JP2006180902A - Noninvasive biological information measuring apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To stabilize the contact pressure of an interface head to a subject. <P>SOLUTION: This apparatus comprises: the interface head 17 provided with an irradiation part 10 for irradiating the subject with single-color light or light close to it and a detection part 11 for detecting acoustic signals radiated from the inside of the subject by irradiation light; a signal processing part 6 for generating biochemical information or physical property information relating to substances present on the surface or in the inside of the subject by processing detection signals; a piezoelectric actuator 18 for supporting the interface head freely movably in the direction of approaching/separating from the subject; a contact pressure detection part 15 for detecting the contact pressure of the interface head to the subject; and a control part 3 for controlling a support part on the basis of the detected contact pressure. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to an apparatus for spectroscopically measuring and analyzing the concentration and physical property information of a substance component contained in a body fluid such as blood or cell fluid of a subject or a biological tissue for health management or treatment of a disease, In particular, by irradiating visible light, near-infrared light, or mid-infrared light, the concentration of substances such as water, glucose, cholesterol, neutral fat, hemoglobin, bilirubin and collagen contained in body fluids and living tissues, oxygen and Non-contains biochemical information or physical property information on the concentration of gases such as carbon dioxide, alcohol, drugs, etc., or tumors such as skin cancer or breast cancer, atopic dermatitis, arteriosclerosis, etc. The present invention relates to a biological information measuring apparatus capable of performing quantitative analysis or qualitative analysis of an accurate tissue property of a subject by invasive measurement.

  A typical conventional apparatus for measuring the components and concentrations of substances present in a subject includes a blood glucose meter that measures glucose concentration (blood glucose level) in blood or body fluid. A blood glucose meter that is widely used at present uses a small amount of blood sample collected by inserting a needle into a part of a subject's finger or arm, and chemically reacts the glucose in the collected blood. And measure its concentration. The most common method for measuring glucose concentration is a method using an enzyme electrode. The enzyme used for glucose detection is an enzyme called glucose oxidase (GOD), which is immobilized on a polymer membrane or the like, and oxygen in the analyte substance is consumed by the glucose in the analyte contacting the GOD immobilization membrane. The glucose concentration is quantified by capturing the change in oxygen. Such a blood collection type blood glucose meter is of a portable size and is used for managing blood glucose levels of diabetic patients.

However, in the above method, it is necessary to puncture a part of a finger or an arm for blood collection, which damages the subject's skin and is painful. Therefore, in order to strictly control the blood glucose level of a diabetic patient, it is desirable to measure 5 or 6 times a day, but at present, the number of measurements is only about 2 or 3 times a day. . In order to reduce the skin damage and pain of the subject, a method of measuring a minute amount of cellular interstitial fluid by opening a minute hole on the skin surface with a fine needle or laser to the extent that does not cause pain, Studies have been made on a method of applying a voltage or ultrasonic wave to the skin surface to improve the permeability of the skin to extract and measure the exudate such as cell interstitial fluid, but it has not been put to practical use.
On the other hand, as a non-invasive glucose measurement method that does not require blood collection or extraction of interstitial fluid, near infrared light as disclosed in Japanese Patent Publication No. 3-47099 or Japanese Patent Publication No. 5-58735 is used. There is a method used. Here, an electromagnetic wave having a wavelength band of about 380 to 770 nm is visible light, an electromagnetic wave of about 770 to 1,500 nm is near infrared light, an electromagnetic wave of about 1,500 to 3,000 nm is mid-infrared light, and 3,000. An electromagnetic wave of about 25,000 nm is taken as far infrared light. In Japanese Patent Publication No. 3-47099 and Japanese Patent Publication No. 5-58735, the skin surface of a subject is irradiated with near-infrared light having a plurality of different wavelengths, and detection signals thereof are used as a reference signal and a measurement signal. And a method for measuring the glucose concentration by computing these values is disclosed. In the above method, the near-infrared light source includes a method of dispersing light emitted from a white light source such as a tungsten / halogen lamp into a predetermined wavelength by a spectroscopic means such as an interference filter, or a semiconductor emitting monochromatic light or light close thereto. A laser (LD) or a light emitting diode (LED) is used. A light receiving element such as a photodiode (PD) is used as a detector for near-infrared light transmitted and diffused through the subject.

