WO2013008447A1 - 分析装置、及び、分析方法 - Google Patents
分析装置、及び、分析方法 Download PDFInfo
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- WO2013008447A1 WO2013008447A1 PCT/JP2012/004426 JP2012004426W WO2013008447A1 WO 2013008447 A1 WO2013008447 A1 WO 2013008447A1 JP 2012004426 W JP2012004426 W JP 2012004426W WO 2013008447 A1 WO2013008447 A1 WO 2013008447A1
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- specimen
- temperature
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- analyzer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/01—Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01K—MEASURING TEMPERATURE; MEASURING QUANTITY OF HEAT; THERMALLY-SENSITIVE ELEMENTS NOT OTHERWISE PROVIDED FOR
- G01K11/00—Measuring temperature based upon physical or chemical changes not covered by groups G01K3/00, G01K5/00, G01K7/00 or G01K9/00
- G01K11/22—Measuring temperature based upon physical or chemical changes not covered by groups G01K3/00, G01K5/00, G01K7/00 or G01K9/00 using measurement of acoustic effects
- G01K11/24—Measuring temperature based upon physical or chemical changes not covered by groups G01K3/00, G01K5/00, G01K7/00 or G01K9/00 using measurement of acoustic effects of the velocity of propagation of sound
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/01—Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue
- A61B5/015—By temperature mapping of body part
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/42—Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems
- A61B5/4222—Evaluating particular parts, e.g. particular organs
- A61B5/4244—Evaluating particular parts, e.g. particular organs liver
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/48—Other medical applications
- A61B5/4869—Determining body composition
- A61B5/4872—Body fat
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
- A61B8/08—Detecting organic movements or changes, e.g. tumours, cysts, swellings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
- A61B8/48—Diagnostic techniques
Definitions
- the present invention relates to an analyzer for analyzing the state of a specimen and an analysis method.
- Spectrometers that measure the light absorption characteristics inside living tissues can measure the concentration distribution of various components using light absorption characteristics (relationship between the wavelength of light and the absorption rate) that differ for each substance. It is used for medical diagnosis in many fields.
- the spectroscopic measurement device can measure the concentration distribution of oxygenated hemoglobin and the concentration distribution of deoxygenated hemoglobin in the body, and can determine the formation of new blood vessels associated with tumor growth, oxygen saturation of hemoglobin, etc. Used for Further, the spectroscopic measurement device can measure the concentration of fat contained in plaques in blood vessels, and is used for diagnosis of plaque properties (fat degree).
- Patent Document 1 Conventionally, measuring devices for measuring local light absorption characteristics in living tissues have been developed (for example, Patent Document 1 and Patent Document 2).
- the device disclosed in Patent Document 1 irradiates a living tissue with light of a specific wavelength, and obtains the light absorption rate of each part by obtaining a change in sound velocity in the living body during irradiation and during non-irradiation. Moreover, it is also possible to obtain
- Patent Document 2 irradiates a living tissue with pulsed light and instantaneously heats the living tissue, thereby generating an elastic wave generated by a photoacoustic effect generated based on light energy. It is possible to measure the light absorption characteristics of a local region.
- an object of the present invention has been made in view of such a problem, and is to provide an analyzer and the like that can analyze the state of a sample with high accuracy.
- an analyzer that analyzes a state of a sample, and includes a temperature adjustment unit that reduces the temperature of the sample by cooling the sample.
- a light source that heats at least a part of the sample cooled by the temperature control unit by irradiating the sample with light, and a first temperature measurement unit that measures a temperature change of the sample due to heating of the light source;
- an analysis unit for analyzing the state of the sample based on a temperature change of the sample.
- the distribution of the light absorption rate in the specimen is measured with higher accuracy, and the concentration distribution of the desired component with higher accuracy. It is possible to provide an analyzer that can measure the above.
- FIG. 1A is a diagram illustrating a first example of a schematic configuration of the analyzer according to the first embodiment.
- FIG. 1B is a functional block diagram of the analyzer according to the first embodiment.
- FIG. 1C is a flowchart showing the operation of the analyzer according to the first embodiment.
- FIG. 2 is a diagram illustrating a second example of a schematic configuration of the analyzer according to the first embodiment.
- FIG. 3 is a diagram illustrating a third example of a schematic configuration of the analyzer according to the first embodiment.
- FIG. 4 is a diagram illustrating a fourth example of a schematic configuration of the analyzer according to the first embodiment.
- FIG. 5 is a diagram illustrating a fifth example of a schematic configuration of the analyzer according to the first embodiment.
- FIG. 6 is a diagram illustrating a first example of a schematic configuration of the light irradiation apparatus according to the second embodiment.
- FIG. 7 is a diagram illustrating a second example of a schematic configuration of the light irradiation apparatus according to the second embodiment.
- FIG. 8 is a diagram illustrating an example of a schematic configuration of the analyzer according to the third embodiment.
- FIG. 9 is a diagram illustrating an example of a schematic configuration of the analyzer according to the fourth embodiment.
- FIG. 10 is a diagram illustrating an example of a schematic configuration of an analyzer according to the fifth embodiment.
- FIG. 11 is a diagram for explaining the problem of the temperature change of the specimen.
- FIG. 12 is a diagram illustrating an example of a temperature change of a sample in the analyzer according to the fifth embodiment.
- FIG. 13 is a diagram illustrating another example of the temperature change of the specimen in the analyzer according to the fifth embodiment.
- FIG. 14 is a diagram showing a schematic configuration of a conventional spectroscopic measurement apparatus.
- FIG. 15 is a diagram showing a schematic configuration of another conventional spectroscopic measurement apparatus.
- Spectrometers that measure the light absorption characteristics inside living tissues can measure the concentration distribution of various components using light absorption characteristics (relationship between the wavelength of light and the absorption rate) that differ for each substance. It is used for medical diagnosis in many fields.
- a spectroscopic measurement device can measure the concentration distribution of oxygenated hemoglobin and deoxygenated hemoglobin in the body, and can determine the formation of new blood vessels associated with tumor growth, oxygen saturation of hemoglobin, etc.
- the spectroscopic measurement device can measure the concentration of fat contained in plaques in blood vessels, and is used for diagnosis of plaque properties (fat degree).
- Such an apparatus uses near-infrared light having a wavelength of about 600 nm to 1500 nm, which has high transmission characteristics for living tissue.
- the light transmitted through the living tissue propagates while repeating strong scattering by cells of a size of several tens of ⁇ m constituting the living body, it becomes multiple scattered light (diffused light).
- diffused light since all the paths through which the light propagates are not specified, it is difficult to obtain local light absorption characteristics in the living tissue.
- Patent Document 1 Conventionally, measuring devices for measuring local light absorption characteristics in living tissues have been developed (for example, Patent Document 1 and Patent Document 2).
- the device disclosed in Patent Document 1 irradiates a living tissue with light of a specific wavelength, and obtains the light absorption rate of each part by obtaining a change in sound velocity in the living body during irradiation and during non-irradiation. Moreover, it is also possible to obtain
- FIG. 14 is a schematic diagram of an ultrasonic measurement apparatus (spectral measurement apparatus) using spectral characteristics disclosed in Patent Document 1.
- the ultrasonic measurement apparatus 102 includes an ultrasonic probe 102a, a measurement apparatus main body 102b, and a cable 102c that connects the two.
- the measurement apparatus main body 102b transmits an electric signal for vibrating the ultrasonic probe 102a via the cable 102c.
- the ultrasonic pulse generated by the ultrasonic probe 102a is applied to the living body 104, and the ultrasonic pulse reflected by each part in the living body 104 is converted again into an electric signal in the ultrasonic probe 102a and the measurement apparatus main body. 102b. (The reflection of the ultrasonic pulse occurs at the boundary between portions having different densities or sound speeds.)
- the measurement apparatus main body 102b stores an electrical signal from the ultrasonic probe 102a.
- the selective heating light 105 is directed toward the living body 104 using the light source 101 including the laser light source 101a and the optical fiber 101b that guides the laser light generated by the laser light source 101a to the living body. Irradiated.
- the selective heating light 105 light having an optimum wavelength is selected according to the application.
- selective heating light having a wavelength of about 1200 nm having a high fat absorption rate is used.
- the fat concentration distribution can be obtained. It becomes.
- pulsed light is irradiated into a living tissue, and the living tissue is instantaneously heated, so that an elastic wave generated by a photoacoustic effect generated based on light energy is used. It is possible to measure the light absorption characteristics of a local region.
- the apparatus of Patent Document 2 includes a pulse light source 1501 and an ultrasonic measurement apparatus 102 as schematically shown in FIG.
- the above spectroscopic measurement apparatus can be applied to applications other than living organisms (gas component analysis and inspection of foreign matters mixed in foods). Further, as shown in Patent Documents 1 and 2, in addition to the example using ultrasonic waves, an example in which a temperature increase due to light heating is measured by a thermocouple, a radiation thermometer, or the like has been studied.
