JP5424229B2 - Optical waveguide mode sensor using oxide film and manufacturing method thereof - Google Patents

Description

  The present invention relates to an optical waveguide mode sensor capable of increasing the detection sensitivity of a sample to be detected by using an optical waveguide mode, and a method for manufacturing the same.

In general, a technique using a surface plasmon resonance (SPR) mode is known as a biosensor such as a DNA, a protein such as an antigen-antibody, a sugar chain, or a chemical substance sensor such as a metal ion or an organic molecule (for example, non (See Patent Documents 1 to 4).
This sensor using surface plasmon resonance is usually called an SPR sensor. An example of its use is shown in FIG. FIG. 1 shows an SPR sensor using a Kretschmann arrangement. It consists of a structure in which a noble metal (gold, silver, etc.) is vapor-deposited on a flat glass substrate, and the surface opposite to the surface on which the noble metal is vapor-deposited is in close contact with an optical prism via refractive index adjusting oil. White light is irradiated onto the glass substrate through the prism. Incident light is incident under the condition of total reflection. Surface plasmon resonance appears at a certain incident angle by the evanescent wave that oozes out to the surface side of the noble metal of incident light. When surface plasmon resonance occurs, the evanescent wave is absorbed by the surface plasmon, so that the intensity of the reflected light is remarkably reduced in the vicinity of the incident angle. The incident angle and reflected light intensity at which surface plasmon resonance appears change depending on the thickness of the deposit on the surface of the noble metal and the dielectric constant, so the incident angle generated when the sample to be detected binds or adsorbs on the surface of the noble metal. And a change in reflectance intensity is detected to detect a sample to be detected.

  As a sensor that has a structure very similar to that of an SPR sensor and detects a substance adsorption or a change in dielectric constant on the detection surface of the sensor, there are optical waveguide mode sensors (see Non-Patent Documents 5 to 8 and Patent Document 1). ).

  An example of this use is shown in FIG. FIG. 2 shows an optical waveguide mode sensor using the Kretschmann arrangement. This optical waveguide mode sensor uses a detection plate comprising a transparent substrate (plate glass or the like), a reflective film layer (also referred to as a clad layer) coated thereon, and an optical waveguide layer formed on the reflective film layer. The optical waveguide layer is made of a material that is transparent to the light used for the sensor. An optical prism is brought into close contact with the surface of the detection plate opposite to the surface on which the optical waveguide layer is formed via refractive index adjusting oil, and laser light or white light is irradiated to the detection plate through the prism. Incident light is incident on the detection plate under the condition of total reflection. When the incident light couples with an optical waveguide mode (also called a leaky mode or leaky mode) that propagates in the optical waveguide at a specific incident angle, the optical waveguide mode is excited, and the reflected light of the light near this light incident angle. The intensity changes greatly. The incident angle of light necessary for this optical waveguide mode excitation and the reflected light intensity of light incident near this incident angle vary depending on the thickness and dielectric constant of the deposit on the surface of the optical waveguide layer. The detected sample can be detected by detecting the change in the incident angle or the change in the reflectance intensity that occurs when the detected sample is bound or adsorbed on the surface of the layer. In the SPR sensor, since surface plasmon is excited only by P-polarized light, only P-polarized light can be used as a light source. On the other hand, in the optical waveguide mode sensor, both P-polarized light and S-polarized light can be used.

  Any material can be used for the reflective film used in the optical waveguide mode sensor unless the extinction coefficient (coefficient representing light attenuation in the substance) is zero. In general, gold or silver is often used. Patent Document 1 shows an example in which zirconium, tungsten, chromium, or the like is used for the reflective layer. The optimum film thickness of the reflective film varies depending on the material, but is about several nm to several hundred nm. Vapor deposition, sputtering, molecular beam epitaxy (MBE), electroless plating, electroplating, and the like can be used as means for coating the reflective film on the glass substrate.

  In the optical waveguide mode sensor, an optical waveguide layer is formed on these reflective films. For the optical waveguide layer reported so far, a transparent dielectric material such as silica glass, silicon oxide film, alumina, polymer material, and dextran gel is used. Conventionally, these optical waveguide layers are formed on a reflective film by depositing these materials by vapor deposition or sputtering, or by applying them by spin coating. Non-Patent Document 7 reports that Al is deposited on the Au reflective film by vapor deposition, this Al layer is anodized to form porous alumina, and this porous alumina layer is used as an optical waveguide layer. Has been made.

