JP2013192913A - Biogenic substance concentration measuring device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a sensor chip with high durability, capable of accurately monitoring an analysis object substance over a long period of time, in a sensor chip to be used in measuring or monitoring an analysis object in a living body by using an optical technique.SOLUTION: Projecting shapes are formed on a solid support body to thereby eliminate contact with a sensor surface, a body tissue, and furthermore, a member to be used when a sensor chip 105 is embedded in a living body. Thus, durability in the sensor chip 105 can be improved.

Description

  The present invention relates to a biological component concentration measuring device used for embedding a sensor in a living body and measuring or monitoring a biological component using an optical technique.

  In particular, metallic microparticles that generate localized surface plasmon resonance and fluorescent microparticles that change their fluorescence characteristics by reacting with a test substance are embedded in the living body, and these microparticles are irradiated with light from outside the living body. The present invention relates to an apparatus for measuring the concentration of a test substance present in a cell interstitial fluid or the like by detecting generated surface-enhanced Raman scattered light or fluorescence percutaneously.

  Conventionally, there has been proposed an apparatus for measuring the concentration of a test substance such as glucose by embedding a sensor in a living body, irradiating light from outside the living body, detecting generated light such as fluorescence or Raman scattered light, and the like.

  For example, by embedding fine particles containing a reagent whose fluorescence characteristics change by reacting with glucose into the upper layer of the skin as a sensor, irradiating the fine particles with light from outside the body, and detecting the fluorescence generated in the fine particles transcutaneously An apparatus for measuring glucose concentration is disclosed. (See Patent Document 1).

Also, a localized surface generated by irradiating a substrate with a metal-coated dielectric fine particle embedded in the living body and irradiating it with a Raman active substance having a stoichiometric relationship with the analyte. A technique for measuring glucose concentration in a living body by surface-enhanced Raman scattering that enhances Raman scattered light intensity via an enhanced electric field by plasmon resonance is disclosed (Non-Patent Document 1).
In the above technique, the sensor is completely embedded in the living body, and when it is desired to measure, the concentration of the living body component can be measured without irritating each time only by irradiating light from the outside.

Japanese translation of PCT publication No. 2004-510527

J. et al. M.M. Yuen, N .; C. Shah et. al. , Anal. Chem. (2010) 82: 8382-8385

  However, in the above-described conventional technology, the position of the sensor embedded in the living body cannot be grasped, light is irradiated to the position of the sensor in the living body, and the generated light cannot be detected with a high capture rate. There was a problem that the light intensity necessary for measuring the concentration of biological components could not be obtained.

  The present invention solves the above-mentioned conventional problems, accurately grasps the position of the sensor embedded in the living body, accurately irradiates the position of the sensor in the living body, and generates a high capture rate of the generated light. It is an object of the present invention to provide a biological component concentration measuring apparatus using surface enhanced Raman scattering that can measure the concentration of biological components with high accuracy.

  In order to solve the above-described conventional problems, the biological component concentration measuring apparatus of the present invention includes a metal microstructure forming unit in which a metal microstructure capable of inducing localized surface plasmon resonance is formed on a solid support, On a solid support, a sensor chip having a plurality of protrusions whose upper part is a flat surface and whose upper surface is a light reflecting part, a light source and reflected light intensity of the light from the light source from the light reflecting part, A detector for measuring surface-enhanced Raman scattered light generated from the metal fine structure forming portion by light from a light source; and the optical measurement device comprising an optical path changing means for changing an optical path.

  The light reflecting portion is preferably made of metal.

  It is preferable that the light reflecting portion reflects only light having a specific wavelength.

  It is preferable that the wavelength of the reflected light irradiation light is different from the wavelength of the surface-enhanced Raman scattering light irradiation light.

  It is preferable that the wavelength of the irradiation light for reflected light and the wavelength of the irradiation light for surface-enhanced Raman scattering light are the same.

  It is preferable that the protrusion shape is formed periodically.

  According to the biological component concentration measuring apparatus of the present invention, by measuring the reflected light intensity from the light reflecting portion on the sensor chip while changing the optical path, the position of the sensor chip embedded in the living body is grasped, Since the light is accurately irradiated to the position of the sensor chip in the living body and the generated light can be detected with a high capture rate, the concentration of the biological component can be measured with high accuracy, which is effective.

