JP2012108044A - Micro substance detector - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new micro substance detector capable of increasing detection sensitivity to a substance to be detected.SOLUTION: A micro substance detector includes: a light source; a first waveguide which is formed on a base plate and propagates a light wave from the light source; an optical ring resonator formed of a ring-shaped second waveguide in contiguity with the first waveguide on the base plate; and a detection part for detecting fluorescence generated by a substance to be detected with a fluorescent label adhering to the optical ring resonator.

Description

  The present invention relates to a minute substance detection device for detecting minute substances.

  2. Description of the Related Art Conventionally, a minute substance detection apparatus for detecting minute substances such as microorganisms using an optical device has been put into practical use. Such a minute substance detection apparatus can detect the presence / absence of various kinds of minute substances, the amount thereof, the kind thereof, and the like by using a sensor for detecting a minute substance, also referred to as a biosensor. As a principle of operation of such a minute substance detection sensor, the fact that a minute substance (a substance to be detected) to be detected adheres to the periphery of the optical device changes the optical characteristics of the optical device. .

  For example, Japanese translations of PCT publication No. 2003-515737 (Patent Document 1) discloses a high-sensitivity and high-throughput biological sensor having a resonant optical assay structure having a flat cylindrical resonant optical cavity. Yes. That is, Patent Document 1 discloses a method using a disc-type (disc-type) whispering gallery mode.

  Japanese Unexamined Patent Application Publication No. 2008-304216 (Patent Document 2) discloses a substance detection apparatus using an optical ring resonator as an optical device. When such an optical ring resonator is used, it is configured so that a minute substance adheres to the periphery of the optical ring resonator, and is configured to detect a change in resonance wavelength in the optical ring resonator. . The change in the resonance wavelength in the optical ring resonator is caused by the change in the refractive index of the optical ring resonator due to the adhesion of a minute substance. In particular, in Patent Document 2, a microring resonator is formed by arranging a second optical waveguide at a position where it is resonantly coupled to a first optical waveguide that does not have wavelength selectivity, The structure which provides the hole into which the substance to be detected can enter is disclosed.

JP-T-2003-515737 JP 2008-304216 A

  Patent Document 1 described above merely discloses a configuration using a disk-shaped optical device. In addition, the configuration disclosed in Patent Document 2 described above uses a ring-shaped optical device, and detects a substance to be detected based on the relationship between incident light and separated light. It does not directly detect optical interactions.

  The present invention has been made to solve the above-described problems, and an object of the present invention is to provide a novel minute substance detection device capable of increasing the detection sensitivity for a substance to be detected.

  A minute substance detection device according to an aspect of the present invention includes a light source, a first waveguide that is formed on a substrate and propagates a light wave from the light source, and is formed on the substrate in proximity to the first waveguide. An optical ring resonator including a ring-shaped second waveguide, and a detection unit that detects fluorescence generated when a substance to be detected with a fluorescent label attached to the optical ring resonator is included.

  Preferably, the light source is configured to generate light having a wavelength band wider than a resonance wavelength band of the optical ring resonator.

  More preferably, the minute substance detection device includes a plurality of optical ring resonators having second waveguides having different ring diameters, and the light source has a wider wavelength band than the entire resonance wavelength band of the plurality of optical ring resonators. It is comprised so that the light which has may be generated.

  More preferably, the plurality of optical ring resonators are aligned along the first waveguide.

  More preferably, the minute substance detection device further includes control means for specifying which of the plurality of optical ring resonators is generating fluorescence based on a detection result by the detection unit.

  More preferably, the control means is any of a plurality of substances in which the substance to be detected is predetermined based on information of the optical ring resonator in which fluorescence is generated among the plurality of optical ring resonators. To identify.

  More preferably, the detection unit is configured to optically measure a plurality of optical ring resonators.

  ADVANTAGE OF THE INVENTION According to this invention, the detection sensitivity with respect to a to-be-detected substance can be improved.

It is a schematic diagram which shows the whole structure of the micro substance detection apparatus according to Embodiment 1 of this invention. It is a schematic diagram which shows the structure for carrying out the living body modification of the optical ring resonator in the minute substance detection apparatus according to Embodiment 1 of the present invention. It is a schematic diagram which shows the mode of the fluorescence generate | occur | produced from an optical ring resonator in the micro substance detection apparatus according to Embodiment 1 of this invention. It is a figure which shows the relationship in the wavelength band about each light wave shown in FIG. It is a figure which shows the relationship in the wavelength band about each light wave shown in FIG. It is a schematic diagram which shows the structure of the micro substance detection sensor in the micro substance detection apparatus according to Embodiment 2 of this invention. It is a figure which shows the relationship in the wavelength band about each light wave shown in FIG. It is a figure which shows the relationship in the wavelength band about each light wave shown in FIG. It is a figure which shows the characteristic in case the resonant wavelength shift | deviates from the original design value by the design error of the optical ring resonator in the micro substance detection apparatus according to Embodiment 2 of the present invention. It is a schematic diagram which shows the structure of the micro substance detection sensor in the micro substance detection apparatus according to Embodiment 3 of this invention. It is a figure which shows the relationship in the wavelength band about each light wave shown in FIG. It is a figure which shows the relationship in the wavelength band about each light wave shown in FIG. It is a figure for demonstrating the outline of the control logic using wavelength decomposition in the microscopic material detection apparatus according to Embodiment 3 of the present invention. It is a figure for demonstrating the outline of the control logic using a space detector in the micromaterial detection apparatus according to Embodiment 3 of this invention.