  As described above, in the conventional optical waveguide mode sensor, when the optical waveguide layer is formed, the material to be the optical waveguide layer is deposited or applied on the reflective film layer. Therefore, there is a problem in the adhesion between the reflective film layer and the optical waveguide layer. For example, when Au is used for the reflective film and the silica glass, silicon oxide film, or anodized porous alumina film as described above is formed as the optical waveguide layer thereon, an adhesive layer is formed between the reflective film and the optical waveguide layer. As a result, it was necessary to form a thin layer of chromium or titanium.

In addition, the material formed by deposition or coating is not uniform in structure and has many disadvantages such as being polycrystalline, containing many structural defects, or having a composition deviating from the stoichiometric ratio. Such a non-uniform film is etched unevenly on the surface of the optical waveguide layer when chemical etching is performed to form pores in the optical waveguide layer as reported in Non-Patent Document 5 and Non-Patent Document 6. There is a disadvantage that it ends up.
C. Nylander, B. Liedberg, and T. Lind, Sensor. Actuat. 3, pp. 79-88 (1982/83). B. Liedberg, C. Nylander, and I. Lundstrom, Actuat. 4, pp. 299-304 (1983). W. Knoll, Annu. Rev. Phys. Chem. 49, pp. 569-638 (1998). DK Kambhampati, TAM Jakob, JW Robertson, M. Cai, JE Pemberton, and W. Knoll, Langmuir 17, pp. 1169-1175 (2001). M. Fujimaki, C. Rockstuhl, X. Wang, K. Awazu, J. Tominaga, T. Ikeda, Y. Ohki, and T. Komatsubara, Microelectronic Engineering 84, pp.1685-1689 (2007) K. Awazu, C. Rockstuhl, M. Fujimaki, N. Fukuda, J. Tominaga, T. Komatsubara, T. Ikeda, Y. and Ohki, Optics Express 15, pp. 2592-2597 (2007) KHA Lau, LS Tan, K. Tamada, MS Sander, and W. Knoll, J. Phys. Chem. B 108, pp. 10812 (2004) FC Chien and SJ Chen, Optics letters 31, pp. 187-189 (2006). U.S. Patent No. 6,483,959

  The present invention aims to solve the above-mentioned problems, and in an optical waveguide mode sensor, a high-sensitivity optical waveguide layer having an optical waveguide layer that does not require an adhesive layer, has high stability, is uniform, and is easily etched. An optical waveguide mode sensor is provided.

The detection plate for an optical waveguide mode sensor of the present invention is an optical waveguide mode sensor detection plate comprising a transparent substrate, a reflective film formed thereon, and an optical waveguide layer formed on the reflective film. optical waveguide layer is formed from a surface portion of the reflective film by oxidizing a surface portion of the reflection film.

An optical waveguide mode sensor detection plate manufacturing method according to the present invention is a method for manufacturing an optical waveguide mode sensor detection plate comprising a transparent substrate, a reflective film formed thereon, and an optical waveguide layer formed on the reflective film. A method of forming a layer to be the reflective film on the transparent substrate, and forming an optical waveguide layer from the surface portion of the layer to be the reflective film by oxidizing the surface portion of the layer to be the reflective film Process.

  The reflective film is made of a semiconductor material or a metal material. The semiconductor material is Si or Ge, and the metal material is Al, Ti, or Ta. The transparent substrate can be a glass such as silica glass. A plurality of pores can be formed in the optical waveguide layer.

Using the detection plate for an optical waveguide mode sensor described above, and detecting the light incident mechanism for entering light to the reflection film from the transparent substrate side of the detection plate, and the reflected light of the light reflected by the reflection film An optical waveguide mode sensor that observes or detects a change in the environment by reading a change in the intensity of the reflected light caused by a change in the environment in the vicinity of the surface of the optical waveguide layer. it can. A detection plate having a molecular recognition group chemically modified on the surface of the optical waveguide layer is used. As a molecular recognition group, a detection plate in which any of —NH ₂ , —COOH, —SCN, succinimide group, and biotinyl group is chemically modified is used. The optical prism has a structure in which a surface of the detection plate opposite to the surface on which the optical waveguide layer is formed is in close contact with a refractive index adjusting oil.