The figure which shows the structure of the biological component concentration measuring apparatus in Embodiment 1 of this invention. The figure which shows the structure at the time of detecting the reflected light of the biological component concentration measuring apparatus in Embodiment 1 of this invention. Sectional drawing of the sensor chip 105 in Embodiment 1 of this invention. Plan view of sensor chip 105 according to Embodiment 1 of the present invention. Process drawing which shows the manufacturing method of the protrusion shape on the solid support body in Embodiment 1 of this invention Process drawing which shows the manufacturing method of the metal microstructure on the solid support body which has protrusion shape in Embodiment 1 of this invention, and a metal thin film The figure which shows the structure of the biological component density | concentration measuring apparatus in Embodiment 2 of this invention. The figure which shows the structure at the time of detecting the reflected light of the biological component concentration measuring apparatus in Embodiment 2 of this invention. Sectional drawing of the sensor chip 105 in Embodiment 2 of this invention. Plan view of sensor chip 105 in Embodiment 2 of the present invention Process drawing which shows the manufacturing method of the metal microstructure on the solid support body which has projection shape in Embodiment 2 of this invention, and a dielectric multilayer The figure which shows the structure of the biological component density | concentration measuring apparatus in Embodiment 3 of this invention. The figure which shows the structure at the time of detecting the reflected light of the biological component concentration measuring apparatus in Embodiment 3 of this invention. Sectional drawing of the sensor chip 105 in Embodiment 3 of this invention. Plan view of sensor chip 105 in Embodiment 3 of the present invention

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

(Embodiment 1)
A first embodiment of the present invention will be described with reference to FIGS.
FIG. 1 is a diagram showing a configuration of a biological component concentration measuring apparatus 100 according to an embodiment of the present invention. In FIG. 1, the biological component concentration measuring device 100 includes a sensor chip 105 and an optical measuring device 200. The optical measuring device 200 includes a laser light source 101 that emits substantially parallel light, a beam splitter 102 that reflects and transmits 50% of the light, a lens group 108 that shapes surface-enhanced Raman scattered light generated from the sensor chip 105, and a surface enhancement. The spectral filter 106 for spectrally dispersing the Raman scattered light, the spectrally enhanced surface-enhanced Raman scattered light, the photodetector 110 for detecting the laser light reflected from the sensor chip 105, and the light intensity detected by the photodetector 110 were calculated and calculated. The position of the sensor chip is determined based on the light intensity, the light intensity detected by the light detector 110 is calculated, and the glucose concentration is calculated based on the calculated light intensity. The microcomputer 111, the memory 112, the beam splitter 102, the laser light source 101, and the lens The positional relationship between the group 108, the spectral filter 106, and the photodetector 110 Consisting of an optical path changer 113 to move while holding. As shown in FIG. 2, the lens group 108 and the spectral filter 106 are movable, and move out of the optical path when detecting reflected light from the sensor chip 105. When detecting the surface-enhanced Raman scattering light generated from the sensor chip 105, the lens group 108 and the spectral filter 106 are arranged at the position shown in FIG.

  The epidermal tissue 103 is on the surface of the living body and has a thickness of about 0.2 to 0.5 mm. The dermis tissue 104 has a thickness of about 0.5 to 2 mm. The sensor chip 105 is embedded in the dermal tissue 104 and is immersed in a body fluid between tissue cells, that is, a cell interstitial fluid. Since there are many capillaries in the dermis tissue 104, the components in these capillaries penetrate into the interstitial fluid. In particular, since glucose is highly permeable, the glucose concentration of the interstitial fluid has a high correlation with the blood glucose level. The subcutaneous tissue 107 mainly consists of fat cells.

  The laser light source 101 corresponds to the light source in the present invention. In the present embodiment, the spectral filter is used for the spectroscopic analysis, but any known technique capable of spectroscopically splitting a predetermined wavelength can be used without any particular limitation. For example, a spectroscope using a slit and a grating element, an acoustooptic element, or the like can be used.

