JP7238537B2 - Concentration measuring device - Google Patents

Description

The present invention relates to a concentration measuring device using photoacoustic waves.

A photoacoustic method is known as a method for noninvasively measuring concentrations of various substances (blood sugar level, etc.) that constitute a living body. The photoacoustic method analyzes acoustic waves generated by irradiating a measurement target with light and deforming the measurement target after absorbing the light. Acoustic waves have higher propagation efficiency in the living body than light, so optical information associated with diffuse absorption of light can be detected with high sensitivity. However, information detected from acoustic waves is susceptible to various noises derived from measuring devices and living organisms, and cannot be obtained with high accuracy.

Japanese Patent Application Laid-Open No. 2002-200000 discloses a technique for correcting temporal changes in the amount of output light from a light irradiation unit used in a photoacoustic method as a countermeasure against apparatus-derived noise. In addition, Patent Literature 2 discloses a technique of canceling biological noise by utilizing the difference in absorbance between an object to be measured and a non-measured object at different wavelengths. Further, Patent Document 3 discloses a technique of correcting an acoustic wave generated from an object to be measured by referring to information obtained from an acoustic wave having a similar wavelength. In addition, Non-Patent Document 1 discloses a technique of using acoustic waves generated by light in a non-absorbing wavelength band of an object to be measured as reference information as a countermeasure against biological noise. However, even if the above techniques are used, it is difficult to obtain in vivo information with sufficient accuracy, and a method for noninvasively measuring blood sugar levels has not yet been realized.

WO2011/052061 Japanese Patent No. 5947761 Japanese Patent No. 3667321

IEEE Transactions on Instrumentation and Measurement (Volume: 67, Issue: 1, Jan. 2018)

SUMMARY OF THE INVENTION It is an object of the present invention to provide a concentration measuring apparatus capable of obtaining with high accuracy the concentration of a predetermined substance contained in a living body.

In order to solve the above problems, the present invention provides the following means.

(1) A concentration measuring device according to an aspect of the present invention is a method for measuring a first substance to be measured and a second substance distributed around the first substance in a larger amount than the first substance. a light irradiation unit that irradiates two lights; an acoustic wave detection unit that detects a first acoustic wave and a second acoustic wave generated respectively from the first substance and the second substance irradiated with light; The first substance corresponding to the first signal based on the first acoustic wave, using a database in which the relationship between the signal and the concentration of the substance that generates the acoustic wave is recorded, and the second signal based on the second acoustic wave and a signal processor for estimating the concentration of

(2) In the concentration measuring device according to (1) above, the distance from the acoustic wave detection unit to the second substance is calculated using the second signal, and based on the calculated distance, the It is preferable to further have a corrector that corrects the intensity of the first signal.

(3) In the concentration measuring device according to any one of (1) and (2) above, the light irradiator includes a first light irradiator that irradiates the first light and a second light irradiator that irradiates the second light. It is preferred to have a dual light illuminator.

(4) The density measuring device according to any one of (1) to (3) above preferably further includes a first light amount measuring section for measuring the light amount of the first light.

(5) The density measuring device according to any one of (1) to (4) above preferably further includes a second light amount measuring section for measuring the light amount of the second light.

(6) The concentration measuring device according to any one of (1) to (5) above, further comprising an acoustic wave generator for generating a third acoustic wave having the same frequency as the first acoustic wave. is preferred.

(7) The density measuring apparatus according to any one of (1) to (6) above preferably further includes a synthesizing section for synthesizing the first light and the second light.

(8) The concentration measuring device according to any one of (1) to (7) above preferably further includes a temperature detection unit that detects the temperature of the first substance.

(9) In the concentration measuring device according to any one of (2) to (8) above, the signal processing unit, based on the correction unit and the corrected first signal, determines the first substance and a calculating unit for calculating the concentration of

(10) In the concentration measuring apparatus according to any one of (1) to (9) above, it is preferable that the first light is a combination of two lights having different frequencies or different wavelengths. .

In the concentration measuring device according to one aspect of the present invention, not only the first substance to be measured but also the second substance widely distributed around the first substance is irradiated with light, It is configured to obtain an acoustic wave signal generated from each of the substances. Therefore, for example, the position of the first substance is estimated from the position of the second substance calculated based on the acoustic wave signal, and the concentration of the first substance is measured from the attenuation of the acoustic wave corresponding to that position. be able to. Furthermore, since there is no need to modulate the light that irradiates the first substance in order to calculate the distance, etc., a modulation method with increased sensitivity regarding the attenuation of the acoustic wave generated from the first substance is selected. and, as a result, the concentration of the first substance can be measured with high accuracy.