  The pores formed in the optical waveguide layer are formed by chemical etching, reactive ion etching, nanoimprinting, or lithography. The pores are formed by chemical etching after ion implantation, and chemical etching is etching with a hydrofluoric acid solution or a hydrofluoric acid vapor.

  According to the present invention, by forming the optical waveguide layer by oxidizing the surface of the layer to be the reflective film, the adhesion between the reflective film layer and the optical waveguide layer is improved much more than the prior art, and stable. A sensor can be provided. Further, by obtaining the optical waveguide layer by oxidizing the reflective film itself, a uniform and high-quality optical waveguide layer with few defects can be formed. Furthermore, by providing a high-quality optical waveguide layer, it is possible to improve the processability of this layer and to provide an optical waveguide mode sensor having an optical waveguide layer that facilitates pore formation.

  The features of the present invention will be specifically described below with reference to the drawings. In addition, the following description is for making an understanding of this invention easy, and is not restrict | limited to this. That is, modifications, embodiments, and other examples based on the technical idea of the present invention are included in the present invention.

  First, the optical waveguide mode will be described. In the present invention, a detection plate as shown in FIG. 3 is used. The detection plate includes a transparent substrate such as glass, a reflective film layer formed thereon, and an optical waveguide layer formed on the reflective film layer. The substrate is basically plate-shaped, but it may be formed in advance so that the prism and the prism are integrated in anticipation of using a prism when light is incident. When light enters the detection plate having such a structure from the transparent substrate side, a phenomenon occurs in which reflected light extremely increases or decreases at a certain incident angle. The light to be used is basically not particularly limited as long as it is an electromagnetic wave, but it is desirable to use light in the infrared to ultraviolet region in terms of easy handling.

  4 shows a prism (an isosceles triangular prism with a vertex of 30 °) arranged on the glass side of the detection plate of FIG. 3 via a refractive index adjusting oil, and the incident angle and reflected light intensity when the light is incident. The relationship is shown. The detection plate is formed of a single-crystal Si (refractive index: 3.882, extinction coefficient: 0.019) having a thickness of 215 nm on a silica glass substrate (refractive index: 1.456) as a reflective film, and a 450 nm thick thickness is formed thereon. What formed the silica glass optical waveguide was used. The surface of the optical waveguide is immersed in water (refractive index: 1.332). The incident light is S-polarized light having a wavelength of 633 nm. The sudden increase and decrease in reflected light intensity seen in FIG. 4 is due to the optical waveguide mode. This reflected light intensity dip does not occur when the optical waveguide layer shown in FIG. 3 is not provided or when the layer is thin. The thickness of the optical waveguide layer in which the optical waveguide mode is generated varies depending on the polarization state of the light used, but generally may be thin when the refractive index of the optical waveguide layer is high or when the wavelength of light is short. On the other hand, when the refractive index of the optical waveguide layer is low or the wavelength of light used is long, a thick optical waveguide layer is required. As the optical waveguide layer becomes thicker, a plurality of waveguide modes are observed. That is, a plurality of sudden changes (dips) in reflectance as seen in FIG. 4 are observed. This is described in Non-Patent Document 6, Non-Patent Document 7, and Patent Document 1.

The relationship between the incident angle of light and the intensity of reflected light varies depending on the material used for the reflective film and the thickness of the material. For example, as in the prior art, a detection plate using gold can obtain characteristics as shown in FIG. In FIG. 5, the prism is an isosceles right angle prism, the incident light is S-polarized light of 633 nm, the transparent substrate is glass with a refractive index of 1.76294, the reflecting film is gold with a thickness of 44 nm, and the optical waveguide is SiO ₂ glass with a thickness of 350 nm. The relationship between the incident angle of light and the intensity of reflected light when used is shown. In the detection plate using tungsten, characteristics as shown in FIG. 6 are obtained. In FIG. 6, the prism is a right-angled isosceles prism, the incident light is S-polarized light of 633 nm, the transparent substrate is glass with a refractive index of 1.76294, the reflective film is tungsten with a thickness of 18 nm, and the optical waveguide is SiO ₂ glass with a thickness of 350 nm. The relationship between the incident angle of light and the intensity of reflected light when used is shown.

  In the present invention, the change in the dielectric constant or the refractive index on the surface of the optical waveguide layer is caused by a phenomenon in which the intensity of the reflected light suddenly increases / decreases due to the optical waveguide mode, that is, a dip or peak occurs. Observe changes. Specifically, for example, adsorption, contact, and binding of molecules to the surface of the optical waveguide, changes in the refractive index of the medium (solution, etc.) on the surface of the optical waveguide, and changes in the environment such as temperature changes are detected.