  Embodiments of the present invention will be described in detail with reference to the drawings. Note that the same or corresponding parts in the drawings are denoted by the same reference numerals and description thereof will not be repeated.

[Overview]
In the minute substance detection device according to the present embodiment, a substance for adsorbing a detected substance with a fluorescent label is arranged on the surface of the optical ring resonator, and fluorescence generated from the detected substance adsorbed on this substance Adopt a method to detect. By adopting such a method, it becomes possible to excite fluorescence in a region enhanced by an electric field as compared with the conventional method, and the detection sensitivity can be increased.

  In addition, by using a light source configured to generate incident light having a wavelength band wider than the resonance wavelength band of the optical ring resonator, the likelihood of manufacturing errors of the optical ring resonator can be increased.

[Embodiment 1]
"I. Device configuration"
FIG. 1 is a schematic diagram showing an overall configuration of a minute substance detection device SYS according to the first embodiment of the present invention. Referring to FIG. 1, the minute substance detection device SYS includes a minute substance detection sensor 1, a light source 10 that supplies excitation light to the minute substance detection sensor 1, a detection unit 20, and a determination processing unit 30.

  The minute substance detection device SYS according to the present embodiment detects fluorescence generated by bringing a substance to be detected, which is attached with a fluorescent label, into contact with / approaching the optical ring resonator included in the minute substance detection sensor 1, and By observing the detected fluorescence, the presence / absence, content, concentration, type, etc. of the substance to be detected are detected.

  The minute substance detection sensor 1 includes one or more optical ring resonators. More specifically, the minute substance detection sensor 1 includes a substrate 2 for manufacturing an optical waveguide, and a primary waveguide 40 (first waveguide) that is formed on the substrate 2 and propagates a light wave from the light source 10. And an optical ring resonator composed of a ring-shaped ring waveguide 3 (second waveguide) formed on the substrate 2 in the vicinity of the primary waveguide 40.

  The primary waveguide 40 and the ring waveguide 3 are formed in the cladding layer 4 on the substrate 2 as a core having a refractive index different from that of the cladding layer 4. That is, each waveguide mainly includes a core (a portion having a relatively high refractive index) formed on the substrate 2 and a cladding layer 4 (a portion having a relatively low refractive index) disposed around the core. It consists of.

  Such a waveguide is preferably made of a material that has no wavelength selectivity and can propagate a light wave in the measurement wavelength range with as low a loss as possible. More specifically, optically transparent materials such as glass, sapphire, quartz, and optical resin, and semiconductor materials such as Si, GaAs, and GaN can be used. The wavelength of light used for measurement can also be determined according to the wavelength transmission performance of the waveguide. That is, the wavelength range in which each waveguide is transparent may be set as the measurement wavelength.

  The primary waveguide 40 has an incident end 6 located on the light source 10 side and an output end 7 opposite to the incident end 6. The junction between the primary waveguide 40 and the ring waveguide 3 functions as the directional coupling unit 5.

  The light source 10 is configured to generate a predetermined wavelength range including a designed resonance wavelength in the minute substance detection sensor 1. In consideration of design variations in the minute substance detection sensor 1, it is preferable to use the light source 10 having a wavelength range with a certain margin. That is, the light source 10 is configured to generate light having a wavelength band wider than the resonance wavelength band of the optical ring resonator. As an example, the light source 10 is preferably a broadband light source such as a (halogen) lamp, a light emitting diode (LED), a super luminescent diode (SLD), or a super continuum light source.

  The detection unit 20 detects fluorescence generated by the minute substance detection sensor 1. More specifically, the detection unit 20 includes a camera unit 22 and an image processing unit 24. The camera unit 22 is configured by an image sensor such as a CCD (Charged Coupled Device). And as an example, the camera part 22 is arrange | positioned at the upper part side of the fine substance detection sensor 1 so that the fine substance detection sensor 1 may be included in the visual field. The image processing unit 24 is connected to the camera unit 22 and extracts only the fluorescent component generated from the optical ring resonator based on the image captured by the camera unit 22. Typically, the camera unit 22 has detection sensitivity in fluorescence (visible wavelength band), and higher luminance (brightness) is detected in a portion where fluorescence is generated. Based on the detected amount of luminance, etc., the amount of fluorescence generated is determined.