The laser light source 101 is a substantially parallel light having a wavelength of 780 nm, and the beam shape is a circle having a diameter of 500 μm. The laser light source 101 passes through the epidermal tissue 102 and irradiates the chip 105 in the dermal tissue 104. Raman scattered light is generated from the chip 105 irradiated with the laser light. In the case of glucose, observation of surface-enhanced Raman scattered light having a wave number smaller by about 1000 to 1200 cm ⁻¹ than the wave number of irradiated light is advantageous because it is relatively less susceptible to interference components such as proteins. In this embodiment, since the wavelength of the irradiation light is 780 nm, it is preferable to use the spectral filter 106 that transmits a wavelength of about 890 nm.

  In the present embodiment, the case of the sensor chip 105 having a cross section as shown in FIG. 3 will be described. Examples of the material constituting the solid support 13 of the sensor chip in the present embodiment include silicon, glass plate, ceramic, and plastic film.

  A cylindrical projection 11 is provided on the solid support 13. A gold thin film 14 is formed on the upper surface of the cylindrical protrusion 11. The gold thin film 14 corresponds to the light reflecting portion in the present invention. The protrusion shape 11 on the surface of the solid support 13 may be a material different from that of the solid support 13, but the same material is preferable in view of simplicity in manufacturing.

  A gold microstructure 12 capable of inducing localized surface plasmon resonance is formed in the recess of the solid support 13. As shown in FIG. 4, the sensor chip 105 has two columnar protrusions 11 having a diameter of 50 μm formed on a circular solid support 13 having a diameter of 500 μm. The protrusion 11 has a center on a straight line A passing through the center of the solid support 13, and has a center at a position symmetrical with respect to a straight line B passing through the center of the solid support 13 and perpendicular to the straight line A. . Further, the circumference of the solid support 13 and the circumference of the protruding shape 11 are formed so as to contact each other. A gold thin film 14 is formed on the upper surface of the protrusion shape 11.

  For example, when the solid support 13 and the protrusion shape 11 are the same material, the protrusion shape 11 can be formed by a combination of a photolithography method and an etching method.

  An example of a method for forming the protrusion shape 11 on the solid support 13 will be described with reference to FIGS. As shown in FIG. 5A, a resist film 31 is first formed on the solid support 13 using a spin coating method or the like. The resist film 31 is selectively exposed (FIG. 5B) and developed to produce a resist pattern 32 having a predetermined shape (FIG. 5C). Thereafter, by etching the portion of the resist pattern 32 of the solid support 13 where the resist film 31 does not exist to a predetermined depth, a projection 11 as shown in FIG. 5D can be formed.

  For the etching method, for example, one or more of physical etching methods such as plasma etching, reactive ion etching, beam etching, and light-assisted etching, and chemical etching methods such as wet etching are combined. Can be used.

  When the solid support 13 is a plastic film, a production method using a support having fine irregularities produced by a molding method is also possible. Thereby, a fine protrusion shape pattern can be formed precisely.

  An example of a method for forming the gold microstructure 12 and the gold thin film 14 on the solid support 13 will be described with reference to FIGS. As shown in FIGS. 5A to 5D, first, an electron beam resist 42 is formed on the solid support 13 having the protruding shape 13 by spin coating or the like (FIG. 6A). Next, exposure is performed with an electronic drawing device to obtain a resist pattern 43 after development (FIG. 6B). Thereafter, the gold thin film 41 is deposited by sputtering or vapor deposition. Next, the resist is removed, and a gold microstructure 12 and a gold thin film 14 having arbitrary shapes can be formed (FIG. 6C).

  In addition to the electron beam drawing apparatus described above, the gold microstructure 12 can be formed by a patterning method using a focused ion beam processing apparatus, an X-ray exposure apparatus, or an EUV exposure apparatus.

  An example of the gold microstructure 12 is a gold nanodisk having a diameter of approximately 130 nm and a height of approximately 30 nm. This gold nanodisk has a localized surface plasmon resonance wavelength of 780 to 900 nm.

  The thickness (W4) of the solid support 13 is not particularly limited, and is appropriately selected in consideration of the place of implantation in the living body. Specifically, the thickness W4 of the solid support 13 is preferably in the range of 5 μm to 1000 μm, more preferably in the range of 100 μm to 500 μm. If the thickness of the solid support 13 is 5 μm or less, the solid support 13 may be damaged or deformed. Moreover, when the thickness of the solid support 13 is 1000 μm or more, the load on the human body is increased when the solid support 13 is embedded in the living body.

