JP4761867B2 - Optical sensor chip - Google Patents

Description

  The present invention relates to an optical sensor chip, and more particularly to an optical sensor chip that analyzes an object to be measured such as a biological substance and a chemical substance by optical means such as absorbance measurement and absorption spectrum measurement.

  Conventionally, an optical sensor chip having a slab type optical waveguide layer having the following structure has been proposed. The glass substrate has an optical waveguide layer having a refractive index higher than that of the substrate on the surface. For example, first optical coupling means such as a prism and a grating are provided on the optical waveguide layer. For example, the second optical coupling means such as a prism and a grating is provided on the end of the optical waveguide layer on the opposite side to the first optical coupling means.

  In the optical sensor chip having such a configuration, light from the outside is guided into the optical waveguide layer through the first optical coupling means. A part of the light guided into the optical waveguide layer oozes out of the optical waveguide layer as evanescent light when propagating through the optical waveguide layer. By disposing the device under test in contact with the optical waveguide layer through which the light is propagated, the device under test interacts with the evanescent light and absorbs a part of the evanescent light according to its characteristics. The guided light that has interacted with the object to be measured is emitted from the second optical coupling means to the outside of the optical waveguide layer, and is received by the light receiving element. The characteristics of the object to be measured are analyzed by analyzing the signal of the light receiving element.

  As the optical waveguide layer formed on the glass substrate, there are a multi-mode optical waveguide layer having a film thickness capable of multiple reflection of light and a single mode optical waveguide layer having a film thickness not capable of multiple reflection. The single-mode optical waveguide layer is advantageous because it can achieve higher sensitivity than that of the multi-mode.

  However, since the thickness of the single mode optical waveguide layer is smaller than that of the multimode optical waveguide layer, conditions for introducing light from the outside become severe. In addition, the light that can be incident on the single-mode optical waveguide layer is difficult for light other than laser light, and is substantially limited to laser light. This causes the following problems.

  (1) When laser light is introduced into the optical waveguide layer through an optical coupling means such as a prism or a grating, since the margin of the incident position and incident angle of the laser light is very small, a mechanism capable of fine adjustment becomes indispensable. The equipment cost is expensive.

  (2) Laser light has good monochromaticity and a very narrow spectrum width. As a result, when measuring the light absorption of an object to be measured with a combination of laser light and an optical waveguide layer, only the absorbance in a wavelength range where the spectral width of the laser light is very narrow can be measured, and the types of objects to be measured are limited. Is done.

  An object of the present invention is to provide an optical sensor chip that has a simple structure and can easily introduce light having a wider wavelength range than a laser beam into a single-mode optical waveguide layer having a small thickness. To do.

According to the present invention, there is provided an optical sensor chip used for analyzing the characteristics of an object to be measured from a change in intensity or light amount of propagating light,
A substrate,
A single mode optical waveguide layer through which the light propagates, formed on the surface of the substrate and having a refractive index higher than that of the substrate;
A self-luminous layer formed on a part of the surface of the optical waveguide layer, having a thickness smaller than a cutoff, and emitting light upon irradiation with excitation light;
An optical element disposed on a part of the optical waveguide layer for emitting light propagating through the optical waveguide layer to the outside;
An optical sensor chip comprising: a sensing film disposed at a position of the optical waveguide layer located between the self-light-emitting layer and the optical element .
Further, according to the present invention, there is provided an optical sensor chip used for analyzing characteristics of an object to be measured from a change in intensity or amount of light that propagates,
A substrate,
A single mode optical waveguide layer through which the light propagates, formed on the surface of the substrate and having a refractive index higher than that of the substrate;
A self-luminous layer formed on a part of the surface of the optical waveguide layer, having a thickness smaller than a cutoff, and emitting light upon irradiation with excitation light;
An optical element disposed on a part of the optical waveguide layer for emitting light propagating through the optical waveguide layer to the outside;
An antibody that causes an immune reaction immobilized at a position of the optical waveguide layer located between the self-luminous layer and the optical element;
An optical sensor chip is provided.
Furthermore, according to the present invention, there is provided an optical sensor chip used for analyzing the characteristics of an object to be measured from a change in intensity or amount of light transmitted,
A substrate,
A single mode optical waveguide layer through which the light propagates, formed on the surface of the substrate and having a refractive index higher than that of the substrate;
A self-luminous layer formed on a part of the surface of the optical waveguide layer, having a thickness smaller than a cutoff, and emitting light upon irradiation with excitation light;
An optical element disposed on a part of the optical waveguide layer for emitting light propagating through the optical waveguide layer to the outside;
Gold fine particles immobilized on the optical waveguide layer located between the self-light-emitting layer and the optical element;
An optical sensor chip is provided.

  According to the present invention, light having a simple structure and a wider wavelength range than laser light can be easily introduced into a single-mode optical waveguide layer having a small thickness. An optical sensor chip that does not require a fine adjustment mechanism that strictly adjusts the incident position and angle of light on the waveguide layer, can be realized at low cost, and can further expand the object to be measured. Can be provided.

  Hereinafter, an optical sensor chip according to an embodiment of the present invention will be described in detail.

