WO2019123662A1 - Bioinstrumentation device, bioinstrumentation system, and bioinstrumentation method - Google Patents

Bioinstrumentation device, bioinstrumentation system, and bioinstrumentation method Download PDF

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Publication number
WO2019123662A1
WO2019123662A1 PCT/JP2017/046256 JP2017046256W WO2019123662A1 WO 2019123662 A1 WO2019123662 A1 WO 2019123662A1 JP 2017046256 W JP2017046256 W JP 2017046256W WO 2019123662 A1 WO2019123662 A1 WO 2019123662A1
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Prior art keywords
light
measurement
biological sample
living body
unit
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PCT/JP2017/046256
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French (fr)
Japanese (ja)
Inventor
関山　健太郎
峰雪 村上
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オリンパス株式会社
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Priority to PCT/JP2017/046256 priority Critical patent/WO2019123662A1/en
Publication of WO2019123662A1 publication Critical patent/WO2019123662A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated

Definitions

  • the present invention relates to a living body measurement device, a living body measurement system, and a living body measurement method.
  • this estimation method first, using measurement values, numerical calculation is performed using a light propagation model assuming the optical characteristic value distribution inside the light scattering material, and backscattered light by the light scattering material is calculated as a predicted value Do.
  • the light scattering material model is divided into meshes (or voxels), and the scattering coefficient and the absorption coefficient are set as parameters for each mesh, and the propagation of light through the light scattering material is represented by the diffusion equation (DE: Diffusion Equation) or light transfer equation (RTE: Radial Transfer Equation).
  • the measured value and the predicted value are compared to determine whether the degree of coincidence is equal to or more than a predetermined value. If the degree of coincidence is lower than a predetermined value, the optical characteristic value distribution inside the light scattering material is again assumed, the predicted value is calculated, and this calculation is repeated until the degree of coincidence becomes a predetermined value or more. This repeated calculation is also called inverse analysis operation.
  • the degree of coincidence can be evaluated by setting an error function from the difference between the measured value and the predicted value. It is possible to reduce the difference between the measured value and the predicted value by again assuming the optical characteristic value distribution inside the light scattering material so that the error function becomes smaller.
  • Various known optimization algorithms can be applied to the inverse analysis operation described above.
  • a living body measurement device for measuring the optical characteristic value distribution inside the light scattering material
  • continuous wave parallel beams with different wavelengths were irradiated from a plurality of directions to a wide area of the living tissue and reflected or scattered by the living tissue
  • a living body measurement apparatus which receives light in a plurality of directions is disclosed (see, for example, Patent Document 1).
  • this living body measuring device assuming that the interface between air and living tissue is flat, the value measured using a radiation transfer model is analyzed to estimate the optical characteristic value distribution.
  • OCT optical Coherence Tomography: optical coherence tomography
  • light from a light source is split into measurement light that is scattered back inside the living body and reference light that is reflected by the reference mirror, and both are superimposed and interference signals are measured and calculated. Acquire the optical property value distribution.
  • Patent No. 4156373 gazette
  • the present invention is made in view of the above, and an object of the present invention is to provide a living body measurement device, a living body measurement system, and a living body measurement method, in which an error due to the surface shape of living body tissue is suppressed.
  • a biological measurement device includes a transparent member having a flat portion in contact with a surface of a biological sample, and the biological sample in contact with the flat portion.
  • a light source unit for irradiating measurement light to a reference point included in a region, and a light receiving unit for receiving the measurement light scattered in the biological sample.
  • a light branching unit that transmits a part of light and reflects a part of the light, the light transmitted through the light branching unit, or the light branching unit reflects And a reference mirror for reflecting the reference light, which is one of the light beams, wherein the light source unit is the other of the light transmitted through the light branching portion or the other of the light reflected by the light branching portion.
  • a biological sample irradiates a reference point included in a region in contact with the flat portion, and the light receiving unit receives the measurement light scattered in the biological sample and the reference light reflected in the reference mirror. It is characterized by
  • the light receiving unit is characterized by receiving backward scattered light in the living body sample of the measurement light.
  • a living body measurement apparatus includes a spectroscopy unit that disperses the measurement light and the reference light.
  • the light source unit can emit the measurement light from a plurality of different positions with respect to the reference point.
  • the light receiving unit can receive the measurement light from the reference point at a plurality of different positions.
  • the light source unit irradiates the measurement light a plurality of times to the reference point, and the light receiving unit receives the measurement light a plurality of times.
  • the light source unit irradiates the reference point with a plurality of the measurement lights having different wavelengths.
  • the light source unit emits the measurement light having a wide wavelength band to the reference point.
  • the transparent member is a container made of a material that transmits the measurement light, and the flat portion is formed on the bottom surface of the transparent member.
  • the sample is characterized in that it is placed on the transparent member so as to be in contact with the surface of the flat portion.
  • the living body measurement apparatus includes a drive unit capable of moving the transparent member on which the biological sample is placed in a horizontal plane and in a gravity direction.
  • the flat surface portion of the transparent member is a surface of the living body sample by gravity or a drive unit capable of moving a container on which the living body sample is mounted in the gravity direction. It is characterized by being in contact with
  • a living body measurement system includes: the living body measurement device described above; and an operation unit that calculates an optical characteristic value distribution inside the living body sample based on a signal received by the light receiving unit. It is characterized by
  • the light irradiation step may include light transmitted through the light branching portion or the light branch at a reference point included in a region where the biological sample is in contact with the flat portion. Irradiating the measurement light which is one of the light reflected by the unit, and the light receiving step includes the measurement light scattered by the biological sample and the light transmitted through the light branch unit reflected by the reference mirror or the light
  • the branching unit is characterized in that it receives the reference light which is the other of the reflected light.
  • the present invention it is possible to realize a living body measurement device, a living body measurement system, and a living body measurement method in which an error due to the surface shape of a living body tissue is suppressed.
  • FIG. 1 is a schematic view showing a configuration of a living body measurement system according to Embodiment 1 of the present invention.
  • FIG. 2 shows a living body measurement apparatus according to a first modification of the first embodiment.
  • FIG. 3 is a schematic view showing a configuration of a living body measurement system according to a second embodiment of the present invention.
  • FIG. 4 is a diagram illustrating another example of the position of the light receiving unit of the biological measurement device.
  • FIG. 5 is a layout view of a biological sample of a biological measurement device according to Embodiment 1 or Modification 2 of Embodiment 2.
  • FIG. 6 is a layout view of a biological sample of a biological measurement device according to Embodiment 1 or Modified Example 3 of Embodiment 2.
  • a living body measurement apparatus a living body measurement apparatus
  • a living body measurement system a living body measurement method according to the present invention
  • the present invention is not limited by these embodiments.
  • the present invention can be applied to a living body measurement device, a living body measurement system, and a living body measurement method in general.
  • FIG. 1 is a schematic view showing a configuration of a living body measurement system according to Embodiment 1 of the present invention.
  • the living body measurement system 1 includes a living body measurement device 2 that measures the living body sample S1, and a control device 3 that controls the entire living body measurement system 1 in an integrated manner.
  • the living body measurement device 2 is a device that estimates the optical characteristic value distribution inside the living body sample S1 by OCT. As shown in FIG. 1, the living body measurement apparatus 2 transmits a part of light while transmitting the stage 4 on which the living body sample S1 is placed, a transparent member 5 having a flat portion 5a in contact with the surface of the living body sample S1.
  • a light branching portion 6 for reflecting a part of the light, and a light source for irradiating a measurement light which is light transmitted through the light branching portion 6 to a reference point P1 included in a region where the biological sample S1 is in contact with the flat portion 5a
  • a lens 7 for converting the light emitted from the light source 7 into substantially parallel light; a galvano scanner 9 for adjusting the position at which the measurement light is irradiated to the biological sample S1; and a lens 10 for collecting the measurement light.
  • Reference mirror 11 that reflects the reference light that is the light reflected by the light branching unit 6, a lens 12 that collects the measurement light and the reference light, a spectroscopy unit 13 that disperses the measurement light and the reference light for each wavelength, and a living body Backscattered light of measurement light in sample S1, reference mirror 1 It includes a light receiving portion 14 for receiving the reference light reflected in, a drive unit 15 for driving the stage 4, the.
  • the stage 4 is under the control of the drive unit 15 in the horizontal plane (in the plane formed by the horizontal direction in FIG. 1 and the direction perpendicular to the paper surface) and in the gravity direction (vertical direction in FIG. 1) Move to
  • the transparent member 5 is a container made of a material that transmits measurement light, and the flat portion 5 a is formed on the bottom surface of the transparent member 5. As a result, the surface of the biological sample S1 placed on the transparent member 5 is in contact with the flat portion 5a. Then, since the biological sample S1 is pressed against the flat portion 5a by gravity, the surface of the biological sample S1 becomes flat at the interface between the biological sample S1 and the flat portion 5a. In addition, only the part which mounts biological sample S1 of the bottom face of a container should just be transparent (transparent member 5), and the whole container does not need to be transparent.
  • the light branching unit 6 is, for example, a half mirror, and transmits a part of the incident light and reflects a part of the incident light. However, when the light from the light source unit 7 is to be propagated through an optical fiber, the light branching unit 6 may be an optical fiber coupler.
  • the light source unit 7 is a low coherence light source such as SLD (Super Luminescent Diode) or LED (Light Emitting Diode), or a wavelength band such as a mercury lamp, a xenon lamp, an LDLS (Laser-Driven Light Source) light source, or a supercontinuum light source. Is a wide white light source.
  • a wavelength band is selected by an optical element such as a filter to irradiate the biological sample S1.
  • the light emitted from the light source unit 7 is, for example, visible light or infrared light.
  • the central wavelength of the wavelength band selected by an optical element such as a filter is set at a wavelength at which it is desired to acquire the optical physical property value of the living body. Further, the wavelength width of the wavelength band is determined based on the balance between the resolution in the depth direction of the living body measurement and the wavelength resolution. This wavelength width is usually selected in the range of 20 nm to 50 nm in full width at half maximum, but is not limited thereto.
  • the light emitted from the light source unit 7 may propagate in space and be irradiated to the light branching unit 6 and other optical elements, but an optical fiber may be used.
  • the optical fiber for example, a single mode fiber, a multimode fiber, a photonic crystal fiber or the like is used. However, other optical fibers may be used as long as the optical fiber does not have a large optical loss.
  • the galvano scanner 9 moves the position where the measurement light is irradiated to the biological sample S1 under the control of the control device 3. Specifically, the measurement light is irradiated to the biological sample S1 so that the galvano scanner 9 two-dimensionally scans the surface where the biological sample S1 and the transparent member 5 are in contact by moving the two mirrors. Move the
  • the reference mirror 11 reflects the reference light reflected by the light branching unit 6 toward the light receiving unit 14.
  • the spectroscope unit 13 is, for example, an optical filter, a dispersive spectroscope, a Fourier transform type spectroscope, or the like, and disperses the measurement light and the reference light for each wavelength.
  • the dispersive spectrometer is a monochromator (Monochromator) or a polychromator (Ppolychromator) having a prism and a diffraction grating.
  • a spectrum analyzer which is a monochromator having the functions of the spectral unit 13 and the light receiving unit 14 may be used.
  • the light receiving unit 14 receives the measurement light and the reference light separated by the light separating unit 13.
  • the light receiving unit 14 is a line sensor in which a plurality of complementary metal oxide semiconductors (CMOSs) and charge coupled devices (CCDs) are arranged in a line, and converts received light into an electrical signal by photoelectric conversion.
  • CMOSs complementary metal oxide semiconductors
  • CCDs charge coupled devices
  • the light receiving unit 14 may be one CMOS or CCD, and moves the light receiving unit 14 in a direction orthogonal to the directions in which the measurement light and the reference light are incident, and light having different wavelengths dispersed by the light separating unit 13 May be received.
  • the light receiving unit 14 may be an area sensor in which a CMOS or a CCD is two-dimensionally arranged.
  • the driving unit 15 is capable of moving the transparent member 5 on which the biological sample S1 is placed in the horizontal plane and in the gravity direction.
  • the control device 3 uses, for example, a workstation or a personal computer including a dedicated processor such as a general-purpose processor such as a central processing unit (CPU) or various arithmetic circuits that execute specific functions such as an application specific integrated circuit (ASIC). Configured The control device 3 controls the light source unit 7, the galvano scanner 9, the light receiving unit 14, the drive unit 15, and the like.
  • a dedicated processor such as a general-purpose processor such as a central processing unit (CPU) or various arithmetic circuits that execute specific functions such as an application specific integrated circuit (ASIC).
  • CPU central processing unit
  • ASIC application specific integrated circuit
  • control device 3 includes an operation unit 3a that calculates the optical characteristic value distribution inside the biological sample S1 based on the signal received by the light receiving unit 14.
  • the optical characteristic value distribution inside the biological sample S1 is, for example, the absorption coefficient distribution, the scattering coefficient distribution, the anisotropic parameter distribution, etc. inside the biological sample S1.
  • Arithmetic unit 3a calculates the optical characteristic value distribution by inverse analysis, assuming that the interface between biological sample S1 and flat portion 5a is flat.
  • the transparent member 5 and the biological sample S1 are arranged such that the flat portion 5a of the transparent member 5 abuts on the surface of the biological sample S1 (arrangement step). Specifically, the biological sample S1 is placed on the flat portion 5a of the transparent member 5. Then, the surface of the biological sample S1 becomes flat at the interface between the biological sample S1 and the flat portion 5a.
  • the light source unit 7 irradiates measurement light to the reference point P1 included in the area where the biological sample S1 is in contact with the flat portion 5a (light irradiation step).
  • the light path length of the measurement light from the light source unit 7 to the light receiving unit 14 is adjusted in advance so that the light path length of the reference light becomes equal.
  • the stage 4 is moved in the direction along the optical axis of the measurement light (vertical direction in FIG. 1), or the reference mirror 11 is in the direction along the optical axis of the reference light (horizontal direction in FIG.
