JP2004333250A - Optical biosensor - Google Patents

Optical biosensor Download PDF

Info

Publication number
JP2004333250A
JP2004333250A JP2003128028A JP2003128028A JP2004333250A JP 2004333250 A JP2004333250 A JP 2004333250A JP 2003128028 A JP2003128028 A JP 2003128028A JP 2003128028 A JP2003128028 A JP 2003128028A JP 2004333250 A JP2004333250 A JP 2004333250A
Authority
JP
Japan
Prior art keywords
side grating
total reflection
optical biosensor
layer
reflection layer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
JP2003128028A
Other languages
Japanese (ja)
Other versions
JP4076902B2 (en
Inventor
Ikuo Uematsu
育生 植松
Ichiro Tono
一郎 東野
Kayoko Oomiya
可容子 大宮
Hideo Eto
英雄 江藤
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Toshiba Corp
Original Assignee
Toshiba Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Toshiba Corp filed Critical Toshiba Corp
Priority to JP2003128028A priority Critical patent/JP4076902B2/en
Publication of JP2004333250A publication Critical patent/JP2004333250A/en
Application granted granted Critical
Publication of JP4076902B2 publication Critical patent/JP4076902B2/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour

Landscapes

  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Plasma & Fusion (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Light Guides In General And Applications Therefor (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)

Abstract

<P>PROBLEM TO BE SOLVED: To provide an optical biosensor capable of measuring the change quantity of evernescent waves with high precision. <P>SOLUTION: This optical biosensor includes a total reflection layer 10 for permitting incident light to transmit while totally reflecting the same, the incident side grating 11a and the emitting side grating 11b brought into contact with the total reflection layer 10 in a mutually spaced-apart state and the sensing film 12 brought into contact with the total reflection layer 10 to contain the enzyme and color forming reagent provided between the incident side grating 11a and the emitting side grating 11b. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