  In addition, as the detection part 20, the structure containing the photodiode array in which several photodiodes were arranged by the predetermined rule is also employable. As described above, any method may be adopted as the detection unit 20 as long as the optical ring resonator can be optically measured.

  The determination processing unit 30 outputs a result including the presence / absence, content, concentration, type, and the like of the substance to be detected based on the detection result by the detection unit 20.

<< Ro. Detection principle using an optical ring resonator >>
Next, the principle for detecting minute substances using the optical ring resonator will be described. In an optical ring resonator, an optical resonance is generated by setting an optical path length for an optical wave having a predetermined wavelength so that the optical wave forms a ring shape and the phase of the optical wave goes around the ring and then overlaps. Since the ring-shaped resonator does not require a reflection structure in the optical waveguide, the structure can be simplified, and there is an advantage that an optical path loss due to reflection is small and highly efficient resonance can be obtained.

  When an optical ring resonator is used as a minute substance detection sensor, the effect of concentrating light energy on the optical ring resonator and the effect of shifting the resonance condition of the optical ring resonator due to the material in the vicinity of the resonator are used. It will be. In an optical ring resonator, a light wave can exist only when the optical path length (effective path length) obtained by multiplying the refractive index of the optical waveguide by the geometric path length matches an integer multiple of the wavelength. If this condition is not satisfied, the amount of light in the optical ring resonator is rapidly attenuated.

Therefore, in the minute substance detection device SYS shown in FIG. 1, the light irradiated from the light source 10 (having a wavelength component over a predetermined width) passes through the directional coupling unit 5 to form an optical ring resonator (ring waveguide). 3). Of this light, only the wavelength component that satisfies the resonance condition in the optical ring resonator is confined in the optical ring resonator. As a result, the transmittance from the entrance end 6 to the exit end 7 of the primary waveguide 40 is greatly reduced for wavelengths satisfying the resonance condition. The resonance wavelength of the optical ring resonator can be expressed by the following equation (1) using the effective refractive index N _eff of the primary waveguide 40 and the resonator length L of the optical ring resonator. Here, m is the resonance order (integer), and λ is the wavelength of light in vacuum.

  Next, when a minute substance adheres to the periphery of the optical ring resonator, the resonance condition of the optical ring resonator is shifted, so that the change in the refractive index of the surrounding medium can be detected with high sensitivity. In other words, when a minute substance adheres around the optical ring resonator, the resonance wavelength in the optical ring resonator changes.

  Next, a method for attaching a minute substance around the optical ring resonator will be described. For example, when a biological minute substance such as a protein is used as a target substance, a method for biomodifying the periphery of the optical ring resonator or a liquid containing the target substance is allowed to flow through the optical ring resonator. There is a method of providing the flow path. These methods will be described with reference to FIG.

  FIG. 2 is a schematic diagram showing a configuration for biologically modifying the optical ring resonator in the minute substance detection device SYS according to the first embodiment of the present invention. Referring to FIG. 2, the optical ring resonator includes a core 301 and a clad 302. Basically, the optical ring resonator is biologically modified so that a biomarker as a detection target is selectively adsorbed on the surface of the core 301. Keep it. That is, as shown in FIG. 2A, a biomodification portion 303 that is a base layer is provided on the surface of the core 301. The biomodifier 303 is typically realized by using an antigen-antibody reaction, and specifically adsorbs only a specific type of protein.

  In the configuration shown in FIG. 2A, when a specimen containing a substance to be detected is dropped on the biological modification unit 303, only the substance to be detected in the specimen is selectively adsorbed on the surface of the core 301. . When a part of the light wave (electromagnetic wave) propagating through the optical waveguide oozes out toward the substance adsorbed on the surface of the core 301 which is the optical waveguide of the optical ring resonator, the transmission refractive index in the optical waveguide slightly changes. Thereby, the resonance wavelength in the optical ring resonator is also changed (shifted). By observing this shift in the resonance wavelength, it is possible to detect a change in the refractive index of the surrounding medium with high sensitivity.

  In addition, since the electromagnetic field concentrates around the optical ring resonator when the optical ring resonator satisfies the resonance condition, this phenomenon is used to efficiently apply the fluorescent material disposed around the optical ring resonator. You can also make it glow. That is, the presence / absence, content, concentration, type, etc. of the substance to be detected in the sample can be detected by adding a fluorescent label to the substance to be detected and detecting the amount of fluorescence generated.

  In addition, after biomodifying the biomarker, which is a substance to be detected, to be selectively adsorbed on the surface of the core 301, a flow for allowing a liquid containing the substance to be detected to pass through these biomodified parts. A road may be provided.