  • the optical path length of the measurement light from the light source unit 7 to the light receiving unit 14 and the optical path length of the reference light are equalized.
  • the area in which the optical physical property value in the living body can be measured is the deep side of the living body from the reference point P1. Therefore, by setting the reference point P1 on the surface of the biological sample S1 as described above, it becomes possible to measure the optical property value distribution in the vicinity of the surface of the living body.
  • the reference point P1 may be set not in the surface of the living body but in the inside of the living body.
  • the light receiving unit 14 receives the measurement light scattered at the reference point P1 of the biological sample S1 and the reference light reflected by the reference mirror 11 (light receiving step).
  • the calculation unit 3a calculates the optical characteristic value distribution inside the biological sample S1 based on the signal received by the light receiving unit 14 (calculation step).
  • the calculation unit 3a interference light due to the measurement light that is incident upon the biological sample S1 and scattered back inside the biological sample S1 and the reference light that is reflected by the reference mirror 11 is received by the spectroscopic unit 13
  • the spectral information thus dispersed is converted into information in the depth direction of the biological sample S1 by calculation such as Fourier transformation, and calculation such as fitting is performed to calculate the optical property value distribution inside the biological sample S1.
  • the measurement light is irradiated to the reference point P1, and the return light is measured with the reference point P1 as a position where the measurement optical path and the reference optical path become approximately equal, and calculation is performed.
  • the interface between the biological sample S1 and the flat portion 5a is flat, it is possible to realize the biological measurement device in which the measurement error due to the unevenness of the biological surface is suppressed.
  • the difference in refractive index between the biological sample S1 and the outside can be reduced, so that the decrease in S / N due to reflected light on the surface of the living body can be prevented.
  • the surrounding of the biological sample S1 is air, so that the refractive index difference between the biological sample S1 and the outside is 0.3 or more.
  • An antireflective coating is applied to the surface of the side where the transparent member 5 is in contact with air (the opposite side of the side where the transparent member 5 is in contact with the biological sample S1). It is possible to reduce the S / N in measurement further.
  • FIG. 2 shows a living body measurement apparatus according to a first modification of the first embodiment.
  • the living body measurement device 2A does not have the light branching unit 6.
  • the living body measurement apparatus 2A measures the transmitted light and the reflected light in the light branching unit 16A as a measurement light and a reference light, respectively.
  • the reference light reflected by the light branching unit 16 is reflected by the reference mirror 11A and then reflected again by the light branching unit 16A, and interferes with the measurement light scattered and returned by the biological sample S1.
  • an optical system in which the light branching portion and the reference mirror are disposed in the objective lens group is referred to as a Mirau interferometer or a Mirau interferometer.
  • the measurement light is irradiated multiple times while scanning the position where the measurement light is applied to the biological sample S1 by the galvano scanner 9
  • the accuracy of the measurement can be further enhanced by receiving the measurement light a plurality of times by the unit 14 and performing the inverse analysis calculation with the irradiation position of the measurement light as a reference point.
  • the SD (Spectral Domain) -OCT including the spectroscope unit 13 has been described as the living body measurement device 2, the present invention is not limited to this.
  • a wavelength sweeping laser such as a wavelength sweeping laser or an optical comb may be used, and the present invention may be applied to SS (Swept Source) -OCT using no spectroscopic unit.
  • SS-OCT SS-OCT
  • the present invention may be applied to TD (Time Domain) -OCT in which the reference mirror 11 is moved in the direction along the reference light.
  • the reference point P1 may be set using information received by the light receiving unit 14 of the living body measurement device 2, but may be set using another measuring means such as a laser displacement meter. For example, by measuring the distance to the surface of the living body by using a laser displacement meter whose position has been adjusted in advance and adjusting the position of the living body, it becomes easy to set the reference point P1 on the living body surface or inside the living body.
  • the transparent member 5 may be a flat plate whose front and back surfaces are parallel, but may be, for example, a wedge-shaped plate whose front and back surfaces are not parallel. In the case where the transparent members 5 are parallel flat plates, the manufacturing is easy, so the manufacturing cost of the manufacturing apparatus can be reduced. On the other hand, when the transparent member 5 is a wedge-shaped plate, it is possible to prevent the light receiving unit 14 from receiving the reflected light from the interface between the transparent member 5 and the air, so the measurement S / N should be high. Is possible.
  • FIG. 3 is a schematic view showing a configuration of a living body measurement system according to a second embodiment of the present invention.
  • the living body measurement system 100 includes a living body measurement device 101 that measures the living body sample S2, and a control device 102 that controls the whole living body measurement system 100 in an integrated manner.
  • the living body measurement apparatus 101 is an apparatus for estimating the optical characteristic value distribution inside the living body sample S1 by diffused light tomography. As shown in FIG. 3, the living body measurement apparatus 101 includes a stage 103 on which the living body sample S2 is mounted, a transparent member 104 having a flat portion 104a in contact with the surface of the living body sample S2, and a flat portion 104a with the living body sample S2.
  • a light source unit 105 that irradiates measurement light to a reference point P2 included in the area in contact, an optical switch 106, a light irradiation unit 107, and a light receiving unit 108 that receives measurement light scattered in the biological sample S2;
  • the light receiving unit driving unit 109 and a driving unit 110 for driving the stage 103 are provided.
  • the stage 103 is under the control of the drive unit 110, in the horizontal plane (in the plane formed by the horizontal direction in FIG. 3 and the direction perpendicular to the paper surface) and in the gravity direction (vertical direction in FIG. 3)
  • Move to The stage 103 includes an X stage 103a for moving the placed transparent member 104 in the X axis direction (left and right direction in FIG. 3) under the control of the drive unit 110, and a Y axis direction (vertical to the sheet of FIG. 3). 3), and a Z stage 103c which is moved in the Z axis direction (vertical direction in FIG. 3).
  • the transparent member 104 is a container made of a material that transmits measurement light, and the flat portion 104 a is formed on the bottom surface of the transparent member 104. As a result, the surface of the biological sample S2 placed on the transparent member 104 is in contact with the flat portion 104a. Then, since the biological sample S2 is pressed against the flat portion 104a by gravity, the surface of the biological sample S2 becomes flat at the interface between the biological sample S2 and the flat portion 104a.
  • the light source unit 105 can emit measurement light from a plurality of different positions with respect to the reference point P2 via the light switch 106 and the light emitting unit 107.
  • the light source unit 105 is a laser light source such as a LD (Laser Diode) light source, a low coherence light source such as an SLD or LED, or a wavelength such as a mercury lamp, a xenon lamp, an LDLS (Laser-Driven Light Source) light source, or a supercontinuum light source. It is a white light source with a wide bandwidth.
  • a wavelength band is selected by an optical element such as a filter and the biological sample S2 is irradiated.
  • the light emitted from the light source unit 105 is, for example, visible light or infrared light.
  • the central wavelength of the wavelength band selected by an optical element such as a filter is set at a wavelength at which it is desired to acquire the optical physical property value of the living body.
  • the wavelength width of the wavelength band is determined based on the balance between the resolution in the depth direction of the living body measurement and the wavelength resolution. This wavelength width is usually selected in the range of 20 nm to 50 nm in full width at half maximum, but is not limited thereto.
  • the light emitted from the light source unit 105 may propagate in space and be irradiated to the light irradiation unit 107 and other optical elements, but an optical fiber may be used.
  • the optical fiber for example, a single mode fiber, a multimode fiber, a photonic crystal fiber or the like is used. However, other optical fibers may be used as long as the optical fiber does not have a large optical loss.
  • the light irradiator 107 includes a first light irradiator 107a, a second light irradiator 107b, and a third light irradiator 107c that irradiate measurement light to the reference point P2 from different positions.
  • the first light irradiator 107a, the second light irradiator 107b, and the third light irradiator 107c are made of an optical fiber, and one of the light irradiators irradiates the measurement light to the reference point P2 by the light switch 106.
  • the first light irradiator 107a, the second light irradiator 107b, and the third light irradiator 107c have directions of 0 °, 30 °, and 60 °, respectively, with the direction perpendicular to the flat portion 104a of the transparent member 104 as 0 °.
  • the measurement light is emitted to the reference point P2.
  • these angles are an example and are not particularly limited.
  • the first light irradiation unit 107a, the second light irradiation unit 107b, and the third light irradiation unit 107c are considered in consideration of the refractive index and the thickness of the transparent member 104.
  • the measurement light is irradiated to the same reference point P2.
  • the light receiving unit 108 can receive the measurement light from the reference point P2 at a plurality of different positions.
  • the light receiving unit 108 is a CMOS or a CCD, and converts the received light into an electric signal by photoelectric conversion.
  • the light receiving unit 108 is moved by the light receiving unit driving unit 109, and receives the measurement light from the reference point P2 at the first light receiving position 108a, the second light receiving position 108b, and the third light receiving position 108c.
  • the first light receiving position 108a, the second light receiving position 108b, and the third light receiving position 108c are directions of 20 °, 45 °, and 70 °, respectively, with the direction perpendicular to the flat portion 104a of the transparent member 104 as 0 °. However, these angles are an example and are not particularly limited.
  • the position is not particularly limited, the first light emitting unit 107a, the second light emitting unit 107b, and the third light emitting unit 107c, and the first light receiving position 108a, the second light receiving position 108b, and the third light receiving position 108c.
  • the position is preferably shifted so as not to be opposite to each other across a direction perpendicular to the flat portion 104 a of the transparent member 104. In this case, it is possible to prevent the occurrence of an error in measurement by receiving the light regularly reflected on the surface of the biological sample S2.
  • the light receiving unit driving unit 109 moves the position of the light receiving unit 108 in an arc shape centering on the reference point P2.
  • the drive unit 110 drives the X stage 103 a, the Y stage 103 b, and the Z stage 103 c under the control of the control device 102.
  • the control device 102 is configured using, for example, a workstation or a personal computer including a general purpose processor such as a CPU or a dedicated processor such as various arithmetic circuits that execute a specific function such as an ASIC.
  • the control device 102 controls the light source unit 105, the light switch 106, the light receiving unit 108, the driving unit 110, and the like.
  • control device 102 includes an operation unit 102a that calculates an optical characteristic value distribution inside the biological sample S2 based on the signal received by the light receiving unit 108.
  • the optical characteristic value distribution inside the biological sample S2 is, for example, an absorption coefficient distribution, a scattering coefficient distribution, or an anisotropic parameter distribution inside the biological sample S2.
  • the calculation unit 102a calculates the optical characteristic value distribution by inverse analysis calculation on the assumption that the interface between the biological sample S2 and the flat portion 104a is flat.
  • the transparent member 104 and the biological sample S2 are disposed such that the flat portion 104a of the transparent member 104 abuts on the surface of the biological sample S2 (arrangement step). Specifically, the biological sample S2 is placed on the flat portion 104a of the transparent member 104. Then, the surface of the biological sample S2 becomes flat at the interface between the biological sample S2 and the flat portion 104a.
  • the light source unit 105 is a reference point P2 included in the area where the biological sample S2 is in contact with the flat unit 104a from the first light irradiation unit 107a via the light switch 106. To the measurement light (light irradiation step).
  • the light receiving unit 108 receives the measurement light scattered in the biological sample S2 at the first light receiving position 108a (light receiving step).
  • the light receiving unit 108 is moved by the driving unit 110, and receives measurement light also at each of the second light receiving position 108b and the third light receiving position 108c.
  • the light source unit 105 emits measurement light to the reference point P2 from the second light irradiation unit 107b and the third light irradiation unit 107c via the light switch 106, and receives light.
  • the unit 108 is moved by the drive unit 110, and receives measurement light at each of the first light receiving position 108a, the second light receiving position 108b, and the third light receiving position 108c.
  • the calculation unit 102a calculates the optical characteristic value distribution inside the biological sample S2 based on the signal received by the light receiving unit 108 (calculation step).
  • the calculation unit 102a calculates the optical characteristic value distribution inside the biological sample S2 by estimating the propagation of the measurement light from the reference point P2 and propagating inside the biological sample S2 by inverse analysis. .
  • the calculation unit 102a acquires these pieces of information in advance from the light irradiation unit 107 and the light reception unit 108.
  • the living body measurement apparatus 101 measurement light is irradiated to the reference point P2, and inverse analysis calculation is performed with the reference point P2 as the position where the measurement light is incident.
  • the reference point P2 is included in a region where the biological sample S2 and the flat portion 104a are in contact, and the surface of the biological sample S2 is flat.
  • the calculation unit 102a performs inverse analysis calculation on the assumption that the interface between the biological sample S2 and the flat portion 104a is flat, no error is generated due to the surface shape of the biological sample S2. Therefore, according to the living body measurement apparatus 101, it is possible to realize a living body measurement apparatus in which an error due to the surface shape of the living body sample S2 is suppressed.
  • the second embodiment it is possible to estimate the optical characteristic value at a deep position farther from the surface of the biological sample S2 than the first embodiment.
  • the light receiving unit 108 may receive regular reflection light reflected on the surface of the biological sample S2.
  • the specular reflection light adversely affects the measurement result due to saturation of the imaging pixel of the light receiving unit 108 or the like.
  • the position where the light receiving unit 108 is affected is not uniform, it may be difficult to estimate the optical characteristic value distribution, or the reliability of the estimated optical characteristic value distribution may decrease.
  • the living body measurement apparatus 101 such a problem does not occur because the surface of the living body sample S2 is flat.
  • the configuration has been described in which the living body measurement apparatus 101 emits measurement light from a plurality of directions and receives measurement light in a plurality of directions.
  • the living body measurement apparatus 101 may emit measurement light from at least one direction and receive the measurement light in at least one direction.
  • the living body measurement apparatus 101 can improve the accuracy of the optical characteristic value distribution to be estimated by increasing the direction in which the measurement light is irradiated and the direction in which the measurement light is received.