【０００１】
【発明の属する技術分野】
本発明は、生体内の体液中に溶存する物質の量を測定するセンサに関し、特に光導波現象を用いた光学式バイオセンサに係わる。
【０００２】
【従来の技術】
生体内の体液中に溶存する物質の量を測定するセンサとして、光導波現象を利用した平面光導波路型測定センサが知られている。この平面光導波路型測定センサは、図７に示す通り、光源６から光が入射する基板１上の位置に入射側グレーティング３、基板１から受光素子に向けて光を出射する位置に出射側グレーティング４を形成し、さらに基板１表面に光を透過させる単一の光導波路層２を形成し、この光導波路層２上に分子認識機能および情報変換機能を有する膜、例えばグルコースオキシダーゼ（ＧＯＤ）固定化膜５を形成した構造を有する。この平面光導波路型測定センサは、生体から注射器等で抽出した血液等をグルコースオキシダーゼ（ＧＯＤ）固定化膜５上に滴下した状態で、レーザ光を入射側グレーティング３を通して光導波路層２に入射させ、エバネッセント波を発生させ、光導波路層２上の膜による血液等に含まれる生体分子との反応に起因するエバネッセント波の変化量を出射側グレーティング４から放出される光を受光する受光素子７により検出して、血液等に含まれる生体分子を分析するものである（例えば、特許文献１参照。）。
【０００３】
【特許文献１】
特開平９−６１３４６号公報
【０００４】
【発明が解決しようとする課題】
しかしながら、平面光導波路型測定センサで、高精度にエバネッセント波の変化量を測定できるように光導波路層２を基板１上に形成するのには、光が所望の屈折をしながら光導波路層２内を透過するようにするため、精密な製造装置と高度の技術が必要である。
【０００５】
本発明は、簡単な作製方法によって、高精度にエバネッセント波の変化量を測定できる光学式バイオセンサを提供しようとするものである。
【０００６】
【課題を解決するための手段】
本発明の特徴は、入射した光が層内を全反射しながら透過する全反射層と、全反射層に接して、互いに離間して設けられた入射側グレーティング及び出射側グレーティングと、全反射層に接して、入射側グレーティング及び出射側グレーティングの間に設けられた酵素と発色試薬を含有するセンシング膜とを含む光学式バイオセンサであることを要旨とする。
【０００７】
【発明の実施の形態】
次に、図面を参照して、本発明の実施の形態を説明する。以下の図面の記載において、同一または類似の部分には同一または類似の符号を付している。ただし、図面は模式的なものであることに留意すべきである。
【０００８】
本発明の実施の形態に係る光学式バイオセンサは、図２に示すように、入射した光が層内を全反射しながら透過する全反射層１０と、全反射層１０に接して、互いに離間して設けられた入射側グレーティング１１ａ及び出射側グレーティング１１ｂと、全反射層１０に接して、入射側グレーティング１１ａ及び出射側グレーティング１１ｂの間に設けられた酵素と発色試薬を含有するセンシング膜１２とを含む。さらに図１に示すように、センシング膜１２を囲いながら、入射側グレーティング１１ａ及び前記出射側グレーティング１１ｂを覆う保護膜１３をさらに含む。
【０００９】
続いて各部の材料や形成方法を詳細に説明する；
（イ）全反射層１０は、石英（酸化シリコン）をプレート状に成型し形成する：
（ロ）入射側グレーティング１１ａ及び出射側グレーティング１１ｂは、全反射層１０より高屈折率の材料、例えば酸化チタン、酸化亜鉛、ニオブ酸リチウム、ガリウム砒素、インジウム錫酸化物、ポリイミド、酸化タンタル等を化学蒸着法（ＣＶＤ）等により全反射層１０上に堆積させ、リソグラフィー技術とドライエッチング技術でパターニングすることにより形成する：
（ハ）センシング膜１２は、酵素と発色試薬をセルロース誘導体等によってゲル状に固定し形成する。例えば、測定する体液中の物質がグルコースである場合、酵素としては、ＧＯＤ、ペルオキシダーゼ（ＰＯＤ）及びムタローゼ等を用いる。発色試薬としては、３，３’，５，５’−テトラメチルベンジジン等を用いる。センシング膜がグルコースによって発色する化学反応式は（１）〜（３）のようになる。なお、右辺には本反応を理解するのに必要な事項のみを記載しており、生成される物質等のすべてを記載してはいない：
グルコース ＋ ＧＯＤ → Ｈ２Ｏ２ ・・・・・（１）
Ｈ２Ｏ２ ＋ ＰＯＤ → Ｏ＊ ・・・・・（２）
Ｏ＊ ＋ 発色試薬 → 発色 ・・・・・（３）
（ニ）保護膜１３は、フッ素系樹脂のような入射側グレーティング１１ａ及び出射側グレーティング１１ｂに比べて低屈折率の材料を塗布して形成する。
【００１０】
図２に示すように、発光素子２１より入射された光は、入射側グレーティング１１ａで回折し、全反射層１０内を全反射しながら透過していく。全反射層１０とセンシング膜１２の境界面で屈折する際に、エバネッセント波がセンシング膜１２の発色によって吸収される。したがってセンシング膜１２の発色の度合い、すなわち測定しようとする物質の量に比例して光が吸収されることになる。最終的に出射側グレーティング１１ｂに到達した光は、全反射層１０から受光素子２２に向けて出射される。そして、発光素子２１より放射した光量と、受光素子２２で受けとった光量との差から測定しようとする物質の量を算出することになる。
【００１１】
本発明の実施の形態によれば、簡単な技術により、単純な構造の光学式バイオセンサを作製することができる。
【００１２】
（第１の変形例）
本発明の実施の形態の第１の変形例に係る光学式バイオセンサは、図３に示すように、全反射層１０が、ガラス層１０ａと、ガラス層１０ａ表面に形成された酸化シリコン層１０ｂから構成させている。それ以外の構成は、前述した光学式バイオセンサと同様である。これは、全反射層１０を石英で形成すると材料が高価で、光学式バイオセンサも高価になってしまうため、安価な材料で作製しようとするものである。
【００１３】
各部の材料や形成方法を説明する；
（イ）ガラス層１０ａは、無アルカリガラスをプレート状に成型し形成する：
（ロ）酸化シリコン層１０ｂは、ＣＶＤやスパッタ等で酸化シリコンをガラス層１０ａ上に堆積させ形成する。
【００１４】
酸化シリコン層１０ｂを設けた理由は、ガラス層１０ａの表面に存在する金属が均一ではないため、ガラス層１０ａ上にセンシング膜１２を設けると、使用する無アルカリガラス材料ごとに測定に影響を及ぼしてしまうからである。図４に示したように、Ｘ線光電子分光分析（ＸＰＳ）の結果、ガラス層１０ａの表面には、シリコン（Ｓｉ）の他に、アルミニウム（Ａｌ）、バリウム（Ｂａ）、カルシウム（Ｃａ）、ストロンチウム（Ｓｒ）が存在していることがわかる。ガラス層１０ａの表面に酸化シリコン層１０ｂを設けると、図５に示したＸＰＳの結果のように、シリコンのみが存在する表面上にセンシング膜１２を設けることができる。そして、測定への影響を除去できる。したがって、第１の変形例では、本発明の実施の形態で述べた効果を低価格で得ることができる。
【００１５】
（第２の変形例）
本発明の実施の形態の第２の変形例に係る光学式バイオセンサは、図６に示すように、全反射層１０が、ガラス層１０ａと、ガラス層１０ａ表面に形成された酸化チタン層１０ｃから構成させている。それ以外の構成は、本発明の実施の形態で述べた光学式バイオセンサと同様である。これは、第１の変形例と同様に、全反射層１０を石英で形成すると材料が高価で、光学式バイオセンサも高価になってしまうため、安価な材料で作製しようとするものである。
【００１６】
各部の材料や形成方法を説明する；
（イ）ガラス層１０ａは、無アルカリガラスをプレート状に成型し形成する：
（ロ）酸化チタン層１０ｃは、ＣＶＤやスパッタ等で酸化チタンをガラス層１０ａ上に堆積させ形成する。センシング膜１２との境界面での光の吸収量を極大とするため、酸化チタン層１０ｃの厚さは、好ましくは１８０ｎｍ〜２００ｎｍ、最も好ましくは２００ｎｍとする。
【００１７】
この形成方法では、入射側グレーティング１１ａ及び出射側グレーティング１１ｂを、酸化チタン層１０ｃからリソグラフィー技術とドライエッチング技術でパターニングすることにより形成することが可能であり、作製が容易となる。
【００１８】
さらに、全反射層１０を、ガラス層１０ａとガラス層１０ａより高屈折率を有する酸化チタン層１０ｃで構成することで、センシング膜１２との境界面でのエバネッセント波の電場強度を増大させられる。
【００１９】
したがって、第２の変形例では、本発明の実施の形態で述べた効果を低価格で得ることができるとともに、作製手順が容易になる。
【００２０】
（その他の実施の形態）
本発明の実施の形態を説明するために各図において示した各部位の厚さや位置関係は、あくまでも例示であって、本発明の機能を実現するために限定したものでない。よって、本発明の機能が実現可能な範囲において、各部位の厚さや位置関係が考え得ることは言うまでもない。
【００２１】
本発明はここでは記載していない様々な実施の形態等を含むことは勿論である。本発明の技術的範囲は上記の説明から妥当な特許請求の範囲に係る発明特定事項によってのみ定められるものである。
【００２２】
【発明の効果】
本発明によれば、簡単な作製方法によって、高精度にエバネッセント波の変化量を測定できる光学式バイオセンサを提供することが可能である。
【図面の簡単な説明】
【図１】本発明の実施の形態に係る光学式バイオセンサの上面図である。
【図２】本発明の実施の形態に係る光学式バイオセンサの図１のＩ−Ｉの断面図である。
【図３】本発明の第１の変形例に係る光学式バイオセンサの断面図である。
【図４】ガラス層のＸ線光電子分光分析（ＸＰＳ）の結果である。
【図５】酸化シリコン層のＸ線光電子分光分析（ＸＰＳ）の結果である。