  Non-invasive spectroscopic analysis of biological materials using near-infrared light and visible light as described above is a method that has attracted attention in recent years, and is a component of the living body compared with spectroscopic analysis using mid-far infrared light. Therefore, since the absorption of water occupying most of the water is small, it is possible to analyze an aqueous solution system and to have a high ability to permeate a living body. On the other hand, the signal attributed to the molecular vibration is as small as about 1/100 compared with the mid-infrared light region, and the signal attribute is difficult to specify. That is, when detecting the signal of the target biological substance in the near infrared region, the signal corresponding to the change in the concentration of the target biological substance is very small, and the attribution of the signal is often not clear. I have it. Furthermore, the signal corresponding to the change in the concentration of the biological substance changes depending on the contact pressure of the light irradiation unit and the signal detection unit to the living body, and ideally a weak constant pressure condition of about 100 gf is desirable. It was difficult to measure with high reproducibility under high pressure and high accuracy.

  As another non-invasive glucose measurement method, a method of irradiating a subject with light such as near infrared light and detecting an acoustic signal generated by glucose in the subject absorbing the energy of the irradiation light, and The apparatus is shown in US Pat. No. 5,348,002, Japanese Patent Application Laid-Open No. 10-189, and Japanese Patent Application Laid-Open No. 11-235331. In the photoacoustic spectroscopic technique disclosed in the above publication, a piezoelectric vibrator such as a microphone or a zircon-lead titanate ceramic (PZT) is generally used for detecting an acoustic signal.

However, an acoustic signal generated from a substance such as glucose due to incident energy at a level that does not damage the subject is very weak. Even if averaging is performed by repeated measurement, the concentration of glucose in the subject is still However, there is a problem that sufficient signal detection capability cannot be obtained. Further, in this measurement method as well, the intensity of the acoustic signal generated from the biological material changes depending on the contact pressure of the light irradiation unit and the detection unit to the living body, and ideally, the condition of a weak constant pressure of about 100 gf is present. Although desirable, in practice, it was difficult to measure with high reproducibility and high accuracy under a minute pressure. In addition to the above, various methods and apparatuses have been developed for non-invasively measuring cholesterol, neutral fat, hemoglobin, bilirubin, oxygen content and the like of a subject.
Japanese Examined Patent Publication No. 3-47099 Japanese Patent Publication No. 5-58735 US Pat. No. 5,348,002 JP-A-10-189 JP 11-235331 A

  It is an object of the present invention to stabilize the contact pressure of the interface head with respect to the subject.

  An aspect of the present invention includes an irradiation unit that irradiates a subject with monochromatic light or light close thereto, and a detection unit that detects an optical signal, an acoustic signal, or a thermal signal radiated from within the subject by the irradiated light. An interface head, a signal processing unit for processing the detected signal to generate biochemical information or physical property information on a substance existing on or inside the subject, and the interface head for the subject. A support unit that is movably supported in an approaching / separating direction; a contact pressure detection unit that detects a contact pressure of the interface head with respect to the subject; and the support unit is controlled based on the detected contact pressure And a control unit.

  According to the present invention, the interface head can be stably brought into contact with the subject.

  Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 is a block diagram showing a configuration of a biological information measuring apparatus according to an embodiment of the present invention. The light source unit 8 generates one or a plurality of monochromatic lights having a desired wavelength or light having a relatively narrow wavelength band approximate to monochromatic light. When there are a plurality of lights emitted from the light source unit 8, the plurality of lights are superimposed on the same optical axis by the right-angle prism and the dichroic prism of the optical multiplexing / waveguide unit 9. The optical multiplexing / waveguide unit 9 is composed of an optical fiber, a thin film optical waveguide, a free space, or the like, and is typically an optical fiber. The light emitted from the light source unit 8 is divided into two by the beam splitter of the optical multiplexing / waveguide unit 9, one of which is guided to the irradiation unit 10 and irradiated to a desired part of the subject 14. The other is detected by a reference light detector through a reference light ND filter (not shown) and a focus lens as reference light in order to generate an electrical reference light signal 16.