  • the light source unit 105 may irradiate the biological sample S2 with pulsed light or light whose light intensity is periodically modulated.
  • the optical characteristic value distribution inside the biological sample S2 can be estimated from TOF (Time Of Flight) information obtained from the phase difference between the irradiated light and the scattered light from the biological sample S2.
  • FIG. 4 is a diagram illustrating another example of the position of the light receiving unit of the biological measurement device.
  • FIG. 3 shows an example in which the light irradiation position of the light irradiation unit 107 and the light receiving position of the light receiving unit 108 are changed in the same plane
  • FIG. 4 shows the light receiving unit 108A in the plane orthogonal to the plane shown in FIG. Changing the light receiving position of. As shown in FIG.
  • the light receiving unit 108A takes + 120 °, + 90 °, + 60 °, + 30 °, + 30 °, 0 °, -30 °, where the direction facing the light source 105A is 0 ° with respect to the reference point P2.
  • the light from the biological sample S2 may be received at the light receiving position 108Aa to the light receiving position 108Ai located at -60 °, -90 °, -120 °.
  • the light irradiation position of the light irradiation unit and the light receiving position of the light receiving unit may be changed in any direction without being limited to the same plane, and may be changed in one or more planes.
  • FIG. 5 is a layout view of a biological sample of a biological measurement device according to Embodiment 1 or Modification 2 of Embodiment 2.
  • the biological sample S3 may be placed on the dish 202 placed on the stage 201, and the transparent member 203 may be arranged on the biological sample S3.
  • the flat portion 203 a of the transparent member 203 is in contact with the surface of the biological sample S 3 by the gravity applied to the transparent member 203.
  • the biological sample S3 becomes flat at the interface between the flat portion 203a of the transparent member 203 and the biological sample S3.
  • the measurement light is irradiated to the reference point P3 included in the flat area. In this configuration, light is applied to the biological sample S3 from above the biological sample S3.
  • FIG. 6 is a layout view of a biological sample of a biological measurement device according to Embodiment 1 or Modified Example 3 of Embodiment 2.
  • the biological sample S4 is placed on the dish 302 placed on the stage 301, and the stage 301 is moved upward by a predetermined amount, whereby the flat portion of the transparent member 303 from above the biological sample S4. 303a is in contact with the biological sample S4.
  • the flat portion 303a of the transparent member 303 is the surface of the biological sample S4 by the drive unit (drive unit 15 or drive unit 110) capable of moving the dish 302, which is a container on which the biological sample S4 is placed, in the direction of gravity.
  • the biological sample S4 becomes flat at the interface between the flat portion 303a of the transparent member 303 and the biological sample S4. Then, the measurement light is irradiated to the reference point P4 included in the flat area. In this configuration, light is irradiated to the biological sample S4 from above the biological sample S4.
  • the transparent member 303 may be fixed, but the flat portion 303a of the transparent member 303 may be brought into contact with the biological sample S4 by driving the transparent member 303.
  • the transparent member may be brought into contact with the biological sample from above the biological sample.

Abstract

Provided are a bioinstrumentation device, a bioinstrumentation system and a bioinstrumentation method in which error due to the surface shape of a biological tissue is suppressed. The bioinstrumentation device according to the present invention is provided with a transparent member having a planar part in contact with the surface of a biological sample, a light source part for radiating a measurement light to a reference point included in a region where the biological sample is in contact with the planar part, and a light-receiving part for receiving the measurement light scattered in the biological sample.

Description

生体計測装置、生体計測システム、及び生体計測方法Living body measurement device, living body measurement system, and living body measurement method
　本発明は、生体計測装置、生体計測システム、及び生体計測方法に関する。 The present invention relates to a living body measurement device, a living body measurement system, and a living body measurement method.
　近年、生体等の光散乱物質に対する吸光分析技術の開発がすすめられている。光散乱物質に照射された光は、物質の内部で多重散乱を繰り返しながら一部が吸収され、一部は生体の外部に出てくる。このような外部に出射した光を計測し、計測した値を解析することにより、光散乱物質の内部の光学特性値分布を推定することができる。 In recent years, development of light absorption analysis technology for light scattering substances such as living bodies has been promoted. The light irradiated to the light scattering material is partially absorbed while repeating multiple scattering inside the material, and partially comes out of the living body. By measuring such light emitted to the outside and analyzing the measured values, it is possible to estimate the optical characteristic value distribution inside the light scattering material.
　この推定方法では、はじめに、計測値を用いて、光散乱物質の内部の光学特性値分布を仮定して光伝播モデルを用いて数値計算を行い、光散乱物質による後方散乱光を予測値として算出する。具体的には、光散乱物質モデルをメッシュ（又はボクセル）に区切り、それぞれのメッシュに対して散乱係数と吸収係数とをパラメータとして設定し、光散乱物質の内部を光が伝播する様子を拡散方程式（ＤＥ：Ｄｉｆｆｕｓｉｏｎ　Ｅｑｕａｔｉｏｎ）や光輸送方程式（ＲＴＥ：Ｒａｄｉａｔｉｖｅ　Ｔｒａｎｓｆｅｒ　Ｅｑｕａｔｉｏｎ）により算出する。 In this estimation method, first, using measurement values, numerical calculation is performed using a light propagation model assuming the optical characteristic value distribution inside the light scattering material, and backscattered light by the light scattering material is calculated as a predicted value Do. Specifically, the light scattering material model is divided into meshes (or voxels), and the scattering coefficient and the absorption coefficient are set as parameters for each mesh, and the propagation of light through the light scattering material is represented by the diffusion equation (DE: Diffusion Equation) or light transfer equation (RTE: Radial Transfer Equation).
　そして、測定値と予測値とを比較し、一致度が所定値以上であるか否かを判定する。一致度が所定値より低い場合には、光散乱物質の内部の光学特性値分布を再度仮定し直して予測値を算出し、一致度が所定値以上になるまでこの計算を繰り返す。この繰り返し計算は逆解析演算とも呼ばれる。なお、計測値と予測値との差から、誤差関数を設定することにより一致度を評価することができる。この誤差関数が小さくなるように、光散乱物質の内部の光学特性値分布を再度仮定し直すことにより、測定値と予測値との差を小さくすることができる。上述した逆解析演算には、公知の様々な最適化アルゴリズムを適用することができる。 Then, the measured value and the predicted value are compared to determine whether the degree of coincidence is equal to or more than a predetermined value. If the degree of coincidence is lower than a predetermined value, the optical characteristic value distribution inside the light scattering material is again assumed, the predicted value is calculated, and this calculation is repeated until the degree of coincidence becomes a predetermined value or more. This repeated calculation is also called inverse analysis operation. The degree of coincidence can be evaluated by setting an error function from the difference between the measured value and the predicted value. It is possible to reduce the difference between the measured value and the predicted value by again assuming the optical characteristic value distribution inside the light scattering material so that the error function becomes smaller. Various known optimization algorithms can be applied to the inverse analysis operation described above.
　光散乱物質の内部の光学特性値分布を計測する生体計測装置として、複数の波長が異なる連続波平行ビームを、生体組織の広範な領域に複数の方向から照射し、生体組織で反射又は散乱した光を複数の方向で受光する生体計測装置が開示されている（例えば、特許文献１参照）。この生体計測装置では、空気と生体組織との界面が平坦であるとして、放射伝達モデルを用いて計測した値を解析し、光学特性値分布を推定する。 As a living body measurement device for measuring the optical characteristic value distribution inside the light scattering material, continuous wave parallel beams with different wavelengths were irradiated from a plurality of directions to a wide area of the living tissue and reflected or scattered by the living tissue A living body measurement apparatus which receives light in a plurality of directions is disclosed (see, for example, Patent Document 1). In this living body measuring device, assuming that the interface between air and living tissue is flat, the value measured using a radiation transfer model is analyzed to estimate the optical characteristic value distribution.
　また、近年では、ＯＣＴ（Ｏｐｔｉｃａｌ　Ｃｏｈｅｒｅｎｃｅ　Ｔｏｍｏｇｒａｐｈｙ：光コヒーレンストモグラフィー）を応用した生体内部の光学物性値計測も進められている。ＯＣＴでは、光源からの光を、生体内部で散乱して戻る測定光と、参照ミラーで反射する参照光に分岐して、両者を重畳して干渉信号を計測し演算することで、生体内部の光学物性値分布を取得する。 Further, in recent years, measurement of optical physical property values inside a living body by applying OCT (Optical Coherence Tomography: optical coherence tomography) is also in progress. In OCT, light from a light source is split into measurement light that is scattered back inside the living body and reference light that is reflected by the reference mirror, and both are superimposed and interference signals are measured and calculated. Acquire the optical property value distribution.
特許第４１５６３７３号公報Patent No. 4156373 gazette
　しかしながら、生体組織の表面形状は平坦ではなく凹凸があるため、特許文献１の技術では、推定した光学特性値分布に誤差が生じる場合がある。 However, since the surface shape of the living tissue is not flat but uneven, an error may occur in the estimated optical characteristic value distribution in the technique of Patent Document 1.
　本発明は、上記に鑑みてなされたものであって、生体組織の表面形状による誤差を抑制した生体計測装置、生体計測システム、及び生体計測方法を提供することを目的とする。 The present invention is made in view of the above, and an object of the present invention is to provide a living body measurement device, a living body measurement system, and a living body measurement method, in which an error due to the surface shape of living body tissue is suppressed.
　上述した課題を解決し、目的を達成するために、本発明の一態様に係る生体計測装置は、生体試料の表面に接する平面部を有する透明部材と、前記生体試料が前記平面部と接している領域に含まれる基準点に測定光を照射する光源部と、前記生体試料において散乱された前記測定光を受光する受光部と、を備えることを特徴とする。 In order to solve the problems described above and achieve the object, a biological measurement device according to an aspect of the present invention includes a transparent member having a flat portion in contact with a surface of a biological sample, and the biological sample in contact with the flat portion. A light source unit for irradiating measurement light to a reference point included in a region, and a light receiving unit for receiving the measurement light scattered in the biological sample.
　また、本発明の一態様に係る生体計測装置は、光の一部を透過するとともに、光の一部を反射する光分岐部と、前記光分岐部を透過した光又は前記光分岐部が反射した光の一方である参照光を反射する参照ミラーと、を備え、前記光源部は、前記光分岐部を透過した光又は前記光分岐部が反射した光の他方である前記測定光を、前記生体試料が前記平面部と接している領域に含まれる基準点に照射し、前記受光部は、前記生体試料において散乱された前記測定光と、前記参照ミラーにおいて反射された前記参照光とを受光することを特徴とする。 Further, in the living body measurement apparatus according to an aspect of the present invention, a light branching unit that transmits a part of light and reflects a part of the light, the light transmitted through the light branching unit, or the light branching unit reflects And a reference mirror for reflecting the reference light, which is one of the light beams, wherein the light source unit is the other of the light transmitted through the light branching portion or the other of the light reflected by the light branching portion. A biological sample irradiates a reference point included in a region in contact with the flat portion, and the light receiving unit receives the measurement light scattered in the biological sample and the reference light reflected in the reference mirror. It is characterized by
　また、本発明の一態様に係る生体計測装置は、前記受光部は、前記測定光の前記生体試料における後方散乱光を受光することを特徴とする。 Further, in the living body measurement apparatus according to one aspect of the present invention, the light receiving unit is characterized by receiving backward scattered light in the living body sample of the measurement light.
　また、本発明の一態様に係る生体計測装置は、前記測定光及び前記参照光を分光する分光部を備えることを特徴とする。 In addition, a living body measurement apparatus according to an aspect of the present invention includes a spectroscopy unit that disperses the measurement light and the reference light.
　また、本発明の一態様に係る生体計測装置は、前記光源部は、前記基準点に対して異なる複数の位置から前記測定光を照射可能であることを特徴とする。 In the living body measurement apparatus according to one aspect of the present invention, the light source unit can emit the measurement light from a plurality of different positions with respect to the reference point.
　また、本発明の一態様に係る生体計測装置は、前記受光部は、前記基準点からの前記測定光を異なる複数の位置で受光可能であることを特徴とする。 In the living body measurement apparatus according to one aspect of the present invention, the light receiving unit can receive the measurement light from the reference point at a plurality of different positions.
　また、本発明の一態様に係る生体計測装置は、前記光源部は、前記基準点に前記測定光を複数回照射し、前記受光部は、前記測定光を複数回受光することを特徴とする。 In the living body measurement apparatus according to one aspect of the present invention, the light source unit irradiates the measurement light a plurality of times to the reference point, and the light receiving unit receives the measurement light a plurality of times. .
　また、本発明の一態様に係る生体計測装置は、前記光源部は、前記基準点に互いに波長が異なる複数の前記測定光を照射することを特徴とする。 In the living body measurement apparatus according to one aspect of the present invention, the light source unit irradiates the reference point with a plurality of the measurement lights having different wavelengths.
　また、本発明の一態様に係る生体計測装置は、前記光源部は、前記基準点に波長帯域が広い前記測定光を照射することを特徴とする。 In the living body measurement apparatus according to one aspect of the present invention, the light source unit emits the measurement light having a wide wavelength band to the reference point.
　また、本発明の一態様に係る生体計測装置は、前記透明部材は、前記測定光を透過する材料からなる容器であり、前記平面部は、前記透明部材の底面に形成されており、前記生体試料は、前記平面部の表面に接するように前記透明部材に載置されていることを特徴とする。 In the living body measurement apparatus according to an aspect of the present invention, the transparent member is a container made of a material that transmits the measurement light, and the flat portion is formed on the bottom surface of the transparent member. The sample is characterized in that it is placed on the transparent member so as to be in contact with the surface of the flat portion.
　また、本発明の一態様に係る生体計測装置は、前記生体試料を載置している前記透明部材を水平面内及び重力方向に移動可能な駆動部を備えることを特徴とする。 Further, the living body measurement apparatus according to an aspect of the present invention includes a drive unit capable of moving the transparent member on which the biological sample is placed in a horizontal plane and in a gravity direction.