  In the minute substance detection apparatus SYS according to the present embodiment, the fluorescence generated when the substance to be detected, to which the fluorescent label is added, is attached to the base layer as shown in FIG. 2 is detected. Note that the fluorescence generated from the substance to be detected has a longer wavelength than the wavelength of light incident (confined) into the optical ring resonator.

  FIG. 3 is a schematic diagram showing a state of fluorescence generated from the optical ring resonator in the minute substance detection device SYS according to the first embodiment of the present invention.

  Referring to FIG. 3, when light I0 having a predetermined wavelength band from the light source is incident on primary waveguide 40, light I1 having a wavelength that matches the resonance wavelength of the optical ring resonator passes through ring waveguide 3. Go around. The light I2 having a wavelength other than the resonance wavelength that has not been confined in the optical ring resonator is emitted as outgoing light. When a substance to be detected supplemented by the underlying layer formed on the surface of the optical ring resonator is present, it is excited by the light I1 to generate fluorescence I4. This fluorescence I4 is measured as signal light.

<< Cha. Wavelength band of light waves >>
Next, the relationship in the wavelength band about each light wave shown in FIG. 3 is demonstrated.

  4 and 5 are diagrams showing the relationship in the wavelength band for each light wave shown in FIG.

  Referring to FIG. 4A, it is assumed that incident light (light I0) emitted from the light source 10 has a sufficiently wide wavelength band as compared to the resonance wavelength band of the optical ring resonator. In FIG. 4A, it is assumed that the center wavelength of the resonance wavelength band of the optical ring resonator is λ1. In this case, the light I2 emitted as the outgoing light from the primary waveguide 40 has a wavelength other than the wavelength region centered on the wavelength λ1 that resonates in the optical ring resonator.

  FIG. 4B shows the light I1 that resonates in the optical ring resonator and the absorption characteristic I3 of the detection target substance that is adsorbed by the optical ring resonator and has a fluorescent label. In general, the absorption characteristic I3 of the fluorescent label (fluorescent substance) imparted to the substance to be detected has a wider wavelength band than the resonance wavelength of the optical ring resonator. In the example shown in FIG. 4B, the fluorescence imparted to the substance to be detected by setting the resonance wavelength band centered on the center wavelength λ1 of the optical ring resonator to be included in the absorption characteristic of the fluorescent substance. The substance can be excited.

  FIG. 5 shows the wavelength distribution characteristics of the light I1 that resonates in the optical ring resonator and the fluorescence I4 that is generated. By making light incident on the fluorescent substance applied to the detection target substance, a fluorescence wavelength distribution is generated in a longer wavelength band.

  By detecting the fluorescence generated in this manner, a result including the presence / absence, content, concentration, type, etc. of the substance to be detected is acquired.

"two. Effect
In the minute substance detection device according to the present embodiment, a substance for adsorbing a detected substance with a fluorescent label is arranged on the surface of the optical ring resonator, and fluorescence generated from the detected substance adsorbed on this substance Adopt a method to detect. By adopting such a method, it becomes possible to excite fluorescence in a region enhanced by an electric field as compared with the conventional method, and the detection sensitivity can be increased.

  The minute substance detection device according to the present embodiment uses an optical ring resonator composed of a ring-shaped optical waveguide. Compared to the case of using a conventional disk-type resonator, such an optical ring resonator has a broader light mode concentrated on the waveguide portion forming the ring, so that stronger light can be detected. It becomes possible to give to. Therefore, detection sensitivity can be increased.

  Further, in the minute substance detection device according to the present embodiment, it is sufficient to form the foundation layer for adsorbing the substance to be detected not only on the entire disk surface but only on the upper surface of the ring. I'll do it. Furthermore, when there are too many underlayers, the influence of non-specific adsorption becomes large, and there is a high possibility that fluorescence (noise) that should not be detected inherently occurs. For this reason, it is better not to form the underlayer on unnecessary portions as much as possible. In this respect, the optical ring resonator is superior to the disk resonator.

  In addition, by using an optical ring resonator as a waveguide in which an underlayer for adsorbing a target substance to which a fluorescent label is attached is used, only a wavelength with a relatively narrow width determined according to the resonant wavelength of the optical ring resonator is used. In addition, it is possible to excite fluorescence and to excite the fluorescent material many times with a small amount of adsorbed material due to ring resonance, so that the detection sensitivity can be increased as compared with the conventional case.

  In addition, by using a light source configured to generate incident light having a wavelength band wider than the resonance wavelength band of the optical ring resonator, the likelihood of manufacturing errors of the optical ring resonator can be increased. That is, the width of the resonance wavelength of the optical ring resonator is very narrow, and there is a possibility that the resonance wavelength is shifted for each individual due to the manufacturing error of the optical ring resonator. However, by adopting incident light having a band wider than the resonance wavelength band of the optical ring resonator, the fluorescence from the detected substance is excited regardless of the individual variation of the optical ring resonator, and the detected substance is It becomes possible to measure.