  The acoustic wave generated in the subject by the light irradiation is detected by the acoustic signal detection unit 11 and converted into an electrical signal. The electrical acoustic signal is amplified to a desired amplitude by the signal amplification unit 12 and sent to the data collection unit 7. The acoustic signal detection unit 11 is configured by a piezoelectric element such as a solid solution type piezoelectric single crystal containing at least lead titanate or PZT ceramics.

  The irradiation unit 10, the acoustic signal detection unit 11, the temperature control unit 13, and the contact pressure detection unit 15 constitute an interface head 17 that is in contact with the subject 14. The interface head 17 is supported by the support unit 18 so as to be close to and away from the subject. The support portion 18 is composed of a piezoelectric actuator in order to achieve miniaturization. The interface head 17 constitutes an interface unit 19 together with the piezoelectric actuator 18 and the case 25 (see FIG. 3).

The temperature control unit 13 is arranged in the vicinity of a desired measurement site of the subject 14 and controls the temperature of the measurement site. As the temperature control element used for the temperature control unit 13, a thermoelectric conversion device that can control the temperature by changing the applied current or applied voltage, such as a Peltier element, can be used. For example, the temperature of the measurement site is controlled to a desired temperature, for example, a constant temperature in the range of 20 ° C. to 40 ° C. by the Peltier element. Since the photoacoustic measurement is affected by the measurement temperature condition, by providing the temperature control unit 13 as described above, the measurement temperature condition of the measurement site of the subject 14 can be kept constant, and the measurement accuracy can be improved. it can.
Further, the contact pressure between the measurement site of the subject 14 and the interface head 17 has a great influence on the photoacoustic measurement. For this reason, the contact pressure between the measurement site of the subject 14 and the interface head 17 is detected by the contact pressure detector 15, and the contact pressure between the measurement site surface of the subject 14 and the interface head 17 substantially matches a predetermined value or within a predetermined range. The projecting amount of the interface head 17 with respect to the bottom plate of the case 25 of the interface unit 19 is adjusted by the piezoelectric actuator 18 so as to be within the range. As the contact pressure detection unit 15, for example, a capacitance type pressure sensor whose capacitance changes according to a pressure change, a strain gauge whose electric resistance changes according to pressure, or the like can be used. When simply detecting the presence or absence of contact, a contact sensor whose electrical resistance or capacitance changes due to contact with the subject, or a distance measuring sensor that transmits and receives ultrasonic waves to measure the distance to the subject can be used. . When there is no object in contact with the interface head 17, the control unit 3 is provided with a mechanism for controlling the irradiation unit 10 not to emit the irradiation light to the outside of the apparatus, thereby reducing the risk of eye damage to the living body due to the irradiation light. It is also possible to provide a safety mechanism to avoid.
The electrical signal sent to the data collection unit 7 is converted into a digital signal and collected by the data collection unit 7. The collected digital signal is subjected to desired signal processing in the signal processing unit 6, and the result is stored in the data storage unit 4 and desired information is displayed on the display unit 1 as necessary. As the information display method of the display unit 1, in addition to visual information transmission means by display on a screen or the like, auditory information transmission means by voice or the like or tactile information transmission means by vibration or the like can be used. Furthermore, it is possible to use a plurality of these means in combination. The device is operated from the operation unit 2. As an operation method, a desired operation means suitable for the user of the apparatus, such as a keyboard, a mouse, a button, a touch key panel, and voice, can be used.
The controller 3 applies a voltage corresponding to a signal reflecting the contact pressure detected by the contact sensor 15 to the piezoelectric actuator 18. The relationship between the signal reflecting the contact pressure detected by the contact sensor 15 and the voltage applied to the piezoelectric actuator 18 is given in advance so that the contact pressure converges to a predetermined value. Thereby, the contact pressure of the interface head 17 with respect to the subject coincides with the predetermined pressure or falls within a range centered on the predetermined pressure.