(First embodiment)
In the optical sensor chip according to the first embodiment, a single mode optical waveguide layer is formed on the main surface of a glass substrate. The self-light-emitting layer having a thickness smaller than the cut-off is disposed in a part of the optical waveguide layer, for example, near one end side. An optical element for emitting light propagating through the optical waveguide layer to the outside is disposed on the other end side of the optical waveguide layer opposite to the self-light-emitting layer.

  The single mode optical waveguide layer can be formed, for example, by changing the surface of a glass substrate with K ions to have a low refractive index. The optical waveguide layer desirably has a thickness of 3 μm or less, more preferably 1.5 to 2.5 μm.

  The cut-off will be described in detail below.

  When attention is paid to a certain thin film constituting the multilayer thin film, the refractive index for light propagating in the thin film is expressed by an equivalent refractive index, unlike the refractive index of the bulk material constituting the thin film. The equivalent refractive index is determined by the refractive index and thickness of the bulk material of the thin film through which light is guided, and the refractive index of the bulk material of the other thin film that comes into contact. Especially when the film thickness is thin, such as a single-mode optical waveguide layer The equivalent refractive index changes with the film thickness. When the film becomes thinner than a certain film thickness, light cannot propagate through the thin film. This condition is called cut-off. In a slab type optical waveguide layer in which the optical waveguide layer is in contact with air, light that is guided cannot propagate through the optical waveguide layer and leaks to the substrate side under the cutoff condition. When the self-luminous layer is provided on the optical waveguide layer of the glass substrate, the self-luminous layer also propagates the same light as the optical waveguide layer. When the refractive index of the glass substrate is lower than that of the self-emitting layer and the optical waveguide layer, and the film thickness of the self-emitting layer is thinner than the cutoff condition, the equivalent refractive index of the self-emitting layer is almost the same value as the equivalent refractive index of the optical waveguide layer. Therefore, the light generated in the self-light-emitting layer is not confined in the self-light-emitting layer and is emitted to the optical waveguide layer side or the air layer side.

  The self-luminous layer can be made of a material that emits light when irradiated with excitation light, such as various inorganic electroluminescent materials (phosphors) or organic electroluminescent materials (organic EL materials). In particular, the self-emitting layer is preferably formed of an organic EL material because it is necessary to satisfy the above-described cutoff condition.

  That is, the self-luminous layer needs to be thinner than the cutoff. Since the inorganic electroluminescent material (phosphor) has a form that emits light in the form of particles, the light emission mechanism restricts the particle size to be a fine dimension that can be cut off.

On the other hand, the organic EL material is suitable as a material for the self-light emitting layer because it is not limited in thickness due to the light emission mechanism. In addition, organic EL materials generally have a wide emission spectrum, and various materials have been put to practical use, so that almost all wavelengths in the visible light region can be obtained, and further, emission of three primary colors is possible by selecting the materials. . Examples of the organic EL material include tris (8-quinolinolato) aluminum complex (Alq ₃ ), tris (2-phenylpyridine) iridium (III) [Ir (ppy) ₃ ], 4,4′-bis [N- (1 -Naphthyl) -N-phenylamino] biphenyl {α-NPD} and the like.

  The self-luminous layer made of the organic EL material is, for example, 1) after a metal plate such as a stainless plate having a hole formed in a film forming portion is closely attached to the optical waveguide layer of the glass substrate, The metal plate is placed so as to face the deposition crucible, the organic EL material is evaporated from the deposition crucible, and is deposited on the surface of the substrate including the optical waveguide layer exposed from the hole of the metal plate. 2) The organic EL material is It can be formed by a method in which a solution dissolved in an organic solvent is applied to a predetermined portion of the optical waveguide layer of the glass substrate by means such as spin coating or ink jet.

  As the optical element, a quartz sheet, a grating, or a prism sheet that is a resin sheet into which a triangular groove is cut can be used.

  Next, the optical sensor chip according to the first embodiment will be specifically described with reference to FIG.

A single mode optical waveguide layer 2 having a thickness of 2 μm is formed on the main surface of the glass substrate 1. This single mode optical waveguide layer 2 performs K ion exchange by immersing, for example, # 200 glass substrate 1 (thickness: 1.15 mm) manufactured by Matsunami Glass Industrial Co., Ltd. in 400 ° C. potassium nitrate molten salt for 2 hours. Is formed. A self-luminous layer 3 made of tris (8-quinolinolato) aluminum complex (Alq ₃ ) having a thickness thinner than the cutoff (for example, about 100 nm) is formed on a part of the optical waveguide layer 2, for example, near one end side. Is formed. The self-luminous layer 3 is formed by adhering a metal plate such as a stainless steel plate having a hole formed in a film formation site to the optical waveguide layer 2 of the glass substrate 1, and then placing the metal plate in the chamber of the vacuum evaporation machine. It is installed by facing the vapor deposition crucible, Alq ₃ is evaporated from the vapor deposition crucible, and vapor deposited on the surface of the glass substrate 1 including the optical waveguide layer 2 exposed from the hole of the metal plate. A high-refractive index glass prism (trade name: S-LAM2 manufactured by OHARA Inc.) 4 that is an optical element for emitting light propagating through the optical waveguide layer 2 to the outside is the light beam on the side opposite to the self-light-emitting layer 3. It is arranged on the other end side of the waveguide layer 2. It is preferable that methylene iodide is interposed between the glass substrate 1 including the optical waveguide layer 2 and the high refractive index glass prism 4 to suppress interface reflection between them.