- an object of the present invention has been made in view of such a problem, and is to provide an analyzer and the like that can analyze the state of a sample with high accuracy.
- an analyzer that analyzes a state of a sample, and includes a temperature adjustment unit that reduces the temperature of the sample by cooling the sample.
- a light source that heats at least a part of the sample cooled by the temperature control unit by irradiating the sample with light, and a first temperature measurement unit that measures a temperature change of the sample due to heating of the light source;
- an analysis unit for analyzing the state of the sample based on a temperature change of the sample.
- the temperature distribution of the specimen can be made substantially uniform, and a part of the specimen can be locally heated by the light source in this state.
- the state of the said location can be analyzed based on the temperature difference with the temperature of the said location when the temperature of the heated location is not heated. That is, the temperature distribution can be made uniform by cooling, and the temperature rise due to heating can be obtained with high accuracy.
- the temperature increase due to heating can be increased by lowering the temperature of the specimen before heating by cooling.
- the blood flow in the sample can be suppressed by cooling, and the movement of the heat quantity in the sample can be suppressed. As a result, information reflecting the state of the part can be obtained in detail. Therefore, the state of the specimen can be analyzed with high accuracy.
- the first temperature measurement unit transmits an ultrasonic pulse to the specimen and receives an ultrasonic wave reflected from the specimen, and the reflection received by the ultrasonic probe.
- An ultrasonic analyzer that measures the temperature of the specimen based on a wave signal, and the analyzer further includes a storage unit that stores the reflected wave signal received by the ultrasonic probe in a storage unit.
- the ultrasonic analysis unit measures the temperature of the specimen based on the reflected wave signal stored in the storage unit.
- the temperature of the specimen can be measured by using the characteristic of the reflected wave of the ultrasonic wave.
- the state of the specimen can be analyzed with higher accuracy by measuring the temperature of the specimen from the reflected wave of the ultrasonic wave received a plurality of times.
- the first temperature measurement unit includes an ultrasonic probe that receives an ultrasonic pulse generated by the sample when the light source heats the sample
- the analysis unit includes a temperature of the sample. The state of the specimen is analyzed based on the change and the intensity of the ultrasonic pulse received by the ultrasonic probe.
- the ultrasonic probe receives the ultrasonic wave generated by the specimen as the part is heated by light irradiation.
- the intensity of this ultrasonic wave changes depending on the state of the part. Therefore, in addition to the temperature change of the specimen, it is possible to analyze the state of the specimen with higher accuracy by using information obtained from ultrasonic waves generated by the specimen with heating.
- the first temperature measurement unit is a radiation thermometer.
- the state of the specimen can be obtained by obtaining the temperature of the specimen without contact with the specimen.
- the temperature adjustment unit is disposed at a position in contact with the sample, a heat absorption unit that absorbs heat from the sample, a heat exchange unit that is disposed in contact with the heat absorption unit and includes Peltier,
- a heat source including a driving power source that supplies driving power for driving the heat exchanging unit to the heat exchanging unit and a fin that is disposed in contact with the heat exchanging unit and that dissipates the amount of heat absorbed from the specimen by the heat exchanging unit.
- the specimen can be efficiently cooled.
- the state of the specimen can be analyzed with higher accuracy.
- the temperature adjustment unit is disposed at a position in contact with a surface of the sample that is close to the light source, is configured of a material that transmits the light, and includes a heat absorption unit that absorbs heat from the sample, The light source irradiates the specimen with light through the heat absorption unit.
- the analysis device includes a second temperature measurement unit that uses a living body as the sample and measures the temperature of the heat absorption unit, and the temperature adjustment unit is further measured by the second temperature measurement unit. Based on the temperature of the heat absorption unit, the driving power is adjusted so that the temperature of the heat absorption unit falls within a temperature range of ⁇ 4 ° C. or more and 30 ° C. or less.
- the light source irradiates the specimen with light including a plurality of wavelength components having different wavelengths.
- the state of the living body can be acquired from a plurality of viewpoints corresponding to the wavelength of light.
- the light source irradiates the specimen with CW (continuous wave laser) light and short pulse light having a pulse width of 0.2 nanoseconds or more and 330 nanoseconds or less at different timings. .
- CW continuous wave laser
- the state of the specimen can be acquired from information obtained from both the temperature rise due to the light irradiation and the ultrasonic wave generated by the specimen by the light irradiation. Therefore, the state of the specimen can be analyzed with higher accuracy.
- the analyzer further includes a multimode fiber that guides light generated by the light source, and the multimode fiber has one or more winding portions in a part of the multimode fiber.
- the sample is irradiated with the uniformed light generated by the light source.
- the temperature of the portion irradiated with light increases uniformly. Therefore, the state of the specimen can be analyzed with higher accuracy.
- the analyzer is further disposed between the ultrasonic probe and the specimen, and has an acoustic impedance of (1.0 to 1.4) ⁇ 10 6 kg / m 2 s, or (1 .6 to 2.25) ⁇ 10 6 kg / m 2 s.
- the temperature of the specimen can be acquired by measuring the time during which the ultrasonic pulse passes through the sonic heat change member.
- the first temperature measurement unit measures at least one of an optical fiber including a fiber grating, a peak reflection wavelength of the fiber grating, and a reflectance of a predetermined wavelength as a reflection characteristic, whereby the specimen A reflection characteristic measuring unit for measuring temperature;
- the temperature of the specimen can be acquired by monitoring the wavelength of the light reflected from the optical fiber provided with the fiber grating.
- the analysis device further includes a water tank that stores water for cooling the specimen
- the temperature control unit further includes a temperature of water in the water tank. Adjust.
- the specimen can be uniformly cooled by the water stored in the water tank.
- the ultrasonic probe includes a piezoelectric body containing crystal, lithium niobate, or lithium tantalate.
- the analysis apparatus uses a living body as the sample, the light source irradiates the sample with light having a wavelength of 1100 nm or more and 1300 nm or less, and the analysis unit sets the state of the sample as the state. The fat concentration of a predetermined part in the living body is measured.
- the fat concentration of the living body can be acquired as the state of the specimen.
- the temperature control unit further raises the temperature of the specimen by heating the specimen.
- the temperature distribution of the specimen can be made uniform by heating the specimen uniformly.
- the temperature control unit includes a microwave transmission source that heats the specimen by irradiating the specimen with microwaves.
- the temperature distribution of the specimen can be made uniform by heating the specimen uniformly by the microwave.
- the ultrasonic probe transmits an ultrasonic pulse to the specimen after the light source irradiates the specimen with light, receives a first reflected wave that is the reflected wave, and the light source
- an ultrasonic pulse is transmitted to the specimen and a second reflected wave that is the reflected wave is received
- the ultrasonic analyzer is configured to transmit the first reflected wave and the second reflected wave.
- the temperature of the specimen is measured as the first temperature and the second temperature.
- the state of the specimen can be acquired based on the temperature of the specimen during heating and after the end of heating at a location heated by light irradiation. After the heating is finished, the amount of change in temperature is large because the temperature rapidly decreases as the amount of heat moves from the location to the periphery. Therefore, since the temperature difference between heating and after heating is large, the state of the specimen can be acquired in more detail.
- the ultrasonic probe receives a first reflected wave and a second reflected wave that are reflected waves from the sample after the light source irradiates the sample with the light, and the ultrasonic analysis unit The temperature of the specimen is measured as the first temperature and the second temperature based on the signals of the first reflected wave and the second reflected wave, respectively.
- the state of the specimen can be acquired based on the temperature of the specimen that is measured at least twice after the end of the heating at the location heated by light irradiation. After the heating is finished, the amount of change in temperature is large because the temperature rapidly decreases as the amount of heat moves from the location to the periphery. Therefore, since the temperature difference between heating and after heating is large, the state of the specimen can be acquired in more detail.
- the ultrasonic probe receives the second reflected wave within 20 seconds after receiving the first reflected wave.
- the ultrasonic probe transmits two ultrasonic pulses having different waveforms to the specimen, and receives the first reflected wave and the second reflected wave as reflected waves of the two ultrasonic pulses. To do.
- the temperature of both the shallow part and the deep part from the surface of the specimen can be measured. Therefore, the state of the specimen can be acquired in more detail.
- a recording medium recording medium such as a system, a method, an integrated circuit, a computer program or a computer-readable CD-ROM, and the system, method, integrated circuit, You may implement
- the light absorption characteristics (light absorption rate) and the heat generation amount of each part are proportional, the light absorption rate and the temperature rise amount are not necessarily uniquely determined. Since the heat capacity and the thermal conductivity are different depending on the structure and material composition of the specimen, the amount of heat transferred from the portion with high heat generation to the portion with low heat generation is different. That is, even if there is a part where the amount of heat generation is particularly large (the light absorption rate is high), if the heat transfer to the surroundings is large, the temperature difference from the surroundings is reduced.