The control unit 3 is configured to display the display unit 1, the data storage unit 4, the power supply unit 5, the signal processing unit 6, the data collection based on the signal of the operation unit 2 operated by the user of the apparatus, the output signal of the touch sensor 15, and the like. The operation of the apparatus such as the unit 7, the light source unit 8, the signal amplification unit 12, and the temperature control unit 13 is controlled. The power supply unit 6 supplies power to the display unit 1, the control unit 3, the light source unit 8, the signal amplification unit 12, and the control unit 3 further includes a data storage unit 4, a signal processing unit 6, Power is supplied to the data collection unit 7, the touch sensor 15 and the like.
As a light source for generating monochromatic light or light close thereto used in the light source unit 9 of the present embodiment, a small light emitting element such as a semiconductor laser (LD) or a light emitting diode (LED) is desirable, and those emitting light at a desired wavelength. One or a plurality of these elements can be used. For example, when measuring the glucose concentration in the subject as one embodiment according to the present invention, a plurality of lights having a wavelength in the range of 400 to 2,500 nm are irradiated. As the LD and LED used at this time, a material such as InGaAlP is used when the emission wavelength is about 550 to 650 nm, GaAlAs is used when the emission wavelength is about 650 to 900 nm, and InGaAs or InGaAsP is used when the emission wavelength is about 900 to 2300 nm. LD and LED can be used. Recently, a light-emitting element using InGaN that emits light at a wavelength of 550 nm or less is becoming available.

  Next, an embodiment of the piezoelectric actuator 18 will be described with reference to FIGS. In the present embodiment, the piezoelectric actuator is constituted by an S-shaped bimorph element 30 as shown in FIG. As is well known, a bimorph element is composed of two piezoelectric plates joined together so that an applied voltage stretches one of the piezoelectric plates and compresses the other. In the present embodiment, two sheets are formed so that the polarization direction is in reverse phase with the approximate center in the longitudinal direction as a boundary so that the interface head 17 is translated into an S-shape according to the applied voltage. The piezoelectric plates 20a and 20b are joined together. The piezoelectric plates 20a and 20b are composed of a solid solution type piezoelectric single crystal containing lead titanate or PZT ceramics. The piezoelectric plates 20a and 20b are attached to each other with a shim material / electrode 22 formed of a metal thin plate or a resin thin plate coated with an electrode. Electrodes 21a and 21b are attached to the surfaces of the piezoelectric plates 20a and 20b, respectively.

  When a voltage is applied to the S-shaped bimorph element 30 as shown in FIG. 2, the rotational component of the displacement is canceled at the free end (displacement extracting portion), so that the free end always moves in parallel. For this reason, as shown in FIG. 3, a plurality of S-shaped bimorph elements 30a, 30b, 30c, and 30d having the same displacement direction are coupled at both ends thereof, thereby reducing the resonance frequency and the generated force without reducing the displacement. The mechanical properties such as can be improved. For example, a PZT ceramic with a thickness of 0.25 mm is used for the piezoelectric body, and four S-shaped bimorph elements with a length of 40 mm and a width of 20 mm are stacked. When 100 V is applied, the displacement is about 0.8 mm and the generated force is about 100 mgf. was gotten.