  The operation of the optical sensor chip having such a configuration will be described with reference to FIG.

When the self-luminous layer 3 made of Alq ₃ is irradiated with ultraviolet light from the excitation light source 21 as excitation light, fluorescence (light having a spectral width of 100 nm or more with light near 500 nm as a peak) is emitted from the self-luminous layer 3. Is done. At this time, the film thickness of the self-light-emitting layer 3 made of Alq ₃ is formed to be equal to or less than the film thickness of the cutoff, and the equivalent refractive index of the self-light-emitting layer 3 is almost the same value as the equivalent refractive index of the optical waveguide layer 2. A part of the light generated in the self-light-emitting layer 3 leaks to the air side and the glass substrate 1 side, but can propagate through the optical waveguide layer 2 with high efficiency. The excitation light source 21 is black light (trade name: FL20S • BLB-A manufactured by Toshiba Lighting & Technology Co., Ltd.) and UV-LED (trade name: NSHU590B manufactured by Nichia Corporation), and ultraviolet light is applied to the self-emitting layer 3. When irradiated, both were able to excite fluorescence.

  A part of the light guided into the optical waveguide layer 2 oozes out of the optical waveguide layer as evanescent light when propagating through the optical waveguide layer 2. The object to be measured is disposed between the self-light-emitting layer 3 and the high refractive index glass prism 4 in contact with the portion of the optical waveguide layer 2 through which the light is propagated, so that the object to be measured can interact with the evanescent light. The action is performed and a part of the evanescent light is absorbed according to the characteristic. The guided light that has interacted with the object to be measured is radiated from the high refractive index glass prism 4 to the outside of the optical waveguide layer, and its intensity is measured by the light receiving element 22. By analyzing the intensity signal of the light receiving element 22, it is possible to analyze the characteristics of the object to be measured.

  In addition, since the light radiated | emitted from the high refractive index glass prism 4 passes the single mode optical waveguide layer 2, its directivity is very high in the perpendicular direction of the glass substrate 1, and the surface direction (self-light-emitting) of the glass substrate 1 is carried out. The layer 3 forming surface) exhibits optical characteristics having no directivity. Therefore, a cylindrical lens may be used for the purpose of increasing the amount of light incident on the light receiving element 22.

  According to the first embodiment described above, since the excitation light is emitted for the purpose of emitting light such as fluorescence from the self-luminous layer, it is not necessary to strictly control the incident angle of the excitation light with respect to the glass substrate. In fact, there is no restriction on the incident angle of the excitation light. As a result, light can be efficiently introduced into the optical waveguide layer from the self-emitting layer without using an optical coupling means (prism, grating, etc.) for introducing light from the outside into the optical waveguide layer as in the past. A light angle and position fine adjustment mechanism is not required, and a simple and low-cost optical sensor chip can be realized.

In addition, a self-emitting layer made of an organic EL material has a wide emission spectrum, and various materials have been put to practical use, so that almost all wavelengths in the visible light region can be obtained. For example, a self-emitting layer made of Alq ₃ can propagate light having a spectral width of 100 nm or more into the optical waveguide layer 2 with light near 500 nm as a peak.

  Furthermore, it is also possible to form a self-emitting layer on the optical waveguide layer by simultaneously depositing a plurality of organic EL materials. Specifically, blue, for example, an organic EL material having a peak in the vicinity of 450 nm, a green color, for example, an organic EL material having a peak in the vicinity of 520 nm, and a red color, for example, an organic EL material having a peak in the vicinity of 630 nm, are simultaneously evaporated. By forming the layer in the optical waveguide layer, white light covering the entire visible light region can be propagated to the single mode optical waveguide layer.

In addition, when light such as fluorescence generated by irradiation of excitation light in the self-emitting layer is not propagated to the optical waveguide layer and is incident on the glass substrate, the light may cause disturbance in light intensity measurement. is there. In this case, it is preferable that a light absorption layer containing a dye that absorbs light emitted from the self-light-emitting layer is formed in the substrate region excluding the optical waveguide layer. Specifically, as shown in FIG. 3, a mode in which a light absorption layer 5 containing a dye that absorbs light emitted from the self-light emitting layer is provided on the back surface of the glass substrate 1 can be adopted. When the organic EL material used for the self-light emitting layer 3 is Alq ₃ , the light absorbing layer 5 can be formed by a red adhesive tape or a red lacquer paint film.

(Second Embodiment)
FIG. 4 is a cross-sectional view showing an inspection apparatus provided with the optical sensor chip according to the second embodiment. In FIG. 4, the same members as those in FIG.