[Embodiment 2]
In the first embodiment described above, the configuration using one optical ring resonator is illustrated, but a plurality of optical ring resonators may be used in parallel. In the second embodiment described below, a minute substance detection device having a plurality of optical ring resonators having ring waveguides having different ring diameters will be described. In particular, a configuration using a plurality of optical ring resonators in order to increase the likelihood of manufacturing errors will be described.

"I. Device configuration"
The entire configuration of the minute substance detection device according to the second embodiment of the present invention is the same as that of the minute substance detection device SYS shown in FIG. 1 except for the configuration of the minute substance detection sensor. Detailed description of will not be repeated.

  FIG. 6 is a schematic diagram showing a configuration of a minute substance detection sensor in the minute substance detection device according to the second embodiment of the present invention.

  Referring to FIG. 6, the minute substance detection sensor according to the present embodiment includes a plurality of optical ring resonators. That is, the minute substance detection sensor according to the present embodiment includes a primary waveguide 40 (first waveguide) that is formed on a substrate and propagates a light wave from the light source 10 (FIG. 1), and 1 on the substrate 2. And an optical ring resonator composed of ring-shaped ring waveguides 31, 32, and 33 (second waveguides) formed close to the next waveguide 40. As shown in FIG. 6, these optical ring resonators are aligned along the primary waveguide 40 (first waveguide).

  The ring waveguides 31, 32, and 33 are formed so that the ring diameters are different from each other. Thus, by making the ring diameters different from each other, the resonance wavelengths in the respective optical ring resonators are different from each other.

  In this embodiment, since the primary purpose is to increase the likelihood of manufacturing errors, as will be described later, the resonance wavelengths of the respective optical ring resonators all have the absorption characteristics of a common fluorescent material. Designed to be included.

  FIG. 6 illustrates a configuration in which three optical ring resonators are arranged, but the number of optical ring resonators is not particularly limited. Therefore, a necessary number of optical ring resonators may be arranged in accordance with the absorption characteristics of the fluorescent material.

<< Ro. Detection principle using an optical ring resonator >>
Since the principle for detecting a minute substance using the optical ring resonator is as described above, detailed description will not be repeated.

<< Cha. Wavelength band of light waves >>
Next, the relationship in the wavelength band for each light wave used in the minute substance detection device according to the present embodiment will be described.

  7 and 8 are diagrams showing the relationship in the wavelength band for each of the light waves shown in FIG.

  It is assumed that incident light (light I0) emitted from the light source 10 (FIG. 1) has a sufficiently wide wavelength band as compared with the resonance wavelength band of each optical ring resonator. In FIG. 6, it is assumed that the center wavelengths of the resonance wavelength bands of the respective optical ring resonators are λ11, λ12, and λ13.

  With reference to FIG. 6 and FIG. 7A, when incident light (light I0) from the light source 10 enters the primary waveguide 40, a wavelength that matches the resonance wavelength λ11 of the first optical ring resonator is obtained. The light I <b> 11 having the light circulates around the ring waveguide 31. On the other hand, light in a wavelength band other than the resonance wavelength λ11 that is not confined in the first optical ring resonator is directed to the second and subsequent optical ring resonators.

  In the second optical ring resonator, the light I12 having a wavelength that matches the resonance wavelength λ12 of the optical ring resonator circulates in the ring waveguide 32. Light in a wavelength band other than the resonance wavelength λ12 that is not confined in the second optical ring resonator is directed to the third and subsequent optical ring resonators.

  In the third optical ring resonator, light I13 having a wavelength that matches the resonance wavelength λ13 of the optical ring resonator circulates in the ring waveguide 33. Light in a wavelength band other than the resonance wavelength λ13 that is not confined in the third optical ring resonator is emitted as outgoing light.

  When a substance to be detected supplemented by the underlayer formed on the surface of the optical ring resonator is present, it is excited by the light I11, I12, and I13, and generates fluorescence I41, I42, and I43, respectively. These fluorescences I41, I42, and I43 are measured as signal light.

  As described above, the light I2 emitted as the outgoing light from the primary waveguide 40 has a wavelength other than the wavelength region centered on the wavelengths λ11, 12, and 13 that resonate in the respective optical ring resonators. As described above, light source 10 according to the present embodiment is configured to generate light having a wider wavelength band than the entire resonance wavelength band of the plurality of optical ring resonators.

  FIG. 7B shows light I11, I12, and I13 that resonate in the optical ring resonator, and the absorption characteristic I3 of the target substance that is adsorbed by the optical ring resonator and has a fluorescent label. In general, the absorption characteristic I3 of the fluorescent label (fluorescent substance) imparted to the substance to be detected has a wider wavelength band than the resonance wavelength of the optical ring resonator. In the example shown in FIG. 7B, by setting each resonance wavelength band centered on the center wavelengths λ11, λ12, and λ13 of each optical ring resonator to be included in the absorption characteristics of the fluorescent material, It becomes possible to excite the fluorescent substance imparted to the substance to be detected.