  When the solid support 13 is not a biocompatible material, the surface of the solid support 13 can be coated with a biocompatible polymer. As the biocompatible polymer, a known material can be used, and it is appropriately selected in consideration of embedding in the living body. For example, polyurethane, silicone resin, PMMA, parylene and the like can be mentioned.

  As a coating method of the biocompatible polymer on the solid support 13, the projection shape 11 formed on the solid support 13 can be uniformly coated, such as a spin coating method, an ink jet method, a dipping method, or a vacuum polymerization method. A method can be appropriately selected.

  In addition, it is preferable that the height (W1) of the protrusion shape 11 in FIG. 3 is in the range of 5 μm to 150 μm.

  The protruding shape 11 is not particularly limited as long as it is disposed at an end on the solid support 13 and at a symmetrical position with respect to the center, and may be a cylinder, a quadrangular column, or a hexagonal column.

  Further, the area of the total light reflecting portion 14 is not particularly limited, but in consideration of the area of the gold microstructure 12 that can induce localized surface plasmon resonance, it may be 20% or less of the surface area of the solid support 13. desirable.

  As shown in FIG. 1, the sensor chip 105 is embedded in the dermis tissue 104 at a depth of 1.5 mm from the surface so that the surface on which the protrusions 11 are formed is parallel to the skin surface. (1.5 mm below the skin surface).

  Next, the operation when the biological component concentration measuring apparatus 100 according to the present embodiment measures the glucose concentration will be described with reference to the drawings. First, the sensor chip 105 is embedded in the dermal tissue 104 in the living body and immersed in a cell interstitial fluid. The optical measuring device 100 is brought into contact with the 1 cm square region in the vicinity of the sensor chip 105 from outside the living body so as to be irradiated with laser light. Thereafter, the laser light source 101 is turned on. At this time, the lens group 108 and the spectral filter 106 are moved using a motor or the like so as to be out of the optical path as shown in FIG.

  The light emitted from the laser light source 101 is reflected by the beam splitter 102 and applied to the skin. Thereafter, the laser beam is moved by a certain distance in the horizontal direction by the optical path changer 113. While the laser beam moves in the lateral direction by a certain distance, the photodetector 110 always detects the light intensity and stores the position information and the light intensity in the memory 112. After moving 1 cm in the horizontal direction, the optical path changer 113 changes the optical path in a direction perpendicular to the horizontal direction moved 1 cm, and moves 1 cm in the horizontal direction. The optical path changer 113 repeats this operation and stores the position information and the light intensity in the memory 112. The microcomputer 111 extracts position information that maximizes the light intensity from the light intensity stored in the memory 112, moves the optical path changer 113, and moves it to a position where the light intensity is maximized. Through a series of operations, the optical measurement device 200 grasps the position of the sensor chip embedded in the living body, accurately irradiates the position of the sensor chip 105 in the living body, and detects the generated light with a high capture rate. can do. The reason why the position of the sensor chip 105 can be grasped by detecting the light intensity is as follows.

  A gold thin film 14 is provided on the sensor chip 105 and strongly reflects the irradiated laser light. There is no site in the skin that strongly reflects laser light. Moreover, in the area | region in which the gold | metal fine structure 12 of the solid support body 13 was formed, scattering is strong and the light intensity which reaches | attains the photodetector 110 is weak. Therefore, the position where the light intensity detected by the photodetector 110 becomes maximum when the optical path is moved is a position where the center of the laser light coincides with the center of the sensor chip 105.

  Next, the microcomputer 111 moves the lens group 108 and the spectral filter 106 to the optical path as shown in FIG. The laser light source 101 irradiates the sensor chip 105 with light, and surface-enhanced Raman scattered light is generated from glucose existing in a region of several tens of nm or less in the immediate vicinity of the sensor chip 105. The generated surface-enhanced Raman scattered light of glucose is collected by the lens group 108 and reaches the photodetector 110. The surface-enhanced Raman scattered light that reaches the photodetector 110 is split by passing through a spectral filter 106 between the lens groups 108. The microcomputer 111 refers to the correlation between the light intensity stored in advance in the memory 112 and the glucose concentration, and calculates the glucose concentration from the light intensity detected by the photodetector 110. The calculated glucose concentration is notified to the user by, for example, voice notification through a speaker (not shown) or display on a display or the like (not shown).