As shown in FIG. 4, the optical sensor chip according to the second embodiment senses on the optical waveguide layer 2 located between the self-light emitting layer 3 made of, for example, Alq ₃ and the high refractive index glass prism 4 that is an optical element. It has a structure in which a film 6 is provided. The sensing film 6 can be designed to absorb a part of the light propagating through the optical waveguide layer 2 by causing a chemical reaction with the object to be measured and changing the light absorption characteristics.

The optical sensor chip having such a configuration, when emitted from the pumping light source 21 such as a black light or UV-LED ultraviolet light self-emitting layer 3 formed of Alq ₃ as the excitation light, photoluminescence from the self-emitting layer 3 Fluorescence is emitted. At this time, the film thickness of the self-light emitting layer 3 made of Alq ₃ is formed to be equal to or less than the cut-off film thickness. Although it leaks to the glass substrate 1 side, it becomes possible to propagate the optical waveguide layer 2 with high efficiency. When the substance to be measured is brought into contact with the sensing film 6, the sensing film causes a chemical reaction with the object to be measured and the light absorption characteristic is changed, so that a part of the light propagating through the optical waveguide layer 2 is absorbed. The light propagated through the optical waveguide layer 2 under the sensing film 6 is emitted to the light receiving element 22 through the high refractive index glass prism 4, and the amount of transmitted light is measured here. Since this transmitted light amount changes according to the concentration of the object to be measured, the concentration of the object to be measured can be obtained from the change in the transmitted light amount.

  Examples of the sensing membrane include the following (1) glucose sensing membrane and (2) alkaline gas sensing membrane.

(1) Glucose Sensing Membrane This glucose sensing membrane is, for example, a color former, a first enzyme that oxidizes or reduces glucose, and a second substance that generates a substance that develops color by reacting with the product of the enzyme. The enzyme is held in a film body containing a film-forming polymer compound.

The enzyme and the color former in the glucose sensing membrane are used in combinations shown in Table 1 below, for example.

  Examples of the film-forming polymer compound used for the glucose sensing membrane include cellulose polymer compounds containing carboxymethyl cellulose, hydroxyethyl cellulose, and the like.

  An optical sensor chip having the glucose sensing membrane will be specifically described.

On the main surface of a glass substrate 1 having a thickness of 1.15 mm (# 200 glass substrate manufactured by Matsunami Glass Industrial Co., Ltd.), a single mode optical waveguide layer 2 having a thickness of 2 μm is the same method as in the first embodiment described above. It is formed by. The self-light emitting layer 3 made of Alq ₃ having a thickness smaller than the cutoff (for example, about 100 nm) is a method similar to that of the first embodiment described above in a part of the optical waveguide layer 2, for example, near one end side. It is formed by. The high refractive index glass prism 4, which is an optical element for emitting light propagating through the optical waveguide layer 2 to the outside, has interface reflection on the other end side of the optical waveguide layer 2 opposite to the self-light-emitting layer 3. Arranged through methylene iodide to prevent. The glucose sensing film 6 is formed on the optical waveguide layer 2 located between the self-light emitting layer 3 and the high refractive index glass prism 4 which is an optical element. The glucose sensing membrane 6 is composed of a peroxidase (POD) which is a reagent that generates a substance that develops a glucose oxidase (GOD) color former, which is a glucose oxidase, and 3,3 ′, 5,5′-tetra, which is a color former. It contains methylbenzidine (TMBZ), carboxymethylcellulose (CMC) and polyethylene glycol (PEG) which are film forming materials.

In the optical sensor chip having a sensing film having such a glucose, is irradiated from the excitation light source 21, such as a black light or UV-LED ultraviolet light self-emitting layer 3 formed of Alq ₃ as the excitation light, self-luminous layer 3 emits fluorescence by photoluminescence, and the emitted light is introduced into the optical waveguide layer 2 and propagated with high efficiency. When an aqueous solution containing glucose is dropped onto the glucose sensing membrane 6, hydrogen peroxide is generated by the reaction of glucose and GOD in the sensing membrane 6, and POD is decomposed when hydrogen peroxide is decomposed by the POD in the sensing membrane 6. The substrate TMBZ is oxidized and changes from colorless to blue. Since light propagating through the optical waveguide layer 2 is absorbed as TMBZ develops in the sensing film 6, an interference filter (not shown) that selectively transmits 580 nm light is disposed on the light receiving surface of the light receiving element 22. By doing so, it can be confirmed that the amount of transmitted light of the light emitted from the optical waveguide layer 2 through the high refractive index glass prism 4 is reduced. The glucose concentration can be detected from the decrease in the amount of transmitted light.

(2) alkaline gas sensing membrane alkaline gas sensing film includes bromothymol blue _{(C 27 H 28 Br 2 O} 5 S) or cresol red can detect alkaline gas. An optical sensor chip including such an alkaline gas sensing film has excellent sensitivity to alkaline gas, particularly ammonia.

  An optical sensor chip having the alkaline gas sensing film will be specifically described.

