JP3346727B2 - Biochip and biochip reader - Google Patents
Biochip and biochip readerInfo
- Publication number
- JP3346727B2 JP3346727B2 JP25480997A JP25480997A JP3346727B2 JP 3346727 B2 JP3346727 B2 JP 3346727B2 JP 25480997 A JP25480997 A JP 25480997A JP 25480997 A JP25480997 A JP 25480997A JP 3346727 B2 JP3346727 B2 JP 3346727B2
- Authority
- JP
- Japan
- Prior art keywords
- biochip
- spots
- dna
- fluorescent substance
- protein
- 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.)
- Expired - Fee Related
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00527—Sheets
- B01J2219/00529—DNA chips
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00527—Sheets
- B01J2219/00531—Sheets essentially square
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00527—Sheets
- B01J2219/00536—Sheets in the shape of disks
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00596—Solid-phase processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00608—DNA chips
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00659—Two-dimensional arrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/0068—Means for controlling the apparatus of the process
- B01J2219/00702—Processes involving means for analysing and characterising the products
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00718—Type of compounds synthesised
- B01J2219/0072—Organic compounds
- B01J2219/00722—Nucleotides
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/04—Libraries containing only organic compounds
- C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
Description
【0001】[0001]
【発明の属する技術分野】本発明は分子生物学全般で使
用されているDNAや蛋白質に蛍光物質を標識して、レ
ーザーで蛍光物質を励起し、蛍光の発光量でDNAや蛋
白質の量を検出する読取り方式で、読取り装置が安価に
実現可能な手法に関する。バイオチップはDNAや蛋白
質を高密度に集積して格納したものに関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for labeling DNA or protein used in general molecular biology with a fluorescent substance, exciting the fluorescent substance with a laser, and detecting the amount of DNA or protein by the amount of fluorescence emitted. in reading method of, reading device relates inexpensively <br/> feasible approach. The biochip relates to a device in which DNAs and proteins are stored at a high density.
【0002】[0002]
【従来の技術】従来のバイオチップは四角形状で、図6
に示すようなスポットが植え付けてある。2はスポット
で、17は蛍光標識されたDNAや蛋白質で、16は蛍
光物質である。バイオチップの読取りは、例えば図2に
示すようなものがある。図2において、1はバイオチッ
プで、2はバイオチップに蛍光物質が標識されたDNA
や蛋白質をスポットしたものであり、1のバイオチップ
を読取るために、5のレーザーを発信させ、6のミラー
でレーザー光を横軸に振り、2のスポットの蛍光物質を
励起させ、発光した蛍光を8の光ファイバーで集光し、
9の光学フィルタで目的の波長を抽出し、7のホトマル
で検出し、1のバイオチップを4の縦軸方向に駆動さ
せ、次のラインを読取り、これを繰り返してバイオチッ
プ全体を読取っていた。2. Description of the Related Art A conventional biochip has a quadrangular shape, and FIG.
Spots as shown in the figure are planted. 2 is a spot, 17 is a fluorescently labeled DNA or protein, and 16 is a fluorescent substance. The reading of the biochip is, for example, as shown in FIG. In FIG. 2, 1 is a biochip, and 2 is a DNA in which a fluorescent substance is labeled on the biochip.
In order to read 1 biochip, a laser 5 is emitted, and a laser beam is moved along the horizontal axis by a mirror 6 to excite the fluorescent substance in the spot 2 and emit fluorescence. With 8 optical fibers,
The target wavelength was extracted by the optical filter 9 and detected by the photomultiplier 7. The biochip 1 was driven in the direction of the vertical axis of 4, the next line was read, and this was repeated to read the entire biochip. .
【0003】[0003]
【発明が解決しようとする課題】しかしながら、このよ
うな従来の方法では、バイオチップを読取るのにチップ
を駆動させるメカニズムとレーザーを振って読取るライ
ンセンサーのメカニズムが必要となり、コストが高くな
り問題となっていた。However, in such a conventional method, a mechanism for driving a chip and a mechanism for a line sensor for reading by shaking a laser are required for reading a biochip. Had become.
【0004】本発明はチップの形状を円形状にし、読取
りは円盤を回転させ、ポイントセンサーで読取ること
で、低コストで読取りを可能とすることを目的とする。An object of the present invention is to make it possible to read at low cost by making a chip into a circular shape, reading by rotating a disk and reading by a point sensor.
