JP2014174140A - Optical probe holder and detector - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an optical probe holder capable of solving a problem in conventional manner that, for example, stray light caused by light coming from ambient environment such as sunlight and illumination light which enters into the optical probe resulting in a reduction of detection accuracy of the optical probe.SOLUTION: The optical probe holder includes: an adhesive layer that adheres to the surface of a specimen and holds the optical probe adjacent to the specimen; a light-shielding layer formed over the adhesive layer to shield stray light; and a holding part that holds the optical probe, the adhesive layer and the light-shielding layer.

Description

  The present invention relates to an optical probe holder for detecting the state of a subject based on return light radiated from the inside of the subject to the outside of the subject, and a detection apparatus using the same.

  Based on the reflected light, scattered light, or transmitted light of the light irradiated on the living body, the concentration of a biological component such as glucose contained in the living body is measured. More specifically, the Raman scattered light of the biological component is observed, and the concentration of the biological component is calculated based on the intensity of the Raman scattered light.

  Conventionally, Raman spectroscopy has been used for various applications. For example, a technique for measuring the concentration of a biological component using Raman spectroscopy has been disclosed (see, for example, Patent Document 1). Using Raman spectroscopy eliminates the need for consumable reagents, test strips, enzymes, etc., as well as the storage safety of these consumables before use and disposal after use. This eliminates problems such as the above-mentioned problems, complicated operations that cause errors, and problems such as interference caused by other components, and it is possible to simultaneously quantitatively measure multiple components.

  Surface-enhanced Raman spectroscopic methods include surface-enhanced Raman by using a surface-enhanced Raman scattering substrate consisting of a group of noble metal colloids in a Raman-active substance that has a stoichiometric relationship with the analyte. A technique for measuring scattering is disclosed (for example, see Patent Document 2). According to this technology, surface-enhanced Raman scattering can be excited with high efficiency using the wavelength of light in the near-infrared region, and analyzed by Raman spectroscopy in the near-infrared region by exciting with light in the near-infrared region. Thus, it is possible to eliminate the influence of light absorption and fluorescence of impurities in the matrix containing the analysis object, and to improve the specificity and selectivity in the detection of the analysis object.

  In Raman spectroscopy, excitation laser light incident on a sample when exciting Raman scattering becomes stray light, which adversely affects measurement accuracy.

  In Patent Document 3, stray light is sufficiently generated by arranging a band elimination filter in which a group I-III-VI2 chalcopyrite type compound semiconductor crystal is arranged between first and second polarizers in the optical path of scattered light. By making it removable and facilitating handling, stray light can be removed with a small size and low cost.

Japanese Patent Laid-Open No. 9-079982 JP 2004-205435 A JP-A-3-277728

Chanda Ranjit Yonzon, Cristy L. Haynes, Xiaoyu Zhang, Joseph T .; Walsh, Jr. , Richard P. Van Duyne, “A Glucose Biosensor Based on Surface-Enhanced Raman Scattering, Improved Partition Layer, Temporary Stability, Inferiority, Reversibilities” 76, 78-85, 2004

  In the conventional method, for example, there is a problem that stray light caused by light from the surrounding environment such as sunlight and illumination light enters the optical probe. For this reason, there existed a subject that the detection accuracy of an optical probe fell.

  In order to solve the above-mentioned conventional problems, the following are provided as exemplary embodiments of the present invention.

  An optical probe holder for holding an optical probe for detecting the state of the subject based on return light radiated from inside the subject to the outside of the subject, the optical probe comprising the subject An adhesive layer that irradiates irradiation light, and a light receiving portion that receives the return light, adheres to the surface of the subject, and holds the optical probe close to the subject; An optical probe holder, comprising: a light shielding layer that blocks stray light, and a holder that holds the optical probe, the adhesive layer, and the light shielding layer, provided on the adhesive layer.

  The present invention can reduce the amount of stray light caused by light from the surrounding environment such as sunlight and illumination light entering the optical probe. Thereby, the detection accuracy of the optical probe can be improved.