In this optical sensor chip, the optical waveguide layer 2 is formed on the glass substrate 1 as in the optical sensor chip having the glucose sensing film described above, and the thickness is smaller than the cutoff on both sides of the optical waveguide layer (for example, A self-luminous layer 3 made of Alq _{3 having a} thickness of about 100 nm and a high refractive index glass prism 4 are disposed. The sensing film 6 of alkaline gas is formed on the optical waveguide layer 2 located between the self-light emitting layer 3 and the high refractive index glass prism 4 which is an optical element. The sensing film 6 of the alkaline gas is formed by attaching a metal plate such as a stainless steel plate having a hole formed in the film forming portion to the optical waveguide layer 2 of the glass substrate 1 and then placing the metal in the chamber of the vacuum evaporation machine. The plate is placed so as to face the deposition crucible, and bromothymol blue is evaporated from the deposition crucible and deposited on the surface of the glass substrate 1 including the optical waveguide layer 2 exposed from the hole of the metal plate so that the thickness is about 100 nm. Was formed.

In the optical sensor chip having a sensing membrane of such alkaline gas, is irradiated from the excitation light source 21, such as a black light or UV-LED ultraviolet light self-emitting layer 3 formed of Alq ₃ as the excitation light, self-luminous Fluorescence due to photoluminescence is emitted from the layer 3, and the emitted light is introduced into the optical waveguide layer 2 and propagated with high efficiency. When a gas containing ammonia is circulated on the sensing membrane 6 of alkaline gas, the bromothymol blue in the sensing membrane 6 changes from yellow (when pH = 6.0 or less) to blue-violet (pH = 7.6 or more). To do. Since light propagating through the optical waveguide layer 2 is absorbed along with the color change of bromothymol blue in the sensing film 6, an interference filter (not shown) that selectively transmits light of 580 nm to the light receiving surface of the light receiving element 22. ) Can be confirmed to reduce the amount of light transmitted from the optical waveguide layer 2 through the high refractive index glass prism 4. The ammonia concentration can be detected from the decrease in the amount of transmitted light.

(Third embodiment)
FIG. 5 is a sectional view showing an inspection apparatus provided with the optical sensor chip according to the third embodiment. In FIG. 5, the same members as those in FIG.

As shown in FIG. 5, the optical sensor chip according to the third embodiment is made of gold on the optical waveguide layer 2 located between the self-light emitting layer 3 made of, for example, Alq ₃ and the high refractive index glass prism 4 that is an optical element. It has a structure in which fine particles 7 are provided. Since a very strong electric field due to surface plasmons is generated on the surface of the gold fine particles (gold colloid), it is suitable for excitation of the fluorescent dye. The gold fine particle absorbs light due to resonance caused by surface plasmons and appears red. However, since the absorption spectrum overlaps with the emission spectrum of Alq ₃ used in the self-light-emitting layer, it is a very efficient combination. Such gold fine particles preferably have an average particle diameter of 5 to 100 nm.

  The optical sensor chip on which the gold fine particles are fixed will be specifically described.

On the main surface of a glass substrate 1 having a thickness of 1.15 mm (# 200 glass substrate manufactured by Matsunami Glass Industrial Co., Ltd.), a single mode optical waveguide layer 2 having a thickness of 2 μm is the same method as in the first embodiment described above. It is formed by. The self-light emitting layer 3 made of Alq ₃ having a thickness smaller than the cutoff (for example, about 100 nm) is a method similar to that of the first embodiment described above in a part of the optical waveguide layer 2, for example, near one end side. It is formed by. The high refractive index glass prism 4, which is an optical element for emitting light propagating through the optical waveguide layer 2 to the outside, has interface reflection on the other end side of the optical waveguide layer 2 opposite to the self-light-emitting layer 3. Arranged through methylene iodide to prevent. For example, gold fine particles 7 having an average particle diameter of 10 nm are fixed to the optical waveguide layer 2 located between the self-light emitting layer 3 and the high refractive index glass prism 4 which is an optical element. The gold fine particles 7 are coated with a 3 mercaptopropyltrimethoxysilane solution at a predetermined position on the optical waveguide layer 2 and then baked at 180 ° C. to introduce thiol groups on the surface of the optical waveguide layer 2. It is immobilized by causing a colloidal solution to react and depositing gold fine particles on the surface of the optical waveguide layer 2.

The optical sensor chip having such a configuration, when emitted from the pumping light source 21 such as a black light or UV-LED ultraviolet light self-emitting layer 3 formed of Alq ₃ as the excitation light, photoluminescence from the self-emitting layer 3 The emitted fluorescence is introduced into the optical waveguide layer 2 and propagated with high efficiency. When single-stranded DNA is immobilized on gold fine particles and Cy3-labeled DNA is hybridized, strong Cy3 fluorescence is generated on the optical waveguide layer 2. The emitted fluorescence is propagated to the optical waveguide layer 2, and its intensity is measured by the light receiving element 22 through the high refractive index glass prism 4. By analyzing the intensity signal of this light receiving element 22, the hybridized DNA can be identified.

(Fourth embodiment)
6 is a cross-sectional view showing an optical sensor chip according to the fourth embodiment, and FIG. 7 is a cross-sectional view showing an inspection apparatus provided with the optical sensor chip of FIG. In FIGS. 6 and 7, the same members as those in FIG.