  The correlation data indicating the correlation between the light intensity and the glucose concentration stored in the memory 112 can be acquired by the following procedure, for example.

  First, the light intensity of surface enhanced Raman scattered light is measured for a user having a known glucose concentration. By performing this measurement for a plurality of users having different glucose concentrations, a data set composed of light intensity and glucose concentration can be obtained.

  According to the present embodiment, the reflected light intensity can be grasped, the position of the sensor chip can be grasped, the sensor chip 105 can be accurately irradiated with laser light, and the generated surface-enhanced Raman scattered light can be detected with a high capture rate. The glucose concentration of the interstitial fluid can be measured with high accuracy. In addition, since only one light source or photodetector is required, the apparatus configuration is simple.

Here, as in this embodiment, 780 nm is used as the wavelength of irradiation light, which is advantageous in the following points. In general, in a living body, the transmittance is extremely high for light of 700 to 900 nm. Moreover, since the specific Raman scattered light of glucose is a wave number that is about 1000 to 1200 cm ⁻¹ smaller than the wave number of the irradiated light, when the irradiated light is set to 700 to 800 nm, both the irradiated light and the surface enhanced Raman scattered light are This is because a wavelength region with high transparency can be used.

(Embodiment 2)
A second embodiment of the present invention will be described with reference to FIGS.

  7 to 10, the same components as those in FIGS. 1 to 4 are denoted by the same reference numerals and description thereof is omitted.

FIG. 7 is a diagram showing a configuration of the biological component concentration measuring apparatus according to Embodiment 2 of the present invention.
In FIG. 7, the configuration different from that of the first embodiment is that the optical measurement device 200 is provided with a laser light source 114 that emits substantially parallel light having a wavelength different from that of the laser light source 101, and the laser light source 101 and the laser light source 114 are switched. It is a point that can be. Further, the sensor chip 105 is different in that the light reflection portion on the upper surface of the protrusion shape 11 is formed of the dielectric multilayer film 15. Since other configurations are the same, description thereof is omitted.

  A laser light source 101 shown in FIG. 7 is a light source that is irradiated when detecting surface-enhanced Raman scattering light, and a laser light source 114 is a light source that is irradiated when measuring reflected light intensity.

  The arrangement shown in FIG. 7 is an arrangement for detecting surface-enhanced Raman scattering light, and the living body is irradiated with the light from the laser light source 101.

  FIG. 8 shows an arrangement for detecting the reflected light intensity, and the living body is irradiated with the light from the laser light source 114.

The laser light source 114 is substantially parallel light having a wavelength of 650 nm, and the beam shape is a circular shape having a diameter of 1000 μm. The laser light source 114 passes through the epidermal tissue 102 and irradiates the chip 105 in the dermal tissue 104.
In this embodiment, the case of the sensor chip 205 having a cross section as shown in FIG. 9 will be described.

  In FIG. 9, the configuration different from that of the first embodiment is that a dielectric multilayer film 15 that reflects only light in the vicinity of 650 nm with a central wavelength of 650 nm is formed on the light reflecting portion on the upper surface of the projection shape 11 on the cylinder. Is a point.

  As shown in FIG. 10, in the present embodiment, the sensor chip 205 is formed in the shape of a columnar protrusion having a diameter of 50 μm on a circular solid support 13 having a diameter of 500 μm, like the sensor chip 105 of the first embodiment. Two are formed. The protrusion 11 has a center on a straight line A passing through the center of the solid support 13, and has a center at a position symmetrical with respect to a straight line B passing through the center of the solid support 13 and perpendicular to the straight line A. . Further, the circumference of the solid support 13 and the circumference of the protruding shape 11 are formed so as to contact each other. A dielectric multilayer film 15 is formed on the upper surface of the protrusion shape 11.