- volume expansion coefficient, heat capacity, or sound speed varies depending on the material composition of the specimen, the relationship between the energy of the elastic wave and the temperature rise is not uniquely determined.
- the analysis device is provided with a function for obtaining at least one of the above-mentioned relationships that cause a decrease in measurement accuracy, thereby improving the accuracy of the analysis results.
- the analysis device suppresses at least one relationship variation (for example, variation between samples or position variation) among the above-described relationships that cause a decrease in measurement accuracy, thereby enabling high accuracy of analysis results.
- a living body such as a human body or an animal is used as a specimen, and the relationship between the light absorption rate and the amount of temperature rise is improved by suppressing the movement of heat due to blood flow, and the light absorption in the specimen is more accurately performed.
- the analyzer which calculates
- FIG. 1A is a diagram illustrating a first example of a schematic configuration of the analyzer 1 according to the present embodiment.
- FIG. 1B is a functional block diagram of the analyzer according to the first embodiment.
- the analysis apparatus 1 includes a light source 101, an ultrasonic measurement apparatus 102, and a specimen contact portion 103.
- the analysis apparatus 1 includes a light source 1a, a first temperature measurement unit 1b, a temperature adjustment unit 1c, an analysis unit 1d, and a storage unit 1e as functional blocks.
- the light source 1a heats at least a part of the specimen cooled by the temperature control unit 1c by irradiating the specimen with light.
- the light source 1a corresponds to the light source 101 in FIG. 1A.
- the 1st temperature measurement part 1b measures the temperature change of the sample by the heating of light source 1a.
- the first temperature measurement unit 1b corresponds to the ultrasonic measurement device 102 in FIG. 1A.
- the temperature control unit 1c cools the specimen to lower the temperature of the specimen.
- the temperature adjustment unit 1c corresponds to the specimen contact unit 103 in FIG. 1A.
- the analysis unit 1d analyzes the state of the sample based on the temperature change of the sample.
- the storage unit 1e stores the signal received by the ultrasonic measurement device 102 in a storage unit (not shown).
- FIG. 1C is a flowchart showing the operation of the analyzer 1 according to the present embodiment.
- the analyzer 1 first cools a living body that is a specimen, and suppresses movement of heat due to blood flow.
- the analyzer 1 measures the speed of sound in the specimen when the selective heating light is irradiated and when it is not irradiated after the living body is sufficiently cooled. Next, the analyzer 1 compares the measured sound velocities and obtains the light absorptance of each part from the change in the sound velocities due to light irradiation, thereby enabling the component concentration distribution measurement.
- the living body 104 is irradiated with the selective heating light 105 having a wavelength of 1100 nm or more and 1300 nm or less, more preferably, a wavelength of about 1200 nm, so that the plaque (intravascular plaque) 106 in the blood vessel is irradiated.
- An analysis apparatus 1 that measures fatness (fat concentration) will be described.
- Adipose tissue has a high light absorptance at a wavelength of about 1200 nm.
- the portion with a high fat concentration in the living body 104 absorbs light having a wavelength of about 1200 nm greatly, and shows a larger temperature rise than the portion with a low fat concentration.
- the propagation speed of sound waves including ultrasonic waves changes according to the temperature change of the medium. Therefore, as described above, the analyzer 1 compares the ultrasonic pulse signals received by the ultrasonic probe 102a when the selective heating light is irradiated and when it is not irradiated, so that the change in the sound speed inside the living body 104 is detected. It becomes possible to obtain the high light absorption rate and to obtain the fat concentration.
- the analyzer 1 by cooling the living body, the blood flow rate is suppressed, and the propagation of heat due to the blood flow is suppressed, whereby the relationship between the light absorption rate and the temperature rise (proportional coefficient). ) Can be suppressed.
- an optical fiber is used as means for guiding laser light emitted from the laser light source 101a to a living body, but an optical system using a lens or a mirror may be used instead.
- the use of an optical fiber is desirable because the light guide means becomes smaller and lighter.
- the light source 101 can be a light source that generates light of a specific wavelength, such as an LED or a lamp with a wavelength filter.
- a specific wavelength such as an LED or a lamp with a wavelength filter.
- an optical fiber is used as the light guide, It is desirable to use a laser light source. By using a laser light source as the light source, an analysis apparatus with lower power consumption can be realized.
- the optical fiber it is desirable to use a multimode fiber as the optical fiber. Moreover, it is desirable for the optical fiber to include a winding portion 101c having at least one turn. As a result, more uniform light irradiation is possible, so that the analyzer can measure the distribution of components in the living body with higher accuracy.
- the specimen contact portion 103 is desirably a material made of a metal such as iron, aluminum or copper, and a material having a high thermal conductivity such as diamond or graphite. Thereby, the temperature of the living body 104 can be lowered at a higher speed. For this reason, since it becomes possible to improve a measurement speed as an analyzer, it is desirable.
- the specimen contact portion 103 has an uneven shape that matches the living body. As a result, higher-speed measurement is possible.
- the temperature adjustment unit includes a heat exchange unit 107 such as a Peltier or a compressor that absorbs heat from the sample contact unit 103, a drive power source 108 that drives the heat exchange unit 107, and heat exchange.
- the unit 107 may include a heat radiating unit 109 that radiates heat absorbed from the specimen contact unit 103.
- the temperature adjustment unit does not include the heat exchanging unit 107 and the specimen contact unit 103 having a large heat capacity is used, a greater cooling effect can be obtained without including the heat exchanging unit, the drive power source, the heat radiating unit, and the like. can get. Therefore, this is a desirable configuration in that a cheaper analyzer can be realized.
- the heat exchange unit 107 driven by the driving power source 108 moves the heat of the specimen contact unit 103 to the fin or the heat radiating unit 109 that combines the fan and the fin, thereby making the analysis lighter and more accurate. This is desirable because it makes it possible to implement the device.
- a temperature measurement unit 110 (also referred to as a first temperature measurement unit) such as a thermistor is installed in the sample contact unit, and the drive power supply 108 is controlled using information on the temperature of the sample contact unit measured by the temperature measurement unit 110. It is desirable. Since it is possible to set the living body 104 to a temperature more suitable for measurement and to suppress the variation for each measurement of the temperature of the living body 104, it is possible to perform measurement with higher reproducibility.
- the analyzer 2 may be configured to irradiate the living body 104 with the selective heating light 105 through the specimen contact portion 201 using the specimen contact portion 201 having a high light transmittance.
- the specimen contact portion 103 is not required to have high light transmission, it is possible to select a material having low thermal conductivity such as copper or aluminum, and an inexpensive apparatus can be selected. This is a desirable configuration in that it becomes possible.
- the analyzer 2 of FIG. 2 since the light intensity is high, the temperature is likely to rise, and as a result, the heat of the living body is deprived from the irradiation surface of the selective heating light 105, which is a portion where blood flow tends to increase. It is possible to lower the temperature of the water more uniformly. For this reason, it becomes possible to uniformly reduce the blood flow volume of the entire specimen from the vicinity of the light irradiation surface to the deep part of the living body. That is, it is possible to measure the component concentration in a wider range and with high accuracy.
- the specimen contact portion 201 is preferably made of a material such as quartz or diamond that has a high thermal resistance and a high transmittance for the selective heating light 105.
- diamond has a high thermal conductivity and is a desirable material for the specimen contact portion in the present embodiment.
- the analyzer 2 of FIG. 2 can measure with high reproducibility by providing the temperature measuring unit 110 as in the case of the analyzer 1.
- a transparent temperature measuring unit is more preferable, and a radiation thermometer is more preferable.
- a radiation thermometer is more preferable.
- This configuration makes it possible to irradiate the living body with the selective heating light 105 more uniformly, so that the component concentration distribution can be measured with higher accuracy.
- the inside of the living body 104 is cooled more uniformly than the analyzing apparatus 2 of FIG. 2 by using the analyzer 3 in which the specimen contact portion 301 is inserted between the ultrasonic probe 102 a and the living body 104. It becomes possible to do. Therefore, it is desirable to cool the entire region more uniformly, so that the analyzer can perform highly accurate measurement.
- the analyzer 3 of FIG. 3 can measure with high reproducibility by providing a temperature measuring unit such as a thermistor, similarly to the analyzer 1 of FIG. 1A.
- the sonic heat change member 302 whose sound speed changes due to temperature change at a location where the ultrasonic pulse radiated from the ultrasonic probe 102a passes.
- the temperature of the specimen contact portion 301 can be obtained only by measuring the time during which the ultrasonic pulse passes through the sonic heat change member 302 by the ultrasonic measurement device 102.
- a material having a large change in sound speed due to temperature change is desirable.
- a material of the sonic heat change member 302 for example, a material such as rubber or resin can be used. Such a material is desirable because an inexpensive and lightweight ultrasonic probe is possible.
- the sonic heat change member 302 it is desirable to use a material having a glass transition point close to room temperature as the material of the sonic heat change member 302, because the sonic change due to temperature change is large and more accurate measurement is possible.