The perspective view which shows the structure of the optical probe holder for biological component concentration measurement which concerns on Embodiment 1 of this invention. Sectional drawing which shows the structure of the optical probe holder for biological component concentration measurement which concerns on Embodiment 1 of this invention. Sectional drawing which shows another structure of the optical probe holder 100 for biological component concentration measurement which concerns on Embodiment 1 of this invention. Sectional drawing which shows another structure of the optical probe holder 100 for biological component concentration measurement which concerns on Embodiment 2 of this invention. Sectional drawing which shows another structure of the optical probe holder 100 for biological component concentration measurement which concerns on Embodiment 3 of this invention. Schematic of a biological component measuring apparatus provided with an optical probe holder 100 for measuring biological component concentration Schematic which shows the use condition of the optical probe holder 100 for biological component density | concentration measurement The figure which shows an example of the ray tracing simulation result at the time of utilizing the optical probe holder for biological component density | concentration measurement concerning Embodiment 1. FIG. The figure which shows an example of the ray tracing simulation result when not using the optical probe holder for biological component concentration measurement of Embodiment 1 of this invention The figure which shows an example of the simulation result which shows the relationship between the magnitude | size of the optical probe holder for biological component density | concentration measurement of Embodiment 1 of this invention, and the detected amount of a stray light The figure which shows the structure of the optical probe holder in Embodiment 1. FIG. The figure which shows the structure of the detection apparatus in Embodiment 1.

  FIG. 11 is a diagram illustrating a configuration of the optical probe holder 1000 according to the embodiment. FIG. 11 also shows the configuration of the optical probe 1103.

  The optical probe holder 1000 in the embodiment is an optical probe holder for holding an optical probe 1103 for detecting the state of the subject based on return light radiated from the inside of the subject to the outside of the subject. .

  The optical probe 1103 includes an irradiation unit 1201 that irradiates a subject with irradiation light, and a light receiving unit 1202 that receives return light.

  The optical probe holder 1000 includes an adhesive layer 1102, a light shielding layer 1101, and a holding unit 1104.

  The adhesive layer 1102 adheres to the surface of the subject and holds the optical probe in close proximity to the subject.

  The light shielding layer 1101 blocks stray light. The light shielding layer 1101 is provided on the adhesive layer.

  The holding unit 1104 holds the optical probe 1103, the adhesive layer 1102, and the light shielding layer 1101.

  According to the above configuration, for example, the amount of stray light caused by light from the surrounding environment such as sunlight and illumination light entering the optical probe can be reduced. Thereby, the detection accuracy of the optical probe can be improved.

  FIG. 12 is a diagram illustrating a configuration of the detection apparatus 2000 according to the embodiment.

  The detection device 2000 in the embodiment includes an optical probe holder 1000, an optical probe 1103, a light emitting unit 2001, and a detection unit 2002.

  The light emitting unit 2001 emits irradiation light.

  The detection unit 2002 detects the state of the subject based on the return light received by the light receiving unit.

  The detection apparatus 2000 may further include a light guide unit that connects the light emitting unit 2001 and the irradiation unit 1201 and guides the irradiation light. The detection device 2000 may further include a light guide unit that connects the light receiving unit 1202 and the detection unit 2002 and guides the return light. These light guide means may be constituted by, for example, a lens or an optical fiber.

  Hereinafter, specific examples of the optical probe holder and the detection device will be described as Embodiments 1 to 4.

(Embodiment 1)
The optical probe holder and the detection apparatus according to Embodiment 1 will be described below with reference to the drawings.

  Hereinafter, in Embodiment 1, a living body is exemplified as the subject.

  In the first embodiment, the detection means measures the concentration of the biological component of the living body as the state of the subject based on the return light received by the light receiving unit.

  That is, in the first embodiment, a biological component concentration measurement device is exemplified as the detection device.

  In the first embodiment, the optical probe for measuring a biological component concentration is exemplified as the optical probe.

  Moreover, in Embodiment 1, an attachment is illustrated as a holding | maintenance part.

  1 and 2 show a biological component concentration measuring optical probe holder 100. FIG. FIG. 6 shows a biological component concentration measuring apparatus 120 using the biological component concentration measuring optical probe holder 100.

  The biological component concentration measuring optical probe holder 100 according to the first embodiment includes a light shielding layer 101, an adhesive layer 102 for fixing and holding the biological component concentration measuring optical probe holder 100 to a biological tissue (not shown), and an optical probe. 103, and an attachment 104 to which the optical probe 103 can be attached and detached.

  The optical fiber 105 is connected to the biological component concentration measuring device (120), delivers light (irradiation light) emitted from the biological component concentration measuring device to the optical probe 103, and light emitted from the living body (outward). Return light) is delivered to the biological component concentration measuring device 120 via the optical probe 103.