1 is a diagram schematically showing the configuration of a concentration measuring device according to a first embodiment of the present invention; FIG. FIG. 4 is a diagram schematically showing the configuration of a concentration measuring device according to a second embodiment of the present invention; FIG. 10 is a diagram schematically showing the configuration of a concentration measuring device according to a third embodiment of the present invention; FIG. 10 is a diagram schematically showing the configuration of a concentration measuring device according to a fourth embodiment of the present invention; FIG. 10 is a diagram schematically showing the configuration of a concentration measuring device according to a fifth embodiment of the present invention; FIG. 10 is a diagram schematically showing the configuration of a concentration measuring device according to a sixth embodiment of the present invention;

Hereinafter, a concentration measuring device according to an embodiment to which the present invention is applied will be described in detail with reference to the drawings. In addition, in the drawings used in the following explanation, in order to make the features easier to understand, the characteristic portions may be enlarged for convenience, and the dimensional ratios of each component may not necessarily be the same as the actual ones. do not have. Also, the materials, dimensions, and the like exemplified in the following description are examples, and the present invention is not limited to them, and can be implemented with appropriate modifications within the scope of the invention.

<First embodiment>
FIG. 1 is a diagram schematically showing the configuration of a concentration measuring device 100 according to the first embodiment of the invention. The concentration measurement device 100 measures the concentration of a predetermined substance contained in an object M such as a living body, and mainly includes a light irradiation unit 101, an acoustic wave detection unit 102, and a signal processing unit 103. ing.

The light irradiation unit 101 includes one or more light sources, and is configured to irradiate the first substance M1 and the second substance M2 contained in the object M with the first light P1 and the second light P2, respectively. . Here, it is assumed that the first substance M1 is a substance to be measured, and the second substance M2 is a substance distributed more than the first substance M1 around the first substance M1. In vivo, for example, glucose and cholesterol correspond to the first substance M1, and hemoglobin corresponds to the second substance M2. The concentration of the second substance M2 is preferably about 50 to 300 times the concentration of the first substance M1. The object M may contain substances other than the first substance M1 and the second substance M2.

The light source included in the light irradiation unit 101 includes a laser diode (LD), a light emitting device (LED), a laser, a black body radiator, a lamp, and the like. A wavelength may be extracted. Also, for example, a DFB (Distributed Feedback) semiconductor laser or the like, which enables change of wavelength, can be used. When using a tunable laser, there are a method of changing the oscillation frequency by temperature adjustment, a method of using an external resonator, and the like.

The first light P1 and the second light P2 are light in wavelength bands that are easily absorbed by the first substance M1 and the second substance M2, respectively, and are discontinuous light whose amplitude changes intermittently. This allows the first substance M1 to absorb only the first light P1 and the second substance M2 to absorb only the second light. For example, the wavelength of the first light P1 is the wavelength that is best absorbed by glucose and cholesterol, and is preferably around 1600 nm or around 2100 nm. Moreover, the wavelength of the second light P2 is a wavelength that is best absorbed by hemoglobin, and is preferably around 700 nm or around 1100 nm.

By applying a predetermined fluorescent member to a portion of the irradiation surface of the light irradiation section 101, the wavelength of the light irradiated from that portion can be converted. In this case, simultaneous irradiation of the first light P1 and the second light P2 can be performed without using two light irradiators as in the second embodiment described later.

The first substance M1 and the second substance M2 irradiated with light generate photoacoustic waves (hereinafter sometimes referred to as acoustic waves) W1 and W2, respectively. A photoacoustic wave is an elastic wave generated when a portion irradiated with light absorbs the light and expands.

The acoustic wave detection unit 102 separately detects the first acoustic wave W1 generated in the first material M1 and the second acoustic wave W2 generated in the second material M2, and further detects the first acoustic wave W1 and the second acoustic wave W1. It is configured to send a signal based on the acoustic wave W2 to the signal processing unit 103 . The acoustic wave detector 102 is arranged at a certain distance from the light irradiation unit 101, detects an acoustic wave generated inside the object M by the light emitted from the light irradiation unit 101, and detects the magnitude of the acoustic wave ( (amplitude), and output as a photoacoustic signal. For example, a microphone, a piezoelectric element, a CMUT (Capacitive Micromachined Ultrasonic Transducer) or a PMUT (Piezoelectric Micromachined Ultrasonic Transducer) manufactured using semiconductor technology can be used.