　また、本発明の一態様に係る生体計測装置は、前記透明部材の前記平面部は、重力又は前記生体試料を載置している容器を重力方向に移動可能な駆動部により前記生体試料の表面に接していることを特徴とする。 Further, in the living body measurement apparatus according to one aspect of the present invention, the flat surface portion of the transparent member is a surface of the living body sample by gravity or a drive unit capable of moving a container on which the living body sample is mounted in the gravity direction. It is characterized by being in contact with
　また、本発明の一態様に係る生体計測システムは、上記の生体計測装置と、前記受光部が受光した信号に基づいて前記生体試料の内部の光学特性値分布を算出する演算部と、を備えることを特徴とする。 Further, a living body measurement system according to an aspect of the present invention includes: the living body measurement device described above; and an operation unit that calculates an optical characteristic value distribution inside the living body sample based on a signal received by the light receiving unit. It is characterized by
　また、本発明の一態様に係る生体計測方法は、透明部材が有する平面部と生体試料の表面とを当接させるように、前記透明部材及び前記生体試料を配置する配置ステップと、前記生体試料が前記平面部と接している領域に含まれる基準点に測定光を照射する光照射ステップと、前記生体試料において散乱された前記測定光を受光する受光ステップと、を含むことを特徴とする。 Further, in the living body measurement method according to one aspect of the present invention, an arrangement step of arranging the transparent member and the living body sample such that the flat portion of the transparent member abuts on the surface of the living body sample; A light irradiation step of irradiating measurement light to a reference point included in a region in contact with the flat portion, and a light reception step of receiving the measurement light scattered in the biological sample.
　また、本発明の一態様に係る生体計測方法は、前記光照射ステップは、前記生体試料が前記平面部と接している領域に含まれる基準点に、光分岐部を透過した光又は前記光分岐部が反射した光の一方である前記測定光を照射し、前記受光ステップは、前記生体試料において散乱された前記測定光と、参照ミラーにおいて反射された前記光分岐部を透過した光又は前記光分岐部が反射した光の他方である参照光とを受光することを特徴とする。 Further, in the living body measurement method according to one aspect of the present invention, the light irradiation step may include light transmitted through the light branching portion or the light branch at a reference point included in a region where the biological sample is in contact with the flat portion. Irradiating the measurement light which is one of the light reflected by the unit, and the light receiving step includes the measurement light scattered by the biological sample and the light transmitted through the light branch unit reflected by the reference mirror or the light The branching unit is characterized in that it receives the reference light which is the other of the reflected light.
　本発明によれば、生体組織の表面形状による誤差を抑制した生体計測装置、生体計測システム、及び生体計測方法を実現することができる。 According to the present invention, it is possible to realize a living body measurement device, a living body measurement system, and a living body measurement method in which an error due to the surface shape of a living body tissue is suppressed.
図１は、本発明の実施の形態１に係る生体計測システムの構成を示す模式図である。FIG. 1 is a schematic view showing a configuration of a living body measurement system according to Embodiment 1 of the present invention. 図２は、実施の形態１の変形例１に係る生体計測装置である。FIG. 2 shows a living body measurement apparatus according to a first modification of the first embodiment. 図３は、本発明の実施の形態２に係る生体計測システムの構成を示す模式図である。FIG. 3 is a schematic view showing a configuration of a living body measurement system according to a second embodiment of the present invention. 図４は、生体計測装置の受光部の位置の他の一例を表す図である。FIG. 4 is a diagram illustrating another example of the position of the light receiving unit of the biological measurement device. 図５は、実施の形態１又は実施の形態２の変形例２に係る生体計測装置の生体試料の配置図である。FIG. 5 is a layout view of a biological sample of a biological measurement device according to Embodiment 1 or Modification 2 of Embodiment 2. 図６は、実施の形態１又は実施の形態２の変形例３に係る生体計測装置の生体試料の配置図である。FIG. 6 is a layout view of a biological sample of a biological measurement device according to Embodiment 1 or Modified Example 3 of Embodiment 2.
　以下に、図面を参照して本発明に係る生体計測装置、生体計測システム、及び生体計測方法の実施の形態を説明する。なお、これらの実施の形態により本発明が限定されるものではない。本発明は、生体計測装置、生体計測システム、及び生体計測方法一般に適用することができる。 Hereinafter, embodiments of a living body measurement apparatus, a living body measurement system, and a living body measurement method according to the present invention will be described with reference to the drawings. Note that the present invention is not limited by these embodiments. The present invention can be applied to a living body measurement device, a living body measurement system, and a living body measurement method in general.
　また、図面の記載において、同一又は対応する要素には適宜同一の符号を付している。また、図面は模式的なものであり、各要素の寸法の関係、各要素の比率等は、現実と異なる場合があることに留意する必要がある。図面の相互間においても、互いの寸法の関係や比率が異なる部分が含まれている場合がある。 Further, in the description of the drawings, the same or corresponding elements are given the same reference numerals as appropriate. In addition, it should be noted that the drawings are schematic, and the relationship between dimensions of each element, the ratio of each element, and the like may differ from reality. Even between the drawings, there may be a case where the dimensional relationships and ratios differ from one another.
（実施の形態１）
　図１は、本発明の実施の形態１に係る生体計測システムの構成を示す模式図である。生体計測システム１は、生体試料Ｓ１の計測を行う生体計測装置２と、生体計測システム１全体を統括的に制御する制御装置３と、により構成される。 Embodiment 1
FIG. 1 is a schematic view showing a configuration of a living body measurement system according to Embodiment 1 of the present invention. The living body measurement system 1 includes a living body measurement device 2 that measures the living body sample S1, and a control device 3 that controls the entire living body measurement system 1 in an integrated manner.
　生体計測装置２は、ＯＣＴにより、生体試料Ｓ１の内部の光学特性値分布を推定する装置である。図１に示すように、生体計測装置２は、生体試料Ｓ１が載置されるステージ４と、生体試料Ｓ１の表面に接する平面部５ａを有する透明部材５と、光の一部を透過するとともに、光の一部を反射する光分岐部６と、光分岐部６を透過した光である測定光を、生体試料Ｓ１が平面部５ａと接している領域に含まれる基準点Ｐ１に照射する光源部７と、光源部７が照射した光を略平行光にするレンズ８と、測定光が生体試料Ｓ１に照射される位置を調整するガルバノスキャナー９と、測定光を集光するレンズ１０と、光分岐部６が反射した光である参照光を反射する参照ミラー１１と、測定光及び参照光を集光するレンズ１２と、測定光及び参照光を波長ごとに分光する分光部１３と、生体試料Ｓ１における測定光の後方散乱光と、参照ミラー１１において反射された参照光とを受光する受光部１４と、ステージ４を駆動する駆動部１５と、を備える。 The living body measurement device 2 is a device that estimates the optical characteristic value distribution inside the living body sample S1 by OCT. As shown in FIG. 1, the living body measurement apparatus 2 transmits a part of light while transmitting the stage 4 on which the living body sample S1 is placed, a transparent member 5 having a flat portion 5a in contact with the surface of the living body sample S1. A light branching portion 6 for reflecting a part of the light, and a light source for irradiating a measurement light which is light transmitted through the light branching portion 6 to a reference point P1 included in a region where the biological sample S1 is in contact with the flat portion 5a A lens 7 for converting the light emitted from the light source 7 into substantially parallel light; a galvano scanner 9 for adjusting the position at which the measurement light is irradiated to the biological sample S1; and a lens 10 for collecting the measurement light. Reference mirror 11 that reflects the reference light that is the light reflected by the light branching unit 6, a lens 12 that collects the measurement light and the reference light, a spectroscopy unit 13 that disperses the measurement light and the reference light for each wavelength, and a living body Backscattered light of measurement light in sample S1, reference mirror 1 It includes a light receiving portion 14 for receiving the reference light reflected in, a drive unit 15 for driving the stage 4, the.
　ステージ４は、駆動部１５による制御のもと、載置された透明部材５を水平面内（図１の左右方向及び紙面に垂直な方向がなす面内）及び重力方向（図１の上下方向）に移動させる。 The stage 4 is under the control of the drive unit 15 in the horizontal plane (in the plane formed by the horizontal direction in FIG. 1 and the direction perpendicular to the paper surface) and in the gravity direction (vertical direction in FIG. 1) Move to
　透明部材５は、測定光を透過する材料からなる容器であり、平面部５ａは、透明部材５の底面に形成されている。その結果、透明部材５に載置された生体試料Ｓ１の表面が平面部５ａに接する。そして、重力により生体試料Ｓ１が平面部５ａに押し付けられた状態となるので、生体試料Ｓ１と平面部５ａとの界面において、生体試料Ｓ１の表面は平坦になる。なお、容器の底面の生体試料Ｓ１を載置する部分のみが透明（透明部材５）であればよく、容器全体が透明でなくてもよい。 The transparent member 5 is a container made of a material that transmits measurement light, and the flat portion 5 a is formed on the bottom surface of the transparent member 5. As a result, the surface of the biological sample S1 placed on the transparent member 5 is in contact with the flat portion 5a. Then, since the biological sample S1 is pressed against the flat portion 5a by gravity, the surface of the biological sample S1 becomes flat at the interface between the biological sample S1 and the flat portion 5a. In addition, only the part which mounts biological sample S1 of the bottom face of a container should just be transparent (transparent member 5), and the whole container does not need to be transparent.
　光分岐部６は、例えばハーフミラーであり、入射した光の一部を透過するとともに、入射した光の一部を反射する。ただし、光源部７からの光を光ファイバで伝搬させる場合には、光分岐部６は光ファイバカプラであってもよい。 The light branching unit 6 is, for example, a half mirror, and transmits a part of the incident light and reflects a part of the incident light. However, when the light from the light source unit 7 is to be propagated through an optical fiber, the light branching unit 6 may be an optical fiber coupler.
　光源部７は、ＳＬＤ（Ｓｕｐｅｒ　Ｌｕｍｉｎｅｓｃｅｎｔ　Ｄｉｏｄｅ）、ＬＥＤ（Ｌｉｇｈｔ　Ｅｍｉｔｔｉｎｇ　Ｄｉｏｄｅ）等の低コヒーレンスな光源、又は水銀ランプ、キセノンランプ、ＬＤＬＳ（Ｌａｓｅｒ－Ｄｒｉｖｅｎ　Ｌｉｇｈｔ　Ｓｏｕｒｃｅ）光源、スーパーコンティニューム光源等の波長帯域が広い白色光源である。なお、光源部７が白色光源である場合、フィルタ等の光学素子により、波長帯域を選択して生体試料Ｓ１に照射する。光源部７から照射する光は、例えば可視光又は赤外光である。フィルタ等の光学素子で選択される波長帯域の中心波長は、生体の光学物性値を取得したい波長で設定する。また、波長帯域の波長幅は、生体計測の深さ方向の分解能と波長分解能とのバランスに基づいて決定される。この波長幅は、通常は半値全幅で２０ｎｍから５０ｎｍの範囲で選択されるが、これに限定されない。光源部７から出射した光は、空間を伝搬して光分岐部６やその他の光学素子へ照射されてもよいが、光ファイバを用いてもよい。光ファイバは、例えばシングルモードファイバ、マルチモードファイバ、フォトニッククリスタルファイバ等が用いられる。ただし、大きな光損失がない光ファイバであれば、これら以外の光ファイバを用いてもよい。 The light source unit 7 is a low coherence light source such as SLD (Super Luminescent Diode) or LED (Light Emitting Diode), or a wavelength band such as a mercury lamp, a xenon lamp, an LDLS (Laser-Driven Light Source) light source, or a supercontinuum light source. Is a wide white light source. When the light source unit 7 is a white light source, a wavelength band is selected by an optical element such as a filter to irradiate the biological sample S1. The light emitted from the light source unit 7 is, for example, visible light or infrared light. The central wavelength of the wavelength band selected by an optical element such as a filter is set at a wavelength at which it is desired to acquire the optical physical property value of the living body. Further, the wavelength width of the wavelength band is determined based on the balance between the resolution in the depth direction of the living body measurement and the wavelength resolution. This wavelength width is usually selected in the range of 20 nm to 50 nm in full width at half maximum, but is not limited thereto. The light emitted from the light source unit 7 may propagate in space and be irradiated to the light branching unit 6 and other optical elements, but an optical fiber may be used. As the optical fiber, for example, a single mode fiber, a multimode fiber, a photonic crystal fiber or the like is used. However, other optical fibers may be used as long as the optical fiber does not have a large optical loss.
　ガルバノスキャナー９は、制御装置３による制御のもと、測定光が生体試料Ｓ１に照射される位置を移動させる。具体的には、ガルバノスキャナー９は、２枚のミラーを動かすことにより、生体試料Ｓ１と透明部材５が接している面を２次元的に走査するように、測定光が生体試料Ｓ１に照射される位置を移動させる。 The galvano scanner 9 moves the position where the measurement light is irradiated to the biological sample S1 under the control of the control device 3. Specifically, the measurement light is irradiated to the biological sample S1 so that the galvano scanner 9 two-dimensionally scans the surface where the biological sample S1 and the transparent member 5 are in contact by moving the two mirrors. Move the
　参照ミラー１１は、光分岐部６で反射した参照光を受光部１４に向けて反射する。 The reference mirror 11 reflects the reference light reflected by the light branching unit 6 toward the light receiving unit 14.