  For such detection, an arrangement called a Kretschmann arrangement as shown in FIG. 2 is often used. Light used for detection is applied to the reflective film from the transparent substrate side via the polarizing plate and the prism, and is combined with the optical waveguide mode of the optical waveguide layer under specific conditions. As a result, the reflected light intensity increases or decreases. Increase or decrease in the light intensity reflected by the reflective film is detected by the detector. Two polarizing plates are often used as shown in FIG. 2. Of the two polarizing plates, the polarizing plate closer to the prism is either P-polarized light whose vibration direction is parallel to the reflecting surface or S-polarized light. Installed to select polarization. The polarizing plate closer to the laser light source is installed to adjust the light intensity incident on the optical waveguide.

  Thus, in the optical waveguide mode sensor, sensing can be performed with the same optical system as the Kretschmann arrangement. Therefore, this optical system is used in the following description of the present invention. As the optical prism, in addition to the triangular prism shown in the drawing, any prism such as a cylindrical prism or a hemispherical prism can be used. However, there are other methods for exciting the optical waveguide mode. Instead of the optical prism, a grating may be used to induce coupling between incident light and the optical waveguide mode. Any conventionally known method can be applied to the optical waveguide mode excitation method in the optical waveguide.

  FIG. 7 shows a configuration example of an optical waveguide mode sensor system, which normally includes a light source (laser, white light source, etc.), a polarizer, a goniometer, a photodetector, and analysis software. A combination of a liquid cell, a detection plate and a prism is placed on an incident angle control goniometer, and P or S polarized laser light is incident from the prism side through a polarizing plate. The reflected light is captured by the photodetector. The liquid cell is used to hold a solution serving as a specimen on the molecular detection surface of the detection plate, that is, the surface of the optical waveguide layer. Various types of liquid cells can be used, such as a container type for holding a solution and a flow channel type (including a micro flow channel). Choppers and lock-in amplifiers are sometimes used to suppress noise from outside light (such as room light) other than laser light.

  As shown in FIG. 8, in the detection plate used in the present invention, a reflection film is first formed on a transparent material to be a base, and this reflection film is oxidized to form an optical waveguide layer. The detection plate formation procedure in the present invention will be described below.

The material used for the substrate is transparent to the light used for detection, and preferably has a refractive index of about 1.4 to 2.2 for the light used for detection. A preferable material for the substrate is a glass material. As described above, basically any material can be used for the reflective film unless the extinction coefficient is zero. However, in the present invention, the optical waveguide layer is formed by oxidizing this reflective film. Since the optical waveguide layer needs to be transparent to the light used for detection, it is necessary to select a material for which the oxide of the material of the reflective film is transparent. For example, Si (oxide is SiO ₂ ), Ge (oxide is GeO ₂ ), Al (oxide is alumina, for example), Ti (oxide is TiO ₂ ), Ta (oxide is Ta ₂ O, etc.) ₅ ). However, the present invention is not limited to these, and any material can be used as the reflective film as long as a transparent oxide can be obtained. Considering the stability of the sensor, it is desirable that the reflective film is a material having good adhesion to the substrate material.

  As a method for forming the reflective film, a method of depositing or coating on the substrate by vapor deposition, sputtering, molecular beam epitaxy (MBE), electroless plating, electroplating, spin coating, or the like can be applied. Furthermore, a bonding technique is also a preferable method that can be applied. The bonding technique is a technique used for manufacturing an SOI (Silicon on Insulator) substrate, and a method for forming various layered materials by bonding surfaces that can be bonded (for example, silica glass surfaces) to each other. It is. As a layered material manufactured using this technology, in addition to SOI, an SOQ (Silicon-on-quartz) substrate, a GeOI (Ge-on-insulator) substrate, a SopSiC (Si-on-poly SiC) substrate, SiCOI (SiC-on-insulator) substrates, GaN-on-insulator (GaNOI) substrates, and the like are known. A case where the substrate is made of silica glass and a Si reflecting film is formed thereon using this method will be described. A Si substrate having a thin silica glass layer is prepared by thinly oxidizing the surface of the Si substrate. By bonding the silica glass layer on the Si substrate and the plate-like silica glass to each other, the substrate on which the Si layer is formed on the silica glass, that is, the substrate having the Si reflection film is formed. Can be obtained. The thickness of the Si layer can be adjusted by polishing or using the Smart Cut technology. The Smart Cut technology is a method in which hydrogen ions are ion-implanted to a certain depth from the surface of a material (eg, Si layer) on which a thin film is to be formed. Or He ions are implanted, and then a stress is applied mechanically or thermally to cut the material at the position of the layer where the ions are implanted to obtain a thin film of the material. In the present invention, any technique that can form a layer to be a reflective film on a transparent substrate can be applied.