  When measuring biological component concentration by optical measurement, light that is not related to biological component concentration measurement, for example, light from the surrounding environment such as sunlight or illumination light, was adversely affected. .

  In contrast, the biological component concentration measurement optical probe holder 100 according to the first embodiment includes a light shielding layer 101.

  In this way, by providing the light shielding layer, the amount of stray light that is not related to the measurement of the concentration of biological components, for example, light from the surrounding environment such as sunlight or illumination light, is incident on the optical probe is reduced. be able to. Thereby, the precision of a biological component density | concentration measurement can be improved.

  Here, in the first embodiment, the light shielding layer 101 may include the light reflecting layer 106. The light reflection layer 106 reflects stray light from outside the living body (subject) and blocks the stray light from entering the living body.

  By doing so, the light reflecting layer is not related to the measurement of the concentration of the biological component, for example, light from the surrounding environment such as sunlight and illumination light is reflected outside the body without entering the living body, It is not detected by the biological component concentration measuring device. Therefore, the biological component concentration measurement is not adversely affected by light from the surrounding environment that is not related to the biological component concentration measurement, for example, sunlight or illumination light. For this reason, measurement accuracy can be improved.

  Here, as the light reflecting layer 106, a known technique can be used without particular limitation as long as it is made of a material capable of reflecting light. As the light reflection layer 106, for example, a metal thin film such as gold, silver, aluminum, titanium, or copper can be used. Use of a thin, malleable, and ductile material such as a metal thin film is preferable because it is flexible when held on a living body.

  When using a metal thin film, the thickness of the metal is 50 nanometers or more, so that it reflects light from the surrounding environment, such as sunlight and illumination light, which is not related to the measurement of biological component concentration. It is preferable from the viewpoint. The metal thickness is more preferably 100 nanometers or more.

  In the first embodiment, an example using a light reflector as the light shielding layer 101 has been described. However, there is no particular limitation as long as it is a material that is not related to the measurement of biological component concentration, and can reduce the amount of light incident on the living body, for example, light from the surrounding environment such as sunlight and illumination light. be able to. For example, as the light shielding layer 101, a light absorbing material, a light scatterer (not shown), or the like can be used as shown in FIG.

  That is, for example, the light shielding layer may include a light absorption layer. The light absorption layer absorbs stray light from outside the living body (subject), and blocks stray light from entering the living body.

  As the light absorbing material constituting the light absorbing layer, a known technique can be used without any particular limitation. As the light absorbing material, for example, a polymer material mixed with a diimonium salt, a nickel dithiol-based material, a polymethine-based material, or a phthalocyanine-based material can be used.

  As the light scatterer, an opaque polymer material such as polyurethane, polymethyl methacrylate, urea resin, or melamine resin can be used.

  FIG. 8 shows an example of a ray tracing simulation result when the biological component concentration measurement optical probe holder according to the first embodiment is used. FIG. 9 shows an example of a ray tracing simulation result when the biological component concentration measurement optical probe holder of the first embodiment is not used.

  As a simulation condition, the light shielding layer (simulation) 111 was a light reflecting layer. The substrate (simulation) 115 was arranged so that the depth between the surface facing the biological tissue (simulation) 135 and the surface of the biological tissue (simulation) 135 was 1 mm. The size of the substrate (simulation) 115 is a rectangular parallelepiped shape having a side of 1 mm and a height of about 0.3 mm. The positions of the light source (simulation) 114 and the optical probe opening (simulation) 113 are set such that the distance from the living tissue (simulation) 135 is 5 mm and 0 mm, respectively. In this simulation, the optical probe is not modeled. The surface (not shown) of the substrate 115 actually includes a metal member having a size of nano order, but is not modeled in the simulation. The biological tissue (simulation) 135 is modeled by five layers of the stratum corneum, epidermis layer, papillary dermis, reticular dermis, and subcutaneous tissue, and the refractive index is 1.50 for the stratum corneum, 1.55, and epidermis. The papillary dermis is 1.36, the reticular dermis is 1.38, and the subcutaneous tissue is 1.44. Further, the phase of scattering of biological tissue is modeled by the Henhey-Greenstein model. 86615, subcutaneous tissue: 0.9. The scattering coefficient of each layer was as follows: stratum corneum: 14.36, epidermis: 9.98626, papillary dermis: 9.98626, reticular dermis: 9.98626, subcutaneous tissue: 11.8, (unit is cm-1), The absorption coefficient is 0.00028, epidermis: 1.4586, papillary dermis: 0.0666, reticular dermis: 0.00546, subcutaneous tissue: 0.11 (unit: cm-1). The light intensity emitted from the light source (simulation) 114 is 1 mW in total, and the number of light rays is 20,000,000, of which 2,000 are drawn as light rays (simulation) 112. ing.