　分光部１３は、例えば光学フィルタ、分散型分光器、フーリエ変換型分光器等であり、測定光及び参照光を波長ごとに分光する。分散型分光器は、プリズムや回折格子を有する単色計（モノクロメーター：Ｍｏｎｏｃｈｒｏｍａｔｏｒ）又は多色計（ポリクロメーター：Ｐｐｏｌｙｃｈｒｏｍａｔｏｒ）である。また、分光部１３及び受光部１４としての機能を兼ね備えた単色計であるスペクトルアナライザーを用いてもよい。 The spectroscope unit 13 is, for example, an optical filter, a dispersive spectroscope, a Fourier transform type spectroscope, or the like, and disperses the measurement light and the reference light for each wavelength. The dispersive spectrometer is a monochromator (Monochromator) or a polychromator (Ppolychromator) having a prism and a diffraction grating. In addition, a spectrum analyzer which is a monochromator having the functions of the spectral unit 13 and the light receiving unit 14 may be used.
　受光部１４は、分光部１３により分光された測定光及び参照光を受光する。受光部１４は、複数のＣＭＯＳ（Ｃｏｍｐｌｅｍｅｎｔａｒｙ　Ｍｅｔａｌ　Ｏｘｉｄｅ　Ｓｅｍｉｃｏｎｄｕｃｔｏｒ）やＣＣＤ（Ｃｈａｒｇｅ　Ｃｏｕｐｌｅｄ　Ｄｅｖｉｃｅｓ）がライン状に並べられたラインセンサであり、受光した光を光電変換により電気信号に変換する。ただし、受光部１４は、１つのＣＭＯＳ又はＣＣＤであってもよく、受光部１４を測定光及び参照光が入射する方向と直交する方向に移動させ、分光部１３により分光された波長が異なる光を受光してもよい。また、受光部１４は、ＣＭＯＳ又はＣＣＤが２次元状に配列されたエリアセンサであってもよい。 The light receiving unit 14 receives the measurement light and the reference light separated by the light separating unit 13. The light receiving unit 14 is a line sensor in which a plurality of complementary metal oxide semiconductors (CMOSs) and charge coupled devices (CCDs) are arranged in a line, and converts received light into an electrical signal by photoelectric conversion. However, the light receiving unit 14 may be one CMOS or CCD, and moves the light receiving unit 14 in a direction orthogonal to the directions in which the measurement light and the reference light are incident, and light having different wavelengths dispersed by the light separating unit 13 May be received. Further, the light receiving unit 14 may be an area sensor in which a CMOS or a CCD is two-dimensionally arranged.
　駆動部１５は、生体試料Ｓ１を載置している透明部材５を水平面内及び重力方向に移動可能である。 The driving unit 15 is capable of moving the transparent member 5 on which the biological sample S1 is placed in the horizontal plane and in the gravity direction.
　制御装置３は、例えばＣＰＵ（Ｃｅｎｔｒａｌ　Ｐｒｏｃｅｓｓｉｎｇ　Ｕｎｉｔ）等の汎用プロセッサ、又はＡＳＩＣ（Ａｐｐｌｉｃａｔｉｏｎ　Ｓｐｅｃｉｆｉｃ　Ｉｎｔｅｇｒａｔｅｄ　Ｃｉｒｃｕｉｔ）等の特定の機能を実行する各種演算回路等の専用プロセッサを含むワークステーションやパーソナルコンピュータを用いて構成される。制御装置３は、光源部７、ガルバノスキャナー９、受光部１４、及び駆動部１５等を制御する。 The control device 3 uses, for example, a workstation or a personal computer including a dedicated processor such as a general-purpose processor such as a central processing unit (CPU) or various arithmetic circuits that execute specific functions such as an application specific integrated circuit (ASIC). Configured The control device 3 controls the light source unit 7, the galvano scanner 9, the light receiving unit 14, the drive unit 15, and the like.
　また、制御装置３は、受光部１４が受光した信号に基づいて生体試料Ｓ１の内部の光学特性値分布を算出する演算部３ａを備える。生体試料Ｓ１の内部の光学特性値分布とは、例えば生体試料Ｓ１の内部の吸収係数分布、散乱係数分布、又は非等方パラメータ分布等である。演算部３ａは、生体試料Ｓ１と平面部５ａとの界面が平坦であるとして逆解析演算により光学特性値分布を算出する。 Further, the control device 3 includes an operation unit 3a that calculates the optical characteristic value distribution inside the biological sample S1 based on the signal received by the light receiving unit 14. The optical characteristic value distribution inside the biological sample S1 is, for example, the absorption coefficient distribution, the scattering coefficient distribution, the anisotropic parameter distribution, etc. inside the biological sample S1. Arithmetic unit 3a calculates the optical characteristic value distribution by inverse analysis, assuming that the interface between biological sample S1 and flat portion 5a is flat.
　次に、生体計測装置２を用いた生体試料Ｓ１に対する生体計測方法について説明する。はじめに、透明部材５が有する平面部５ａと生体試料Ｓ１の表面とを当接させるように、透明部材５及び生体試料Ｓ１を配置する（配置ステップ）。具体的には、透明部材５の平面部５ａ上に生体試料Ｓ１を載置する。すると、生体試料Ｓ１と平面部５ａとの界面において、生体試料Ｓ１の表面は平坦になる。 Next, a living body measurement method for the living body sample S1 using the living body measurement device 2 will be described. First, the transparent member 5 and the biological sample S1 are arranged such that the flat portion 5a of the transparent member 5 abuts on the surface of the biological sample S1 (arrangement step). Specifically, the biological sample S1 is placed on the flat portion 5a of the transparent member 5. Then, the surface of the biological sample S1 becomes flat at the interface between the biological sample S1 and the flat portion 5a.
　続いて、光源部７が、制御装置３による制御のもと、生体試料Ｓ１が平面部５ａと接している領域に含まれる基準点Ｐ１に測定光を照射する（光照射ステップ）。なお、光源部７が、基準点Ｐ１に測定光を照射した場合に、光源部７から受光部１４までの測定光の光路長と参照光の光路長とが等しくなるように予め調整されている。具体的には、ステージ４を測定光の光軸に沿った方向（図１の上下方向）に移動させる、又は参照ミラー１１を参照光の光軸に沿った方向（図１の左右方向）に移動させることにより、光源部７から受光部１４までの測定光の光路長と参照光の光路長とを等しくする。生体内部の光学物性値の計測が可能な領域は、基準点Ｐ１から生体の深部側となる。従って、このように基準点Ｐ１を生体試料Ｓ１の表面に設定することにより、生体の表面付近の光学物性値分布を計測することが可能となる。なお、生体のより深部の光学物性値分布を計測したい場合には、基準点Ｐ１を生体の表面ではなく、生体の内部に設定してもよい。 Subsequently, under the control of the control device 3, the light source unit 7 irradiates measurement light to the reference point P1 included in the area where the biological sample S1 is in contact with the flat portion 5a (light irradiation step). When the light source unit 7 irradiates the measurement light to the reference point P1, the light path length of the measurement light from the light source unit 7 to the light receiving unit 14 is adjusted in advance so that the light path length of the reference light becomes equal. . Specifically, the stage 4 is moved in the direction along the optical axis of the measurement light (vertical direction in FIG. 1), or the reference mirror 11 is in the direction along the optical axis of the reference light (horizontal direction in FIG. 1) By moving, the optical path length of the measurement light from the light source unit 7 to the light receiving unit 14 and the optical path length of the reference light are equalized. The area in which the optical physical property value in the living body can be measured is the deep side of the living body from the reference point P1. Therefore, by setting the reference point P1 on the surface of the biological sample S1 as described above, it becomes possible to measure the optical property value distribution in the vicinity of the surface of the living body. When it is desired to measure the optical property value distribution in the deeper part of the living body, the reference point P1 may be set not in the surface of the living body but in the inside of the living body.
　その後、受光部１４が、生体試料Ｓ１の基準点Ｐ１において散乱された測定光と、参照ミラー１１において反射された参照光とを受光する（受光ステップ）。 Thereafter, the light receiving unit 14 receives the measurement light scattered at the reference point P1 of the biological sample S1 and the reference light reflected by the reference mirror 11 (light receiving step).
　そして、演算部３ａが、受光部１４が受光した信号に基づいて生体試料Ｓ１の内部の光学特性値分布を算出する（演算ステップ）。ここで、演算部３ａは、測定光が生体試料Ｓ１に入射して、生体試料Ｓ１の内部で散乱して戻る測定光と参照ミラー１１で反射された参照光とによる干渉光が分光部１３により分光された分光情報を、フーリエ変換等の演算により生体試料Ｓ１の深さ方向の情報に変換して、フィッティング等の演算を行うことにより生体試料Ｓ１の内部の光学物性値分布を算出する。 Then, the calculation unit 3a calculates the optical characteristic value distribution inside the biological sample S1 based on the signal received by the light receiving unit 14 (calculation step). Here, in the calculation unit 3a, interference light due to the measurement light that is incident upon the biological sample S1 and scattered back inside the biological sample S1 and the reference light that is reflected by the reference mirror 11 is received by the spectroscopic unit 13 The spectral information thus dispersed is converted into information in the depth direction of the biological sample S1 by calculation such as Fourier transformation, and calculation such as fitting is performed to calculate the optical property value distribution inside the biological sample S1.
　以上説明したように、生体計測装置２では、基準点Ｐ１に測定光を照射し、基準点Ｐ１を測定光路と参照光路とが略等しくなる位置として戻り光を計測して、演算を行うことにより生体内部の光学物性値分布を導出する。実施の形態１によれば、生体試料Ｓ１と平面部５ａとの界面が平坦になるので、生体表面の凹凸による計測誤差を抑制した生体計測装置を実現することができる。 As described above, in the living body measurement apparatus 2, the measurement light is irradiated to the reference point P1, and the return light is measured with the reference point P1 as a position where the measurement optical path and the reference optical path become approximately equal, and calculation is performed. We derive the optical property value distribution inside the living body. According to the first embodiment, since the interface between the biological sample S1 and the flat portion 5a is flat, it is possible to realize the biological measurement device in which the measurement error due to the unevenness of the biological surface is suppressed.
　また、生体試料Ｓ１と透明部材５とが接することで、生体試料Ｓ１と外部との屈折率差を小さくすることができるため、生体表面における反射光によるＳ／Ｎの低下を防ぐことができる。なお、透明部材５がない場合には、生体試料Ｓ１の周囲は空気であるため、生体試料Ｓ１と外部との屈折率差が０．３以上になってしまう。透明部材５を配置することにより、生体試料Ｓ１と外部との屈折率差を０．１以下に抑えることができる。なお、透明部材５が空気と接する側（透明部材５が生体試料Ｓ１と接する側の反対側）の表面に反射防止コートを施すことにより、透明部材５の２つの光学面の双方の反射光を小さくし、計測におけるＳ／Ｎの低下をさらに抑制することができる。 In addition, since the biological sample S1 and the transparent member 5 are in contact with each other, the difference in refractive index between the biological sample S1 and the outside can be reduced, so that the decrease in S / N due to reflected light on the surface of the living body can be prevented. In the case where the transparent member 5 is not present, the surrounding of the biological sample S1 is air, so that the refractive index difference between the biological sample S1 and the outside is 0.3 or more. By arranging the transparent member 5, the refractive index difference between the biological sample S1 and the outside can be suppressed to 0.1 or less. An antireflective coating is applied to the surface of the side where the transparent member 5 is in contact with air (the opposite side of the side where the transparent member 5 is in contact with the biological sample S1). It is possible to reduce the S / N in measurement further.
　また、生体試料Ｓ１と透明部材５との間を生理食塩水等の液体で満たすことにより、計測のＳ／Ｎの低下を防ぐことができる。生体試料Ｓ１の表面に凹凸があると、生体試料Ｓ１と透明部材５との間に空気が存在し、大きな屈折率差を生じることとなるが、液体を介在させることにより、空気をなくして屈折率差を小さく保つことができるためである。なお、上記液体は生理食塩水以外のものを用いてもよい。 In addition, by filling the space between the biological sample S1 and the transparent member 5 with a liquid such as physiological saline, it is possible to prevent a decrease in S / N of measurement. If the surface of the biological sample S1 has irregularities, air will be present between the biological sample S1 and the transparent member 5 and a large difference in refractive index will be produced. This is because the rate difference can be kept small. In addition, you may use the said liquid other than a physiological saline.
（変形例１）
　図２は、実施の形態１の変形例１に係る生体計測装置である。図２に示すように、実施の形態１の変形例１に係る生体計測システム１Ａにおいて、生体計測装置２Ａは、光分岐部６を有しない。生体計測装置２Ａは、光分岐部１６Ａにおける透過光及び反射光をそれぞれ測定光及び参照光として計測する。光分岐部１６において反射された参照光は、参照ミラー１１Ａで反射した後に光分岐部１６Ａで再び反射され、生体試料Ｓ１で散乱して戻ってくる測定光と干渉する。そして、干渉光を分光部１３で分光し、受光部１４で受光した後、演算部３ａで演算することにより生体内部の光学物性値分布を導出することができる。このように、対物レンズ群のなかに光分岐部と参照ミラーとを配置する光学系をミロー（Ｍｉｒａｕ）干渉計、又はミラウ干渉計と呼ぶ。 (Modification 1)
FIG. 2 shows a living body measurement apparatus according to a first modification of the first embodiment. As shown in FIG. 2, in the living body measurement system 1A according to the first modification of the first embodiment, the living body measurement device 2A does not have the light branching unit 6. The living body measurement apparatus 2A measures the transmitted light and the reflected light in the light branching unit 16A as a measurement light and a reference light, respectively. The reference light reflected by the light branching unit 16 is reflected by the reference mirror 11A and then reflected again by the light branching unit 16A, and interferes with the measurement light scattered and returned by the biological sample S1. Then, after the interference light is split by the splitting unit 13 and received by the light receiving unit 14, the optical physical property value distribution inside the living body can be derived by calculation by the calculation unit 3 a. Thus, an optical system in which the light branching portion and the reference mirror are disposed in the objective lens group is referred to as a Mirau interferometer or a Mirau interferometer.