As shown in FIG. 6, the optical sensor chip according to the fourth embodiment is formed on the optical waveguide layer 2 positioned between the self-light emitting layer 3 made of, for example, Alq ₃ and the high refractive index glass prism 4 that is an optical element. This is an optical immunosensor chip on which the next antibody 8 is immobilized. This optical immunosensor chip can utilize an antibody-immobilized secondary antibody, a dye-labeled secondary antibody, or a secondary antibody labeled with gold fine particles. In particular, since colloidal gold has an absorption spectrum that overlaps with the emission spectrum of Alq ₃ used for the self-emitting layer 3, an immunosensor chip using a secondary antibody labeled with gold fine particles is used as an organic EL material for the self-emitting layer. Alq ₃ is preferred.

  The optical immunosensor chip will be specifically described below.

On the main surface of a glass substrate 1 having a thickness of 1.15 mm (# 200 glass substrate manufactured by Matsunami Glass Industrial Co., Ltd.), a single mode optical waveguide layer 2 having a thickness of 2 μm is the same method as in the first embodiment described above. It is formed by. The self-light emitting layer 3 made of Alq ₃ having a thickness smaller than the cutoff (for example, about 100 nm) is a method similar to that of the first embodiment described above in a part of the optical waveguide layer 2, for example, near one end side. It is formed by. The high refractive index glass prism 4, which is an optical element for emitting light propagating through the optical waveguide layer 2 to the outside, has interface reflection on the other end side of the optical waveguide layer 2 opposite to the self-light-emitting layer 3. Arranged through methylene iodide to prevent. The primary antibody 8 is immobilized on the optical waveguide layer 2 located between the self-light emitting layer 3 and the high refractive index glass prism 4 which is an optical element. That is, a 3 aminopropyltrimethoxysilane solution is applied to a predetermined portion on the optical waveguide layer 2 and then baked at 180 ° C. to introduce amino groups on the surface of the optical waveguide layer. Next antibody 8 is immobilized.

In the optical immunosensor chip having such a configuration, as shown in FIG. 7, a solution containing the protein 9 that reacts with the primary antibody 8 is reacted with the immobilized site of the primary antibody 8, washed, and then gold fine particles The secondary antibody 10 labeled with is reacted. In this state, is irradiated from the excitation light source 21, such as a black light or UV-LED ultraviolet light self-emitting layer 3 formed of Alq ₃ as the excitation light, fluorescence by photoluminescence from the self-emitting layer 3 is emitted, the The emitted light is introduced into the optical waveguide layer 2 with high efficiency and propagated. Since the light propagating through the optical waveguide layer 2 is absorbed by the gold fine particles labeled with the secondary antibody 10, the amount of light propagating through the optical waveguide layer 2 is reduced. By disposing an interference filter (not shown) that selectively transmits 520 nm light on the light receiving surface of the light receiving element 22, a change in the amount of transmitted light emitted from the optical waveguide layer 2 through the high refractive index glass prism 4 is changed. Can be measured. Therefore, the target protein concentration can be detected from this transmitted light amount change.

  The same effect can be obtained by using a secondary antibody labeled with a dye whose fluorescent substance can absorb guided light. In the case of an enzyme-labeled secondary antibody, the substrate solution is reacted after the secondary antibody reaction, but the same effect can be obtained by using a substrate capable of absorbing guided light as the substrate after the reaction.

(Fifth embodiment)
In the optical sensor chip according to the fifth embodiment, a plurality of optical waveguide layers are formed on a glass substrate, and a self-luminous layer having a thickness smaller than the cutoff is formed on a part of each optical waveguide layer. In addition, an optical element for emitting light propagating through each optical waveguide layer to the outside is disposed on a part of each optical waveguide layer.

  An optical sensor chip having such a plurality of optical waveguide layers will be specifically described with reference to FIG.

On the main surface of the glass substrate 1, a plurality of, for example, two single mode optical waveguide layers (first and second optical waveguide layers) 2 ₁ and 2 ₂ having a thickness of 2 μm are formed. These single mode optical waveguide layers 2 ₁ and 2 ₂ are formed by the following method, for example. A silicon nitride film was formed on the surface of # 200 glass substrate 1 manufactured by Matsunami Glass Industry Co., Ltd. with a thickness of 1.15 mm using a thin film processing technique, and two optical waveguide layer formation scheduled portions of the silicon nitride film were formed. A mask having a band-shaped opening is formed by selective removal by etching. Two single-mode optical waveguide layers are obtained by immersing a glass substrate having this mask in 400 ° C. potassium nitrate molten salt for 2 hours and selectively exchanging K ions on the surface of the glass substrate exposed from the two strip openings of the mask. 2 ₁ and 2 ₂ are formed. After the formation of the optical waveguide layer, the silicon nitride film that is a mask is removed.