  The radiation characteristic of the light beam (simulation) 112 emitted from the light source (simulation) 114 is approximated by Lambertian, and the light source (simulation) 114 simulates stray light from the outside.

  As can be seen from the light beam (simulation) 112 in FIGS. 8 and 9, the light beam emitted from the light source (simulation) 114 is reflected by the light shielding layer (simulation) 111. For this reason, the number of light rays incident on the living tissue (simulation) 135 is smaller than that in the case where the light shielding layer (simulation) 111 does not exist. As a result, the number of light rays reaching the opening (simulation) 113 of the optical probe is reduced. As a result, it becomes difficult to detect stray light.

  FIG. 10 shows an example of a simulation result showing the relationship between the size of the optical probe holder for measuring the biological component concentration of Embodiment 1 and the detected amount of stray light. The simulation conditions in FIG. 10 are the same as the simulation conditions in FIGS. 8 and 9 described above, except for the diameter of the light shielding layer.

  FIG. 10 shows that stray light is hardly detected if the diameter of the light shielding layer is larger than 20 mm. For this reason, it is preferable that the diameter of a light shielding layer is 20 mm or more.

  That is, the light shielding layer may be provided over a range of a circle centered on the position of the optical probe. At this time, the diameter of the circle may be 20 mm or more.

  According to this configuration, stray light can be more reliably shielded.

  As described above, by using the optical probe holder according to Embodiment 1, the influence of stray light can be reduced.

(Embodiment 2)
The optical probe holder according to the second embodiment will be described below with reference to FIG. In FIG. 4, the same components as those in FIG.

  The difference from the first embodiment is that a light absorbing layer 107 is provided as the light shielding layer 101 together with the light reflecting layer 106.

  That is, in the optical probe holder in the second embodiment, the light shielding layer includes a light reflecting layer. The light reflecting layer reflects stray light from outside the subject and blocks stray light from entering the subject.

  Furthermore, in the optical probe holder in the second embodiment, the light shielding layer includes a light absorption layer. At this time, the light absorption layer is provided between the light reflection layer and the adhesive layer. The light absorption layer absorbs stray light from within the subject.

  The light absorption layer 107 is provided between the light reflection layer 106 and the adhesive layer 102. By doing so, the light is absorbed when the light scattered in the living tissue reaches the light absorption layer 107. For this reason, the efficiency which removes a stray light goes up, and the influence of a stray light can be made smaller.

  As a light absorbing material constituting the light absorbing layer, a known technique can be used without any particular limitation.

  In addition, it is preferable to absorb light in a wavelength range of 785 to 930 nm of light used in the biological component concentration measuring apparatus. For example, diimonium salts, nickel dithiol-based materials, polymethine-based materials, and phthalocyanine-based materials can be used as the light-absorbing material that absorbs light having the above wavelengths.

  As described above, the influence of stray light can be reduced by using the optical probe holder according to the second embodiment.

(Embodiment 3)
The optical probe holder according to Embodiment 3 will be described below with reference to FIG. In FIG. 5, the same components as those in FIG.

  The difference from Embodiment 1 is that a ventilation layer 108 is provided between the light shielding layer 101 and the adhesive layer 102.

  That is, the optical probe holder of Embodiment 3 further includes a ventilation layer containing air. At this time, the ventilation layer is provided between the adhesive layer and the light shielding layer.

  In this way, when the biological component concentration measuring optical probe holder is attached to the living body, it is possible to reduce discomfort due to sweat secreted from the user or generated heat.

  As the ventilation layer, a known technique can be used without particular limitation. For example, as the ventilation layer, a cloth with a high air content, a nonwoven fabric, a mesh-processed cloth, or the like can be used.

  As described above, by using the optical probe holder according to Embodiment 3, the influence of stray light can be reduced and the user's discomfort can be reduced.