　なお、上述した生体計測方法では、測定及び演算を１回行う例について説明したが、ガルバノスキャナー９によって測定光が生体試料Ｓ１に照射される位置を走査しながら測定光を複数回照射し、受光部１４により測定光を複数回受光し、測定光の照射位置を基準点として逆解析演算を行うことにより、測定の精度をさらに高くすることができる。 In the living body measurement method described above, an example in which measurement and calculation are performed once has been described, but the measurement light is irradiated multiple times while scanning the position where the measurement light is applied to the biological sample S1 by the galvano scanner 9 The accuracy of the measurement can be further enhanced by receiving the measurement light a plurality of times by the unit 14 and performing the inverse analysis calculation with the irradiation position of the measurement light as a reference point.
　また、複数の異なる波長で計測を行うことにより、光学物性値分布の波長依存性に関する情報をさらに取得することができる。 Further, by performing measurement at a plurality of different wavelengths, it is possible to further acquire information on the wavelength dependency of the optical physical property value distribution.
　また、生体計測装置２として、分光部１３を備えるＳＤ（Ｓｐｅｃｔｒａｌ　Ｄｏｍａｉｎ）－ＯＣＴについて説明したが、これに限られない。例えば、光源部７として、波長掃引レーザや光コム等の波長掃引光源を用いるとともに、分光部を用いないＳＳ（Ｓｗｅｐｔ　Ｓｏｕｒｃｅ）－ＯＣＴに適用してもよい。ＳＳ－ＯＣＴとすることにより、ＳＤ－ＯＣＴより高速化が可能であるだけでなく、生体試料Ｓ１の表面から離れた深い位置の光学特性値を推定することができる。また、参照ミラー１１を参照光に沿った方向に移動させるＴＤ（Ｔｉｍｅ　Ｄｏｍａｉｎ）－ＯＣＴに適用してもよい。 Further, although the SD (Spectral Domain) -OCT including the spectroscope unit 13 has been described as the living body measurement device 2, the present invention is not limited to this. For example, as the light source unit 7, a wavelength sweeping laser such as a wavelength sweeping laser or an optical comb may be used, and the present invention may be applied to SS (Swept Source) -OCT using no spectroscopic unit. By using SS-OCT, it is possible not only to achieve higher speed than SD-OCT, but also to estimate the optical property value at a deep position away from the surface of the biological sample S1. The present invention may be applied to TD (Time Domain) -OCT in which the reference mirror 11 is moved in the direction along the reference light.
　また、基準点Ｐ１は、生体計測装置２の受光部１４で受光する情報を用いて設定してもよいが、レーザ変位計などの別の計測手段を用いて設定してもよい。例えば、予め位置が調整されたレーザ変位計により、生体表面までの距離を計測して、生体の位置を調整することによって、基準点Ｐ１を生体表面又は生体内部に設定することが容易となる。 Further, the reference point P1 may be set using information received by the light receiving unit 14 of the living body measurement device 2, but may be set using another measuring means such as a laser displacement meter. For example, by measuring the distance to the surface of the living body by using a laser displacement meter whose position has been adjusted in advance and adjusting the position of the living body, it becomes easy to set the reference point P1 on the living body surface or inside the living body.
　また、透明部材５は、表面と裏面とが平行な平板でもよいが、表面と裏面とが平行でない例えばくさび形の板でもよい。透明部材５が平行な平板である場合、製造が簡単であるため、製造装置の製作コストを抑えることができる。一方、透明部材５がくさび形の板である場合、透明部材５と空気との界面からの反射光を受光部１４が受光することを防ぐことができるので、計測のＳ／Ｎを高くすることが可能となる。 The transparent member 5 may be a flat plate whose front and back surfaces are parallel, but may be, for example, a wedge-shaped plate whose front and back surfaces are not parallel. In the case where the transparent members 5 are parallel flat plates, the manufacturing is easy, so the manufacturing cost of the manufacturing apparatus can be reduced. On the other hand, when the transparent member 5 is a wedge-shaped plate, it is possible to prevent the light receiving unit 14 from receiving the reflected light from the interface between the transparent member 5 and the air, so the measurement S / N should be high. Is possible.
（実施の形態２）
　図３は、本発明の実施の形態２に係る生体計測システムの構成を示す模式図である。生体計測システム１００は、生体試料Ｓ２の計測を行う生体計測装置１０１と、生体計測システム１００全体を統括的に制御する制御装置１０２と、により構成される。 Second Embodiment
FIG. 3 is a schematic view showing a configuration of a living body measurement system according to a second embodiment of the present invention. The living body measurement system 100 includes a living body measurement device 101 that measures the living body sample S2, and a control device 102 that controls the whole living body measurement system 100 in an integrated manner.
　生体計測装置１０１は、拡散光トモグラフィーにより、生体試料Ｓ１の内部の光学特性値分布を推定する装置である。図３に示すように、生体計測装置１０１は、生体試料Ｓ２が載置されるステージ１０３と、生体試料Ｓ２の表面に接する平面部１０４ａを有する透明部材１０４と、生体試料Ｓ２が平面部１０４ａと接している領域に含まれる基準点Ｐ２に測定光を照射する光源部１０５と、光スイッチ１０６と、光照射部１０７と、生体試料Ｓ２内において散乱された測定光を受光する受光部１０８と、受光部駆動部１０９と、ステージ１０３を駆動する駆動部１１０と、を備える。 The living body measurement apparatus 101 is an apparatus for estimating the optical characteristic value distribution inside the living body sample S1 by diffused light tomography. As shown in FIG. 3, the living body measurement apparatus 101 includes a stage 103 on which the living body sample S2 is mounted, a transparent member 104 having a flat portion 104a in contact with the surface of the living body sample S2, and a flat portion 104a with the living body sample S2. A light source unit 105 that irradiates measurement light to a reference point P2 included in the area in contact, an optical switch 106, a light irradiation unit 107, and a light receiving unit 108 that receives measurement light scattered in the biological sample S2; The light receiving unit driving unit 109 and a driving unit 110 for driving the stage 103 are provided.
　ステージ１０３は、駆動部１１０による制御のもと、載置された透明部材１０４を水平面内（図３の左右方向及び紙面に垂直な方向がなす面内）及び重力方向（図３の上下方向）に移動させる。ステージ１０３は、駆動部１１０による制御のもと、載置された透明部材１０４をＸ軸方向（図３の左右方向）に移動させるＸステージ１０３ａと、Ｙ軸方向（図３の紙面に垂直な方向）に移動させるＹステージ１０３ｂと、Ｚ軸方向（図３の上下方向）に移動させるＺステージ１０３ｃと、を有する。 The stage 103 is under the control of the drive unit 110, in the horizontal plane (in the plane formed by the horizontal direction in FIG. 3 and the direction perpendicular to the paper surface) and in the gravity direction (vertical direction in FIG. 3) Move to The stage 103 includes an X stage 103a for moving the placed transparent member 104 in the X axis direction (left and right direction in FIG. 3) under the control of the drive unit 110, and a Y axis direction (vertical to the sheet of FIG. 3). 3), and a Z stage 103c which is moved in the Z axis direction (vertical direction in FIG. 3).
　透明部材１０４は、測定光を透過する材料からなる容器であり、平面部１０４ａは、透明部材１０４の底面に形成されている。その結果、透明部材１０４に載置された生体試料Ｓ２の表面が平面部１０４ａに接する。そして、重力により生体試料Ｓ２が平面部１０４ａに押し付けられた状態となるので、生体試料Ｓ２と平面部１０４ａとの界面において、生体試料Ｓ２の表面は平坦になる。 The transparent member 104 is a container made of a material that transmits measurement light, and the flat portion 104 a is formed on the bottom surface of the transparent member 104. As a result, the surface of the biological sample S2 placed on the transparent member 104 is in contact with the flat portion 104a. Then, since the biological sample S2 is pressed against the flat portion 104a by gravity, the surface of the biological sample S2 becomes flat at the interface between the biological sample S2 and the flat portion 104a.
　光源部１０５は、光スイッチ１０６及び光照射部１０７を介して、基準点Ｐ２に対して異なる複数の位置から測定光を照射可能である。光源部１０５は、ＬＤ（Ｌａｓｅｒ　Ｄｉｏｄｅ）光源等のレーザ光源、ＳＬＤ、ＬＥＤ等の低コヒーレンスな光源、又は水銀ランプ、キセノンランプ、ＬＤＬＳ（Ｌａｓｅｒ－Ｄｒｉｖｅｎ　Ｌｉｇｈｔ　Ｓｏｕｒｃｅ）光源、スーパーコンティニューム光源等の波長帯域が広い白色光源である。なお、光源部１０５が白色光源である場合、フィルタ等の光学素子により、波長帯域を選択して生体試料Ｓ２に照射する。光源部１０５から照射する光は、例えば可視光又は赤外光である。フィルタ等の光学素子で選択される波長帯域の中心波長は、生体の光学物性値を取得したい波長で設定する。また、波長帯域の波長幅は、生体計測の深さ方向の分解能と波長分解能とのバランスに基づいて決定される。この波長幅は、通常は半値全幅で２０ｎｍから５０ｎｍの範囲で選択されるが、これに限定されない。光源部１０５から出射した光は、空間を伝搬して光照射部１０７やその他の光学素子へ照射されてもよいが、光ファイバを用いてもよい。光ファイバは、例えばシングルモードファイバ、マルチモードファイバ、フォトニッククリスタルファイバ等が用いられる。ただし、大きな光損失がない光ファイバであれば、これら以外の光ファイバを用いてもよい。 The light source unit 105 can emit measurement light from a plurality of different positions with respect to the reference point P2 via the light switch 106 and the light emitting unit 107. The light source unit 105 is a laser light source such as a LD (Laser Diode) light source, a low coherence light source such as an SLD or LED, or a wavelength such as a mercury lamp, a xenon lamp, an LDLS (Laser-Driven Light Source) light source, or a supercontinuum light source. It is a white light source with a wide bandwidth. When the light source unit 105 is a white light source, a wavelength band is selected by an optical element such as a filter and the biological sample S2 is irradiated. The light emitted from the light source unit 105 is, for example, visible light or infrared light. The central wavelength of the wavelength band selected by an optical element such as a filter is set at a wavelength at which it is desired to acquire the optical physical property value of the living body. Further, the wavelength width of the wavelength band is determined based on the balance between the resolution in the depth direction of the living body measurement and the wavelength resolution. This wavelength width is usually selected in the range of 20 nm to 50 nm in full width at half maximum, but is not limited thereto. The light emitted from the light source unit 105 may propagate in space and be irradiated to the light irradiation unit 107 and other optical elements, but an optical fiber may be used. As the optical fiber, for example, a single mode fiber, a multimode fiber, a photonic crystal fiber or the like is used. However, other optical fibers may be used as long as the optical fiber does not have a large optical loss.
　光照射部１０７は、互いに異なる位置から基準点Ｐ２に測定光を照射する第１光照射部１０７ａと、第２光照射部１０７ｂと、第３光照射部１０７ｃと、を有する。第１光照射部１０７ａ、第２光照射部１０７ｂ、及び第３光照射部１０７ｃは、光ファイバからなり、光スイッチ１０６によっていずれか１つの光照射部が基準点Ｐ２に測定光を照射する。第１光照射部１０７ａ、第２光照射部１０７ｂ、及び第３光照射部１０７ｃは、透明部材１０４の平面部１０４ａに垂直な方向を０°として、それぞれ０°、３０°、６０°の方向から基準点Ｐ２に測定光を照射する。ただし、これらの角度は一例であり、特に限定されない。なお、基準点Ｐ２に測定光を照射する際には、透明部材１０４の屈折率や厚みを考慮して、第１光照射部１０７ａ、第２光照射部１０７ｂ、及び第３光照射部１０７ｃから同一の基準点Ｐ２に測定光を照射する。 The light irradiator 107 includes a first light irradiator 107a, a second light irradiator 107b, and a third light irradiator 107c that irradiate measurement light to the reference point P2 from different positions. The first light irradiator 107a, the second light irradiator 107b, and the third light irradiator 107c are made of an optical fiber, and one of the light irradiators irradiates the measurement light to the reference point P2 by the light switch 106. The first light irradiator 107a, the second light irradiator 107b, and the third light irradiator 107c have directions of 0 °, 30 °, and 60 °, respectively, with the direction perpendicular to the flat portion 104a of the transparent member 104 as 0 °. The measurement light is emitted to the reference point P2. However, these angles are an example and are not particularly limited. When the measurement light is irradiated to the reference point P2, the first light irradiation unit 107a, the second light irradiation unit 107b, and the third light irradiation unit 107c are considered in consideration of the refractive index and the thickness of the transparent member 104. The measurement light is irradiated to the same reference point P2.
　受光部１０８は、基準点Ｐ２からの測定光を異なる複数の位置で受光可能である。受光部１０８は、ＣＭＯＳやＣＣＤであり、受光した光を光電変換により電気信号に変換する。受光部１０８は、受光部駆動部１０９により移動し、第１受光位置１０８ａ、第２受光位置１０８ｂ、及び第３受光位置１０８ｃにおいて、基準点Ｐ２からの測定光を受光する。第１受光位置１０８ａ、第２受光位置１０８ｂ、及び第３受光位置１０８ｃは、透明部材１０４の平面部１０４ａに垂直な方向を０°として、それぞれ２０°、４５°、７０°の方向である。ただし、これらの角度は一例であり、特に限定されない。 The light receiving unit 108 can receive the measurement light from the reference point P2 at a plurality of different positions. The light receiving unit 108 is a CMOS or a CCD, and converts the received light into an electric signal by photoelectric conversion. The light receiving unit 108 is moved by the light receiving unit driving unit 109, and receives the measurement light from the reference point P2 at the first light receiving position 108a, the second light receiving position 108b, and the third light receiving position 108c. The first light receiving position 108a, the second light receiving position 108b, and the third light receiving position 108c are directions of 20 °, 45 °, and 70 °, respectively, with the direction perpendicular to the flat portion 104a of the transparent member 104 as 0 °. However, these angles are an example and are not particularly limited.