The self-light-emitting layer 3 made of Alq _{3 having a} thickness thinner than the cutoff (for example, about 100 nm) is a part of the first and second optical waveguide layers 2 ₁ , 2 ₂ (near one end side). The glass substrate 1 is formed by the same method as that of the first embodiment described above across the respective optical waveguide layers 2 ₁ and 2 ₂ . The high refractive index glass prism 4, which is an optical element for emitting light propagating through the optical waveguide layers 2 ₁ , 2 ₂ to the outside, has the optical waveguide layers 2 ₁ , opposite to the self-light-emitting layer 3, the glass substrate 1 of 2 ₂ at the other end are disposed across each of these optical waveguide layer 2 _1, 2 _2. The high refractive index glass prism 4 is formed on the glass substrate 1 including the optical waveguide layers 2 ₁ and 2 ₂ with methylene iodide for preventing interface reflection. Sensing membrane 6 of glucose is formed on the first optical waveguide layer 2 ₁ portion located between the self-luminous layer 3 and the high refractive index glass prism 4 is an optical element. The glucose sensing membrane 6 is, for example, a peroxidase (POD), which is a reagent that generates a substance that develops a color oxidant of glucose oxidase (GOD), which is a glucose oxidase, as in the second embodiment described above. , 3 ′, 5,5′-tetramethylbenzidine (TMBZ), carboxymethylcellulose (CMC) and polyethylene glycol (PEG) which are film forming materials.

In such an optical sensor chip having two optical waveguide layers and a glucose sensing film, self comprising Alq ₃ using ultraviolet light as excitation light from an excitation light source (not shown) such as black light or UV-LED. When the light emitting layer 3 is irradiated, fluorescence by photoluminescence is emitted from the self-light emitting layer 3, and the emitted light is introduced into the two optical waveguide layers 2 ₁ and 2 ₂ with high efficiency and propagated. When dropping an aqueous solution containing glucose to the first optical waveguide layer 2 ₁ part sensing formed glucose layer 6, the second is a POD substrate glucose and the sensing film 6 as described in the embodiment TMBZ oxide And changes from colorless to blue. Therefore, light propagating through the first optical waveguide layer 2 ₁ medium is absorbed with the color of TMBZ in sensing membrane 6, it is emitted through the high-refractive-index glass prism 4 as an optical 23 of low light intensity. On the other hand, the light propagating through the second optical waveguide layer 2 ₂ Medium the sensing film is not present, without interference with the sensing film, is emitted through the high-refractive-index glass prism 4 as an optical 24 having a light intensity during propagation . The light concentrations of the lights 23 and 24 are detected by a light receiving element (not shown), and the glucose concentration can be detected by measuring the difference in light intensity. The detection of the glucose concentration can further improve the accuracy as compared with the case of using one optical waveguide layer as in the second embodiment described above.

  As described above, according to the fifth embodiment, light can be efficiently introduced from the self-light-emitting layer into a plurality of optical waveguide layers, and a fine adjustment mechanism for the angle and position of incident light is not required, which is a simple and low-cost optical sensor. A chip can be realized.

  That is, in the conventional optical sensor chip in which a plurality of optical waveguide layers are formed on the same substrate, a laser beam is made incident on each optical waveguide layer. It becomes more complicated and expensive.

  In the fifth embodiment, the excitation light is irradiated for the purpose of emitting light such as fluorescence from the self-luminous layer, and the incident angle of the excitation light does not need to be strictly controlled with respect to the glass substrate. There is no restriction on the incident angle, and since the self-emitting layer can be used as a common light source for each optical waveguide layer, a complicated fine-tuning mechanism is not required, which is simpler and lower than the conventional one. A cost-effective optical sensor chip can be realized.

(Sixth embodiment)
FIG. 9 is a cross-sectional view showing an inspection apparatus including the optical sensor chip according to the sixth embodiment. In FIG. 9, the same members as those in FIG.

As shown in FIG. 9, the optical sensor chip according to the sixth embodiment has the same configuration as that of the third embodiment, that is, between the self-light emitting layer 3 made of Alq ₃ and the high refractive index glass prism 4 that is an optical element. It has a structure in which gold fine particles 7 are provided in the portion of the optical waveguide layer 2 positioned.

Specifically, the single-mode optical waveguide layer 2 having a thickness of 2 μm is formed on the main surface of the glass substrate 1 having a thickness of 1.15 mm (# 200 glass substrate manufactured by Matsunami Glass Industry Co., Ltd.) as described above. It is formed by the same method as the form. The self-light emitting layer 3 made of Alq ₃ having a thickness smaller than the cutoff (for example, about 100 nm) is a method similar to that of the first embodiment described above in a part of the optical waveguide layer 2, for example, near one end side. It is formed by. The high refractive index glass prism 4, which is an optical element for emitting light propagating through the optical waveguide layer 2 to the outside, has interface reflection on the other end side of the optical waveguide layer 2 opposite to the self-light-emitting layer 3. Arranged through methylene iodide to prevent. The gold fine particles 7 are fixed on the optical waveguide layer 2 positioned between the self-light emitting layer 3 and the high refractive index glass prism 4 which is an optical element by the same method as in the third embodiment.