(Embodiment 4)
A biological component concentration measuring apparatus using the optical probe holder according to Embodiment 4 will be described below with reference to FIGS. 6 and 7, the same components as those in FIG. 1 are denoted by the same reference numerals and description thereof is omitted.

  FIG. 6 shows a schematic diagram of a biological component concentration measuring apparatus including the biological component concentration measuring optical probe holder 100. As shown in FIG. 6, the biological component concentration measuring device 120 is connected via the optical fiber 105.

  FIG. 7 is a schematic view showing a usage state of the biological probe concentration measuring optical probe holder 100. As shown in FIG. 7, the skin includes an epidermis 131, a dermis 132, and a subcutaneous tissue 133. The epidermis 131, dermis 132, and subcutaneous tissue 133 are laminated in this order.

  The epidermis 131 is located on the surface of the living body. The epidermis 131 has a thickness of approximately 0.2 to approximately 0.5 mm. The dermis 132 has a thickness of approximately 0.5-2 mm. The substrate 150 is embedded in the dermis 132 and maintained by being immersed in an interstitial fluid that is a body fluid between tissue cells. The subcutaneous tissue 133 is mainly composed of adipose tissue.

  Since the dermis 132 has a plurality of capillaries, the body fluid contains a biological component in the capillaries. In particular, since glucose has high permeability, the glucose concentration in the body fluid has a high correlation with the blood glucose level.

  In the detection device of the fourth embodiment, glucose is exemplified as the biological component.

  In the detection apparatus of the fourth embodiment, the substrate is embedded in the subject. The substrate includes a metal member, and generates surface-enhanced Raman scattering light by the irradiation light irradiated from the irradiation unit. At this time, the return light is surface-enhanced Raman scattering light generated from the substrate.

  That is, for example, as shown in FIG. 7, the substrate 150 is embedded in the dermis 132 so as to face the epidermis 131. The distance from the skin 131 to the substrate 150 is approximately 1 mm. The metal member (not shown) is formed on the surface on the skin 131 side.

  The biological component concentration measuring apparatus 120 includes a light source as a part of the light emitting means and a spectroscope for spectrally detecting and detecting the surface enhanced Raman scattered light generated from the substrate 150 as a part of the detecting means.

  The substrate 150 includes a metal member, and generates surface-enhanced Raman scattered light by light emitted from the light source.

  Here, the substrate 150 has a diameter of approximately 1 mm and a thickness of approximately 1 mm. Examples of the material of the substrate 150 are biocompatible resins such as polypropylene, high-density polyethylene, polyethylene terephthalate, and polyurethane, glass, or silicon.

  When forming metal particles, known techniques can be used without any particular limitation. For example, when forming the metal particles 13, a photolithography technique, a nanosphere lithography technique, or the like can be used.

  Next, the operation of the biological component concentration measuring apparatus according to the fourth embodiment will be described.

  The measuring device includes a light source 9 and a spectrometer 7. The measurement apparatus includes a band pass filter, a lens system, a beam splitter, and a computer as necessary. The substrate 150 is previously embedded in the dermis 132 as shown in FIG.

  Irradiation light emitted from a light emitting means (for example, a light source) is irradiated onto the living body by an irradiation unit (for example, a condensing lens) and passes through the surface of the skin. The substrate 150 embedded in the skin is illuminated by the transmitted light and generates surface enhanced Raman light there.

  Next, the surface-enhanced Raman light (return light) generated from the substrate is received by the light receiving unit and then detected by the detecting means. For example, surface-enhanced Raman light generated from the substrate is collected by a lens system, reflected by a beam splitter, collected by a lens system, and then detected by a spectroscope.

  Here, as a spectroscope, a well-known technique can be utilized without particular limitation. For example, a Czerny Turner spectrometer, an echelle spectrometer, a flat field spectrometer, a filter spectrometer, or the like can be used.

  When the substrate 150 is irradiated with light from the light source, surface plasmon resonance occurs on the metal particles, and the electromagnetic field strength in the vicinity of the metal particles is enhanced. This results in enhancement of Raman scattered light of the biological material located in the vicinity of the metal particles (within 0.5 to 30 nm). In this way, surface enhanced Raman scattered light is generated. The enhancement effect of the surface-enhanced Raman scattered light is proportional to the product of the electric field enhancement effect of the excitation light 5 and the electric field enhancement effect of the Raman scattering wavelength. For this reason, it is preferable to match the surface plasmon resonance wavelength with the light wavelength of the light source and the localized resonance plasmon resonance wavelength with, for example, the Raman scattering wavelength of glucose.

