JPH1194747A - Biochip and biochip reader - Google Patents

Biochip and biochip reader

Info

Publication number
JPH1194747A
JPH1194747A JP25480997A JP25480997A JPH1194747A JP H1194747 A JPH1194747 A JP H1194747A JP 25480997 A JP25480997 A JP 25480997A JP 25480997 A JP25480997 A JP 25480997A JP H1194747 A JPH1194747 A JP H1194747A
Authority
JP
Japan
Prior art keywords
biochip
spots
circular
dna
fluorescent light
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
JP25480997A
Other languages
Japanese (ja)
Other versions
JP3346727B2 (en
Inventor
Naganori Nasu
永典 奈須
Kenji Yamamoto
顕次 山本
Hitoshi Fujimiya
仁 藤宮
Noriko Yurino
以子 百合野
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.)
Hitachi Software Engineering Co Ltd
Original Assignee
Hitachi Software Engineering Co Ltd
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 Hitachi Software Engineering Co Ltd filed Critical Hitachi Software Engineering Co Ltd
Priority to JP25480997A priority Critical patent/JP3346727B2/en
Publication of JPH1194747A publication Critical patent/JPH1194747A/en
Application granted granted Critical
Publication of JP3346727B2 publication Critical patent/JP3346727B2/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00497Features relating to the solid phase supports
    • B01J2219/00527Sheets
    • B01J2219/00529DNA chips
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00497Features relating to the solid phase supports
    • B01J2219/00527Sheets
    • B01J2219/00531Sheets essentially square
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00497Features relating to the solid phase supports
    • B01J2219/00527Sheets
    • B01J2219/00536Sheets in the shape of disks
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00596Solid-phase processes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00605Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00605Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00608DNA chips
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00659Two-dimensional arrays
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068Means for controlling the apparatus of the process
    • B01J2219/00702Processes involving means for analysing and characterising the products
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718Type of compounds synthesised
    • B01J2219/0072Organic compounds
    • B01J2219/00722Nucleotides
    • CCHEMISTRY; METALLURGY
    • C40COMBINATORIAL TECHNOLOGY
    • C40BCOMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00Libraries per se, e.g. arrays, mixtures
    • C40B40/04Libraries containing only organic compounds
    • C40B40/06Libraries containing nucleotides or polynucleotides, or derivatives thereof

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)

Abstract

PROBLEM TO BE SOLVED: To obtain a biochip reader by which a circular biochip can be read out at low costs by a method wherein the circular biochip in which labeled DNA's or proteins are spotted in a circular arrangement is turned so as to be read out. SOLUTION: Spots 2 of labeled DNA's or proteins are arranged sequentially on a biochip 10 in units of tracks. The circular biochip 10 is turned by a motor 11, and it is read out while a point sensor 18 is driven to the center direction 19 of a circle. That is to say, a laser beam is oscillated by a semiconductor pumped solid-state laser 5, the laser beam is emitted toward the spots 2 by a dichroic mirror 13, a fluorescent substance with which the DNA's or the proteins in the spots 2 are labeled is excited, and fluorescent light is emitted. Then, the fluorescent light is condensed by a lens 12, light other than the fluorescent light is cut off by an optical interference filter 9, and the fluorescent light is narrowed down by a lens 15 so as to be detected by a photomultiplier tube 7. Thereby, a mechanism which deflects and scans a laser beam is not required, and the cost of a biochip reader is reduced.

Description

【発明の詳細な説明】DETAILED DESCRIPTION OF THE INVENTION

【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、読取りが安価で実現
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. The present invention relates to an inexpensive and feasible reading method. 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 a horizontal axis by a mirror 6 to excite a fluorescent substance in a spot 2 to emit fluorescent light. With 8 optical fibers,
The objective 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.

【図面の簡単な説明】[Brief description of the drawings]

【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 shows a spot structure.

【符号の説明】 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 Signs] 1 ... Square biochip, 2 ... Spot, 3 ... Scanning direction of laser light, 4 ... Drive 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 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Jin Fujimiya 6-81 Ouecho, Naka-ku, Yokohama-shi, Kanagawa Prefecture In-house Hitachi Software Engineering Co., Ltd. 81 Hitachi Software Engineering Co., Ltd.

Claims (3)

【特許請求の範囲】[Claims] 【請求項1】 プローブDNAや蛋白質を円状の配列で
スポットしたことを特徴とするバイオチップ。
1. A biochip comprising probe DNAs and proteins spotted in a circular array.
【請求項2】 円の形状のバイオチップを回転させて読
取ることを特徴とするバイオチップ読取り装置。
2. A biochip reader characterized in that a circular biochip is rotated and read.
【請求項3】 請求項2のバイオチップ読取において、
DNAや蛋白質に蛍光物質を標識し、レーザーで励起し
て読取る手段と、DNAや蛋白質を化学発光させて読取
る手段を備えたことを特徴とする読取り装置。
3. The biochip reader according to claim 2, wherein
A reading device comprising: means for labeling DNA or protein with a fluorescent substance, exciting by laser and reading; and means for reading DNA or protein by chemiluminescence.
JP25480997A 1997-09-19 1997-09-19 Biochip and biochip reader Expired - Fee Related JP3346727B2 (en)

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)

Application Number Priority Date Filing Date Title
JP25480997A JP3346727B2 (en) 1997-09-19 1997-09-19 Biochip and biochip reader

Publications (2)

Publication Number Publication Date
JPH1194747A true JPH1194747A (en) 1999-04-09
JP3346727B2 JP3346727B2 (en) 2002-11-18

Family

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Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000068668A1 (en) * 1999-05-11 2000-11-16 Hitachi Software Engineering Co., Ltd. Method and device for fluorescence measurement
WO2001016600A1 (en) * 1999-08-31 2001-03-08 Mitsubishi Chemical Corporation Method of analyzing mutual interaction between protein and molecule
WO2001038875A1 (en) * 1999-11-19 2001-05-31 Hitachi Software Engineering Co., Ltd. Biochip reader and labeling reagent
WO2001057180A1 (en) * 2000-01-31 2001-08-09 Matsushita Seiko Co., Ltd. Kit for detecting microorganisms, apparatus for quanitifying microorganisms and method for quantifying microorganisms
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