- the material has an acoustic impedance different from that of the living body or the ultrasonic probe.
- the material is desirably 1.4 ⁇ 10 6 kg / m 2 s or less, or 1.6 ⁇ 10 6 kg / m 2 s or more.
- the acoustic impedance of the sonic heat change member is (1.0 to 1.4) ⁇ 10 6 kg / m 2 s or (1.6 to 2.25) ⁇ 10 6 kg / m 2 s. It is more desirable, and a more sensitive ultrasonic probe is possible.
- polyethylene a mixture of silica and acrylic can be used as the sonic heat change material.
- an optical fiber including a fiber grating 401 in a region where the selective heating light 105 is irradiated.
- the fiber grating 401 can be designed so that the reflectance of light of an arbitrary wavelength is high depending on the grating period. Further, since the refractive index of the grating portion changes as the temperature of the fiber grating 401 changes, the wavelength of the reflected light changes.
- it can be used as a temperature measuring means by monitoring the wavelength of the reflected light.
- the fiber grating 401 as a temperature measuring means, it becomes possible to install a temperature measuring unit in a portion through which light and ultrasonic waves pass, so that the temperature can be adjusted with higher accuracy. That is, it is possible to further reduce the occurrence of measurement variations due to temperature variations for each measurement.
- the heat exchanging unit 107 driven by the driving power supply 108 moves the heat of the specimen contact unit to the fin or the heat dissipating unit 109 combining the fan and the fin, thereby reducing the weight. This is desirable because an analyzer can be realized.
- a configuration including a heat exchanging portion made of Peltier and a heat dissipating portion having only fins is desirable. In that case, it is possible to realize an analyzer that can be measured with high accuracy with less vibration.
- a temperature measurement unit such as a thermistor is installed in the sample contact unit and the drive power supply 108 is controlled using information on the temperature of the sample contact unit measured by the temperature measurement unit.
- the living body 104 is set to a temperature more suitable for measurement and variation in the temperature measurement of the living body 104 can be suppressed, measurement with higher reproducibility is possible.
- the analysis apparatus preferably includes means for monitoring the drive current of the laser light source 101a and the output of the selective heating light 105, and after the light heating to the living body is started, the heat exchange unit 107 is provided. It is desirable to increase the driving current to increase the cooling effect. As a result, it is possible to irradiate the living body 104 with the selective heating light 105 having a larger output, and thus it is possible to realize a more accurate analyzer.
- the temperature of the specimen contact portion at the time of measuring the internal structure of the living body by the ultrasonic measuring device is controlled to be ⁇ 4 ° C. or higher. This can prevent frostbite on the skin of the specimen.
- the temperature of the specimen contact portion it is more desirable to control the temperature of the specimen contact portion to be 15 ° C. or higher. In that case, since it becomes possible to supply oxygen required for the cells, even if measurement is performed for a long time, it becomes difficult to feel fatigue due to a decrease in body temperature.
- the temperature of the specimen contact portion it is desirable to control the temperature of the specimen contact portion to be 25 ° C. or lower. In that case, the living body can be cooled without being affected by individual differences in body temperature.
- the temperature of the specimen contact portion 201 is controlled to be room temperature or higher. It becomes possible to prevent dew condensation from occurring in the specimen contact portion, and it is possible to suppress non-uniformity of irradiation of the selective heating light 105 to the living body 104 due to dew condensation. That is, highly reproducible light irradiation is possible, and variation in accuracy for each measurement can be suppressed.
- the temperature of the specimen contact portion 201 is 30 ° C. or lower. Since it is possible to suppress non-uniformity of irradiation of the selective heating light 105 to the living body 104 due to sweating on the skin surface, highly reproducible light irradiation is possible, and variation in accuracy for each measurement can be suppressed. It becomes.
- the temperature of the specimen contact portion 201 is measured so that the temperature does not exceed the temperature after the sweating temperature of the living body that is the subject is measured. It is desirable to adjust.
- an ultrasonic probe using a transparent piezoelectric material it is possible to irradiate a living body with both light and ultrasonic waves from the same location.
- an ultrasonic probe using a bulk type transparent piezoelectric material such as crystal, lithium niobate, lithium tantalate, etc., which are transparent piezoelectric materials
- light irradiation on the contact surface between the ultrasonic probe and the living body can be performed at low cost. Both are possible at the same time. This is desirable because the light intensity in the vicinity of the ultrasonic probe of the living body becomes more uniform and strong, and more accurate and sensitive measurement is possible.
- a transparent piezoelectric material using a single crystal thin film technology such as ZnO (zinc oxide) or AlN (aluminum nitride) because a smaller analyzer can be realized.
- ZnO zinc oxide
- AlN aluminum nitride
- an ultrasonic probe that applies a voltage to the piezoelectric material using a transparent electrode such as ITO (Indium Tin Oxide), which has excellent light transmission characteristics, and has a higher sensitivity and accuracy. Concentration measurement is possible.
- ITO Indium Tin Oxide
- a transparent electrode made of zinc oxide or magnesium it is more desirable to use a transparent electrode made of zinc oxide or magnesium, and it is possible to measure the component concentration with low cost, high sensitivity and high accuracy.
- water 502 is placed in a water tank 501, and the living body 104 placed therein is irradiated with ultrasonic waves from the selective heating light 105 and the ultrasonic probe 102 a, and the inside of the living body 104. It is good also as an analyzer which measures again the ultrasonic wave reflected in by the ultrasonic probe 102a.
- the living body 104 can be cooled by adjusting the temperature of the water 502.
- the temperature of the water 502 is 15 ° C. or higher, and the blood flow that can supply oxygen necessary for cells in the living body is maintained. It becomes difficult to feel tiredness due to a decrease in body temperature.
- the temperature of the water 502 is 25 ° C. or less, and the living body can be cooled without being affected by individual differences in body temperature.
- the liquid has a relatively low viscosity.
- the living body can be effectively cooled by the movement of heat by convection, so that the component concentration can be measured with high accuracy.
- ethanol may be used. Since ethanol has a high bactericidal effect, it does not need to be mixed with preservatives, and because the heat released into the atmosphere by the heat of vaporization is large, the analyzer can adjust the specimen to a low temperature with less energy .
- Water when water is used, an inexpensive analyzer can be realized.
- Water is desirable because it has a refractive index and an acoustic impedance that are comparable to those of a living body, and can irradiate both light and ultrasonic waves with high efficiency. Measurement can be performed without directly pressing the ultrasonic probe 102a against the living body, and the shape of the living body is not deformed by pressing the ultrasonic probe. In comparison with past measurement results, it is desirable because comparison can be made with higher accuracy.
- the analyzer when nicotine is ingested by smoking or passive smoking, it is desirable that the analyzer performs spectroscopic measurement within one and a half hours after ingesting nicotine. Since measurement is possible in a state where the blood flow rate due to nicotine is reduced, highly accurate component concentration measurement is possible.
- a method of reducing the blood flow rate by using an anti-inflammatory analgesic or electrical stimulation may be used.
- the component concentration in a state where the component concentration measurement part and its peripheral part are pressurized. Since the blood flow can be suppressed by pressurization, the component concentration can be measured with high accuracy.
- the analysis device for obtaining the light absorption rate from the amount of change in the temperature of sound velocity has been described.
- the analysis device for obtaining the light absorption rate from the energy of elastic waves as shown in FIG.
- the component concentration in a state in which the living body as the specimen is cooled the movement of heat due to the blood flow can be suppressed, and the component concentration can be measured with higher accuracy.
- an analyzer equipped with a light source capable of driving both pulsed light and CW (continuous wave laser) light and an analyzer equipped with two light sources, a pulse light source and a CW light source, light heating is used. It is desirable to measure both the change in sound velocity and the elastic wave energy, and to measure the component concentration with high accuracy.
- an analyzer that measures the concentration of fat has been described.
- the present invention can be applied to all component concentration measurement using the light heating phenomenon.
- an analyzer that measures the oxygen saturation level of hemoglobin (ratio of oxidized hemoglobin concentration to deoxygenated hemoglobin concentration) using light having a wavelength of 650 nm to 800 nm can be realized.
- it can be applied to the judgment of cancer and benign tumor and the depth diagnosis of burns.
- the absorption rate of light of multiple wavelengths It is desirable to obtain a high-precision component concentration measurement.
- the pulse width of the pulsed light (full width at half maximum of output) is 0.33 ⁇ s or less, which is useful for diagnosing cancer properties.
- the required resolution can be obtained.
- the pulse width of the pulsed light is less than 0.07 ⁇ s, and the resolution necessary for diagnosing the intravascular plaque can be obtained.
- the pulse width of the pulsed light is 0.2 ns or more. In this case, since it is possible to generate an ultrasonic wave having a higher biological transmittance, it is possible to measure a component concentration in a deeper part.
- the present embodiment may be applied to an analyzer that targets other than a living body.