  An example of a method for forming the gold microstructure 12 and the dielectric multilayer film 15 on the solid support 13 will be described with reference to FIGS. A resist film 51 is formed on the solid support 13 having the protrusion 11 formed by the method shown in FIGS. 5A to 5D by using a spin coating method or the like. The resist film 51 is selectively exposed and developed to produce a resist pattern 52 having a predetermined shape (FIG. 10B). Thereafter, a dielectric multilayer film 53 is formed by sputtering or the like (FIG. 10C). Next, the resist is removed to obtain the dielectric multilayer film 54 (FIG. 10D). Next, an electron beam resist 55 is formed by spin coating or the like (FIG. 10E). Next, the resist pattern 56 is obtained after exposure with an electronic drawing apparatus and development (FIG. 10F). Thereafter, gold is deposited by sputtering or vapor deposition. Next, the resist is removed, and a gold microstructure 12 and a dielectric multilayer film 15 having an arbitrary shape can be formed (FIG. 10G).

  The material constituting the dielectric multilayer film 15 can be used without particular limitation as long as it is a transparent material for two types of light of 650 nm. For example, a dielectric periodic multilayer film of SiO2 and TiO2 can be raised.

  Next, the operation when the biological component concentration measuring apparatus in the present embodiment measures the glucose concentration will be described with reference to the drawings. First, the sensor chip 205 is embedded in the dermal tissue 104 in the living body and immersed in a cell interstitial fluid. The optical measuring device 200 is brought into contact with the 1 cm square region in the vicinity of the sensor chip 205 from outside the living body so that the laser beam is irradiated. Thereafter, the laser light source 114 is turned on. At this time, the lens group 108 and the spectral filter 106 are moved using a motor or the like so as to be out of the optical path as shown in FIG.

  The light emitted from the laser light source 114 is reflected by the beam splitter 102 and applied to the skin. Thereafter, the laser beam is moved by a certain distance in the horizontal direction by the optical path changer 113. While the laser beam moves in the lateral direction by a certain distance, the photodetector 110 always detects the light intensity and stores the position information and the light intensity in the memory 112. After moving 1 cm in the horizontal direction, the optical path changer 113 changes the optical path in a direction perpendicular to the horizontal direction moved 1 cm, and moves 1 cm in the horizontal direction. The optical path changer 113 repeats this operation and stores the position information and the light intensity in the memory 112. The microcomputer 111 extracts position information that maximizes the light intensity from the light intensity stored in the memory 112, moves the optical path changer 113, and moves it to a position where the light intensity is maximized. Through a series of operations, the optical measurement device 200 grasps the position of the sensor chip 205 embedded in the living body, accurately irradiates the position of the sensor chip 205 in the living body, and generates generated light with a high capture rate. Can be detected.

  Next, the microcomputer 111 moves the lens group 108 and the spectral filter 106 to the optical path as shown in FIG. At the same time, the microcomputer 111 replaces the laser light source 101 with the laser light source 114. The laser light source 101 irradiates the sensor chip 205 with light, and surface-enhanced Raman scattered light is generated from glucose existing in the region of several tens of nm or less in the immediate vicinity of the sensor chip 205. The generated surface-enhanced Raman scattered light of glucose is collected by the lens group 108 and reaches the photodetector 110. The surface-enhanced Raman scattered light that reaches the photodetector 110 is split by passing through a spectral filter 106 between the lens groups 108. The microcomputer 111 refers to the correlation between the light intensity stored in advance in the memory 112 and the glucose concentration, and calculates the glucose concentration from the light intensity detected by the photodetector 110. The calculated glucose concentration is notified to the user by, for example, voice notification through a speaker (not shown) or display on a display or the like (not shown).

  According to the present embodiment, the reflected light intensity at 780 nm of the gold microstructure is strong, and is particularly effective when the change in the reflected light intensity is small depending on the position on the sensor chip 105.

(Embodiment 3)
A third embodiment of the present invention will be described with reference to FIGS.

12-15, the same code | symbol is used about the same component as FIGS. 1-4, and description is abbreviate | omitted.
The configuration different from the first embodiment is that the protruding shapes 11 of the sensor chip 305 are periodically arranged.

  In FIG. 12, the configuration different from the first embodiment is that the protruding shapes 11 of the sensor chip 305 are periodically arranged. Since other configurations are the same, description thereof is omitted.

  FIG. 13 shows an arrangement for detecting the reflected light intensity, and a configuration different from the first embodiment is that the protruding shapes 11 of the sensor chip 305 are periodically arranged. Since other configurations are the same, description thereof is omitted.