【図６】本発明の第２の変形例に係る光学式バイオセンサの断面図である。
【図７】従来の平面光導波路型測定センサの断面図である。
【符号の説明】
１…基板、２…光導波路層、３…入射側グレーティング、４…出射側グレーティング、５…ＧＯＤ固定化膜、６…光源、７…受光素子、１０…全反射層、１０ａ…ガラス層、１０ｂ…酸化シリコン層、１０ｃ…酸化チタン層、１１ａ…入射側グレーティング、１１ｂ…出射側グレーティング、１２…センシング膜、１３…保護膜、２１…発光素子、２２…受光素子[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a sensor for measuring the amount of a substance dissolved in a body fluid in a living body, and more particularly, to an optical biosensor using an optical waveguide phenomenon.
[0002]
[Prior art]
2. Description of the Related Art As a sensor for measuring the amount of a substance dissolved in a body fluid in a living body, a planar optical waveguide type measurement sensor using an optical waveguide phenomenon is known. As shown in FIG. 7, this planar optical waveguide type measurement sensor has an incident-side grating 3 at a position on a substrate 1 where light from a light source 6 enters, and an emission-side grating at a position where light exits from the substrate 1 toward a light receiving element. 4, a single optical waveguide layer 2 for transmitting light is formed on the surface of the substrate 1, and a film having a molecular recognition function and an information conversion function, such as glucose oxidase (GOD), is immobilized on the optical waveguide layer 2. It has a structure in which the oxide film 5 is formed. In this planar optical waveguide type measurement sensor, a laser beam is incident on the optical waveguide layer 2 through the incident side grating 3 in a state where blood or the like extracted from a living body with a syringe or the like is dropped on a glucose oxidase (GOD) immobilized film 5. , An evanescent wave is generated, and a change amount of the evanescent wave caused by a reaction of the film on the optical waveguide layer 2 with a biomolecule contained in blood or the like is detected by a light receiving element 7 for receiving light emitted from the emission side grating 4. It detects and analyzes biomolecules contained in blood and the like (for example, see Patent Document 1).
[0003]
[Patent Document 1]
JP-A-9-61346 [0004]
[Problems to be solved by the invention]
However, in order to form the optical waveguide layer 2 on the substrate 1 so that the change amount of the evanescent wave can be measured with high accuracy by the planar optical waveguide type measurement sensor, the optical waveguide layer 2 needs to be refracted in a desired manner. Precise manufacturing equipment and advanced technology are required to allow transmission inside.
[0005]
An object of the present invention is to provide an optical biosensor capable of measuring an evanescent wave change amount with high accuracy by a simple manufacturing method.
[0006]
[Means for Solving the Problems]
A feature of the present invention is that a total reflection layer through which incident light is transmitted while totally reflecting inside the layer, an incident-side grating and an emission-side grating provided in contact with the total reflection layer and separated from each other, and a total reflection layer. The present invention is directed to an optical biosensor including an enzyme provided between the incident-side grating and the output-side grating and a sensing film containing a coloring reagent.
[0007]
BEST MODE FOR CARRYING OUT THE INVENTION
Next, an embodiment of the present invention will be described with reference to the drawings. In the following description of the drawings, the same or similar parts are denoted by the same or similar reference numerals. However, it should be noted that the drawings are schematic.
[0008]
As shown in FIG. 2, the optical biosensor according to the embodiment of the present invention includes a total reflection layer 10 through which incident light is transmitted while totally reflecting the inside of the layer, and a distance between the total reflection layer 10 and the total reflection layer 10. The incident-side grating 11a and the exit-side grating 11b provided in contact with the total reflection layer 10 and the sensing film 12 containing an enzyme and a coloring reagent provided between the incident-side grating 11a and the exit-side grating 11b. including. Further, as shown in FIG. 1, a protective film 13 that further covers the incident-side grating 11a and the emission-side grating 11b while surrounding the sensing film 12 is further included.