  The S-shaped drive bimorph element 30 has a rectangular shape, a trapezoidal shape shown in FIG. 4, or a circular shape shown in FIG. If the bimorph element 30 has a quadrangular or trapezoidal shape, the interface head 17 is attached to one end thereof, and the other end is fixed to the side wall of the case 25 as a cantilever. The trapezoidal bimorph element 30 is more suitable for generating the necessary force with a smaller interface head 17 than in the rectangular shape. When the bimorph element 30 has a circular shape as shown in FIG. 5, the bimorph element 30 is formed so that the polarization direction is in reverse phase with respect to the approximate center in the radial direction, and is deformed into an S shape along the radial direction. . A central portion of the bimorph element 30 having a circular shape is opened in a circular shape, and the interface head 17 is attached thereto. The circular edge of the bimorph element 30 is fixed to the side wall of the case 25. The circular bimorph element 30 is suitable for a case where a large generated force is required although the size is slightly larger than that of a rectangular or trapezoidal shape.

  FIG. 6 shows an example of the voltage-displacement characteristics of the bimorph element. The amount of displacement at voltage = 0 V differs between boosting and stepping down, that is, there is hysteresis. By measuring this characteristic or the generated force-voltage characteristic in advance and setting the relationship between the detected pressure and the applied voltage in advance according to the characteristic, the control unit 3 controls the contact pressure with higher accuracy, or The contact pressure can be converged to the predetermined pressure in a shorter time.

  7, 8, and 9 show structural examples of the interface unit 19. For example, the acrylic case 25 has a rectangular shape with a size of about 30 mm × 70 mm so that it can be handled by hand. A trapezoidal piezoelectric actuator 18 is fixed to the inner surface of the case 25, and the interface head 17 is fixed to the end of the piezoelectric actuator 18. A window 27 is opened in a part of the bottom surface of the case 25 corresponding to the interface head 17, and the interface head 17 can protrude from the case 25 through the window 27. In use, the operator holds the interface unit 19 in contact with the bottom surface of the case 25 to the surface of the subject. As a result, the bottom face of the case 25 becomes the reference plane, and the interface head 17 is moved back and forth by the piezoelectric actuator 18 so that the contact pressure can be adjusted to a predetermined level.

  As shown in FIGS. 10, 11, 12, and 13, the interface unit 19 may be configured as a wristwatch. The interface unit 19 has a thin cylindrical case 28. The circular piezoelectric actuator 18 shown in FIG. 5 is accommodated in the cylindrical case 28. An interface head 17 is attached to the center of the piezoelectric actuator 18. On the bottom surface of the case 28, for example, a rubber band structure 24 for fixing the interface 19 to the arm of the subject is mounted. In this example, the interface unit 19 is provided with an LD 8 as a light source together with a short waveguide 9. The LD 8 and the waveguide 9 are attached to the interface head 17 so as to move back and forth together with the interface head 17.

  Further, the interface unit 19 may be configured as an earring type as shown in FIG. The interface unit 19 includes a cylindrical case 36 that is small, thin, and light. The cantilever piezoelectric actuator 18 shown in FIG. 4 is accommodated in the cylindrical case 36. The case 36 is provided with a clip structure 37 using, for example, a spring 38 for fixing the interface unit 19 to the earlobe of the subject.

  As described above in detail, according to the present invention, the subject is irradiated with monochromatic light having at least one wavelength or desired light close thereto, and the desired substance absorbs the energy of the irradiation light in the subject. In a biological information measuring apparatus that detects a generated acoustic signal and non-invasively obtains biochemical information, physical property information, etc. relating to a component or concentration of a substance existing in the subject surface or in the subject, or tissue properties, It is possible to detect acoustic signals with high reproducibility and high accuracy by accurately controlling the minute contact pressure with the piezoelectric actuator and applying a constant or predetermined change in the measurement conditions. . In addition, by using an S-shaped drive bimorph element for the piezoelectric actuator, the pressure control mechanism can be made compact, so that the apparatus can be downsized.

  The present invention can be implemented with various modifications other than those described above. For example, light irradiation of a non-invasive spectroscopic analyzer for biological materials using near-infrared light and visible light, and application to a subject of a photodetector unit The same can be applied to the contact pressure control. Further, the present invention is not limited to the above-described embodiments as they are, and can be embodied by modifying the constituent elements without departing from the scope of the invention in the implementation stage. In addition, various inventions can be formed by appropriately combining a plurality of components disclosed in the embodiment. For example, some components may be deleted from all the components shown in the embodiment. Furthermore, constituent elements over different embodiments may be appropriately combined.