  In the present invention, after the reflective film layer is formed, the optical waveguide layer is formed by oxidizing the surface of the reflective film. At this time, since the thickness of the reflective film layer decreases, it is necessary to set the oxidation process so that the thickness of the reflective film layer remaining after the optical waveguide is formed becomes an optimum thickness for sensing. is there. On the other hand, as described above, the optical waveguide layer needs to have a certain thickness in order to excite the optical waveguide mode. Therefore, it is necessary to form the reflective film layer in consideration of how thick the optical waveguide layer is formed by oxidation and how much of the reflective film layer is left. In general, the volume increases when a material is oxidized. Therefore, as shown in FIG. 8, the reflection layer is thinned by oxidation in the optical waveguide forming step, but the total thickness of the formed reflection layer and the optical waveguide layer is larger than that of the reflection layer before oxidation. Become thicker.

In the oxidation step, heat treatment in an oxygen-containing atmosphere or oxygen (also called thermal oxidation or dry oxidation), heat treatment in an atmosphere containing water vapor (H ₂ O) or water vapor (water vapor oxidation, wet oxidation) It is also possible to use any oxidation method such as anodic oxidation. Heat treatment (thermal oxidation) in an oxygen-containing atmosphere or oxygen is the most common and easy. Steam oxidation (wet oxidation) is known to be capable of forming a thick oxide film at a low temperature and in a short time, and is suitable for forming a thick optical waveguide layer. In steam oxidation, an atmosphere containing water vapor, for example, oxygen gas, nitrogen gas, or a gas in which water vapor is mixed in air is sent to a thermal oxidation furnace, and oxidation is performed by heat treatment. Water vapor is mixed by passing oxygen gas, nitrogen gas, air, or the like through boiling water. Only steam may be sent into the furnace for heat treatment. Thermal oxidation or wet oxidation of Si requires heat treatment at a high temperature near 1000 ° C. or higher. Therefore, when Si is used as the reflective film, the substrate must also be a material that can withstand this heat treatment. For this reason, silica glass or the like is a preferred substrate material.

  In summary, in the present invention, first, a transparent substrate material is prepared, a layer to be a reflective film is formed on one surface thereof, and the layer to be the reflective film itself is oxidized to form an optical waveguide layer. Thus, a detection plate (detection plate) for detection is obtained. That is, the surface of the layer that becomes the reflective film is processed into an optical waveguide, and the remaining layer functions as a reflective layer.

  The optical waveguide layer formed by oxidation is very uniform and has low internal stress, resulting in a high-quality film. Therefore, there is an advantage that even when this film is processed, the film can be processed uniformly. As described in Non-Patent Document 5 and Non-Patent Document 6, it is known that the sensitivity of an optical waveguide mode sensor can be improved by forming many nanoscale fine holes (pores) in an optical waveguide layer. ing. The optical waveguide layer formed according to the present invention is also optimal when performing such nanoscale processing.

  The pores of the optical waveguide layer can be formed by chemical etching using a solution that dissolves the surface of the optical waveguide or dry etching such as reactive ion etching. The most common method for forming pores is to apply a resist on the surface of the optical waveguide, form a dot pattern on the resist by lithography, and then transfer the dot pattern to the optical waveguide layer by chemical etching or dry etching. This is a method of forming a hole. Since the optical waveguide formed by oxidation has a characteristic that it is uniformly etched in the etching process, there is an advantage that the surface roughness on the surface of the optical waveguide after the process is small. Nanoimprinting technology can also be used for pore formation.