　なお、上述したように、第１光照射部１０７ａ、第２光照射部１０７ｂ、及び第３光照射部１０７ｃと、第１受光位置１０８ａ、第２受光位置１０８ｂ、及び第３受光位置１０８ｃとの位置は特に限定されないが、第１光照射部１０７ａ、第２光照射部１０７ｂ、及び第３光照射部１０７ｃと、第１受光位置１０８ａ、第２受光位置１０８ｂ、及び第３受光位置１０８ｃとの位置は、透明部材１０４の平面部１０４ａに垂直な方向を挟んで対向する位置にならないようにずらされていることが好ましい。この場合、生体試料Ｓ２の表面で正反射した光を受光することにより計測に誤差が生じることを防止することができる。 As described above, the first light emitting unit 107a, the second light emitting unit 107b, and the third light emitting unit 107c, and the first light receiving position 108a, the second light receiving position 108b, and the third light receiving position 108c. Although the position is not particularly limited, the first light emitting unit 107a, the second light emitting unit 107b, and the third light emitting unit 107c, and the first light receiving position 108a, the second light receiving position 108b, and the third light receiving position 108c. The position is preferably shifted so as not to be opposite to each other across a direction perpendicular to the flat portion 104 a of the transparent member 104. In this case, it is possible to prevent the occurrence of an error in measurement by receiving the light regularly reflected on the surface of the biological sample S2.
　受光部駆動部１０９は、基準点Ｐ２を中心とした円弧状に受光部１０８の位置を移動させる。 The light receiving unit driving unit 109 moves the position of the light receiving unit 108 in an arc shape centering on the reference point P2.
　駆動部１１０は,制御装置１０２による制御のもと、Ｘステージ１０３ａ、Ｙステージ１０３ｂ、及びＺステージ１０３ｃを駆動する。 The drive unit 110 drives the X stage 103 a, the Y stage 103 b, and the Z stage 103 c under the control of the control device 102.
　制御装置１０２は、例えばＣＰＵ等の汎用プロセッサ、又はＡＳＩＣ等の特定の機能を実行する各種演算回路等の専用プロセッサを含むワークステーションやパーソナルコンピュータを用いて構成される。制御装置１０２は、光源部１０５、光スイッチ１０６、受光部１０８、及び駆動部１１０等を制御する。 The control device 102 is configured using, for example, a workstation or a personal computer including a general purpose processor such as a CPU or a dedicated processor such as various arithmetic circuits that execute a specific function such as an ASIC. The control device 102 controls the light source unit 105, the light switch 106, the light receiving unit 108, the driving unit 110, and the like.
　また、制御装置１０２は、受光部１０８が受光した信号に基づいて生体試料Ｓ２の内部の光学特性値分布を算出する演算部１０２ａを備える。生体試料Ｓ２の内部の光学特性値分布とは、例えば生体試料Ｓ２の内部の吸収係数分布、散乱係数分布、又は非等方パラメータ分布等である。演算部１０２ａは、生体試料Ｓ２と平面部１０４ａとの界面が平坦であるとして逆解析演算により光学特性値分布を算出する。 Further, the control device 102 includes an operation unit 102a that calculates an optical characteristic value distribution inside the biological sample S2 based on the signal received by the light receiving unit 108. The optical characteristic value distribution inside the biological sample S2 is, for example, an absorption coefficient distribution, a scattering coefficient distribution, or an anisotropic parameter distribution inside the biological sample S2. The calculation unit 102a calculates the optical characteristic value distribution by inverse analysis calculation on the assumption that the interface between the biological sample S2 and the flat portion 104a is flat.
　次に、生体計測装置１０１を用いた生体試料Ｓ２に対する生体計測方法について説明する。はじめに、透明部材１０４が有する平面部１０４ａと生体試料Ｓ２の表面とを当接させるように、透明部材１０４及び生体試料Ｓ２を配置する（配置ステップ）。具体的には、透明部材１０４の平面部１０４ａ上に生体試料Ｓ２を載置する。すると、生体試料Ｓ２と平面部１０４ａとの界面において、生体試料Ｓ２の表面は平坦になる。 Next, a living body measurement method for the living body sample S2 using the living body measurement device 101 will be described. First, the transparent member 104 and the biological sample S2 are disposed such that the flat portion 104a of the transparent member 104 abuts on the surface of the biological sample S2 (arrangement step). Specifically, the biological sample S2 is placed on the flat portion 104a of the transparent member 104. Then, the surface of the biological sample S2 becomes flat at the interface between the biological sample S2 and the flat portion 104a.
　続いて、光源部１０５が、制御装置１０２による制御のもと、光スイッチ１０６を介して、第１光照射部１０７ａから、生体試料Ｓ２が平面部１０４ａと接している領域に含まれる基準点Ｐ２に測定光を照射する（光照射ステップ）。 Subsequently, under the control of the control device 102, the light source unit 105 is a reference point P2 included in the area where the biological sample S2 is in contact with the flat unit 104a from the first light irradiation unit 107a via the light switch 106. To the measurement light (light irradiation step).
　その後、受光部１０８が、生体試料Ｓ２において散乱された測定光を、第１受光位置１０８ａで受光する（受光ステップ）。なお、受光部１０８は、駆動部１１０によって移動し、第２受光位置１０８ｂ、及び第３受光位置１０８ｃの各位置においても測定光を受光する。 Thereafter, the light receiving unit 108 receives the measurement light scattered in the biological sample S2 at the first light receiving position 108a (light receiving step). The light receiving unit 108 is moved by the driving unit 110, and receives measurement light also at each of the second light receiving position 108b and the third light receiving position 108c.
　同様に、光源部１０５は、制御装置１０２による制御のもと、光スイッチ１０６を介して、第２光照射部１０７ｂ及び第３光照射部１０７ｃから、基準点Ｐ２に測定光を照射し、受光部１０８は、駆動部１１０によって移動し、第１受光位置１０８ａ、第２受光位置１０８ｂ、及び第３受光位置１０８ｃの各位置において測定光を受光する。 Similarly, under the control of the control device 102, the light source unit 105 emits measurement light to the reference point P2 from the second light irradiation unit 107b and the third light irradiation unit 107c via the light switch 106, and receives light. The unit 108 is moved by the drive unit 110, and receives measurement light at each of the first light receiving position 108a, the second light receiving position 108b, and the third light receiving position 108c.
　そして、演算部１０２ａが、受光部１０８が受光した信号に基づいて生体試料Ｓ２の内部の光学特性値分布を算出する（演算ステップ）。ここで、演算部１０２ａは、測定光が基準点Ｐ２から入射して、生体試料Ｓ２の内部を伝搬する様子を逆解析演算により推定することによって生体試料Ｓ２の内部の光学特性値分布を算出する。なお、光を複数の角度から照射し、複数の角度で受光する場合（拡散光トモグラフィー）、光学物性値分布を算出する際に、生体試料Ｓ２のどの位置にどの方向から光が入射し、どの方向で光を受光したかの情報が必要になるため、演算部１０２ａは、光照射部１０７及び受光部１０８から予めこれらの情報を取得している。 Then, the calculation unit 102a calculates the optical characteristic value distribution inside the biological sample S2 based on the signal received by the light receiving unit 108 (calculation step). Here, the calculation unit 102a calculates the optical characteristic value distribution inside the biological sample S2 by estimating the propagation of the measurement light from the reference point P2 and propagating inside the biological sample S2 by inverse analysis. . When light is irradiated from a plurality of angles and received at a plurality of angles (diffuse optical tomography), when calculating the optical property value distribution, the light is incident on which position of the biological sample S2 from which direction, Since information on whether light is received in the direction is required, the calculation unit 102a acquires these pieces of information in advance from the light irradiation unit 107 and the light reception unit 108.
　以上説明したように、生体計測装置１０１では、基準点Ｐ２に測定光を照射し、基準点Ｐ２を測定光が入射した位置として逆解析演算を行う。そして、基準点Ｐ２は、生体試料Ｓ２と平面部１０４ａとが接している領域に含まれており、生体試料Ｓ２の表面は平坦である。その結果、演算部１０２ａが、生体試料Ｓ２と平面部１０４ａとの界面が平坦であるとして逆解析演算を行っても、生体試料Ｓ２の表面形状による誤差が生じない。従って、生体計測装置１０１によれば、生体試料Ｓ２の表面形状による誤差を抑制した生体計測装置を実現することができる。なお、実施の形態２によれば、実施の形態１よりも生体試料Ｓ２の表面から離れた深い位置の光学特性値を推定することができる。 As described above, in the living body measurement apparatus 101, measurement light is irradiated to the reference point P2, and inverse analysis calculation is performed with the reference point P2 as the position where the measurement light is incident. The reference point P2 is included in a region where the biological sample S2 and the flat portion 104a are in contact, and the surface of the biological sample S2 is flat. As a result, even if the calculation unit 102a performs inverse analysis calculation on the assumption that the interface between the biological sample S2 and the flat portion 104a is flat, no error is generated due to the surface shape of the biological sample S2. Therefore, according to the living body measurement apparatus 101, it is possible to realize a living body measurement apparatus in which an error due to the surface shape of the living body sample S2 is suppressed. According to the second embodiment, it is possible to estimate the optical characteristic value at a deep position farther from the surface of the biological sample S2 than the first embodiment.
　また、生体試料Ｓ２の表面に凹凸がある場合、生体試料Ｓ２の表面で反射した正反射光を受光部１０８が受光する場合がある。この場合、受光部１０８の撮像画素の飽和等により、正反射光が測定結果に悪影響を及ぼす。さらに、受光部１０８が影響を受ける位置が一律ではないため、光学特性値分布の推定が困難になる、又は推定した光学特性値分布の信頼性が低下する場合があった。これに対して、生体計測装置１０１によれば、生体試料Ｓ２の表面が平坦であるため、このような問題が生じない。 When the surface of the biological sample S2 is uneven, the light receiving unit 108 may receive regular reflection light reflected on the surface of the biological sample S2. In this case, the specular reflection light adversely affects the measurement result due to saturation of the imaging pixel of the light receiving unit 108 or the like. Furthermore, since the position where the light receiving unit 108 is affected is not uniform, it may be difficult to estimate the optical characteristic value distribution, or the reliability of the estimated optical characteristic value distribution may decrease. On the other hand, according to the living body measurement apparatus 101, such a problem does not occur because the surface of the living body sample S2 is flat.
　なお、実施の形態２では、生体計測装置１０１が、複数の方向から測定光を照射するとともに、複数の方向で測定光を受光する構成を説明したが、これに限られない。生体計測装置１０１は、少なくとも１つの方向から測定光を照射し、少なくとも１つの方向で測定光を受光すればよい。生体計測装置１０１は、測定光を照射する方向及び測定光を受光する方向を増やすことにより、推定する光学特性値分布の精度を向上させることができる。 In the second embodiment, the configuration has been described in which the living body measurement apparatus 101 emits measurement light from a plurality of directions and receives measurement light in a plurality of directions. However, the present invention is not limited to this. The living body measurement apparatus 101 may emit measurement light from at least one direction and receive the measurement light in at least one direction. The living body measurement apparatus 101 can improve the accuracy of the optical characteristic value distribution to be estimated by increasing the direction in which the measurement light is irradiated and the direction in which the measurement light is received.
　また、光源部１０５は、生体試料Ｓ２にパルス光又は周期的に光強度を変調させた光を照射してもよい。この場合、照射した光と生体試料Ｓ２からの散乱光との位相差から求まるＴＯＦ（Ｔｉｍｅ　Ｏｆ　Ｆｌｉｇｈｔ）情報により、生体試料Ｓ２の内部の光学特性値分布を推定することができる。 The light source unit 105 may irradiate the biological sample S2 with pulsed light or light whose light intensity is periodically modulated. In this case, the optical characteristic value distribution inside the biological sample S2 can be estimated from TOF (Time Of Flight) information obtained from the phase difference between the irradiated light and the scattered light from the biological sample S2.
　また、受光部１０８の位置は上述した位置に限られない。図４は、生体計測装置の受光部の位置の他の一例を表す図である。図３では、光照射部１０７の光照射位置及び受光部１０８の受光位置を同一面内で変化させる例を示したが、図４では、図３に示す平面に直交する面内で受光部１０８Ａの受光位置を変化させている。図４に示すように、受光部１０８Ａは、例えば基準点Ｐ２を挟んで光源部１０５Ａに対向する方向を０°として、それぞれ＋１２０°、＋９０°、＋６０°、＋３０°、０°、－３０°、－６０°、－９０°、－１２０°に位置する受光位置１０８Ａａ～受光位置１０８Ａｉにおいて、生体試料Ｓ２からの光を受光してもよい。このように、光照射部の光照射位置及び受光部の受光位置は、同一面内に限られず任意の方向に変化させてよく、１又は複数の面内において変化させることが可能である。 Further, the position of the light receiving unit 108 is not limited to the above-described position. FIG. 4 is a diagram illustrating another example of the position of the light receiving unit of the biological measurement device. Although FIG. 3 shows an example in which the light irradiation position of the light irradiation unit 107 and the light receiving position of the light receiving unit 108 are changed in the same plane, FIG. 4 shows the light receiving unit 108A in the plane orthogonal to the plane shown in FIG. Changing the light receiving position of. As shown in FIG. 4, the light receiving unit 108A, for example, takes + 120 °, + 90 °, + 60 °, + 30 °, + 30 °, 0 °, -30 °, where the direction facing the light source 105A is 0 ° with respect to the reference point P2. The light from the biological sample S2 may be received at the light receiving position 108Aa to the light receiving position 108Ai located at -60 °, -90 °, -120 °. As described above, the light irradiation position of the light irradiation unit and the light receiving position of the light receiving unit may be changed in any direction without being limited to the same plane, and may be changed in one or more planes.