In the present embodiment, the case of a sensor chip 305 having a cross section as shown in FIG. 14 will be described. In FIG. 14, the configuration different from the first embodiment is that the protruding shapes 11 of the sensor chip 305 are periodically arranged. Since other configurations are the same, description thereof is omitted.
On the solid support 13, periodic cylindrical projections 11 arranged in a square are provided. A gold thin film 14 is formed on the upper surface of the cylindrical protrusion 11. As shown in FIG. 15, in the sensor chip 305, 36 cylindrical protrusions 13 having a diameter of 20 μm and 36 pitch intervals (W2) of 60 μm are formed on a circular solid support 13 having a diameter of 500 μm. W2 is the distance between the centers of the cylindrical shapes.

In addition, it is preferable that the height (W1) of the protrusion shape 11 in FIG. 3 is in the range of 5 μm to 150 μm.
The protruding shape 11 is not particularly limited as long as it is disposed at an end on the solid support 13 and at a symmetrical position with respect to the center, and may be a cylinder, a quadrangular column, or a hexagonal column. The shape of the protrusion 11 may be a cylinder, a square column, or a hexagonal column, and is not particularly limited. The method of arranging the columnar protrusions may be square, triangular, or hexagonal, and there is no particular limitation as long as they are regularly arranged.

  Since the operation of the biological component concentration measuring apparatus in the present embodiment is the same as that in the first embodiment, the description thereof is omitted.

  According to the present embodiment, since the light reflection portions are periodically arranged, the change in the reflected light intensity with respect to the change in the optical path becomes large, so that the sensor chip position can be grasped more accurately.

  In the present embodiment, the periodic protrusion shape is provided on the sensor chip of the biological component concentration measuring device in the first embodiment, but the periodic protrusion shape is similarly provided on the biological component concentration measuring device sensor chip in the second embodiment. It may be provided.

  According to the biological component concentration measuring apparatus of the present invention, by measuring the reflected light intensity from the light reflecting portion on the sensor chip while changing the optical path, the position of the sensor chip embedded in the living body is grasped, Since the light is accurately irradiated to the position of the sensor chip in the living body and the generated light can be detected with a high capture rate, the concentration of the biological component can be measured with high accuracy, which is effective.

11 Protrusion shape 12 Gold microstructure 13 Solid support 14 Gold thin film 15 Dielectric multilayer 31 Resist film 32 Resist pattern 41 Gold thin film 42 Electron beam resist 43 Resist pattern
W1 Projection height
W2 pitch interval
W4 Solid support thickness 51 Resist film 52 Resist pattern 53, 54 Dielectric multilayer film 55 Electron beam resist 56 Resist pattern 100 Biological component concentration measuring device 101 Laser light source 102 Beam splitter 103 Epidermis tissue 104 Dermal tissue 105, 205, 305 Sensor chip 106 Spectral Filter 107 Subcutaneous Tissue 108 Lens Group 110 Photodetector 111 Microcomputer 112 Memory 113 Optical Path Changer 114 Laser Light Source 200 Optical Measuring Device

Claims (6)

  A metal microstructure forming portion in which a metal microstructure capable of inducing localized surface plasmon resonance is formed on a solid support, and the upper portion is a plane on the solid support, and the upper surface is a light reflecting portion. Sensor chip having a plurality of protrusions, intensity of reflected light from the light reflecting portion of the light source and light from the light source, and surface-enhanced Raman scattered light generated from the metal microstructure forming portion by the light from the light source A biological component concentration measuring device comprising the optical measuring device comprising a detector for measuring light and an optical path changing means for changing the optical path.   The biological component concentration measuring apparatus according to claim 1, wherein the light reflecting portion is made of metal.   The biological component concentration measuring apparatus according to claim 1, wherein the light reflecting unit reflects only light having a specific wavelength.   The biological component concentration measuring apparatus according to claim 1, wherein the wavelength of the reflected light irradiation light is different from the wavelength of the surface enhanced Raman scattered light irradiation light.   The biological component concentration measuring apparatus according to any one of claims 1 to 3, wherein the wavelength of the reflected light irradiation light and the wavelength of the surface enhanced Raman scattered light irradiation light are the same.   The biological component concentration measuring apparatus according to claim 1, wherein the protrusion shape is formed periodically.

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