  In general, lithography is suitable for forming a regular pattern, but in the case of an optical waveguide mode sensor, the arrangement of the pores may not be regular. For the formation of randomly arranged pores, when the reflective film is silicon and the optical waveguide material is silicon oxide, the combination of ion implantation and chemical etching described in Non-Patent Document 5 and Non-Patent Document 6 is also effective. This is a pore formation method. When ions are accelerated and injected into silicon oxide with high energy of MeV order or higher, the part where the ions have passed is chemically and selectively etched with hydrofluoric acid or borohydrofluoric acid, resulting in a fine diameter of several tens of nanometers. Formation of pores is possible. In particular, if etching using hydrofluoric acid vapor is used, fine pores having a high aspect ratio can be formed.

  The formed pores preferably have a diameter equal to or less than the wavelength of light used. This is because if the hole diameter is larger than the wavelength of light, light interference occurs due to the hole, and the analysis at the time of sensing becomes complicated. The hole may penetrate the optical waveguide to reach the reflection layer, or may not penetrate the optical waveguide layer and reach the reflection film.

This sensor detects changes in the environment such as molecular adsorption, contact, binding, change in the refractive index of the medium (solution, gas, etc.), temperature change, etc. on the detection plate surface. Here, in order to observe the adsorption and binding of molecules, it is necessary to specifically adsorb a detection target molecule or to chemically modify a molecular recognition group that specifically binds to the detection target molecule. Examples of this molecular recognition group include —NH ₂ , —COOH, —SCN, succinimide group, biotinyl group and the like.

Silica glass with a thickness of 1 mm was used for the substrate. A single-crystal Si layer having a thickness of 440 nm was formed on the silica glass by a bonding technique. This substrate was placed in a steam oxidation furnace, and steam oxidation was performed at 1000 ° C. for 1 hour in an oxygen atmosphere containing steam at 1 atm. A SiO ₂ layer having a thickness of 484 nm was formed on the surface of the single crystal Si layer. Further, the Si layer which was 440 nm before the heat treatment was thinned to 220 nm by the heat treatment. FIG. 9 shows how the detection plate is formed. The 484 nm thick SiO ₂ layer formed by this heat treatment serves as an optical waveguide layer, and the 220 nm thick Si layer serves as a reflective film layer.

  A prism is brought into close contact with the substrate side of the detection plate via refractive index adjustment oil to form a Kretschmann arrangement as shown in FIG. As the prism, an isosceles triangular prism having a vertex of 30 ° was used. FIG. 10 shows the relationship between the incident angle and the reflected light intensity when S-polarized light having a wavelength of 633 nm is incident from the prism side. At this time, the surface of the optical waveguide is immersed in water. Dips due to optical waveguide mode excitation can be observed.

  Surface modification was performed on the surface of the optical waveguide of the detection plate, and molecular adsorption was observed. The detection plate was immersed in a weak alkaline aqueous solution for 10 hours and then dried, and then immersed in an ethanol solution of 0.2 wt.% 3-aminopropyltriethoxysilane for 10 hours to modify reactive amino groups on the silicon oxide surface. After rinsing with ethanol and drying, it was immersed in a 1/15 M phosphate buffer containing 0.1 mM sulfosuccinimidyl-N- (D-biotinyl) -6-aminohexanate. The mixture was allowed to stand for 5 hours, the amino group and the succinimide group were reacted, and a biotinyl group was introduced. In this way, specific adsorption of streptavidin to the biotinyl group can be observed.

  Thereafter, a detection plate was attached to the liquid cell so that the optical waveguide surface was in contact with the 1/15 M phosphate buffer. As shown in FIG. 2, the surface opposite to the optical waveguide surface was brought into close contact with a triangular prism having a vertex of 30 ° through a refractive index adjusting oil. This was mounted on an incident angle control goniometer, and the substrate was irradiated with S-polarized light having a wavelength of 633 nm through a prism. A 1 / 15M phosphate buffer containing 0.5 μM of streptavidin was injected into the liquid cell, and the reflected light intensity was measured while the optical waveguide surface was immersed in this phosphate buffer.

  FIG. 11 shows reflected light intensity characteristics before and after injection of a phosphate buffer containing streptavidin. It can be seen that the dip shifted to the high angle side by the adsorption of streptavidin to the biotinyl group. The shift amount was 0.19 °. FIG. 12 shows the result of subtracting the pre-injection data from the data after streptavidin injection in order to see how much the reflectance changes at each incident angle. A reflectance increase of 0.332 was obtained at an incident angle of 69.69 °, and a reflectance reduction of 0.369 was obtained at an incident angle of 69.97 °. Thus, it can be seen that highly sensitive biomolecule detection can be performed by the detection plate produced by the present technology.