【0005】[0005]
【課題を解決するための手段】図1は本発明の原理説明
図である。本発明は10のバイオチップを円形状に作成
し、11のモータで回転させ、18のポイントセンサ部
を、19の円の中心方向に駆動させて読むことを特徴と
する。FIG. 1 is a diagram illustrating the principle of the present invention. The present invention is characterized in that 10 biochips are formed in a circular shape, rotated by 11 motors, and 18 point sensor units are driven in the direction of the center of 19 circles for reading.
【0006】また、2のスポット内が化学発光で光って
いる光を読取るときは5のレーザーを切って読取り、蛍
光方式でも化学発光方式でも読取りができることを特徴
とする。[0006] Further, when reading light in which the inside of the spot 2 shines by chemiluminescence, reading is performed by turning off the laser 5 and reading can be performed by a fluorescent method or a chemiluminescent method.
【0007】このような方式によれば、回転式でバイオ
チップを読取ることができ、センサーもポイントセンサ
ーであるため、ラインセンサーに比べ安価に装置の実現
ができる。バイオチップの読取装置が安価であれば各研
究室で手軽にバイオチップを使用した実験ができるよう
になり、遺伝子解明の研究のスピードアップに役立つ。[0007] According to such a system, the biochip can be read in a rotating manner, and since the sensor is also a point sensor, an apparatus can be realized at lower cost than a line sensor. If the biochip reader is inexpensive, it will be possible to easily carry out experiments using the biochip in each laboratory, which will help speed up research on gene elucidation.
【0008】[0008]
【発明の実施の形態】以下、本発明の実施の形態を図面
に基づいて説明する。図6はスポット構造で、2はスポ
ット、17は標識されたDNAあるいは蛋白質、16は
蛍光物質のTexasRedである。図3はスポットがトラック
単位に順次並んでいるバイオチップで、2はスポット、
10はチップ全体である。チップの素材としてはガラス
を使用する。図4はスポットが同一角度で並んでいるバ
イオチップで、2はスポットで、10はチップ全体であ
る。図5はスポットが渦巻きの形で並んでいるバイオチ
ップで、2はスポットで、10は全体像である。図3、
図4及び図5はいずれも円盤型バイオチップの実施例を
示す図である。Embodiments of the present invention will be described below with reference to the drawings. FIG. 6 shows a spot structure, 2 is a spot, 17 is a labeled DNA or protein, and 16 is a fluorescent substance, TexasRed. FIG. 3 shows a biochip in which spots are sequentially arranged in track units.
10 is the whole chip. Glass is used as a chip material. FIG. 4 shows a biochip in which spots are arranged at the same angle, 2 is a spot, and 10 is the entire chip. FIG. 5 shows a biochip in which spots are arranged in a spiral, 2 is a spot, and 10 is a whole image. FIG.
4 and 5 are diagrams each showing an embodiment of a disc-shaped biochip.
【0009】図1は本発明の一実施の形態に係わる全体
構成図である。図1において、10は円盤型のバイオチ
ップであり、11のモーターで回転させる。18はポイ
ントセンサー部であり、5は半導体励起固体レーザーで
532nmのレーザー光を発信させ、13のダイクロイ
ックミラーでレーザー光の波長のみを2のスポットに向
けて反射させ、12のレンズでレーザー光を絞って、2
のスポットに照射し、スポット中のDNAや蛋白質に標識
している蛍光物質を励起し、蛍光を発光させる。12は
レンズで発光した蛍光を集光して平行光にし、13のダ
イクロイックミラーを通り抜け、625nmを選択的に
透過する光学干渉フィルター9で蛍光以外の光をカット
し、15のレンズで絞り込み、7のホトマルへ光を入れ
て検出する。FIG. 1 is an overall configuration diagram according to an embodiment of the present invention. In FIG. 1, reference numeral 10 denotes a disk-shaped biochip, which is rotated by a motor 11. Reference numeral 18 denotes a point sensor unit. Reference numeral 5 denotes a semiconductor-excited solid-state laser that emits 532 nm laser light, 13 dichroic mirrors reflect only the wavelength of the laser light toward 2 spots, and 12 lenses transmit laser light. Squeeze 2
The spot is irradiated to excite a fluorescent substance labeled on DNA or protein in the spot to emit fluorescence. Numeral 12 converges the fluorescent light emitted by the lens into parallel light, passes through a dichroic mirror 13, cuts off light other than fluorescent light with an optical interference filter 9 that selectively transmits 625 nm, and narrows down with a lens 15. Light is injected into the photomultiplier to detect.
