm (λ10), and the wavelength λ2 of light output from the second light source 202 is 1380 nm (λ20). It was said. The wavelengths λ10 and λ20 are different wavelengths having the same absorption of the background component. In the figure, the pairs of wavelengths λ11 and λ21 are also different wavelengths having the same absorption of the background component. In this figure, the absorbance of the background components of wavelengths λ10 and λ20 is indicated by α20, and the absorbance of the background components of wavelengths λ11 and λ21 is indicated by α21. The intensity of the photoacoustic signal converted by the sound wave detector 111 is proportional to the absorbance. As shown in FIG. 3, the photoacoustic signals A20 and A21 corresponding to the wavelengths λ20 and λ21 have a certain slope C ′. Are related.

  FIG. 4 shows a differential spectrum (glucose differential absorption spectrum) obtained by subtracting the absorbance spectrum of water from the absorbance spectrum of the aqueous glucose solution. FIG. 4 shows the glucose differential absorption spectrum when the glucose concentration is 1 g / dL and 2 g / dL. In this glucose differential absorption spectrum, peaks exist in the vicinity of 1600 nm and 2150 nm in the spectrum of a stable region excluding a region where the fluctuation is severe.

  FIG. 5 shows the temperature dependence of the absorbance spectrum of water (absorbance change (characteristic curve III shown by a solid line) and absorbance change rate% (characteristic curve IV shown by a dotted line)). In the figure, the horizontal axis represents wavelength, the left vertical axis represents absorbance change per 1 ° C., and the right vertical axis represents absorbance change rate per 1 ° C. temperature. In the object to be measured 110, it is inevitable that the background component 110W fluctuates, which causes a decrease in the measurement accuracy of the concentration of the target component 110G.

  In the present embodiment, the wavelength λ1 of light output from the first light source 101 and the wavelength λ2 of light output from the second light source 102 are set to different wavelengths having the same temperature-dependent absorbance change rate of the background component 110W. . In FIG. 5, 1608 nmm and 1312 nm are illustrated as different wavelengths having the same temperature-dependent absorbance change rate of the background component 110W. Thereby, when the difference value (A1-A2) between the photoacoustic signal A1 generated by the light of wavelength λ1 and the photoacoustic signal A2 generated by the light of wavelength λ2 is measured, the temperature-dependent absorbance change of the background component 110W is measured. It will be canceled.

  In the present embodiment, it is preferable that at least one of the first light source 101 and the second light source 102 has a wavelength that maximizes the absorption exhibited by the target component 110G. For example, if the DUT 110 is a living body and the target component 110G is glucose in blood, the first light source 101 has the maximum absorption exhibited by glucose as shown in the glucose differential absorption spectrum shown in FIG. The wavelength is preferably 1600 nm or 2150 nm. In this case, the continuous light output from the first light source 101 becomes the measurement light having the wavelength λ1, and the continuous light output from the second light source 102 becomes the reference light having the wavelength λ2.

  From the above, in this embodiment, the wavelength λ1 of the light from the first light source 101 is set to 1608 nm, and the wavelength λ2 of the light from the second light source 102 is set to 1312 nm. That is, the wavelength λ1 of the light from the first light source 101 is set to a wavelength at which the target component 110G exhibits characteristic absorption, and the wavelength λ2 of the light from the second light source 102 does not exhibit characteristic absorption at the target component 110G. The wavelength λ1 of the light from the first light source 101 and the wavelength λ2 of the light from the second light source 102 are set to the same wavelength with the same rate of change in absorbance due to the temperature dependence of the background component 110W in the DUT 110. Set to.

  The absorbance α and the photoacoustic signal A are in a proportional relationship by a proportional multiplier C. Assuming that the optical power applied to the measurement object 110 is I, it is expressed as A = C · α · I = C ′ · α. Here, the proportional multiplier C ′ (C ′ = C · I) including the optical power is a coefficient that changes and is difficult to control or predict. For example, the acoustic coupling between the sound wave detector 111 and the object to be measured 110 in FIG. 1, the sensitivity of the sound wave detector 111, the distance between the light emitting unit 109 and the object to be measured 110, the specific heat of the object to be measured 110, the object to be measured. It is an unknown that depends on the coefficient of thermal expansion of the object 110, the speed of sound at the object 110 to be measured, the oscillation frequency of the oscillator 105, and the absorbance α. The amplitude and phase of the photoacoustic signal depend on the cavity size and the internal structure of the device under test 110 due to the acoustic resonance within the device under test 110. For this reason, the amplitude and phase of the photoacoustic signal change due to these fluctuations, which causes an error in the concentration of the target component to be measured.