  Further, in order to measure the surface-enhanced Raman scattering light of glucose, as shown in Non-Patent Document 1, in order to temporarily hold glucose in the vicinity of the metal particles 14, for example, 11-mercaptoun on the metal particles 14 is used. It is preferable to provide a self-assembled monolayer of decanol triethylene glycol ether. By doing so, not only can glucose be held in the vicinity of the metal particles 14, but also a large number of proteins present in the living body can be prevented from adsorbing to the substrate 150.

Intensity of surface-enhanced Raman scattering light is 10 ⁴ times to 10 ⁹ times the intensity of normal Raman scattered light greater. Accordingly, the surface-enhanced Raman scattered light generated in the vicinity of the metal particles 8 has a much higher intensity than the Raman scattered light generated on the skin surface (including the stratum corneum), the epidermis 131, or the dermis 132. This means that the Raman scattered light derived from biological components contained in the body fluid in the vicinity of the metal particles is selectively enhanced. In this way, the influence of disturbing components other than those near the metal particles among the biological components is reduced.

  The amount of biological components such as glucose contained in the living body is much lower than the amount of interfering components contained in the living body. Therefore, the normal Raman scattered light of glucose has an extremely small intensity compared to the Raman scattered light of the disturbing component contained in the skin surface (the stratum corneum of the epidermis 131), the epidermis 131, or the dermis 132. For this reason, it is difficult to extract normal Raman scattered light of glucose.

  However, the substrate 150 can selectively enhance the Raman scattered light of glucose in the vicinity of the metal particles contained in the body fluid in the dermis 132. This results in the intensity of the Raman scattered light of glucose being selectively increased compared to the intensity of the Raman scattered light of the interfering substance. Since the intensity of the surface enhanced Raman scattered light of glucose is proportional to the concentration of glucose, the concentration of glucose can be calculated from the intensity of the surface enhanced Raman scattered light of glucose.

  An example of calculating the glucose concentration is described below.

As shown in Non-Patent Document 1, the surface enhanced Raman scattering spectrum of ^glucose in the range of the Raman shift is 1000cm ^-1 ~1500cm -1, having a plurality of peaks of glucose-specific.

Among the plurality of peaks, the peak having a Raman shift at 1120 (cm ⁻¹ ) does not overlap with the peaks of the Raman scattered light spectra of albumin and creatinine. Therefore, the intensity of the surface-enhanced Raman scattered light having the Raman shift of 1120 (cm ⁻¹ ) is proportional only to the glucose concentration.

When the excitation light 5 has a wavelength of 785 nm, a filter 13 that transmits light having a wavelength of 860.7 nm is used. The wavelength of 860.7 nm corresponds to a wave number that is smaller by 1120 cm ⁻¹ than the wave number corresponding to the wavelength of 785 nm.

  The relationship between wavelength λ and wavenumber k satisfies the following equation (I):

k (cm ⁻¹ ) = 10 ⁷ / λ (nm) (I)
A value obtained by converting a wavelength λ of 785 nm into a wave number k is 12739 (cm ⁻¹ ). The wave number of the peak peculiar to glucose is smaller by 1120 (cm ⁻¹ ) than 12739 (cm ⁻¹ ). Therefore, the wave number is calculated by the following equation: 12739 (cm ⁻¹ ) −1120 (cm ⁻¹ ) = 11619 (cm ⁻¹ ). The value of the wave number of 11619 (cm ⁻¹ ) converted to the wavelength is 860.7 nm.

Spectroscopy of these surface-enhanced Raman scattered light 6 is performed by a spectrometer 7. A glucose concentration can be calculated by using a calibration curve prepared in advance for a spectral spectrum of 1000-1500 cm ⁻¹ characteristic of glucose, for example, spectrally separated by the spectroscope 7. As a method of creating a calibration curve, for example, a partial least square algorithm can be used.

  As described above, by using the detection device according to Embodiment 4, the concentration of a biological component, for example, the concentration of glucose can be calculated.