【0010】なお、本発明において、化学発光でDNA
や蛋白質の標識を発光させたときは、5のレーザーを切
り、14の光学干渉フィルターを発光波長を選択的に透
過する光学干渉フィルターに変更し読取れば、蛍光方式
と同様に、10のバイオチップを読取ることができると
いう特長を有する。[0010] In the present invention, DNA is produced by chemiluminescence.
When the label of protein or protein is emitted, the laser of 5 is turned off, the optical interference filter of 14 is changed to an optical interference filter that selectively transmits the emission wavelength, and reading is performed. It has the feature that a chip can be read.
【0011】更に、チップの両面にDNAなどをスポット
し、読み取ることにより、少ない検体の量で、効率的に
読み取ることが可能である。Further, by spotting and reading DNA or the like on both sides of the chip, it is possible to read efficiently with a small amount of sample.
【0012】[0012]
【発明の効果】以上説明をしたように、本発明によれば
円盤型のバイオチップを回転して読めば、従来のレーザ
ー光を振って、光ファイバで集光して読む機構が不要と
なり、低コストで読取装置の実現ができる。As described above, according to the present invention, if a disk-shaped biochip is rotated and read, a conventional mechanism for shaking a laser beam and condensing it with an optical fiber to read it is unnecessary. A reading device can be realized at low cost.
【図1】本発明の原理説明図である。FIG. 1 is a diagram illustrating the principle of the present invention.
【図2】従来の説明図である。FIG. 2 is a conventional explanatory diagram.
【図3】スポットがトラック単位に順次並んでいるバイ
オチップである。FIG. 3 is a biochip in which spots are sequentially arranged in track units.
【図4】スポットが同一角度で並んでいるバイオチップ
である。FIG. 4 is a biochip in which spots are arranged at the same angle.
【図5】スポットが渦巻きの形で並んでいるバイオチッ
プである。FIG. 5 is a biochip in which spots are arranged in a spiral.
【図6】スポットの構造である。FIG. 6 is a structure of a spot.
1…四角型バイオチップ、2…スポット、3…レーザー
光のスキャン方向、4…チップの駆動方向、5…レーザ
ー、6…振動ミラー、7…ホトマル、8…集光光ファイ
バー、9…光学フィルター、10…円型バイオチップ、
11…回転モーター、12…集光レンズ、13…ダイク
ロイックミラー、15…ホトマル用集光レンズ、16…
蛍光物質、17…DNAまたは蛋白質、18…ポイントセ
ンサー部、19…ポイントセンサー部の駆動方向。DESCRIPTION OF SYMBOLS 1 ... Square biochip, 2 ... Spot, 3 ... Scanning direction of laser light, 4 ... Driving direction of chip, 5 ... Laser, 6 ... Vibrating mirror, 7 ... Photomaru, 8 ... Condensing optical fiber, 9 ... Optical filter, 10. Circular biochip,
11: rotating motor, 12: condensing lens, 13: dichroic mirror, 15: condensing lens for photomaru, 16 ...
Fluorescent substance, 17: DNA or protein, 18: Point sensor section, 19: Drive direction of the point sensor section.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 藤宮 仁 神奈川県横浜市中区尾上町6丁目81番地 日立ソフトウェアエンジニアリング株 式会社内 (72)発明者 百合野 以子 神奈川県横浜市中区尾上町6丁目81番地 日立ソフトウェアエンジニアリング株 式会社内 (56)参考文献 特開 平4−315947(JP,A) (58)調査した分野(Int.Cl.7,DB名) G01N 33/53 G01N 21/78 G01N 33/483 G01N 33/58 G01N 37/00 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Jin Fujimiya 6-81 Onoecho, Naka-ku, Yokohama-shi, Kanagawa Prefecture Within Hitachi Software Engineering Co., Ltd. 81 81 Hitachi Software Engineering Co., Ltd. (56) References JP-A-4-315947 (JP, A) (58) Fields investigated (Int. Cl. 7 , DB name) G01N 33/53 G01N 21/78 G01N 33/483 G01N 33/58 G01N 37/00
Claims (8)
から成る検体を格納する複数のスポットが、円盤状の表
面に径方向に向かって放射状に配列されていることを特
徴とするバイオチップ。1. DNA or protein labeled with a fluorescent substance
The spots containing specimens consisting of
A biochip characterized by being radially arranged on a surface in a radial direction .