  For this reason, the conventional component concentration measuring apparatus 200 (FIG. 11) employs a method of eliminating the influence by normalizing the proportional multiplier C using a photoacoustic signal acquired at a predetermined wavelength. However, in this component concentration measuring apparatus 200, it is premised that the proportional multiplier C does not depend on the absorbance α, and if the resonance mode strongly depends on the absorbance α, it is difficult to standardize the proportional multiplier C. Therefore, in the component concentration measuring apparatus 100 of the present embodiment, the photoacoustic signal is detected and recorded using two wavelengths having different absorbances, and the slope C ′ of the photoacoustic signal with respect to the absorbance α is directly obtained.

  Specifically, using the first light source 101 and the second light source 102 having the same power, the object 110 is irradiated with light having a wavelength λ1 (1608 nm) from the first light source 101, and the photoacoustic signal A1. And the photoacoustic signal A2 is measured by irradiating the object 110 with light having a wavelength λ2 (1312 nm) from the second light source 102 (FIG. 6: step S101), and the measured photoacoustic signals A1 and A2 And the known absorbances α1 and α2 (values of known absorbance spectra measured in advance by a spectroscope or the like) to obtain the slope C ′ of the photoacoustic signal with respect to the absorbance α (see step S102, FIG. 7). The inclination C ′ of the photoacoustic signal with respect to the absorbance α may be acquired once before the measurement or may be performed every measurement.

  Next, the photoacoustic signal A1 from the DUT 110 generated by the light having the wavelength λ1 (1608 nm) from the first light source 101 and the light generated by the light having the wavelength λ2 (1312 nm) from the second light source 102. The power of the second light source 102 is adjusted so that the photoacoustic signal A2 from the measurement object 110 becomes equal, that is, the difference between the photoacoustic signal A1 and the photoacoustic signal A2 is substantially zero (step S103). ). At the time of power adjustment, the intensity of the first light source 101 and the second light source 102 may be modulated with signals having the same frequency and opposite phases.

  In this example, the power of the second light source 102 is adjusted. However, the power of the first light source 101 may be adjusted, and both the first light source 101 and the second light source 102 may be adjusted. You may make it adjust the power of. The optical power I may be recorded by a photodetector and calibrated later, or the output voltage of the photodetector may be monitored to control the output of the light source.

  Subsequently, the light from the first light source 101 (light having the wavelength λ1 (1608 nm)) and the light from the second light source 102 (light having the wavelength λ2 (1312 nm)), which are intensity-modulated by signals of the opposite phase at the same frequency. ) Are simultaneously irradiated onto the object 110 to be measured, and a photoacoustic signal (A1-A2) having an intensity proportional to the concentration of the target component 110G in the object 110 to be measured is measured (step S104). This measured photoacoustic signal (A1-A2) is defined as a photoacoustic signal Ad. The frequency is 400 kHz, for example, and a frequency with high sensitivity of the acoustic sensor used for signal detection may be used.

  Then, from the photoacoustic signal Ad and the proportional multiplier C ′ calculated in step S102, the absorbance α of the target component 110G is calculated as α = Ad / C ′ (step S105). This calculated absorbance α corresponds to the product of the molar concentration M of the target component 110G and the molar absorbance αg. Therefore, from the calculated absorbance α of the target component 110G and the known molar absorbance αg of the target component 210G (known value obtained in advance by a spectroscope or the like), the molar concentration M (M = α / αg) of the target component 110G. ) Is calculated (step S106). This molar concentration is a relative value from step S103.

  In the processing shown in the flowchart shown in FIG. 6, the photoacoustic signal is measured with the powers of the first light source 101 and the second light source 102 made equal in step S101, and the first light source 101 in step S104. Measurement of the difference value of the photoacoustic signal using the second light source 102 is performed by the photoacoustic signal acquisition unit 113-1 in the waveform observer 113. This photoacoustic signal acquisition unit 113-1 corresponds to the photoacoustic signal acquisition means in the present invention.

  In the processing shown in the flowchart of FIG. 6, the calculation of the proportional multiplier C ′ of the photoacoustic signal in step S102 is performed by the proportional multiplier calculation unit 114-1 in the recorder 114, and the target in step S105. The calculation of the absorbance α of the component 110G and the calculation of the molar concentration M of the target component 110G in step S106 are performed by the molar concentration calculation unit 114-2 in the recorder 114. The proportional multiplier calculator 114-1 and the molar concentration calculator 114-2 correspond to the proportional multiplier calculator and the molar concentration calculator in the present invention.