  FIG. 8 shows the wavelength distribution characteristics of the lights I11, I12, and I13 that resonate in the optical ring resonator and the fluorescence I4 that is generated. By making light incident on the fluorescent substance applied to the detection target substance, a fluorescence wavelength distribution is generated in a longer wavelength band.

  Note that the fluorescence I41, I42, and I43 generated from each of the ring waveguides 31, 32, and 33 can be detected using the detection unit 20 (FIG. 1) according to the generation location. In any case, since the detected fluorescence is centered around a common wavelength, it is not necessary to spatially decompose which ring waveguide emits the light, and the detection unit 20 What is necessary is just to evaluate the absolute value of the light quantity detected by (1).

  By detecting the fluorescence generated in this manner, a result including the presence / absence, content, concentration, type, etc. of the substance to be detected is acquired.

"two. Effect
FIG. 9 is a diagram showing characteristics when the resonance wavelength is deviated from the original design value due to the design error of the optical ring resonator in the minute substance detection device according to the second embodiment of the present invention.

  As shown in FIG. 9, by using a plurality of optical ring resonators, each ring diameter slightly deviates from a design value due to a manufacturing error, so that the resonance wavelengths are changed from λ11, λ12, λ13 to λ11 ′, λ12 ′. , Λ13 ′, any one of the resonance wavelengths can enter the absorption characteristic I3 of the substance to be detected with a fluorescent label, so that the influence of such a manufacturing error can be reduced.

  In the minute substance detection device according to the present embodiment, in addition to the effects obtained by the minute substance detection device according to the first embodiment described above, a plurality of optical ring resonators having different ring diameters are used, so that the entire device can be obtained. As a result, the width of the resonance wavelength band of the optical ring resonator group can be increased. As a result, it becomes possible to excite the substance to be detected in a wider wavelength bandwidth.

  Further, by using incident light having a wavelength band wider than the entire wavelength band of the optical ring resonator group, it is possible to absorb the influence of individual variations in the optical ring resonator.

[Embodiment 3]
In the above-described second embodiment, the configuration using a plurality of optical ring resonators to increase the likelihood of manufacturing errors has been described. However, a plurality of light beams are selected so as to selectively detect a plurality of types of substances to be detected. Ring resonators may be used in parallel. In the third embodiment described below, a configuration using a plurality of optical ring resonators will be described so that a substance to be detected can be specified from among a plurality of predetermined substances.

"I. Device configuration"
The overall configuration of the minute substance detection device according to the third embodiment of the present invention is the same as that of the minute substance detection device SYS shown in FIG. 1 except for the configuration of the minute substance detection sensor and the detection unit and the determination processing unit. Detailed description of the configuration other than the minute substance detection sensor will not be repeated.

  FIG. 10 is a schematic diagram showing a configuration of a minute substance detection sensor in the minute substance detection device according to the third embodiment of the present invention.

  Referring to FIG. 10, the minute substance detection sensor according to the present embodiment includes a plurality of optical ring resonators. That is, the minute substance detection sensor according to the present embodiment includes a primary waveguide 40 (first waveguide) that is formed on a substrate and propagates a light wave from the light source 10 (FIG. 1), and 1 on the substrate 2. And an optical ring resonator composed of ring-shaped ring waveguides 34, 35, and 36 (second waveguides) formed close to the next waveguide 40. As shown in FIG. 10, these optical ring resonators are aligned along the primary waveguide 40 (first waveguide).

  The ring waveguides 34, 35, and 36 are formed so as to have different ring diameters. Thus, by making the ring diameters different from each other, the resonance wavelengths in the respective optical ring resonators are different from each other.

  In the present embodiment, it is a primary purpose to selectively detect a plurality of types of substances to be detected. Therefore, as will be described later, the resonance wavelengths of the respective optical ring resonators are different from each other. Designed to be included in the absorption characteristics of

  FIG. 10 illustrates a configuration in which three optical ring resonators are arranged, but the number of optical ring resonators is not particularly limited. Therefore, a necessary number of optical ring resonators may be arranged in accordance with the absorption characteristics of the fluorescent material.

<< Ro. Detection principle using an optical ring resonator >>
Since the principle for detecting a minute substance using the optical ring resonator is as described above, detailed description will not be repeated.

<< Cha. Wavelength band of light waves >>
Next, the relationship in the wavelength band for each light wave used in the minute substance detection device according to the present embodiment will be described.

  FIG. 11 and FIG. 12 are diagrams showing the relationship in the wavelength band for each light wave shown in FIG.