　（変形例２）
　図５は、実施の形態１又は実施の形態２の変形例２に係る生体計測装置の生体試料の配置図である。図５に示すように、ステージ２０１上に載置されたディッシュ２０２の上に生体試料Ｓ３を置き、生体試料Ｓ３上に透明部材２０３を配置してもよい。換言すると、透明部材２０３の平面部２０３ａは、透明部材２０３にかかる重力により生体試料Ｓ３の表面に接している。その結果、透明部材２０３の平面部２０３ａと生体試料Ｓ３との界面において、生体試料Ｓ３が平坦になる。そして、この平坦な領域に含まれる基準点Ｐ３に測定光を照射する。なお、この構成では、生体試料Ｓ３の上方から生体試料Ｓ３に光を照射する。 (Modification 2)
FIG. 5 is a layout view of a biological sample of a biological measurement device according to Embodiment 1 or Modification 2 of Embodiment 2. As shown in FIG. 5, the biological sample S3 may be placed on the dish 202 placed on the stage 201, and the transparent member 203 may be arranged on the biological sample S3. In other words, the flat portion 203 a of the transparent member 203 is in contact with the surface of the biological sample S 3 by the gravity applied to the transparent member 203. As a result, the biological sample S3 becomes flat at the interface between the flat portion 203a of the transparent member 203 and the biological sample S3. Then, the measurement light is irradiated to the reference point P3 included in the flat area. In this configuration, light is applied to the biological sample S3 from above the biological sample S3.
　（変形例３）
　図６は、実施の形態１又は実施の形態２の変形例３に係る生体計測装置の生体試料の配置図である。図６に示すように、ステージ３０１上に載置されたディッシュ３０２の上に生体試料Ｓ４を置き、ステージ３０１を上方に所定量移動させることにより、生体試料Ｓ４の上から透明部材３０３の平面部３０３ａが生体試料Ｓ４に当接している。換言すると、透明部材３０３の平面部３０３ａは、生体試料Ｓ４を載置している容器であるディッシュ３０２を重力方向に移動可能な駆動部（駆動部１５又は駆動部１１０）により生体試料Ｓ４の表面に接している。その結果、透明部材３０３の平面部３０３ａと生体試料Ｓ４との界面において、生体試料Ｓ４が平坦になる。そして、この平坦な領域に含まれる基準点Ｐ４に測定光を照射する。なお、この構成では、生体試料Ｓ４の上方から生体試料Ｓ４に光を照射する。なお、透明部材３０３は、固定されていてもよいが、透明部材３０３を駆動することにより、透明部材３０３の平面部３０３ａと生体試料Ｓ４とを当接させてもよい。 (Modification 3)
FIG. 6 is a layout view of a biological sample of a biological measurement device according to Embodiment 1 or Modified Example 3 of Embodiment 2. As shown in FIG. 6, the biological sample S4 is placed on the dish 302 placed on the stage 301, and the stage 301 is moved upward by a predetermined amount, whereby the flat portion of the transparent member 303 from above the biological sample S4. 303a is in contact with the biological sample S4. In other words, the flat portion 303a of the transparent member 303 is the surface of the biological sample S4 by the drive unit (drive unit 15 or drive unit 110) capable of moving the dish 302, which is a container on which the biological sample S4 is placed, in the direction of gravity. I am in contact with As a result, the biological sample S4 becomes flat at the interface between the flat portion 303a of the transparent member 303 and the biological sample S4. Then, the measurement light is irradiated to the reference point P4 included in the flat area. In this configuration, light is irradiated to the biological sample S4 from above the biological sample S4. The transparent member 303 may be fixed, but the flat portion 303a of the transparent member 303 may be brought into contact with the biological sample S4 by driving the transparent member 303.
　変形例２又は変形例３のように、生体試料の上方から生体試料に透明部材を当接させてもよい。 As in the second modification or the third modification, the transparent member may be brought into contact with the biological sample from above the biological sample.
　さらなる効果や変形例は、当業者によって容易に導き出すことができる。よって、本発明のより広範な態様は、以上のように表し、かつ記述した特定の詳細及び代表的な実施の形態に限定されるものではない。従って、添付のクレーム及びその均等物によって定義される総括的な発明の概念の精神又は範囲から逸脱することなく、様々な変更が可能である。 Further effects and modifications can be easily derived by those skilled in the art. Thus, the broader aspects of the invention are not limited to the specific details and representative embodiments presented and described above. Accordingly, various modifications may be made without departing from the spirit or scope of the general inventive concept as defined by the appended claims and their equivalents.
　１、１Ａ、１００　生体計測システム
　２、２Ａ、１０１　生体計測装置
　３、１０２　制御装置
　３ａ、１０２ａ　演算部
　４、１０３、２０１、３０１　ステージ
　５、１０４、２０３、３０３　透明部材
　５ａ、１０４ａ、２０３ａ、３０３ａ　平面部
　６、１６Ａ　光分岐部
　７、１０５、１０５Ａ　光源部
　８、１０、１２　レンズ
　９　ガルバノスキャナー
　１１、１１Ａ　参照ミラー
　１３　分光部
　１４、１０８、１０８Ａ　受光部
　１５、１１０　駆動部
　１０３ａ　Ｘステージ
　１０３ｂ　Ｙステージ
　１０３ｃ　Ｚステージ
　１０６　光スイッチ
　１０７　光照射部
　１０７ａ　第１光照射部
　１０７ｂ　第２光照射部
　１０７ｃ　第３光照射部
　１０８ａ　第１受光位置
　１０８ｂ　第２受光位置
　１０８ｃ　第３受光位置
　１０８Ａａ～１０８Ａｉ　受光位置
　１０９　受光部駆動部
　２０２、３０２　ディッシュ
　Ｐ１、Ｐ２、Ｐ３、Ｐ４　基準点
　Ｓ１、Ｓ２、Ｓ３、Ｓ４　生体試料 DESCRIPTION OF SYMBOLS 1, 1A, 100 living body measurement system 2, 2A, 101 living body measurement device 3, 102 Control device 3a, 102a Arithmetic unit 4, 103, 201, 301 Stage 5, 104, 203, 303 Transparent member 5a, 104a, 203a, 303a Flat part 6, 16A Light branching part 7, 105, 105A Light source part 8, 10, 12 Lens 9 Galvano scanner 11, 11A Reference mirror 13 Spectroscopic part 14, 108, 108A Light receiving part 15, 110 Driving part 103a X stage 103b Y stage 103c Z stage 106 light switch 107 light irradiation unit 107a first light irradiation unit 107b second light irradiation unit 107c third light irradiation unit 108a first light reception position 108b second light reception position 108c third light reception position 108Aa to 108Ai light reception position 109 Unit driver 202, 02 dish P1, P2, P3, P4 reference points S1, S2, S3, S4 biological sample

Claims (15)

  1. 　生体試料の表面に接する平面部を有する透明部材と、
    　前記生体試料が前記平面部と接している領域に含まれる基準点に測定光を照射する光源部と、
    　前記生体試料において散乱された前記測定光を受光する受光部と、
    　を備えることを特徴とする生体計測装置。     A transparent member having a flat portion in contact with the surface of a biological sample;
    A light source unit configured to irradiate measurement light to a reference point included in a region where the biological sample is in contact with the flat portion;
    A light receiving unit that receives the measurement light scattered in the biological sample;
    A biological measurement apparatus comprising:
  2. 　光の一部を透過するとともに、光の一部を反射する光分岐部と、
    　前記光分岐部を透過した光又は前記光分岐部が反射した光の一方である参照光を反射する参照ミラーと、
    　を備え、
    　前記光源部は、前記光分岐部を透過した光又は前記光分岐部が反射した光の他方である前記測定光を、前記生体試料が前記平面部と接している領域に含まれる基準点に照射し、
    　前記受光部は、前記生体試料において散乱された前記測定光と、前記参照ミラーにおいて反射された前記参照光とを受光することを特徴とする請求項１に記載の生体計測装置。     A light branching unit that transmits part of the light and reflects part of the light;
    A reference mirror that reflects reference light which is one of the light transmitted through the light branching portion and the light reflected by the light branching portion;
    Equipped with
    The light source unit irradiates the measurement light, which is the other of the light transmitted through the light branching unit or the light reflected by the light branching unit, on a reference point included in a region where the biological sample is in contact with the flat unit. And
    The living body measurement apparatus according to claim 1, wherein the light receiving unit receives the measurement light scattered in the biological sample and the reference light reflected by the reference mirror.
  3. 　前記受光部は、前記測定光の前記生体試料における後方散乱光を受光することを特徴とする請求項１又は２に記載の生体計測装置。 The living body measurement apparatus according to claim 1, wherein the light receiving unit receives backward scattered light in the biological sample of the measurement light.
  4. 　前記測定光及び前記参照光を分光する分光部を備えることを特徴とする請求項２に記載の生体計測装置。 The living body measurement apparatus according to claim 2, further comprising: a spectroscope unit that disperses the measurement light and the reference light.
  5. 　前記光源部は、前記基準点に対して異なる複数の位置から前記測定光を照射可能であることを特徴とする請求項１に記載の生体計測装置。 The living body measurement apparatus according to claim 1, wherein the light source unit can emit the measurement light from different positions with respect to the reference point.
  6. 　前記受光部は、前記基準点からの前記測定光を異なる複数の位置で受光可能であることを特徴とする請求項１に記載の生体計測装置。 The living body measurement apparatus according to claim 1, wherein the light receiving unit can receive the measurement light from the reference point at a plurality of different positions.
  7. 　前記光源部は、前記基準点に前記測定光を複数回照射し、
    　前記受光部は、前記測定光を複数回受光することを特徴とする請求項１～６のいずれか１つに記載の生体計測装置。     The light source unit irradiates the measurement light multiple times to the reference point,
    The living body measurement apparatus according to any one of claims 1 to 6, wherein the light receiving unit receives the measurement light a plurality of times.
  8. 　前記光源部は、前記基準点に互いに波長が異なる複数の前記測定光を照射することを特徴とする請求項１～７のいずれか１つに記載の生体計測装置。 The biological measurement apparatus according to any one of claims 1 to 7, wherein the light source unit irradiates the reference point with a plurality of the measurement lights having different wavelengths.
  9. 　前記光源部は、前記基準点に波長帯域が広い前記測定光を照射することを特徴とする請求項１～８のいずれか１つに記載の生体計測装置。 The biological measurement apparatus according to any one of claims 1 to 8, wherein the light source unit irradiates the measurement light having a wide wavelength band to the reference point.
  10. 　前記透明部材は、前記測定光を透過する材料からなる容器であり、
    　前記平面部は、前記透明部材の底面に形成されており、
    　前記生体試料は、前記平面部の表面に接するように前記透明部材に載置されていることを特徴とする請求項１～９のいずれか１つに記載の生体計測装置。     The transparent member is a container made of a material that transmits the measurement light,
    The flat portion is formed on the bottom surface of the transparent member,
    The biological measurement device according to any one of claims 1 to 9, wherein the biological sample is placed on the transparent member so as to be in contact with the surface of the flat portion.
  11. 　前記生体試料を載置している前記透明部材を水平面内及び重力方向に移動可能な駆動部を備えることを特徴とする請求項１０に記載の生体計測装置。 The living body measurement apparatus according to claim 10, further comprising: a drive unit capable of moving the transparent member on which the biological sample is placed in a horizontal plane and in a gravity direction.
  12. 　前記透明部材の前記平面部は、重力又は前記生体試料を載置している容器を重力方向に移動可能な駆動部により前記生体試料の表面に接していることを特徴とする請求項１～９のいずれか１つに記載の生体計測装置。 The flat surface portion of the transparent member is in contact with the surface of the biological sample by an actuator capable of moving gravity or a container on which the biological sample is placed in the direction of gravity. The biometric apparatus according to any one of the above.
  13. 　請求項１～１２のいずれか１つに記載の生体計測装置と、
    　前記受光部が受光した信号に基づいて前記生体試料の内部の光学特性値分布を算出する演算部と、
    　を備えることを特徴とする生体計測システム。     A living body measurement apparatus according to any one of claims 1 to 12,
    An operation unit that calculates an optical characteristic value distribution inside the biological sample based on a signal received by the light receiving unit;
    A biological measurement system comprising:
  14. 　透明部材が有する平面部と生体試料の表面とを当接させるように、前記透明部材及び前記生体試料を配置する配置ステップと、
    　前記生体試料が前記平面部と接している領域に含まれる基準点に測定光を照射する光照射ステップと、
    　前記生体試料において散乱された前記測定光を受光する受光ステップと、
    　を含むことを特徴とする生体計測方法。     Arranging the transparent member and the biological sample such that the flat portion of the transparent member abuts on the surface of the biological sample;
    A light irradiation step of irradiating measurement light to a reference point included in a region where the biological sample is in contact with the flat portion;
    A light receiving step of receiving the measurement light scattered in the biological sample;
    A living body measuring method characterized by including.
  15. 　前記光照射ステップは、前記生体試料が前記平面部と接している領域に含まれる基準点に、光分岐部を透過した光又は前記光分岐部が反射した光の一方である前記測定光を照射し、
    　前記受光ステップは、前記生体試料において散乱された前記測定光と、参照ミラーにおいて反射された前記光分岐部を透過した光又は前記光分岐部が反射した光の他方である参照光とを受光することを特徴とする請求項１４に記載の生体計測方法。     The light irradiation step irradiates the measurement light, which is one of the light transmitted through the light branching portion or the light reflected by the light branching portion, on a reference point included in the region where the biological sample is in contact with the flat portion. And
    The light receiving step receives the measurement light scattered in the biological sample and the reference light which is the other of the light transmitted through the light branch reflected by the reference mirror or the light reflected by the light branch. The living body measurement method according to claim 14, characterized in that.
PCT/JP2017/046256 2017-12-22 2017-12-22 Bioinstrumentation device, bioinstrumentation system, and bioinstrumentation method WO2019123662A1 (en)

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