[0009]
Next, the materials and forming methods of each part will be described in detail;
(A) The total reflection layer 10 is formed by molding quartz (silicon oxide) into a plate shape:
(B) The incident-side grating 11a and the emission-side grating 11b are made of a material having a higher refractive index than the total reflection layer 10, such as titanium oxide, zinc oxide, lithium niobate, gallium arsenide, indium tin oxide, polyimide, and tantalum oxide. It is deposited on the total reflection layer 10 by a chemical vapor deposition method (CVD) or the like, and is formed by patterning with a lithography technique and a dry etching technique:
(C) The sensing film 12 is formed by immobilizing an enzyme and a coloring reagent in a gel state with a cellulose derivative or the like. For example, when the substance in the body fluid to be measured is glucose, GOD, peroxidase (POD), mutarose, or the like is used as the enzyme. As the coloring reagent, 3,3 ′, 5,5′-tetramethylbenzidine or the like is used. The chemical reaction formulas in which the sensing membrane develops color with glucose are as shown in (1) to (3). In addition, only the matters necessary for understanding this reaction are described on the right-hand side, and not all of the generated substances and the like are described:
Glucose + GOD → H 2 O 2 ... (1)
H 2 O 2 + POD → O * (2)
O * + coloring reagent → coloring ... (3)
(D) The protective film 13 is formed by applying a material having a lower refractive index than the incidence-side grating 11a and the emission-side grating 11b, such as a fluororesin.
[0010]
As shown in FIG. 2, the light incident from the light emitting element 21 is diffracted by the incident side grating 11 a and transmitted while being totally reflected in the total reflection layer 10. When the light is refracted at the interface between the total reflection layer 10 and the sensing film 12, the evanescent wave is absorbed by the color of the sensing film 12. Therefore, light is absorbed in proportion to the degree of color development of the sensing film 12, that is, the amount of the substance to be measured. The light that finally reaches the emission-side grating 11b is emitted from the total reflection layer 10 toward the light receiving element 22. Then, the amount of the substance to be measured is calculated from the difference between the amount of light emitted from the light emitting element 21 and the amount of light received by the light receiving element 22.
[0011]
According to the embodiment of the present invention, an optical biosensor having a simple structure can be manufactured by a simple technique.
[0012]
(First Modification)
As shown in FIG. 3, the optical biosensor according to the first modification of the embodiment of the present invention includes a glass layer 10a and a silicon oxide layer 10b formed on the surface of the glass layer 10a. It consists of. Other configurations are the same as those of the optical biosensor described above. This is because if the total reflection layer 10 is made of quartz, the material is expensive, and the optical biosensor is also expensive.
[0013]
Explain the materials and forming method of each part;
(A) The glass layer 10a is formed by molding non-alkali glass into a plate shape:
(B) The silicon oxide layer 10b is formed by depositing silicon oxide on the glass layer 10a by CVD, sputtering, or the like.
[0014]
The reason for providing the silicon oxide layer 10b is that the metal present on the surface of the glass layer 10a is not uniform. Therefore, providing the sensing film 12 on the glass layer 10a affects the measurement for each non-alkali glass material used. It is because. As shown in FIG. 4, as a result of X-ray photoelectron spectroscopy (XPS), in addition to silicon (Si), aluminum (Al), barium (Ba), calcium (Ca), It can be seen that strontium (Sr) is present. When the silicon oxide layer 10b is provided on the surface of the glass layer 10a, the sensing film 12 can be provided on the surface where only silicon exists, as shown by the XPS result shown in FIG. Then, the influence on the measurement can be removed. Therefore, in the first modification, the effects described in the embodiment of the present invention can be obtained at low cost.