  In the process shown in the flowchart of FIG. 6, in step S104, the light of wavelengths λ1 and λ2 that has been intensity-modulated from the first light source 101 and the second light source 102 by signals having the same frequency and opposite phases from each other. The object to be measured 110 is irradiated at the same time, and this is performed using the first drive circuit 103, the second drive circuit 104, the oscillator 105, and the delay adjuster 106, and this configuration is the drive means referred to in the present invention. It corresponds to.

  In the component concentration measuring apparatus 100, the waveform observer 113 and the recorder 114 are realized by hardware including a processor and a storage device, and a program that realizes various functions in cooperation with these hardware. .

[Embodiment 2]
FIG. 8 is a diagram showing a basic configuration of a component concentration measuring apparatus 100 ′ according to Embodiment 2 of the present invention. In this figure, the same reference numerals as those in FIG. 1 denote the same or equivalent components as those described with reference to FIG.

  In the component concentration measuring apparatus 100 ′ of the second embodiment, the frequency f of the oscillator 105 is variable, and this is different from the component concentration measuring apparatus 100 of the first embodiment. FIG. 9 shows a flowchart corresponding to the flowchart shown in FIG.

  In the component concentration measuring apparatus 100 ′, the waveform observer 113 measures the relationship between the absorbance α and the photoacoustic signal A while sweeping the frequency f of the oscillator 105 (see FIG. 10), and the proportional multiplier C ′ is the maximum. Is obtained and set for the oscillator 105 (steps S201 to S204). This processing is performed by the frequency determination unit 113-2 in the waveform observer 113. This frequency determination unit 113-2 corresponds to a means for obtaining a frequency in the present invention. In the flowchart shown in FIG. 9, the processing after step S205 is the same as the processing after step S103 in the flowchart shown in FIG.

  In the second embodiment, a large amplitude change can be obtained even with a small change in absorbance, the sensitivity can be improved, and the measurement limit of the concentration of the target component can be lowered. Also in the second embodiment, as in the first embodiment, the acquisition of the proportional multiplier C ′ of the photoacoustic signal with respect to the absorbance α may be performed once before the measurement or may be performed every measurement.

[Extension of the embodiment]
The present invention has been described above with reference to the embodiment. However, the present invention is not limited to the above embodiment. Various changes that can be understood by those skilled in the art can be made to the configuration and details of the present invention within the scope of the technical idea of the present invention.

  INDUSTRIAL APPLICABILITY The present invention can be used for a noninvasive component concentration measuring device for a solution existing in a human or an animal and a component concentration measuring device for a solution collected from a human or an animal.

DESCRIPTION OF SYMBOLS 100,100 '... Component density | concentration measuring apparatus, 101 ... 1st light source, 102 ... 2nd light source, 103 ... 1st drive circuit, 104 ... 2nd drive circuit, 105 ... Oscillator, 106 ... Delay adjuster, DESCRIPTION OF SYMBOLS 107 ... Optical multiplexer, 108 ... Optical fiber, 109 ... Light emission part, 110 ... Object to be measured, 110G ... Target component, 110W ... Background component, 111 ... Sound wave detector (acoustic sensor), 112 ... Amplifier, 113 ... Waveform Observer, 113-1 ... Photoacoustic signal acquisition unit, 113-2 ... Frequency determination unit, 114 ... Recorder, 114-1 ... Proportional multiplier calculation unit, 114-2 ... Molar concentration calculation unit.

Claims (6)