The signal processing unit 103 includes a correction unit 103A that corrects the first signal S1, and a calculation unit 103B that calculates the concentration of the first substance M1 based on the corrected first signal S1.

The signal processing unit 103 obtains the concentration of the first substance M1 by the following procedure. First, the attenuation (amplitude) of the first acoustic wave W1 with respect to the first light P1 is calculated from the first signal S1. However, since the attenuation of the acoustic wave changes in proportion to the propagation distance of the acoustic wave, the position of the first substance M1, which is the source of the acoustic wave, that is, the distance from the first substance M1 to the acoustic wave detector 102 If the distance D1 is unknown, it cannot be evaluated correctly. This distance D1 can be obtained, for example, by multiplying the speed of the radiated acoustic wave by the time it takes for the first substance M1 to be irradiated with the acoustic wave and reflected back. As the signal processing unit 103, for example, a computer having a memory and a CPU can be used.

However, when the concentration of the first substance M1 is extremely low, it is difficult to apply acoustic waves to the first substance M1, and it is difficult to directly measure the distance D1. Therefore, in this case, the second acoustic wave W2 (second signal S2) generated from the second substance M2 is used to calculate the distance D2 from the acoustic wave detection unit 102 to the second substance M2, and the calculated The intensity of the first signal is corrected based on the distance D2. Specifically, the acoustic wave for measuring the distance D1 is applied not to the first substance M1, but to the second substance M2, which is more distributed around the first substance M1 than the first substance M1. The correction unit that corrects the intensity of the first signal may be built in the signal processing unit, or may be provided side by side. For example, a computer having a memory and a CPU can be used as the correction unit.

Since the second material M2 is more distributed than the first material M1, it is easier to apply the acoustic wave, so the distance D2 from the second material M2 to the acoustic wave detector 102 can be measured easily and accurately. The second substance M2 is distributed in the vicinity of the first substance M1, and the distance D2 can be regarded as approximately equal to the distance D1. Therefore, by knowing the distance D2, the distance D1 can be known indirectly. can.

The attenuation of the first acoustic wave W1 generated from the first material M1 is corrected (divided) by the distance D1 to obtain the attenuation of the acoustic wave W1 per unit length, that is, the attenuation rate. Then, referring to a database in which the relationship between the signal based on the acoustic wave and the concentration of the substance that generates the acoustic wave is recorded, the first signal S1 based on the first acoustic wave W1 (specifically, the obtained Attenuation rate), the concentration of the first substance M1 is obtained.

Note that the first light P1 may be a combination of two lights having different wavelengths. In this case, since the two lights are intensity-modulated with each other, it is possible to apply a known accuracy improvement means (Patent Document 2) for detecting the difference between the two lights, which does not include the influence of the error related to absorbance. The concentration of one substance M1 can be measured with high accuracy.

As described above, the concentration measuring apparatus 100 according to the present embodiment irradiates light not only on the first substance M1 to be measured, but also on the second substance M2 distributed widely around the first substance M1. , the first material M1, and the second material M2. Therefore, for example, the position of the first substance M1 is estimated from the position of the second substance M2 calculated based on the acoustic wave signal, and the concentration of the first substance M1 is calculated from the attenuation of the acoustic wave corresponding to that position. can be measured.

Furthermore, since there is no need to perform modulation for calculating the distance, etc., of the light that irradiates the first substance M1, the modulation means with increased sensitivity for the attenuation of the acoustic wave generated from the first substance M1 can be selected, and as a result, the concentration of the first substance M1 can be measured with high accuracy.

<Second embodiment>
FIG. 2 is a diagram schematically showing the configuration of a concentration measuring device 200 according to the second embodiment of the invention. In the density measurement device 200, the light irradiation unit 101 includes a first light irradiation device 101A that emits only the first light P1 and a second light irradiation device 101B that emits only the second irradiation light 101B. The first light irradiator 101A and the second light irradiator 101B are light sources, and the same light sources as listed in the first embodiment can be used. Other configurations are the same as those of the concentration measuring apparatus 100 of the first embodiment, and corresponding portions are indicated by the same reference numerals regardless of the difference in shape.