[0015]
(Second Modification)
As shown in FIG. 6, in the optical biosensor according to the second modification of the embodiment of the present invention, a total reflection layer 10 includes a glass layer 10a and a titanium oxide layer 10c formed on the surface of the glass layer 10a. It consists of. Other configurations are the same as those of the optical biosensor described in the embodiment of the present invention. As in the first modification, if the total reflection layer 10 is formed of quartz, the material is expensive, and the optical biosensor is also expensive.
[0016]
Explain the materials and forming method of each part;
(A) The glass layer 10a is formed by molding non-alkali glass into a plate shape:
(B) The titanium oxide layer 10c is formed by depositing titanium oxide on the glass layer 10a by CVD, sputtering, or the like. In order to maximize the amount of light absorbed at the interface with the sensing film 12, the thickness of the titanium oxide layer 10c is preferably from 180 nm to 200 nm, most preferably 200 nm.
[0017]
According to this forming method, the incidence-side grating 11a and the emission-side grating 11b can be formed by patterning the titanium oxide layer 10c by a lithography technique and a dry etching technique, which facilitates the fabrication.
[0018]
Furthermore, by forming the total reflection layer 10 from the glass layer 10a and the titanium oxide layer 10c having a higher refractive index than the glass layer 10a, the electric field intensity of the evanescent wave at the interface with the sensing film 12 can be increased.
[0019]
Therefore, in the second modified example, the effects described in the embodiment of the present invention can be obtained at a low price, and the manufacturing procedure is simplified.
[0020]
(Other embodiments)
The thickness and positional relationship of each part shown in each drawing for describing the embodiment of the present invention are merely examples, and are not limited to realize the functions of the present invention. Therefore, it goes without saying that the thickness and the positional relationship of each part can be considered as long as the functions of the present invention can be realized.
[0021]
The present invention naturally includes various embodiments not described herein. The technical scope of the present invention is determined only by the matters specifying the invention according to the claims that are appropriate from the above description.
[0022]
【The invention's effect】
According to the present invention, it is possible to provide an optical biosensor capable of measuring a change amount of an evanescent wave with high accuracy by a simple manufacturing method.
[Brief description of the drawings]
FIG. 1 is a top view of an optical biosensor according to an embodiment of the present invention.
FIG. 2 is a cross-sectional view taken along line II of FIG. 1 of the optical biosensor according to the embodiment of the present invention.
FIG. 3 is a sectional view of an optical biosensor according to a first modification of the present invention.
FIG. 4 shows the result of X-ray photoelectron spectroscopy (XPS) of the glass layer.
FIG. 5 is a result of X-ray photoelectron spectroscopy (XPS) of a silicon oxide layer.
FIG. 6 is a sectional view of an optical biosensor according to a second modified example of the present invention.
FIG. 7 is a sectional view of a conventional planar optical waveguide measurement sensor.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 ... Substrate, 2 ... Optical waveguide layer, 3 ... Incident side grating, 4 ... Outgoing side grating, 5 ... GOD fixed film, 6 ... Light source, 7 ... Light receiving element, 10 ... Total reflection layer, 10a ... Glass layer, 10b ... silicon oxide layer, 10c ... titanium oxide layer, 11a ... incident side grating, 11b ... exit side grating, 12 ... sensing film, 13 ... protective film, 21 ... light emitting element, 22 ... light receiving element