から成る検体を格納する複数のスポットが、円盤状の表
面に螺旋状に配列されていることを特徴とするバイオチ
ップ。 2. DNA or protein labeled with a fluorescent substance
The spots containing specimens consisting of
Biochi characterized by being spirally arranged on the surface
Up.
から成る検体を格納する複数のスポットが、円盤状の表
面に同心円状に配列されているバイオチップと、前記各
スポットの検体にレーザー光を照射し、蛍光物質を励起
させ、蛍光発光量を検出する手段とを備えたことを特徴
とするバイオチップ読取り装置。3. A DNA or protein labeled with a fluorescent substance
The spots containing specimens consisting of
Biochips arranged concentrically on the surface,
Irradiate laser light to spot sample to excite fluorescent substance
Means for detecting the amount of fluorescence emission
Biochip reader .
る複数のスポットが、円盤状の表面に同心円状に配列さ
れているバイオチップと、前記各スポットの検体を化学
発光させ、その発光量を検出する手段とを備えたことを
特徴とするバイオチップ読取り装置。 4. A biochip in which a plurality of spots storing DNA or protein specimens are arranged concentrically on a disk-shaped surface, and the specimens in each of the spots are subjected to chemiluminescence, and the amount of luminescence is detected. A biochip reader.
から成る検体を格納する複数のスポットが、円盤状の表
面に径方向に向かって放射状に配列されているバイオチ
ップと、前記各スポットの検体にレーザー光を照射し、
蛍光物質を励起させ、蛍光発光量を検出する手段とを備
えたことを特徴とするバイオチップ読取り装置。 5. A biochip in which a plurality of spots storing a DNA or protein sample labeled with a fluorescent substance are radially arranged on a disk-shaped surface in a radial direction, and a sample at each spot. Irradiate the laser light to
Means for exciting a fluorescent substance and detecting a fluorescence emission amount.
る複数のスポットが、円盤状の表面に径方向に向かって
放射状に配列されているバイオチップと、前記各スポッ
トの検体を化学発光させ、その発光量を検出する手段と
を備えたことを特徴とするバイオチップ読取り装置。 6. A biochip in which a plurality of spots storing DNA or protein specimens are radially arrayed on a disk-shaped surface in a radial direction, and the specimens in each of the spots are subjected to chemiluminescence. A biochip reader, comprising: means for detecting a light emission amount.
から成る検体を格納する複数のスポットが、円盤状の表
面に螺旋状に配列されているバイオチップと、前記各ス
ポットの検体にレーザー光を照射し、蛍光物質を励起さ
せ、蛍光発光量を検出する手段とを備えたことを特徴と
するバイオチップ読取り装置。 7. A biochip in which a plurality of spots storing a DNA or protein sample labeled with a fluorescent substance are spirally arranged on a disk-shaped surface, and a laser beam is applied to each of the spot samples. Means for irradiating, exciting a fluorescent substance, and detecting the amount of fluorescent light emission.
る複数のスポットが、円盤状の表面に螺旋状に配列され
ているバイオチップと、前記各スポットの検体を化学発
光させ、その発光量を検出する手段とを備えたことを特
徴とするバイオチップ読取り装置。 8. A biochip in which a plurality of spots storing DNA or protein specimens are spirally arranged on a disk-shaped surface, and the specimens in each of the spots are subjected to chemiluminescence, and the amount of luminescence is detected. A biochip reader.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP25480997A JP3346727B2 (en) | 1997-09-19 | 1997-09-19 | Biochip and biochip reader |
Applications Claiming Priority (1)
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JP25480997A JP3346727B2 (en) | 1997-09-19 | 1997-09-19 | Biochip and biochip reader |
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JP3346727B2 true JP3346727B2 (en) | 2002-11-18 |
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1997
- 1997-09-19 JP JP25480997A patent/JP3346727B2/en not_active Expired - Fee Related
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