Both the first substance M1 and the second substance M2 can be irradiated with light at the same time. As a result, for example, it is possible to avoid a problem in which one of the first substance M1 and the second substance M2 moves immediately after the other is irradiated with light, hindering accurate distance measurement. Therefore, the distance of the first substance M1 can be corrected with higher accuracy than the same degree measuring device 100 of the first embodiment, and the accuracy of concentration measurement of the first substance M1 can be further improved.

<Third Embodiment>
FIG. 3 is a diagram schematically showing the configuration of a concentration measuring device 300 according to the third embodiment of the invention. The density measuring device 300 includes a light intensity measuring section 104 that measures the light intensity of the first light P1 and the second light P2. As shown in FIG. 3, the light amount measurement unit 104 includes a first light amount measurement unit 104A that measures the light amount of the first light P1 and a second light amount measurement unit 104B that measures the light amount of the second light P2. preferably. This makes it possible to simultaneously measure the light intensities of the first light P1 and the second light P2. Other configurations are the same as those of the concentration measuring apparatus 100 of the first embodiment, and corresponding portions are indicated by the same reference numerals regardless of the difference in shape. The light irradiation unit 101 may be replaced with the configuration in the second embodiment.

The light intensity measurement unit 104 is connected to the signal processing unit 103 and configured to send information on the light intensity measured by the light intensity measurement unit 104 to the signal processing unit 103 . The signal processing unit 103 corrects the signal of the acoustic wave sent from the detection unit 102 by the amount of change in the signal estimated from the amount of light emitted from the light irradiation unit. As a result, the measured concentration of the first substance M1 is less affected by the amount of irradiation light, and has high accuracy. As the light amount measuring unit 104, for example, a light receiving element such as a photodiode (PD) can be used.

<Fourth embodiment>
FIG. 4 is a diagram schematically showing the configuration of a concentration measuring device 400 according to the fourth embodiment of the invention. The concentration measuring apparatus 400 includes an acoustic wave generator 105 that generates a third acoustic wave W3 having the same frequency as the first acoustic wave W1 and hits (acts on) the medium of the object M. FIG. Other configurations are the same as those of the concentration measuring apparatus 100 of the first embodiment, and corresponding portions are indicated by the same reference numerals regardless of the difference in shape. The light irradiation unit 101 may be replaced with the configuration in the second embodiment. Moreover, you may provide the light quantity measurement part like 3rd embodiment. The acoustic wave generating unit 105 is arranged at a certain distance from the light irradiating unit 101. In order to generate an acoustic wave having the same frequency as the first acoustic wave W1 inside the object M, a piezoelectric element, A CMUT (Capacitive Micromachined Ultrasonic Transducer) or a PMUT (Piezoelectric Micromachined Ultrasonic Transducer) manufactured using semiconductor technology can be used.

In the concentration measuring device 400, the acoustic wave detection unit 102 detects the fourth acoustic wave W4 generated from the object M after the third acoustic wave W3 hits the medium of the object M, and the detected signal S3 is processed by the signal processing unit. 103 can be analyzed. In the signal processing unit 103, the detected signal S1 of the first acoustic wave W1 is corrected for the signal change estimated from the modulation from the third acoustic wave W3 to the fourth acoustic wave W4. As a result, the measured concentration of the first substance M1 is less affected by the medium of the object M, and has high accuracy.

<Fifth Embodiment>
FIG. 5 is a diagram schematically showing the configuration of a concentration measuring device 500 according to the fifth embodiment of the invention. The concentration measuring device 500 includes a temperature detection section 106 that detects the temperature T of the object M (first substance M1). Other configurations are the same as those of the concentration measuring apparatus 100 of the first embodiment, and corresponding portions are indicated by the same reference numerals regardless of the difference in shape. The light irradiation unit 101 may be replaced with the configuration in the second embodiment. Moreover, a light amount measuring unit may be provided as in the third embodiment, or an acoustic wave generation unit may be provided as in the fourth embodiment.

The concentration measuring apparatus 500 is configured such that the signal S4 based on the temperature T of the object M detected by the temperature detection unit 106 can be analyzed by the signal processing unit 103 . In the signal processing unit 103, the detected signal S1 of the first acoustic wave W1 is corrected for the signal change estimated from the temperature modulation of the object M. FIG. As a result, the measured concentration of the first substance M1 is less affected by the temperature of the object M, and has high accuracy. A thermistor, a thermocouple, or the like, for example, can be used as the temperature detection unit 106 .