Claims (9)

入射した光が層内を全反射しながら透過する全反射層と、
前記全反射層に接して、互いに離間して設けられた入射側グレーティング及び出射側グレーティングと、
前記全反射層に接して、前記入射側グレーティング及び前記出射側グレーティングの間に設けられた酵素と発色試薬を含有するセンシング膜
とを含むことを特徴とする光学式バイオセンサ。A total reflection layer through which incident light is transmitted while totally reflecting inside the layer,
In contact with the total reflection layer, an entrance-side grating and an exit-side grating provided apart from each other,
An optical biosensor comprising: an enzyme provided between the incident-side grating and the output-side grating in contact with the total reflection layer; and a sensing film containing a coloring reagent. 前記入射側グレーティング及び前記出射側グレーティングは、前記全反射層よりも高屈折率の材料からなることを特徴とする請求項１に記載の光学式バイオセンサ。2. The optical biosensor according to claim 1, wherein the incident side grating and the exit side grating are made of a material having a higher refractive index than the total reflection layer. 前記入射側グレーティング及び前記出射側グレーティングを覆う保護膜をさらに含むことを特徴とする請求項１または２に記載の光学式バイオセンサ。The optical biosensor according to claim 1, further comprising a protective film that covers the incident-side grating and the output-side grating. 前記全反射層は、酸化シリコンからなることを特徴とする請求項１乃至３のいずれか１項に記載の光学式バイオセンサ。The optical biosensor according to any one of claims 1 to 3, wherein the total reflection layer is made of silicon oxide. 前記全反射層が、ガラス層と、前記ガラス層表面に形成された酸化シリコン層から構成させていることを特徴とする請求項１乃至３のいずれか１項に記載の光学式バイオセンサ。The optical biosensor according to claim 1, wherein the total reflection layer includes a glass layer and a silicon oxide layer formed on a surface of the glass layer. 前記全反射層が、ガラス層と、前記ガラス層表面に形成された酸化チタン層から構成させていることを特徴とする請求項１乃至３のいずれか１項に記載の光学式バイオセンサ。The optical biosensor according to claim 1, wherein the total reflection layer includes a glass layer and a titanium oxide layer formed on a surface of the glass layer. 前記酵素は、グルコースオキシダーゼ、ペルオキシダーゼ及びムタローゼの内の少なくとも１種類であることを特徴とする請求項１乃至６のいずれか１項に記載の光学式バイオセンサ。The optical biosensor according to any one of claims 1 to 6, wherein the enzyme is at least one of glucose oxidase, peroxidase, and mutarose. 前記発色試薬は、３，３’，５，５’−テトラメチルベンジジンであることを特徴とする請求項１乃至７のいずれか１項に記載の光学式バイオセンサ。The optical biosensor according to any one of claims 1 to 7, wherein the coloring reagent is 3,3 ', 5,5'-tetramethylbenzidine. 前記センシング膜が、セルロース誘導体を含むことを特徴とする請求項１乃至８のいずれか１項に記載の光学式バイオセンサ。The optical biosensor according to any one of claims 1 to 8, wherein the sensing film includes a cellulose derivative.
JP2003128028A 2003-05-06 2003-05-06 Optical biosensor Expired - Fee Related JP4076902B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2003128028A JP4076902B2 (en) 2003-05-06 2003-05-06 Optical biosensor