Next, formation of micropores for an optical waveguide produced by the production method according to the present invention will be described. The formation of the optical waveguide is the same as described above. First, a single-crystal Si layer having a thickness of 440 nm is formed on a silica glass substrate having a thickness of 1 mm by a bonding technique. This substrate is subjected to water vapor oxidation at 1000 ° C. for 1 hour in an oxygen atmosphere containing water vapor at 1 atm to form an optical waveguide. The thickness of the formed SiO ₂ optical waveguide layer was 484 nm, and the thickness of the Si reflective film layer was 220 nm.

This optical waveguide layer was irradiated with gold ions accelerated at 137 MeV vertically from the surface in a vacuum. The irradiation amount of gold ions was 5 × 10 ⁹ pieces / cm ² . After ion irradiation, the sample was taken out from the vacuum chamber and etched with hydrofluoric acid vapor. An etching method using hydrofluoric acid vapor is described below. First, a sample is put in a container containing a 20% hydrofluoric acid solution and the container is sealed. At this time, the sample is held so as not to be immersed in hydrofluoric acid. The hydrofluoric acid temperature is kept at 20 ° and the sample temperature at 36 °. In this state, etching was performed for 30 minutes. By this etching, ion tracks formed on the sample surface, that is, ion trajectories formed by passing ions during ion irradiation, are selectively etched to form pores with a diameter of several tens of nanometers. Since one pore is formed for one ion track, the number of holes is equivalent to the ion irradiation amount. However, in practice, the ion tracks may overlap each other, so that the number of holes formed tends to be somewhat smaller than the ion irradiation amount. Details regarding the vapor etching of hydrofluoric acid are described in Non-Patent Documents 5 and 6. An electron micrograph of the surface of the optical waveguide layer of the detection plate formed by the above production method is shown in FIG. It can be seen that pores having a diameter of about 30 nm are formed.

  Using this detection plate, specific adsorption of biotin and streptavidin was detected. The method of introducing a biotinyl group onto the detection plate surface and detecting streptavidin is as described above. FIG. 14 shows reflected light intensity characteristics before and after injection of a phosphate buffer containing streptavidin. It can be seen that the dip shifted to the high angle side by the adsorption of streptavidin to the biotinyl group. The obtained shift amount is 0.32 °, which is 0.12 ° larger than the peak shift amount before forming the pores as seen in FIG. In addition, FIG. 15 shows the result of subtracting the data before injection from the data after injection of streptavidin in order to see how much the reflectance changes at each incident angle at this time. When the incident angle was 70.83 °, a reflectivity increase of 0.393 was obtained, and when the incident angle was 71.34 °, a reflectivity decrease of 0.394 was obtained. These values are all larger than the values before the formation of the pores, and it can be seen that the sensitivity of the sensor is enhanced by the formation of the pores.

Even in the case of a SiO ₂ optical waveguide formed by using a conventional deposition technique, if the pores are formed in the optical waveguide, the peak shift amount at the time of molecular adsorption is larger than when there are no pores. , 6. However, since the optical waveguide formed using the deposition technique has a non-uniform film quality, it has been observed that the surface is roughened by etching, which is a problem. Also, the surface roughness reduces the amount of increase or decrease in reflected light intensity, that is, the depth of the dip. Therefore, even if the peak shift amount increases due to hole formation, the amount of change in reflectance itself decreases. It was reported that it was a problem.

  In the method disclosed in this specification for forming an optical waveguide by oxidation of the reflective film itself, a very uniform film can be formed, so that the optical waveguide layer surface is hardly roughened by etching. This can be seen from the electron micrograph of the optical waveguide layer surface after etching shown in FIG. For this reason, the dip seen in the reflected light intensity after etching does not become so shallow, but the shift amount of the dip position increases, so that high detection sensitivity can be obtained. In fact, as a result of pore formation, all of the shift amount of the dip position, the reflectance increase amount, and the reflectance decrease amount are larger than those before the pore formation.

  As described above, the present invention provides a sensor that utilizes an optical waveguide mode (also referred to as a leaky mode or a leaky mode). By forming the optical waveguide by thermally oxidizing the reflective film itself, the detection height of the sample to be detected is increased. Since it has an excellent effect that sensitivity can be improved, and has a remarkable effect that it can detect a sample to be detected with a stable and high sensitivity and a small size, compared with a technique using a conventional optical waveguide mode, DNA It can be applied to proteins such as antigen-antibodies, biosensors such as sugar chains, chemical sensors such as metal ions and organic molecules, thermometers, etc., and can be used in fields such as medicine, drug discovery, food and environment. Further, when the pores are formed on the surface of the optical waveguide layer for further improvement of the sensor sensitivity, the surface of the optical waveguide is less likely to be roughened, so that the sensitivity of the sensor can be further increased compared to the prior art.