<Sixth Embodiment>
FIG. 6 is a diagram schematically showing the configuration of a concentration measuring device 600 according to the sixth embodiment of the invention. The density measuring device 600 includes a synthesizing unit 107 that synthesizes the first light P1 and the second light P2. Other configurations are the same as those of the concentration measuring apparatus 100 of the first embodiment, and corresponding portions are indicated by the same reference numerals regardless of the difference in shape. The light irradiation unit 101 may be replaced with the configuration in the second embodiment. Further, it may be provided with a light amount measuring section as in the third embodiment, an acoustic wave generation section as in the fourth embodiment, or a temperature detection section as in the fifth embodiment. can be

The density measuring device 600 is configured to combine the first light P1 and the second light P2 and emit the combined light P1+P2. As a result, the optical waveguide from the light source to the light irradiation port is shared, and the size of the concentration measuring apparatus can be reduced. In addition, since the light irradiation openings of the first light P1 and the second light P2 are the same, the optical paths of the first light P1 and the second light P2 to the measurement target are the same, so errors due to differences in the optical paths can be eliminated. It becomes possible to suppress it, and the measurement accuracy is improved.

For example, an optical fiber or the like can be used as the synthesizing section. By using an optical fiber as a synthesizing unit, the first light P1 and the second light P2 are synthesized, and only one of the synthesized light and the non-synthesized light is guided to the light irradiation port and irradiated to the object M. In addition, according to the surface shape of the object M, a rectangular prism, an optical fiber collimator, a fill rule, or the like may be adhered to the light irradiation side of the synthesizing portion.

100, 200, 300, 400, 500 Concentration measuring device 101 Light irradiator 101A First light irradiator 101B Second light irradiator 102 Acoustic wave detector 103 Signal processing unit 103A Correction unit 103B Calculation unit 104 Light amount measurement unit 104A First light amount measurement unit 104B Second light amount measurement unit 105 Acoustic wave generation unit 106 Temperature detection unit 107 Synthesis unit D1, D2 Distance M Object M1 First substance M2 Second substance P1 First light P2 Second light S1 First signal S2 Second signal S3 Third signal S4 Fourth signal T Temperature W1 First acoustic wave W2 Second Acoustic wave W3... Third acoustic wave W4... Fourth acoustic wave

Claims (9)

a light irradiation unit that irradiates a first light and a second light to a first substance to be measured and a second substance distributed around the first substance in a larger amount than the first substance, respectively;
an acoustic wave detection unit that detects a first acoustic wave and a second acoustic wave respectively generated from the first substance and the second substance irradiated with light;
Using a database in which the relationship between a signal based on an acoustic wave and the concentration of a substance that generates the acoustic wave is recorded, and a second signal based on the second acoustic wave, corresponding to the first signal based on the first acoustic wave a signal processing unit that estimates the concentration of the first substance ,
further comprising a correction unit that calculates the distance from the acoustic wave detection unit to the second substance using the second signal, and corrects the intensity of the first signal based on the calculated distance. A concentration measuring device characterized by: 2. The density measuring apparatus according to claim 1 , wherein said light irradiation unit has a first light irradiation device for irradiation of said first light and a second light irradiation device for irradiation of said second light. . 3. The density measuring apparatus according to claim 1, further comprising a first light amount measuring section for measuring the light amount of said first light. 4. The density measuring apparatus according to claim 1, further comprising a second light amount measuring section for measuring the light amount of said second light. 5. The concentration measuring apparatus according to claim 1, further comprising an acoustic wave generator for generating a third acoustic wave having the same frequency as said first acoustic wave. 6. The concentration measuring device according to claim 1, further comprising a synthesizing unit for synthesizing the first light and the second light. The concentration measuring device according to any one of claims 1 to 6 , further comprising a temperature detection unit that detects the temperature of the first substance. 8. The signal processing unit according to any one of claims 1 to 7 , wherein the signal processing unit includes the correction unit and a calculation unit that calculates the concentration of the first substance based on the corrected first signal. The concentration measuring device according to the item. 9. The concentration measuring apparatus according to any one of claims 1 to 8 , wherein said first light is a combination of two lights having different frequencies or different wavelengths.

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