- it can be applied to measurement of foreign matters mixed in food.
- an analysis apparatus that measures the heating by light with an ultrasonic wave.
- the analysis apparatus of the present invention does not necessarily use an ultrasonic wave.
- the same effect can be obtained with the same configuration in an analyzer that measures a temperature change caused by light heating using a thermocouple or a radiation thermometer.
- thermocouple it is desirable to use a thermocouple because it allows for cheaper component concentration measurement.
- thermometer it is desirable to use a radiation thermometer because it enables non-contact measurement of component concentration.
- the analyzer using the change in sound speed due to temperature rise measures the heating by light using ultrasonic waves, which is an inexpensive means that is excellent in straightness in the living body. Therefore, it is desirable because it enables inexpensive component concentration (distribution) measurement with excellent position resolution even inside the living body.
- the analyzer that measures the expansion due to temperature rise as elastic wave energy can detect the difference in light absorption rate (difference in expansion rate) more prominently, and it is inexpensive and has high contrast component concentration (distribution). This is desirable because it enables measurement.
- the configuration in which the specimen contact portion is provided between the ultrasound probe and the specimen (living body) is shown in FIGS. 3 and 4, but the contact surface itself of the ultrasound probe with the living body is the same.
- the specimen contact portion may be configured to absorb the heat of the living body.
- the present invention is effective in an analyzer that utilizes a light heating phenomenon, but is also effective in another device that utilizes light heating.
- hypothermia for the purpose of cancer treatment that heats and kills cancer tissue.
- cancer tissues are weaker than heat compared with normal tissues, and are killed in a few minutes by heating to 46 ° C., for example. However, at 46 ° C., part of the normal tissue is also killed.
- the normal tissue can be suppressed to 42 ° C. and only the cancer tissue can be heated to 46 ° C., only the cancer tissue can be killed without damaging the normal tissue.
- FIG. 6 is a diagram illustrating a first example of a schematic configuration of the light irradiation device 6 according to the present embodiment.
- the light irradiation device 6 in FIG. 6 includes a light source 101 and a specimen contact unit 103 as in the analysis device 1 of the first embodiment.
- the living body 603 is irradiated with the selective heating light 602 generated by the light source 101 in a state where the heat of the living body 603 is absorbed by the specimen contact unit 103 and the temperature of the living body 603 is lowered.
- the living body 603 is a part including a cancer tissue 601 such as a breast or a prostate.
- the light source 101 generates light in which the light absorption rate of cancer tissue is higher than that of normal tissue.
- a laser light source or an LED that generates selective heating light 602 having a wavelength of 600 nm to 800 nm is used.
- the selective heating light 602 can selectively heat the cancer tissue 601 in the living body 603.
- the light irradiation device 6 has an effect of suppressing blood flow by reducing the temperature of the living body, and can increase the temperature of only the cancer tissue 601 more selectively. Become. As a result, when the cancer tissue 601 is killed, the number of normal tissues killed at the same time can be reduced.
- FIG. 7 is a diagram showing a second example (light irradiation device 7) of the schematic configuration of the light irradiation device according to the present embodiment.
- the light irradiation device 7 in FIG. 7 is a light irradiation device for the purpose of cancer treatment, similar to the light irradiation device 6 in FIG.
- the light irradiation apparatus 7 irradiates the living body 603 with the selective heating light 602 generated by the light source 101 in a state where the specimen contact portion 201 absorbs the heat of the living body 603 and the temperature of the living body 603 is lowered.
- the selective heating light 602 is irradiated to the living body 603 through the specimen contact portion 201.
- the specimen contact portion 201 is configured with a member that transmits the selective heating light 602.
- the living body 603 can be efficiently irradiated with the selective heating light 602. It becomes power consumption.
- the specimen contact portion 201 is made of a transparent material having a high thermal conductivity, such as diamond, the cooling effect on the living body 603 can be further enhanced, so that the normal tissue to be killed is further reduced. Can be reduced.
- the specimen contact unit 201 preferably includes a heat exchange unit 107, a drive power supply 108, and a heat dissipation unit 109. This makes it possible to reduce the number of normal tissues that are killed.
- the specimen contact portion 103 is not required to have high light transmittance, it is possible to select inexpensive and high thermal conductivity materials such as aluminum and copper, and thus inexpensive light. This configuration is desirable in that an irradiation apparatus can be used.
- the light irradiation device 7 in FIG. 7 takes away the heat of the living body from the light irradiation surface where the light intensity is high and the temperature easily rises in the living body, the temperature in the living body can be made more uniform. For this reason, it becomes possible to reduce the blood flow volume in the entire region from the vicinity of the light irradiation surface to the deep part of the specimen. In particular, this is a desirable configuration when cancer tissue near the light irradiation surface is killed. Further, since the surface to be irradiated with light and the surface to be cooled by the specimen contact portion 201 are in the same direction, it can be applied to a thick (large) living body part as a specimen, which is desirable.
- the light irradiation device 7 of the present embodiment kills cancer tissue more selectively by the same configuration as that of the analysis device 1 of the first embodiment for controlling the blood flow in the living body. This is desirable because
- the temperature depends on the material composition and composition ratio of each part. It aims at suppressing the fall of the measurement precision by the proportionality coefficient between change and sound speed change differing.
- the speed of sound and the proportionality coefficient between the temperature change and the sound speed change vary depending on the substance.
- the speed of sound propagating in water is 1483 m / s at 24 ° C. and 1530 m / s at 37 ° C. Accordingly, the sound velocity temperature change coefficient is 3.6 m / s / ° C.
- the speed of sound propagating in the adipose tissue is 1476 m / s at 24 ° C. and 1412 m / s at 37 ° C. Therefore, the sound speed temperature change coefficient is -4.9 m / s / ° C.
- the sound velocity and the sound velocity temperature change coefficient differ depending on the concentrations of moisture and fat.
- a living body for the purpose of measuring a fat concentration distribution in a living body, an analysis in which a living body is irradiated with light having a wavelength of about 1200 nm as in the first embodiment, and a change in sound speed of each part is measured with an ultrasonic probe.
- the sound speed change is not proportional to the temperature change. That is, depending on the component ratio of components other than fat, the sound velocity temperature change coefficient is affected differently depending on the location.
- FIG. 8 is a diagram showing an example of a schematic configuration of the analyzer 8 according to the present embodiment.
- a light source 101 includes a light source 101, an ultrasonic measurement device 102, a specimen contact unit 801, a heat exchanging unit 107, and a drive power source 108.
- the analyzer 8 uses a measurement method different from that of the first embodiment.
- the analyzer 8 performs measurement in the following order in a state where the ultrasonic probe 102a and the specimen contact unit 801 are brought into contact with the living body 104 in advance.
- the analyzer 8 performs ultrasonic sound velocity measurement at least three times as described above.
- the living body 104 is heated and not heated (or cooled) using the specimen contact portion 801, the drive power source 108, and the heat exchange portion 107.
- the ultrasonic pulse signals reflected from inside the living body 104 at the time and at the time of non-cooling are compared. Since the temperature change of the living body 104 using the heating (cooling) method is independent of the composition of each part in the living body 104 and its concentration, the temperature of each part in the living body 104 is uniformly heated (cooled). Is possible.
- ultrasonic sound velocity measurement (first time) during uniform non-heating (uniform non-cooling) and non-selective heating
- ultrasonic wave during uniform heating (uniform cooling) and non-selective heating
- the sound velocity temperature change coefficient is obtained by comparing the sound velocity of each part in the living body 104 with the sound velocity measurement (second time).
- ultrasonic sound velocity measurement (second time) during uniform heating (uniform cooling) and selective heating light irradiation, and uniform heating (uniform)
- the ultrasonic pulse signal reflected from the living body 104 is compared with the ultrasonic sound velocity measurement (third time) at the time of (cooling) and without the selective heating light irradiation.
- Light of a specific wavelength is irradiated to generate a heat generation (temperature rise) distribution according to a desired material concentration, and a change in sound velocity due to a temperature change in each part is obtained.
- the analyzer 8 includes means (steps) for obtaining a sonic temperature change coefficient, so that the temperature rise closer to the actual condition can be obtained from the change in the sonic speed when the selective heating light is irradiated or not. Since the quantity distribution can be calculated, the component concentration can be detected with higher accuracy.
- the sound velocity change coefficient can be obtained with higher accuracy, and therefore, component concentration can be measured with higher accuracy.
- the same effect can be obtained in the present embodiment by using an improved configuration such as the location where the temperature measuring means and the heating / cooling means are brought into contact with the living body and the respective constituent materials as shown in the first embodiment. Play.
- the selective heating light 105 having a wavelength of 1100 nm or more and 1300 nm or less, more preferably about 1200 nm, and measure the fat degree of the intravascular plaque 106. It becomes.
- uniform cooling is performed because the effect shown in the first embodiment by suppressing blood flow is also achieved by uniform cooling. It is more desirable.