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2003128028A JP4076902B2 (en) 2003-05-06 2003-05-06 Optical biosensor

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2007325278A Division JP4649467B2 (en) 2007-12-17 2007-12-17 Optical biosensor

Publications (2)

Publication Number Publication Date
JP2004333250A true JP2004333250A (en) 2004-11-25
JP4076902B2 JP4076902B2 (en) 2008-04-16

Family

ID=33504331

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2003128028A Expired - Fee Related JP4076902B2 (en) 2003-05-06 2003-05-06 Optical biosensor

Country Status (1)

Country Link
JP (1) JP4076902B2 (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006208359A (en) * 2004-12-27 2006-08-10 Toshiba Corp Biochemical sensor chip of optical waveguide type and manufacturing method therefor
JP2007178325A (en) * 2005-12-28 2007-07-12 Toshiba Corp Chip for inspecting optical measuring instrument, inspection method of the optical measuring instrument, manufacturing method of the optical measuring instrument and usage method of the optical measuring instrument
US7269308B2 (en) 2005-09-29 2007-09-11 Kabushiki Kaisha Toshiba Optical waveguide type biochemical sensor chip and method of manufacturing the same
JP2008008828A (en) * 2006-06-30 2008-01-17 Toshiba Corp Coloration reaction detection instrument and its manufacturing method
JP2008022763A (en) * 2006-07-20 2008-02-07 Toshiba Corp Optical glucose sensor chip and method for producing the same
KR100899811B1 (en) * 2006-12-05 2009-05-27 한국전자통신연구원 Guided mode resonance filter including high refractive index organic material and optical biosensor having the same
JP2009150908A (en) * 2004-12-27 2009-07-09 Toshiba Corp Optical waveguide type biochemical sensor chip, its design method, and method of measuring object to be measured
US8837871B2 (en) 2010-07-16 2014-09-16 Kabushiki Kaisha Toshiba Optical waveguide sensor chip, optical waveguide sensor, and method for manufacturing optical waveguide sensor chip