The optical sensor chip having such a configuration, when emitted from the pumping light source 21 such as a black light or UV-LED ultraviolet light self-emitting layer 3 formed of Alq ₃ as the excitation light, photoluminescence from the self-emitting layer 3 The emitted fluorescence is introduced into the optical waveguide layer 2 and propagated with high efficiency. The propagated light is radiated to the outside by the high refractive index glass prism 4, collected by the cylindrical lens 25, and then incident on the spectroscope 26 for spectral analysis of the transmitted light. When liquids having different refractive indexes are dropped on the immobilization site of the gold fine particles 7, the peaks of the spectrum (absorption spectrum) absorbed by the light propagating to the optical waveguide layer 2 differ according to the refractive index of the liquid. FIG. 10 shows the relationship between the refractive index of the object to be measured and the wavelength of the absorption spectrum. Therefore, the refractive index of the liquid can be detected by analyzing the spectrum of the transmitted light.

  In the detection apparatus including the optical sensor chip, a lens for condensing the light emitted from the quartz prism onto a light receiving element such as a spectrometer is not limited to a cylindrical lens, but a refractive index distribution called a green lens. A mold lens or a green lens array may be used.

  The transmitted light spectrum analysis is not limited to refractive index measurement, and can also measure an absorption spectrum of an object to be measured that is in contact with the optical waveguide layer.

  The means for radiating the light propagating through the optical waveguide layer to the outside of the substrate is not limited to the prism, and the same effect can be obtained by bonding a prism sheet having a plurality of triangular grooves on the film surface such as a grating or PET. Is obtained.

1 is a cross-sectional view showing an optical sensor chip according to a first embodiment of the present invention. The schematic sectional drawing which shows the inspection apparatus provided with the sensor chip of FIG. Sectional drawing which shows many forms of the optical sensor chip which concerns on 1st Embodiment of this invention. The schematic sectional drawing which shows the test | inspection apparatus provided with the optical sensor chip which concerns on 2nd Embodiment of this invention. The schematic sectional drawing which shows the test | inspection apparatus provided with the optical sensor chip which concerns on 3rd Embodiment of this invention. Sectional drawing which shows the optical sensor chip which concerns on 4th Embodiment of this invention. FIG. 7 is a schematic cross-sectional view illustrating an inspection apparatus including the sensor chip of FIG. 6. Sectional drawing which shows the optical sensor chip which concerns on 5th Embodiment of this invention. The schematic sectional drawing which shows the test | inspection apparatus provided with the optical sensor chip which concerns on 3rd Embodiment of this invention. The figure which shows the relationship between the refractive index of a to-be-measured object, and the wavelength of an absorption spectrum.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Glass substrate, 2, 2 ₁ , 2 ₂ ... Optical waveguide layer, 3 ... Self-luminous layer, 4 ... High refractive index glass prism, 5 ... Light absorption layer, 6 ... Sensing film, 7 ... Gold fine particle, 8 ... 1 Next antibody, 21 ... excitation light source, 22 ... light receiving element, 25 ... cylindrical lens (condensing lens), 26 ... spectrometer.

Claims (5)

An optical sensor chip used for analyzing the characteristics of an object to be measured from a change in intensity or light amount of propagating light,
A substrate,
A single mode optical waveguide layer through which the light propagates, formed on the surface of the substrate and having a refractive index higher than that of the substrate;
A self-luminous layer formed on a part of the surface of the optical waveguide layer, having a thickness smaller than a cutoff, and emitting light upon irradiation with excitation light;
An optical element disposed on a part of the optical waveguide layer for emitting light propagating through the optical waveguide layer to the outside ;
An optical sensor chip, comprising: a sensing film disposed at a position of the optical waveguide layer located between the self-luminous layer and the optical element . The sensing film comprises a color former, a first enzyme that oxidizes or reduces glucose, and a second enzyme that generates a substance that develops color by reacting with the product of the enzyme. The optical sensor chip according to claim 1, wherein the optical sensor chip has a configuration in which the film body is held. An optical sensor chip used for analyzing the characteristics of an object to be measured from a change in intensity or light amount of propagating light,
A substrate,
A single mode optical waveguide layer through which the light propagates, formed on the surface of the substrate and having a refractive index higher than that of the substrate;
A self-luminous layer formed on a part of the surface of the optical waveguide layer, having a thickness smaller than a cutoff, and emitting light upon irradiation with excitation light;
An optical element disposed on a part of the optical waveguide layer for emitting light propagating through the optical waveguide layer to the outside;
An antibody that causes an immune reaction immobilized at a position of the optical waveguide layer located between the self-luminous layer and the optical element;
An optical sensor chip comprising: An optical sensor chip used for analyzing the characteristics of an object to be measured from a change in intensity or light amount of propagating light,
A substrate,
A single mode optical waveguide layer through which the light propagates, formed on the surface of the substrate and having a refractive index higher than that of the substrate;
A self-luminous layer formed on a part of the surface of the optical waveguide layer, having a thickness smaller than a cutoff, and emitting light upon irradiation with excitation light;
An optical element disposed on a part of the optical waveguide layer for emitting light propagating through the optical waveguide layer to the outside;
Gold fine particles immobilized on the optical waveguide layer located between the self-light-emitting layer and the optical element;
An optical sensor chip comprising: 5. The optical system according to claim 1, wherein a plurality of the optical waveguide layers are formed on the substrate, and the self-luminous layer is formed on a part of the surface of each optical waveguide layer. Sensor chip.

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