The object to be measured is irradiated with light, the sound wave from the object to be measured generated by the irradiated light is measured as a photoacoustic signal, and the target component in the object to be measured is determined from the intensity of the measured photoacoustic signal. In a component concentration measuring apparatus for measuring the concentration of
The slope of the photoacoustic signal is proportional to the absorbance of the object to be measured based on the intensity of the photoacoustic signal from the object to be measured that is generated by the light from the first light source and the second light source set to have the same power. A proportional multiplier calculating means for calculating as a multiplier;
The first and second light sources, whose powers are adjusted so that the intensities of the photoacoustic signals from the object to be measured are equal, are light whose intensity is modulated by signals having the same frequency and opposite phases. Driving means for simultaneously irradiating the object to be measured;
Photoacoustic signal acquisition means for acquiring a photoacoustic signal from the object to be measured generated by light irradiated by the driving means;
The absorbance of the target component is calculated from the proportional multiplier calculated by the proportional multiplier calculation means and the intensity of the photoacoustic signal acquired by the photoacoustic signal acquisition means, and the target component obtained in advance as a known value A molar concentration calculating means for calculating the molar concentration of the target component using the molar absorbance of
When the wavelength of the light of the first light source is λ1, and the wavelength of the light of the second light source is λ2,
The wavelength λ1 of the light from the first light source is
The target component is set to a wavelength exhibiting characteristic absorption;
The wavelength λ2 of the light from the second light source is
The target component is set to a wavelength that does not exhibit characteristic absorption,
The wavelength λ1 of the light from the first light source and the wavelength λ2 of the light from the second light source are:
The component concentration measuring apparatus, wherein the temperature dependence of the background component in the object to be measured is set to the same wavelength. In the component concentration measuring apparatus according to claim 1,
The proportional multiplier calculating means includes
Calculating the slope of the photoacoustic signal with respect to the absorbance of the object to be measured as a proportional multiplier C ′;
The photoacoustic signal acquisition means includes
Obtaining a photoacoustic signal from the object to be measured as a photoacoustic signal Ad having an intensity proportional to the concentration of the target component in the object to be measured;
The molar concentration calculating means includes
The absorbance of the target component is calculated as α = Ad / C ′ from the proportional multiplier C ′ calculated by the proportional multiplier calculation means and the photoacoustic signal Ad acquired by the photoacoustic signal acquisition means, and the known value A molar concentration of the target component calculated as follows is calculated as αg, and a molar concentration of the target component is calculated as M = α / αg. In the component concentration measuring apparatus according to claim 1 or 2,
Measuring the relationship between the absorbance of the object to be measured and the intensity of the photoacoustic signal from the object to be measured by changing the frequency of the signal for intensity-modulating the light from the first light source and the second light source; A component concentration measuring device further comprising means for obtaining a frequency at which the proportional multiplier calculated by the proportional multiplier calculating means is maximized. The object to be measured is irradiated with light, the sound wave from the object to be measured generated by the irradiated light is measured as a photoacoustic signal, and the target component in the object to be measured is determined from the intensity of the measured photoacoustic signal. In the component concentration measurement method for measuring the concentration of
The slope of the photoacoustic signal is proportional to the absorbance of the object to be measured based on the intensity of the photoacoustic signal from the object to be measured that is generated by the light from the first light source and the second light source set to have the same power. A first step of calculating as a multiplier;
The first and second light sources, whose powers are adjusted so that the intensities of the photoacoustic signals from the object to be measured are equal, are light whose intensity is modulated by signals having the same frequency and opposite phases. A second step of simultaneously irradiating the measurement object;
A third step of acquiring a photoacoustic signal from the object to be measured generated by the light irradiated in the second step;
The absorbance of the target component is calculated from the proportional multiplier calculated in the first step and the intensity of the photoacoustic signal acquired in the third step, and the molar absorbance of the target component obtained in advance as a known value. And a fourth step of calculating the molar concentration of the target component using
When the wavelength of the light of the first light source is λ1, and the wavelength of the light of the second light source is λ2,
The wavelength λ1 of the light from the first light source is
The target component is set to a wavelength exhibiting characteristic absorption;
The wavelength λ2 of the light from the second light source is
The target component is set to a wavelength that does not exhibit characteristic absorption,
The wavelength λ1 of the light from the first light source and the wavelength λ2 of the light from the second light source are:
The component concentration measurement method, wherein the temperature dependence of the background component in the object to be measured is set to the same wavelength. In the component concentration measuring method according to claim 4,
The first step includes
Calculating the slope of the photoacoustic signal with respect to the absorbance of the object to be measured as a proportional multiplier C ′;
The third step includes
Obtaining a photoacoustic signal from the object to be measured as a photoacoustic signal Ad having an intensity proportional to the concentration of the target component in the object to be measured;
The fourth step includes
The absorbance of the target component is calculated as α = Ad / C ′ from the proportional multiplier C ′ calculated in the first step and the photoacoustic signal Ad acquired in the third step, and is obtained as the known value. And calculating the molar concentration of the target component as M = α / αg. In the component concentration measuring method according to claim 4 or 5,
Measuring the relationship between the absorbance of the object to be measured and the intensity of the photoacoustic signal from the object to be measured by changing the frequency of the signal for intensity-modulating the light from the first light source and the second light source; A component concentration measuring method, further comprising: obtaining a frequency at which the proportional multiplier calculated in the first step is maximized.

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