- the optical fiber is used as means for guiding the laser light emitted from the laser light source 101a to the living body, but an optical system using a lens or a mirror may be used instead.
- an optical fiber is desirable because the light guide means becomes smaller and lighter.
- the light source 101 may be a light source that generates light of a specific wavelength, such as an LED or a lamp with a wavelength filter.
- a specific wavelength such as an LED or a lamp with a wavelength filter.
- the optical fiber has at least one turn of the winding portion 101c.
- the analyzer can measure the component concentration in the living body with high accuracy.
- the specimen contact portion 801 is desirably a material made of a metal such as iron, aluminum or copper, and a material having a high thermal conductivity such as diamond or graphite. Thereby, the temperature of the living body 104 can be lowered at a higher speed. For this reason, since it becomes possible to improve a measurement speed as an analyzer, it is desirable.
- the specimen contact portion 801 desirably has an uneven shape that matches the living body, and further enables high-speed measurement.
- the temperature tends to rise due to high light intensity, and as a result, the living body heat is taken away from the irradiation surface of the selective heating light 105, which is a portion where blood flow is likely to increase, so that the temperature inside the living body can be lowered more uniformly. It becomes possible to make it. For this reason, it becomes possible to uniformly reduce the blood flow volume of the entire specimen from the vicinity of the light irradiation surface to the deep part of the living body. That is, it is possible to measure the component concentration in a wider range and with high accuracy.
- the specimen contact portion 801 does not require high light transmittance, it is possible to select an inexpensive and high thermal conductivity material such as copper or aluminum, which is inexpensive. This configuration is desirable in that the apparatus can be used.
- a material such as quartz or diamond having a high thermal resistance and a high transmittance of the selective heating light 105 is desirable.
- diamond has a high thermal conductivity and is a desirable material for the specimen contact portion in the present embodiment.
- a transparent temperature measurement part is more desirable, and it is more desirable to use a radiation thermometer. This is desirable because it is possible to measure the surface temperature of the living body regardless of the contact (contact thermal resistance) between the living body and the specimen contact portion, and the response speed is also high.
- the inside of the living body 104 is further heated uniformly by adopting a configuration in which the specimen contact portion is inserted between the ultrasonic probe 102a and the living body 104.
- it is further desirable because it becomes an analyzer capable of measuring with higher accuracy.
- a sonic heat change member whose sound speed changes due to a temperature change is installed at a location where an ultrasonic pulse radiated from the ultrasonic probe 102a passes. It is more desirable.
- the sonic heat change member a material having a large sonic change due to a temperature change is desirable as in the first embodiment.
- a material of the sonic heat change member for example, a material such as rubber or resin is preferably used because an inexpensive and lightweight ultrasonic probe can be obtained.
- the material has an acoustic impedance different from that of the living body or the ultrasonic probe, and in particular, 1.4 ⁇ 10 6 kg / m 2 s or less. Or a material of 1.6 ⁇ 10 6 kg / m 2 s or more.
- reflection of a larger ultrasonic pulse occurs at the boundary surface between the sonic heat change member and the living body and the boundary surface between the ultrasonic probe, so that the temperature can be measured with high accuracy.
- the acoustic impedance of the sonic heat change member is (1.0 to 1.4) ⁇ 10 6 kg / m 2 s, or (1.6 to 2.25) ⁇ 10 6 kg / m 2 s is more desirable, and a more sensitive ultrasonic probe is possible.
- polyethylene a mixture of silica and acrylic can be used as the sonic heat change material.
- thermometer It is desirable that an inexpensive temperature measurement means can be realized and an inexpensive analyzer can be provided as compared with the case where a thermistor or a radiation thermometer is used.
- an optical fiber including a fiber grating in the region where the selective heating light is irradiated. By monitoring the wavelength of the reflected light, it can be used as a temperature measuring means.
- the fiber grating as a temperature measuring means, it becomes possible to install the temperature measuring means in a portion through which light and ultrasonic waves pass, so that the temperature can be adjusted with higher accuracy. That is, it is possible to further reduce the occurrence of measurement variations due to temperature variations for each measurement.
- the temperature of the specimen contact portion at the time of measuring the internal structure of the living body by the ultrasonic measuring device is controlled to be ⁇ 4 ° C. or higher. This can prevent frostbite of the skin.
- the temperature of the specimen contact portion it is more desirable to control the temperature of the specimen contact portion to be 15 ° C. or higher. In that case, since it becomes possible to supply oxygen required for the cells, even if measurement is performed for a long time, it becomes difficult to feel fatigue due to a decrease in body temperature.
- the temperature of the specimen contact portion it is desirable to control the temperature of the specimen contact portion to be 25 ° C. or lower. In that case, the living body can be cooled without being affected by individual differences in body temperature.
- the temperature of the specimen contact portion when the selective heating light is irradiated through the specimen contact portion, it is desirable to control the temperature of the specimen contact portion to be room temperature or higher. It becomes possible to prevent dew condensation from occurring in the specimen contact portion, and it is possible to suppress non-uniformity of selective heating light irradiation to the living body due to dew condensation. That is, highly reproducible light irradiation is possible, and variation in accuracy for each measurement can be suppressed. In this case, it is desirable to control the temperature of the specimen contact portion to be 30 ° C. or lower. Because it is possible to suppress non-uniformity of selective heating light irradiation to the living body due to sweating on the skin surface, it is possible to perform light irradiation with high reproducibility and suppress variation in accuracy for each measurement. .
- the temperature of the specimen contact part should not be exceeded. It is desirable to adjust.
- an ultrasonic probe using a transparent piezoelectric material it is possible to irradiate a living body with both light and ultrasonic waves from the same location.
- an ultrasonic probe using a bulk type transparent piezoelectric material such as crystal, lithium niobate, lithium tantalate, etc., which are transparent piezoelectric materials
- light irradiation on the contact surface between the ultrasonic probe and the living body can be performed at low cost. Both are possible at the same time. This is desirable because the light intensity in the vicinity of the ultrasonic probe of the living body becomes more uniform and strong, and more accurate and sensitive measurement is possible.
- an ultrasonic probe that applies a voltage to the piezoelectric material using a transparent electrode such as ITO having excellent light transmission characteristics, and it becomes possible to measure the component concentration with high sensitivity and high accuracy.
- a transparent electrode made of zinc oxide or magnesium it is more desirable to use a transparent electrode made of zinc oxide or magnesium, and it is possible to measure the component concentration with low cost, high sensitivity and high accuracy.
- the living body placed in the temperature-controlled water in the water tank is irradiated with selective heating light, and an ultrasonic probe is used. It is desirable to transmit and receive sound wave pulses, it is possible to keep the entire living body at a more uniform temperature, it is possible to measure the sound velocity temperature change coefficient with higher accuracy, and more accurate component concentration measurement is possible Become.
- the temperature of the water be 15 ° C. or higher, and the blood flow that can supply the necessary oxygen to cells in the living body is maintained. It becomes difficult to feel fatigue due to the decrease.
- the temperature of the water is 25 ° C. or less, and the living body can be cooled without being affected by individual differences in body temperature.
- the liquid has a relatively low viscosity.
- the living body can be effectively cooled by the movement of heat by convection, so that the component concentration can be measured with high accuracy.
- ethanol may be used. Since ethanol has a high bactericidal effect, it is not necessary to mix preservatives.
- Water when water is used, an inexpensive analyzer can be realized.
- Water is desirable because it has a refractive index and an acoustic impedance that are comparable to those of a living body, and can irradiate both light and ultrasonic waves with high efficiency. Measurement can be performed without directly pressing the ultrasonic probe 102a against the living body, and the shape of the living body is not deformed by pressing the ultrasonic probe. In comparison with past measurement results, it is desirable because comparison can be made with higher accuracy.
- an analyzer that measures the concentration of fat has been described.
- the present invention can be applied to all component concentration measurement using the light heating phenomenon.
- an analyzer that measures the oxygen saturation level of hemoglobin (ratio of oxidized hemoglobin concentration to deoxygenated hemoglobin concentration) using light having a wavelength of 650 nm to 800 nm can be realized.
- it can be applied to the judgment of cancer and benign tumor and the depth diagnosis of burns.
- the absorption rate of light of multiple wavelengths It is desirable to obtain a high-precision component concentration measurement.
- the present embodiment may be applied to an analyzer that targets other than a living body.
- the present invention can be applied to an example of measuring foreign matters mixed in food or detecting the concentration of components contained in gas.
- an analysis apparatus that measures the heating by light with an ultrasonic wave.
- the analysis apparatus of the present invention does not necessarily use an ultrasonic wave.
- an effect of suppressing a measurement error due to a difference in the radiation spectrum measured by the radiation thermometer depending on the material composition can be obtained.
- Use of a radiation thermometer is desirable because it enables non-contact measurement of component concentration.
- the analyzer using the change in sound speed due to temperature rise measures the heating by light using ultrasonic waves, which is an inexpensive means that is excellent in straightness in the living body. This is desirable because it enables inexpensive component concentration measurement with excellent position resolution even inside the living body.