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006208359A (en) * 2004-12-27 2006-08-10 Toshiba Corp Biochemical sensor chip of optical waveguide type and manufacturing method therefor
JP2009150908A (en) * 2004-12-27 2009-07-09 Toshiba Corp Optical waveguide type biochemical sensor chip, its design method, and method of measuring object to be measured
JP4673714B2 (en) * 2004-12-27 2011-04-20 株式会社東芝 Optical waveguide type biochemical sensor chip and manufacturing method thereof
US7269308B2 (en) 2005-09-29 2007-09-11 Kabushiki Kaisha Toshiba Optical waveguide type biochemical sensor chip and method of manufacturing the same
JP2007178325A (en) * 2005-12-28 2007-07-12 Toshiba Corp Chip for inspecting optical measuring instrument, inspection method of the optical measuring instrument, manufacturing method of the optical measuring instrument and usage method of the optical measuring instrument
JP2008008828A (en) * 2006-06-30 2008-01-17 Toshiba Corp Coloration reaction detection instrument and its manufacturing method
JP2008022763A (en) * 2006-07-20 2008-02-07 Toshiba Corp Optical glucose sensor chip and method for producing the same
KR100899811B1 (en) * 2006-12-05 2009-05-27 한국전자통신연구원 Guided mode resonance filter including high refractive index organic material and optical biosensor having the same
US8837871B2 (en) 2010-07-16 2014-09-16 Kabushiki Kaisha Toshiba Optical waveguide sensor chip, optical waveguide sensor, and method for manufacturing optical waveguide sensor chip

Also Published As

Publication number Publication date
JP4076902B2 (en) 2008-04-16

Similar Documents

Publication Publication Date Title
CN1940529B (en) Biochemical sensor chip of optical waveguide type and manufacturing method therefor
US5814565A (en) Integrated optic waveguide immunosensor
EP1121583B1 (en) Optical sensor having dielectric film stack
JP3886153B2 (en) Lens and connectable flow cell
US20160122794A1 (en) System, method and apparatus for pathogen detection
US20050025421A1 (en) Substrate index modification for increasing the sensitivity of grating-coupled waveguides
JP4673714B2 (en) Optical waveguide type biochemical sensor chip and manufacturing method thereof
JPWO2005078415A1 (en) Surface plasmon resonance sensor
JPH06507708A (en) Analysis method
EP1751591A1 (en) Integrated optical waveguide sensors with reduced signal modulation
JP2000504829A (en) Analysis method and analyzer
US7829327B2 (en) Optical waveguide type antibody chip and method of measuring antigen concentration
EP0404900A1 (en) Improvements in or relating to optical biosensors
JPS6375542A (en) Chemical sensitive surface plasmon resonator
JP2924707B2 (en) Optical waveguide type fluorescent immunosensor and method of manufacturing the same
JP2005308658A (en) Surface plasmon resonance sensor apparatus
JP4649467B2 (en) Optical biosensor
JP4076902B2 (en) Optical biosensor
Campbell et al. Interferometric biosensors
JP2012021936A (en) Optical waveguiding type sensor chip and optical waveguiding type sensor
JP4823330B2 (en) Optical waveguide type biochemical sensor chip and measuring method for measuring object
WO2004092250A1 (en) Biocompatible material
JP5777277B2 (en) Optical waveguide type biochemical sensor chip
WO2004092730A2 (en) Method and device for detecting the presence of an analyte
Socorro et al. Fiber-optic immunosensor based on lossy mode resonances induced by indium tin oxide thin-films

Legal Events

Date Code Title Description
A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20051004

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20070608

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20070619

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20070807

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20071016

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20071217

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20080122

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20080130

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20110208

Year of fee payment: 3

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20120208

Year of fee payment: 4

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20120208

Year of fee payment: 4

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20130208

Year of fee payment: 5

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20140208

Year of fee payment: 6

LAPS Cancellation because of no payment of annual fees