It is explanatory drawing which shows the example of the optical arrangement | positioning of the sensor using the surface plasmon resonance which is a prior art. It is explanatory drawing which shows the example of the optical arrangement | positioning of an optical waveguide mode sensor. It is a figure which shows the structure of the detection board which expresses an optical waveguide mode. In the arrangement of FIG. 3, an isosceles prism having a vertex of 30 ° is arranged, a light having a wavelength of 633 nm is used, a single crystal Si having a thickness of 215 nm is formed on a silica glass as a reflective film, and a silica glass light having a thickness of 450 nm It is a figure which shows the relationship between the incident angle of light and reflected light intensity at the time of using the detection board which formed the waveguide. It is a figure which shows the relationship between the incident angle of light and reflected light intensity at the time of using the detection board which used the reflecting film as gold | metal | money. It is a figure which shows the relationship between the incident angle of light and reflected light intensity at the time of using the detection board which used the reflecting film as the tungsten. It is explanatory drawing which shows the system structural example of an optical waveguide mode sensor. It is explanatory drawing of the detection plate formation procedure in this invention. In a present Example, it is a figure explaining a mode that the single crystal Si layer formed on the silica glass by the bonding technique carries out water vapor oxidation, and forms a detection plate. In a present Example, it is a figure which shows the incident angle and reflected light intensity change of incident light which were observed using the produced detection board. In a present Example, it is a figure which shows the reflected light intensity characteristic before and behind injection | pouring of the phosphate buffer containing streptavidin. In a present Example, it is a figure which shows the result of having subtracted the reflected light intensity data before injection | pouring from the reflected light intensity data after streptavidin injection | pouring. It is an electron micrograph of the detection plate surface produced in the present Example. In a present Example, it is a figure which shows the reflected light intensity characteristic before and behind injection | pouring of the phosphate buffer containing streptavidin at the time of using the detection board which formed the pore in the optical waveguide layer. In the present Example, it is a figure which shows the result of having subtracted the reflected light intensity data before injection | pouring from the reflected light intensity data after streptavidin injection | pouring at the time of using the detection board which formed the pore in the optical waveguide layer.

Claims (10)

A method of manufacturing a detection plate for an optical waveguide mode sensor comprising a transparent substrate, a reflective film having a predetermined thickness formed thereon, and an optical waveguide layer formed on the reflective film,
Forming a layer to be the reflective film on the transparent substrate;
Forming the optical waveguide layer from the surface of the layer to be the reflective film by oxidizing the surface of the layer to be the reflective film so that the thickness of the reflective film becomes the predetermined thickness;
A method for producing a detection plate for an optical waveguide mode sensor, comprising: The reflective film according to claim 1 optical waveguide mode sensor detection board manufacturing method according to, characterized in that it is a semiconductor or metal material. 3. The method of manufacturing a detection plate for an optical waveguide mode sensor according to claim 2 , wherein the semiconductor material is Si or Ge. 3. The detection plate manufacturing method for an optical waveguide mode sensor according to claim 2 , wherein the metal material is Al, Ti, or Ta. The said transparent substrate is glass, The detection plate manufacturing method for optical waveguide mode sensors in any one of Claims 1-4 characterized by the above-mentioned. 6. The detection plate manufacturing method for an optical waveguide mode sensor according to claim 5 , wherein the glass is silica glass. The method for producing a detection plate for an optical waveguide mode sensor according to claim 1, further comprising a step of forming pores in the optical waveguide layer. 8. The method of manufacturing a detection plate for an optical waveguide mode sensor according to claim 7 , wherein the pores are formed by chemical etching, reactive ion etching, nanoimprinting, or lithography. 8. The method of manufacturing a detection plate for an optical waveguide mode sensor according to claim 7 , wherein the pores are formed by chemical etching after ion implantation. 10. The detection plate manufacturing method for an optical waveguide mode sensor according to claim 9, wherein the chemical etching is etching with a hydrofluoric acid solution or a vapor of hydrofluoric acid.