  It is assumed that incident light (light I0) emitted from the light source 10 (FIG. 1) has a sufficiently wide wavelength band as compared with the resonance wavelength band of each optical ring resonator. In FIG. 6, it is assumed that the center wavelengths of the resonance wavelength bands of the respective optical ring resonators are λ14, λ15, and λ16.

  Referring to FIG. 10 and FIG. 11A, when incident light (light I0) from the light source 10 enters the primary waveguide 40, a wavelength that matches the resonance wavelength λ14 of the first optical ring resonator is obtained. The light I 14 having the light circulates around the ring waveguide 34. On the other hand, light in a wavelength band other than the resonance wavelength λ14 that is not confined in the first optical ring resonator is directed to the second and subsequent optical ring resonators.

  In the second optical ring resonator, the light I15 having a wavelength that matches the resonance wavelength λ15 of the optical ring resonator circulates in the ring waveguide 35. Light in a wavelength band other than the resonance wavelength λ15 that is not confined in the second optical ring resonator is directed to the third and subsequent optical ring resonators.

  In the third optical ring resonator, light I16 having a wavelength that matches the resonance wavelength λ16 of the optical ring resonator circulates in the ring waveguide. Light in a wavelength band other than the resonance wavelength λ16 that is not confined in the third optical ring resonator is emitted as outgoing light.

  When a substance to be detected supplemented by the underlayer formed on the surface of the optical ring resonator is present, it is excited by the light I14, I15, and I16, respectively, and generates fluorescence I44, I45, and I46, respectively. These fluorescences I44, I45, and I46 are measured as signal light.

  As described above, the light I2 emitted as the emitted light from the primary waveguide 40 has a wavelength other than the wavelength region centered on the wavelengths λ14, 15, and 16 that resonate in the respective optical ring resonators. As described above, light source 10 according to the present embodiment is configured to generate light having a wider wavelength band than the entire resonance wavelength band of the plurality of optical ring resonators.

  FIG. 11B shows the light I14, I15, and I16 that resonate in the optical ring resonator, and the absorption characteristics I31, I32, and I33 of the target substance that is adsorbed by the optical ring resonator and has a fluorescent label. Indicates. In general, each of the absorption characteristics I31, I32, and I33 of the fluorescent label (fluorescent substance) imparted to the substance to be detected has a wider wavelength band than the corresponding resonance wavelength of the optical ring resonator. In the example shown in FIG. 11B, by setting each resonance wavelength band centered on the center wavelengths λ14, λ15, and λ16 of each optical ring resonator to be included in the absorption characteristics of the fluorescent material, It becomes possible to excite the fluorescent substance imparted to the substance to be detected.

  In particular, in the minute substance detection device according to the present embodiment, in order to vary the type of specimen (detected substance) to be detected for each optical ring resonator, the fluorescent substance to be fluorescently added to each detected substance The absorption wavelength is different.

  FIG. 12 shows the wavelength distribution characteristics of the fluorescence I41, I42, and I43 generated in correspondence with the lights I14, I15, and I16 that resonate in the optical ring resonator. By making light incident on the fluorescent substance applied to the detection target substance, a fluorescence wavelength distribution is generated in a longer wavelength band.

  As shown in FIG. 12, by setting the resonance wavelength of each optical ring resonator so that each fluorescent label emits light with different absorption characteristics of the fluorescent label for each target substance to be detected. It is possible to selectively measure a substance to be detected. For example, the first substance to be detected is attached with the first fluorescent label having the wavelength distribution characteristic (center wavelength λ41) of the fluorescence I41, and the wavelength distribution of the fluorescence I42 is given to the second substance to be detected. The second fluorescent label having the characteristic (center wavelength λ42) is attached, and the third fluorescent substance having the wavelength distribution characteristic (center wavelength λ43) of the fluorescence I43 is attached to the third substance to be detected. Keep it.

  The determination processing unit according to the present embodiment has a function of specifying which optical ring resonator among the plurality of optical ring resonators is generating fluorescence based on the detection result by the detecting unit. For this reason, by specifying which optical ring resonator among the plurality of optical ring resonators (ring waveguides 34, 35, and 36 shown in FIG. 10), which type of detection target substance is specified. It can be determined whether (the fluorescent substance-tagged substance to be detected) is present.

  That is, the determination processing unit according to the present embodiment selects any one of a plurality of substances in which a substance to be detected is predetermined based on information of the optical ring resonator in which fluorescence is generated among the plurality of optical ring resonators. It is specified whether it is a substance. By selectively detecting the fluorescence generated in this manner, it is possible to obtain a result including presence / absence, content, concentration, type, and the like for each type of substance to be detected.

  As described above, as a method for judging from which optical ring resonator the fluorescence is generated, (1) using the fact that the wavelength of the generated fluorescence is different, the total generated fluorescence is measured, and these The wavelength of the measured fluorescence is wavelength-resolved to detect each fluorescence independently, or (2) the light is emitted from any optical ring resonator (any location) using a spatial detector. And a method of simultaneously detecting each generated fluorescence by measuring spatially separated or not.