  When detecting the state of the living body that is the subject based on the return light, it is more preferable to measure the same place from the non-uniformity of the living tissue. In addition, when using the return light from the substrate embedded in the subject, it is necessary to irradiate the embedded substrate with light, so it is necessary to measure the same place. For this reason, as in the optical probe holder and the detection apparatus in the first to fourth embodiments, first, the holding portion is fixed to the subject with the adhesive layer, and the optical probe is detachable from the holding portion. Thereby, it becomes possible to measure the same place. Therefore, the accuracy of detection / measurement can be further improved.

  In the first to fourth embodiments, the subject may be a human body or an animal. Alternatively, the subject may be inanimate.

  In the first to fourth embodiments, the detection means may detect the presence or absence of a test substance in the subject as the state of the subject. Or in Embodiment 1-4, a detection means may measure the density | concentration of the to-be-tested substance in a subject as a state of a subject.

  At this time, the test substance may be, for example, glucose, lactic acid, pyruvic acid, acetoacetic acid, 3-hydroxybutyric acid (β-hydroxybutyric acid), or the like.

  In the first to fourth embodiments, the size of the light shielding layer may not be the same as the size of the adhesive layer. For example, the light shielding layer may be larger than the adhesive layer. Alternatively, the light shielding layer may be smaller than the adhesive layer.

  In the first to fourth embodiments, the return light is not limited to the surface enhanced Raman scattered light. The return light may be Raman scattered light, reflected light, fluorescence, or the like from a substrate embedded in the subject. Alternatively, the return light may be reflected light or fluorescence from a part of the subject. The return light may be any light that can detect the state of the subject such as the concentration of the biological component based on the return light.

  The present invention can be used, for example, to measure the concentration of biological components such as glucose in a living body.

DESCRIPTION OF SYMBOLS 100 Optical probe holder for biological component concentration measurement 101 Light shielding layer 102 Adhesive layer 103 Optical probe 104 Attachment 105 Optical fiber 106 Light reflection layer 107 Light absorption layer 108 Ventilation layer 111 Light shielding layer (simulation)
112 rays (simulation)
113 Optical probe aperture (simulation)
114 Light source (simulation)
115 Substrate (simulation)
120 Biological Component Concentration Measuring Device 130 Biological Tissue 131 Epidermis 132 Dermis 133 Subcutaneous Tissue 135 Biological Tissue (Simulation)
150 substrates

Claims (10)

An optical probe holder for holding an optical probe for detecting the state of the subject based on return light radiated from inside the subject to the outside of the subject,
The optical probe includes an irradiation unit that irradiates the subject with irradiation light, and a light receiving unit that receives the return light,
An adhesive layer that adheres to the surface of the subject and holds the optical probe close to the subject;
A light shielding layer for blocking stray light, provided on the adhesive layer;
An optical probe holder, comprising: a holder that holds the optical probe, the adhesive layer, and the light shielding layer. The light shielding layer is provided over a range of a circle centered on the position of the optical probe,
The circle has a diameter of 20 mm or more.
The optical probe holder according to claim 1. The light shielding layer includes a light reflecting layer,
The light reflecting layer reflects stray light from outside the subject and blocks the stray light from entering the subject;
The optical probe holder according to claim 1 or 2. The light shielding layer includes a light absorption layer,
The light absorbing layer is provided between the light reflecting layer and the adhesive layer,
The light absorbing layer absorbs stray light from within the subject;
The optical probe holder according to claim 3. The light shielding layer includes a light absorption layer,
The light absorbing layer absorbs stray light from outside the subject and blocks the stray light from entering the subject;
The optical probe holder according to claim 1 or 2. The light absorption layer is formed of a light absorbing material that absorbs light of 785 to 930 nm.
The optical probe holder according to claim 4 or 5, wherein the optical probe holder is provided. Further comprising a ventilation layer containing air,
The ventilation layer is provided between the adhesive layer and the light shielding layer.
The optical probe holder according to claim 1. The optical probe holder according to any one of claims 1 to 7,
The optical probe;
A light emitting means for emitting the irradiation light;
Detection means for detecting the state of the subject based on the return light received by the light receiving unit;
A detection device comprising: A substrate is embedded in the subject,
The substrate includes a metal member, and generates surface-enhanced Raman scattering light by irradiation light irradiated from the irradiation unit,
The return light is the surface enhanced Raman scattered light generated from the substrate.
The detection device according to claim 8. The subject is a living body,
The detection means measures the concentration of the biological component of the living body as the state of the subject based on the return light received by the light receiving unit.
The detection device according to claim 8 or 9.