- the configuration in which the specimen contact portion is provided between the ultrasound probe and the specimen (living body) has been described.
- the living body is heated by using the contact surface itself of the ultrasound probe as the specimen contacting section. It may have a function of (cooling) and may have a multi-configuration.
- the sound velocity during selective heating light irradiation and non-irradiation is calculated.
- the temperature rise distribution (component concentration distribution) closer to the actual condition can be measured from the change (uniform cooling cannot be performed in this embodiment).
- the present embodiment is different from the third embodiment in the uniform heating means.
- uniform heating is performed by irradiating the living body 104 with the microwave generated by the microwave transmission source 901.
- the microwave Compared to near-infrared light (wavelength 600 nm to 1500 nm) used as selective heating light, the microwave has a smaller difference in absorption rate depending on the material composition of each part in the living body 104 and can be used as a uniform heating means. .
- a living body when used as a specimen, uniform heating is possible by irradiating the living body with microwaves around 2.45 GHz, specifically, 2 to 3 GHz, which have a high water absorption rate. desirable.
- microwaves of 3 to 7 GHz or 1 to 2 GHz it is desirable to irradiate the living body with microwaves of 3 to 7 GHz or 1 to 2 GHz, so that the living body can be uniformly heated to a deeper portion than when irradiated with microwaves of 2 to 3 GHz.
- the analyzer of the present embodiment enables highly accurate component concentration measurement by the same operation as in the third embodiment.
- the uniform heating means using microwaves as in the present embodiment enables high accuracy even in a spectroscopic measurement apparatus that measures component concentration from the energy of elastic waves as shown in FIG.
- the analyzer provided with the means for cooling the specimen of the first embodiment, it is possible to irradiate a living body with higher-output microwaves, and more accurately measure the concentration of components. Is possible.
- FIG. 10 shows an example of a schematic configuration of the analysis apparatus 10 of the present embodiment.
- the analysis device 10 includes a light source 101, an ultrasonic measurement device 102, and a signal transmission line 1001.
- the living body 104 is irradiated with selective heating light 1202 having a wavelength of 1100 nm or more and 1300 nm or less, and more preferably, a wavelength of about 1200 nm.
- selective heating light 1202 having a wavelength of 1100 nm or more and 1300 nm or less, and more preferably, a wavelength of about 1200 nm.
- An analyzer that measures fatness (fat concentration) is used.
- a sound velocity change (temperature change) in the living body 104 is obtained by measuring and comparing the sound speed of each part in the living body 104 when the selective heating light 1002 is irradiated and not irradiated by the light source 101 with the ultrasonic measuring device 102. It becomes possible. Thereby, a desired component concentration distribution in the living body 104 can be obtained.
- the light source 101 and the ultrasonic measurement apparatus 102 are connected by the signal transmission line 1001, the timing at which the living body 104 is irradiated with the selective heating light 1002, and the superposition to the living body 104. It is possible to more accurately adjust the timing for measuring the speed of sound in the living body 104 by transmitting and receiving sound wave pulses.
- the analysis apparatus 10 for example, as shown in FIG. 12, from ultrasonic sound speed measurement (first time) 1201 (or start of selective light heating 1102) to ultrasonic sound speed measurement (second time) 1202. It is desirable to shorten the time. Thereby, it is possible to suppress a decrease in measurement accuracy due to a positional deviation between the living body and the ultrasonic probe, and to measure a component concentration with higher accuracy.
- ultrasonic sound velocity measurement (first time) 1301 is performed immediately before the end of selective light heating 1102, and ultrasonic sound velocity measurement (second time) is performed immediately after the end of selective light heating 1102. It is more desirable to implement 1302. Immediately after the start of the selective light heating 1102, the temperature 1304 of the portion (peripheral part) other than the plaque 106 also rises in the same manner, but immediately after the selective light heating 1102 ends, the peripheral part is compared with the decrease in the temperature 1305 of the plaque 106. Since the decrease in the temperature 1304 is small, it is possible to measure the component concentration with higher contrast by measuring the ultrasonic velocity at the timing shown in FIG.
- the ultrasonic probe 102a in the case where ultrasonic sound velocity measurement is performed at a timing when the time change of the temperature 1205 (or 1305) of the plaque 106 is large, as the ultrasonic probe 102a, a convex type, an electronic sector type, an electron It is desirable to use a linear type or an ultrasonic probe in which transducers are arranged two-dimensionally. In that case, more accurate component concentration measurement can be performed by high-speed ultrasonic sound velocity measurement.
- the temperature 1205 (or 1305) depends on the size of the plaque 106 and the blood flow around the plaque 106.
- the time constant of change is different. For this reason, it is desirable to perform ultrasonic sound velocity measurement (third time) 1203 and 1303 within 10 seconds from ultrasonic sound velocity measurement (second time) 1202 or 1302. As a result, the time constant for each plaque can be obtained, and the component concentration can be measured with high accuracy.
- ultrasonic sound velocity measurement is performed a plurality of times within 20 seconds, and at least two ultrasonic sound velocity measurement results are compared to obtain a sound velocity change distribution.
- 20 seconds is a time during which breathing can be stopped regardless of individual differences, and it is possible to suppress the occurrence of measurement errors due to breathing.
- each component may be configured by dedicated hardware or may be realized by executing a software program suitable for each component.
- Each component may be realized by a program execution unit such as a CPU or a processor reading and executing a software program recorded on a recording medium such as a hard disk or a semiconductor memory.
- the software that realizes the analyzers of the above-described embodiments is a program as follows.
- this program is an analysis method for analyzing the state of a sample on a computer, by adjusting the temperature of the sample by cooling the sample and irradiating the sample with light.
- a heating step of heating at least a part of the specimen cooled in the temperature adjustment step, a first temperature measurement step of measuring a temperature change of the specimen due to heating in the heating step, and a temperature change of the specimen And an analysis step for analyzing the state of the specimen.
- the analyzer according to one or more aspects of the present invention has been described based on the embodiment, the present invention is not limited to this embodiment. Unless it deviates from the gist of the present invention, one or more of the present invention may be applied to various modifications that can be conceived by those skilled in the art, or forms constructed by combining components in different embodiments. It may be included within the scope of the embodiments.
- the analyzer according to the present invention can be applied to liver fat concentration measurement, intravascular plaque property diagnosis, tumor property diagnosis, gas component distribution measurement, and the like. This is a useful means for improving the accuracy of these measurements.