The block diagram which shows the structure of the biological information measuring device which concerns on embodiment of this invention. Sectional drawing of the S-shaped drive bimorph element which comprises the piezoelectric actuator of FIG. Sectional drawing of the piezoelectric actuator of FIG. The top view of the piezoelectric actuator of FIG. The top view which shows the other structure of the piezoelectric actuator of FIG. The figure which shows the voltage-displacement characteristic example of the bimorph element of FIG. The figure which shows an example of the interface part of FIG. The figure which looked at the interface part of FIG. 7 from the biological body side. Sectional drawing of the interface part of FIG. FIG. 7 is an external view showing another example of the interface unit in FIG. 1. The enlarged view of the interface part of FIG. The figure which looked at the interface part of FIG. 10 from the biological body side. FIG. 11 is a cross-sectional view of the interface unit of FIG. 10. Sectional drawing which shows the further another example of the interface part of FIG.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 ... Display part, 2 ... Operation part, 3 ... Control part, 4 ... Data storage part, 5 ... Power supply part, 6 ... Signal processing part, 7 ... Data collection part, 8 ... Light source part, 9 ... Optical multiplexing and waveguide , 10 ... irradiation part, 11 ... acoustic signal detection part, 12 ... signal amplification part, 13 ... temperature control part, 14 ... subject, 15 ... contact pressure detection part, 16 ... reference light signal, 17 ... interface part, 18 ... Piezoelectric actuator, 20... Piezoelectric body, 21... Electrode, 22.

Claims (13)

An interface head having an irradiation unit that irradiates a subject with monochromatic light or light close thereto, and a detection unit that detects an optical signal, an acoustic signal, or a thermal signal emitted from the subject by the irradiated light;
A signal processing unit that processes the detected signal to generate biochemical information or physical property information relating to a substance present on the surface or inside of the subject;
A support part for supporting the interface head so as to be movable in a direction approaching / separating from the subject;
A contact pressure detector that detects a contact pressure of the interface head with respect to the subject;
A biological information measuring apparatus comprising: a control unit that controls the support unit based on the detected contact pressure. The biological information measuring apparatus according to claim 1, wherein the control unit controls the support unit so that a contact pressure of the interface head with respect to the subject substantially matches a predetermined pressure. The biological information measuring apparatus according to claim 1, wherein the support portion includes a piezoelectric actuator. The biological information measuring apparatus according to claim 3, wherein the piezoelectric actuator is a piezoelectric bimorph element. The biological information measuring apparatus according to claim 4, wherein the piezoelectric bimorph element has a trapezoidal shape. The biological information measuring apparatus according to claim 4, wherein the piezoelectric bimorph element has a circular shape. The biological information measuring apparatus according to claim 3, wherein the piezoelectric actuator has a structure in which a plurality of piezoelectric bimorph elements having an S-shaped displacement with voltage application are stacked. The biological information measuring device according to claim 4, wherein the contact pressure detecting unit is a strain gauge installed on the piezoelectric bimorph element. The biological information measuring apparatus according to claim 4, wherein the contact pressure detection unit uses a part of the piezoelectric bimorph element. The interface head constitutes an interface part together with the support part, and the interface part is provided with a band structure for fixing the interface part to an arm part of the subject. The biological information measuring device described. The living body according to claim 1, wherein the interface head constitutes an interface part together with the support part, and the interface part is provided with a clip structure for fixing the interface part to the earlobe of the subject. Information measuring device. The specific substance is glucose, and the irradiation light is light having one or more types of wavelengths composed of all or a part of a region selected from a region of at least 400 to 2,500 nm. The biological information measuring device according to claim 11. The specific substance is hemoglobin, and the irradiation light is light having one or more types of wavelengths composed of an entire region or a partial region selected from at least a region of 500 to 1,600 nm. The biological information measuring device according to any one of claims 1 to 11.

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