Hereinafter, these methods will be described.
FIG. 13 is a diagram for illustrating an outline of control logic using wavelength decomposition in the minute substance detection device according to the third embodiment of the present invention. Referring to FIG. 13, detection unit 20 according to the present embodiment includes wavelength filters 311, 312, and 313, and integrators 321, 322, and 323 associated with the wavelength filters.

  The wavelength filters 311, 312, and 313 extract the corresponding wavelength components (center wavelengths λ41, λ42, and λ43) included in the measurement image acquired by the imaging of the camera unit 22 (FIG. 1). The integrators 321, 322, and 323 integrate the wavelength components extracted by the corresponding wavelength filters, and output the corresponding fluorescence measurement results.

Thus, each fluorescence existing in the space can be measured independently.
FIG. 14 is a diagram for illustrating an outline of control logic using a spatial detector in the minute substance detection device according to the third embodiment of the present invention.

  First, as shown in FIG. 14A, it is assumed that the respective ring waveguides 34, 35, and 36 (optical ring resonators) exist. Assume that the existence positions of these optical ring resonators are registered in advance.

  Next, as shown in FIG. 14B, it is assumed that fluorescence is generated from the optical ring resonator formed by the ring waveguide 34 by adsorbing the substance to be detected. Note that the camera unit 22 has detection sensitivity for any fluorescence. In the image measured by the camera unit 22, it is possible to identify from which optical ring resonator the fluorescence is generated by identifying the region where the fluorescence is detected.

  According to such a method, as shown in FIG. 14C, even if fluorescence is generated simultaneously from the two optical ring resonators composed of the ring waveguides 34 and 36, these two optical rings. The fluorescence generation from the resonator can be observed simultaneously.

"two. Effect
According to the minute substance detection device according to the present embodiment, a plurality of optical ring resonators having different ring diameters are arranged in addition to the operational effects obtained by the minute substance detection device according to the first and second embodiments. Thus, the width of the resonance wavelength band of the optical ring resonator group as the entire device can be widened. As a result, it becomes possible to excite the substance to be detected in a wider wavelength bandwidth.

  In addition, according to the minute substance detection device according to the present embodiment, the resonance wavelength of each optical ring resonator is made different, and an independent fluorescent indicator is excited by the resonance wavelength of each optical ring resonator. In this way, by setting the characteristic wavelength of the optical ring resonator group and the fluorescence index imparted to the substance to be detected to be independent wavelengths, various kinds of substances to be detected can be detected simultaneously.

  The embodiment disclosed this time should be considered as illustrative in all points and not restrictive. The scope of the present invention is shown not by the above description of the embodiments but by the scope of claims, and is intended to include all modifications within the meaning and scope equivalent to the scope of claims.

  DESCRIPTION OF SYMBOLS 1 Minute substance detection sensor, 2 Substrate, 3, 31, 32, 33, 31, 32, 33, 34, 35, 36, 34, 35, 36 Ring waveguide, 4 Cladding layer, 5 Directional coupling part, 6 Incident End, 7 emission end, 10 light source, 20 detection unit, 22 camera unit, 24 image processing unit, 30 determination processing unit, 40 primary waveguide, 301 core, 302 cladding, 303 biomodification unit, 311, 312, 313 wavelength Filter, 321, 322, 323 integrator, SYS fine substance detection device.

Claims (7)

A light source;
A first waveguide formed on a substrate and propagating a light wave from the light source;
An optical ring resonator comprising a ring-shaped second waveguide formed on the substrate in proximity to the first waveguide;
A minute substance detection apparatus comprising: a detection unit that detects fluorescence generated when a substance to be detected with a fluorescent label attached to the optical ring resonator.   The minute substance detection device according to claim 1, wherein the light source is configured to generate light having a wavelength band wider than a resonance wavelength band of the optical ring resonator. The minute substance detection device includes a plurality of the optical ring resonators having the second waveguides having different ring diameters,
The minute substance detection device according to claim 2, wherein the light source is configured to generate light having a wider wavelength band than an entire resonance wavelength band of the plurality of optical ring resonators.   4. The minute substance detection device according to claim 3, wherein the plurality of optical ring resonators are aligned along the first waveguide. 5.   5. The minute substance detection according to claim 4, further comprising a control unit that specifies which of the plurality of optical ring resonators is generating fluorescence based on a detection result by the detection unit. apparatus.   The control means determines which of the plurality of predetermined substances the detected substance is based on information of the optical ring resonator in which fluorescence is generated among the plurality of optical ring resonators. The minute substance detection device according to claim 5, wherein:   The minute substance detection device according to claim 5 or 6, wherein the detection unit is configured to optically measure the plurality of optical ring resonators.

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