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Abstract
Description
本発明者は、「背景技術」の欄において記載した分光計測装置等に関し、以下の問題が生じることを見出した。
本実施の形態は、人体や動物などの生体を検体とし、血流による熱の移動を抑制することにより光吸収率と温度上昇量との関係性を高め、より高精度に検体内の光吸収率の分布を求める分析装置の例である。
(2)[超音波音速計測工程(一回目)(S102)]
(3)[選択光加熱工程(開始)(S103)]
(4)[超音波音速計測工程(二回目)(S104)]
(5)[音速変化計算工程(S)105]
本発明は、実施の形態1に示したように、光加熱現象を利用した分析装置において有効であるが、光加熱を利用した別の装置においても効果を発揮する。
本実施の形態では、特定の波長の光で検体を加熱し、各部の吸光特性の違いによる温度上昇量の違いを音速の変化として計測する分析装置において、各部の材料組成や構成比によって、温度変化と音速変化の間の比例係数が異なることによる計測精度の低下を抑制することを目的とする。
(2)[均一加熱・冷却開始]:駆動電源108を用いて、熱交換部107による生体104の加熱(又は、冷却)を開始する。
(3)[超音波音速計測工程(二回目)]
(4)[選択光加熱開始]
(5)[超音波音速計測工程(三回目)]
(6)[音速変化計算(一回目)]:(1)と(3)で得られた生体104から反射してきた超音波パルス波形(電気信号)を比較し、(2)の工程の前後の生体104内各部の音速変化量を求める。
(7)[音速変化計算(二回目)]:(3)と(5)で得られた生体104から反射してきた超音波パルス波形(電気信号)を比較し、(2)の工程の前後の生体104内各部の音速変化量を求める。
(8)[温度上昇量計算]:(6)の結果から、生体104内の各位置の音速温度変化係数を求めて、(7)の結果と、音速温度変化係数から生体104内の各位置の温度上昇量を求める。
本実施の形態では、実施の形態3と同様に、特定の波長の光で検体を加熱し、各部の光吸収率の違いによる温度上昇量の違いを音速の変化として計測する分析装置において、各部の材料組成や構成比によって、温度変化と音速変化の間の比例係数が異なることによる計測精度の低下を抑制する例について示す。
図14に示すような分光計測装置では、図11に示すように、超音波音速計測(一回目)1101の後、選択加熱光照射による選択光加熱1102を開始する。その後、生体104内のプラーク106の温度1105が十分上昇し、発熱と放熱が均衡することで、温度の時間変化が小さくなるタイミングで、超音波音速計測(二回目)1103を実施していた。
1a、101 光源
1b、110 第一温度計測部
1c 調温部
1d 分析部
1e 格納部
6、7 光照射装置
101a レーザ光源
101b、1501b 光ファイバ
101c 光ファイバの巻き部
102、1502 超音波計測装置
102a 超音波プローブ
102b 計測装置本体
102c ケーブル
103、201、301、801 検体接触部
104、603 生体
105、602、1002 選択加熱光
106 プラーク
107 熱交換部
108 駆動電源
109 放熱部
302 音速熱変化部材
401 ファイバグレーティング
501 水槽
502 水
601 癌組織
901 マイクロ波発信源
1001 信号伝送線
1101 超音波音速計測(一回目)
1102 選択光加熱
1103 超音波音速計測(二回目)
1104、1204、1304 周辺部の温度
1105、1205、1305 プラークの温度
1201 超音波音速計測(一回目)
1202 超音波音速計測(二回目)
1203 超音波音速計測(三回目)
1301 超音波音速計測(一回目)
1302 超音波音速計測(二回目)
1303 超音波音速計測(三回目)
1501 パルス光源
1501a パルスレーザ光源
1502 選択加熱パルス光
Claims (22)
- 検体の状態を分析する分析装置であって、
前記検体を冷却することで、前記検体の温度を低下させる調温部と、
前記検体に光を照射することで、前記調温部により冷却された前記検体の少なくとも一部を加熱する光源と、
前記光源の加熱による前記検体の温度変化を計測する第一温度計測部と、
前記検体の温度変化に基づいて前記検体の状態を分析する分析部とを備える
分析装置。 - 前記第一温度計測部は、
前記検体に超音波パルスを送信し、前記超音波パルスの前記検体からの反射波を受信する超音波プローブと、
前記超音波プローブが受信した前記反射波の信号に基づいて前記検体の温度を計測する超音波分析部とを有し、
前記分析装置は、さらに、
前記超音波プローブが受信した前記反射波の信号を記憶部に格納する格納部を備え、
前記超音波分析部は、前記記億部に格納された前記反射波の信号に基づいて前記検体の温度を計測する
請求項1に記載の分析装置。 - 前記第一温度計測部は、
前記光源が前記検体を加熱するときに、前記検体が発生させる超音波パルスを受信する超音波プローブを有し、
前記分析部は、
前記検体の温度変化と、前記超音波プローブが受信した前記超音波パルスの強度とに基づいて、前記検体の状態を分析する
請求項1に記載の分析装置。 - 前記第一温度計測部は、放射温度計である
請求項1に記載の分析装置。 - 前記調温部は、
前記検体に接する位置に配置され、前記検体から熱量を吸収する熱吸収部と、
前記熱吸収部に接して配置され、ペルチエを含む熱交換部と、
前記熱交換部を駆動させるための駆動電力を前記熱交換部に供給する駆動電源と、
前記熱交換部に接して配置され、前記熱交換部が前記検体から吸収した熱量を放熱するフィンを含む放熱部とを有する
請求項1~4のいずれか1項に記載の分析装置。 - 前記調温部は、
前記検体の前記光源に近い面に接する位置に配置され、前記光を透過する材料で構成され、前記検体から熱量を吸収する熱吸収部を有し、
前記光源は、前記熱吸収部を通して前記検体に光を照射する
請求項1~4のいずれか1項に記載の分析装置。 - 前記分析装置は、
生体を前記検体とし、
前記熱吸収部の温度を計測する第二温度計測部を備え、
前記調温部は、さらに、
前記第二温度計測部が計測した前記熱吸収部の温度に基づいて、前記熱吸収部の温度を-4℃以上、かつ、30℃以下の温度範囲内に収めるように、前記駆動電力を調節する
請求項5に記載の分析装置。 - 前記光源は、互いに異なる波長を有する複数の波長成分を含む光を前記検体に照射する
請求項1~7のいずれか1項に記載の分析装置。 - 前記光源は、
CW(continuous wave laser)光と、0.2ナノ秒以上、かつ、330ナノ秒以下のパルス幅を有する短パルス光とを、互いに異なるタイミングで前記検体に照射する
請求項3に記載の分析装置。 - 前記分析装置は、さらに、
前記光源が生成する光を導光するマルチモードファイバを備え、
前記マルチモードファイバは、前記マルチモードファイバの一部に1巻き以上の巻き部を有する
請求項1~9のいずれか1項に記載の分析装置。 - 前記分析装置は、さらに、
前記超音波プローブと前記検体との間に配置され、音響インピーダンスが(1.0~1.4)×106kg/m2s、又は、(1.6~2.25)×106kg/m2sである音速熱変化部材を備える
請求項2又は3に記載の分析装置。 - 前記第一温度計測部は、
ファイバグレーティングを含む光ファイバと、
前記ファイバグレーティングのピーク反射波長と、所定波長の反射率との少なくとも一方を反射特性として計測することで、前記検体の温度を計測する反射特性計測部とを有する
請求項1~11のいずれか1項に記載の分析装置。 - 前記分析装置は、さらに、
防腐剤を含む水であって、前記検体を冷却するための水を貯留する水槽を備え、
前記調温部は、さらに、
前記水槽内の水の温度を調節する
請求項1に記載の分析装置。 - 前記超音波プローブは、
水晶、ニオブ酸リチウム、又は、タンタル酸リチウムを含む圧電体を備える
請求項2又は3に記載の分析装置。 - 前記分析装置は、
生体を前記検体とし、
前記光源は、1100nm以上、かつ、1300nm以下の波長を有する光を前記検体に照射し、
前記分析部は、
前記検体の状態として、前記生体内の所定の部位の脂肪濃度を計測する
請求項1~14のいずれか1項に記載の分析装置。 - 前記調温部は、さらに、
前記検体を加熱することで、前記検体の温度を上昇させる
請求項1~15のいずれか1項に記載の分析装置。 - 前記調温部は、
前記検体にマイクロ波を照射することで、前記検体を加熱するマイクロ波発信源を有する
請求項16に記載の分析装置。 - 前記超音波プローブは、
前記光源が前記検体に前記光を照射した後に、前記検体に超音波パルスを送信し、前記反射波である第一反射波を受信し、
前記光源が前記検体に前記光を照射している時に、前記検体に超音波パルスを送信し、前記反射波である第二反射波を受信し、
前記超音波分析部は、
前記第一反射波及び前記第二反射波の信号それぞれに基づいて、前記検体の温度を前記第一温度及び前記第二温度として計測する
請求項2に記載の分析装置。 - 前記超音波プローブは、
前記光源が前記検体に前記光を照射した後に、前記検体からの反射波である第一反射波及び第二反射波を受信し、
前記超音波分析部は、
前記第一反射波及び前記第二反射波の信号それぞれに基づいて、前記検体の温度を前記第一温度及び前記第二温度として計測する
請求項2に記載の分析装置。 - 前記超音波プローブは、
前記第一反射波を受信してから20秒以内に、前記第二反射波を受信する
請求項18又は19に記載の分析装置。 - 前記超音波プローブは、
互いに異なる波形の2つの超音波パルスを前記検体に送信し、当該2つの超音波パルスの反射波として、前記第一反射波及び前記第二反射波を受信する
請求項18又は19に記載の分析装置。 - 検体の状態を分析する分析方法であって、
前記検体を冷却することで、前記検体の温度を低下させる調温ステップと、
前記検体に光を照射することで、前記調温ステップにおいて冷却された前記検体の少なくとも一部を加熱する加熱ステップと、
前記加熱ステップにおける加熱による前記検体の温度変化を計測する第一温度計測ステップと、
前記検体の温度変化に基づいて前記検体の状態を分析する分析ステップとを含む
分析方法。
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JP2011072701A (ja) * | 2009-10-01 | 2011-04-14 | Konica Minolta Medical & Graphic Inc | 超音波診断装置、超音波診断システム及び超音波診断用プログラム |
JP2011083363A (ja) * | 2009-10-14 | 2011-04-28 | Konica Minolta Medical & Graphic Inc | 超音波プローブ、及び超音波診断装置 |
WO2011074217A1 (ja) * | 2009-12-18 | 2011-06-23 | パナソニック株式会社 | 成分濃度計、成分濃度測定方法、出荷検査システム、及び健康管理システム |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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TWI493169B (zh) * | 2013-01-18 | 2015-07-21 | Univ Nat Cheng Kung | 評估皮膚生理參數濃度及分布之光學系統及其方法 |
JP2017012692A (ja) * | 2015-07-06 | 2017-01-19 | キヤノン株式会社 | 光音響装置、情報取得装置、情報取得方法、およびプログラム |
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CN103096810A (zh) | 2013-05-08 |
US20130172741A1 (en) | 2013-07-04 |
JPWO2013008447A1 (ja) | 2015-02-23 |
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