JP4327174B2 - Capillary array unit and manufacturing method thereof - Google Patents

Capillary array unit and manufacturing method thereof Download PDF

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JP4327174B2
JP4327174B2 JP2006119443A JP2006119443A JP4327174B2 JP 4327174 B2 JP4327174 B2 JP 4327174B2 JP 2006119443 A JP2006119443 A JP 2006119443A JP 2006119443 A JP2006119443 A JP 2006119443A JP 4327174 B2 JP4327174 B2 JP 4327174B2
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resin
capillary
capillary array
capillaries
coating
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貴康 古川
雅義 三富
義則 大越
司 大平
真典 軍司
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Hitachi Ltd
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Description

本発明は、核酸、蛋白質等を分離して検出できる電気泳動装置、特にＤＮＡ試料の塩基配列等を高速に解析できるキャピラリアレイ電気泳動装置に組み込まれるキャピラリアレイ・ユニット、及びその製造方法に関するものである。   The present invention relates to an electrophoresis apparatus capable of separating and detecting nucleic acids, proteins, etc., particularly a capillary array unit incorporated in a capillary array electrophoresis apparatus capable of analyzing a base sequence of a DNA sample at high speed, and a method for producing the same. is there.

ＤＮＡ、蛋白質等の試料分析は最近ますます重要になってきている。このため、ＤＮＡシーケンサには高速かつ大処理能力が求められている。この要求に応える装置として、複数本のキャピラリを平面状に配列したキャピラリアレイ電気泳動装置がある。キャピラリアレイ電気泳動装置は、キャピラリアレイ、キャピラリアレイに励起用のレーザ光を照射する励起光学系、試料から発せられた蛍光を検出する受光光学系等より構成される。キャピラリは通常、扱い易いようにポリイミドなどの樹脂による被覆が施されており、その端部からある一定の位置において、ある長さだけ被覆を除去し、石英管を剥き出しの状態にしてある。キャピラリアレイは、このキャピラリを平面状に配列した構造で、この石英管剥き出しの部分を光検出部としてキャピラリアレイの配列面と平行方向から励起用のレーザ光を照射する。レーザ光はキャピラリ石英管のレンズ作用によって集光され、キャピラリアレイの全てのキャピラリ内を泳動している蛍光体標識試料に照射される。レーザ光を照射された試料は蛍光を発光し、それを検出することにより試料測定を行なう。   Analysis of samples such as DNA and proteins has recently become more and more important. For this reason, the DNA sequencer is required to have a high speed and a large throughput. As an apparatus that meets this requirement, there is a capillary array electrophoresis apparatus in which a plurality of capillaries are arranged in a plane. The capillary array electrophoresis apparatus includes a capillary array, an excitation optical system that irradiates the capillary array with excitation laser light, a light receiving optical system that detects fluorescence emitted from a sample, and the like. The capillaries are usually coated with a resin such as polyimide so that they can be easily handled. The caps are removed by a certain length from the end of the capillaries, and the quartz tube is exposed. The capillary array has a structure in which the capillaries are arranged in a planar shape, and an excitation laser beam is emitted from a direction parallel to the array surface of the capillary array using the exposed portion of the quartz tube as a light detection unit. The laser light is condensed by the lens action of the capillary quartz tube, and is irradiated to the phosphor-labeled sample that migrates in all the capillaries of the capillary array. The sample irradiated with the laser light emits fluorescence, and the sample is measured by detecting it.

特開２００１−４５９３号公報JP 2001-4593 A 特開平１０−１６０７０５号公報JP-A-10-160705 特開平５−２４９０８０号公報JP-A-5-249080 特開平３−４６５５９号公報Japanese Patent Laid-Open No. 3-46559

キャピラリの光検出部において被覆を除去する方法としてトーチやライター等の炎で樹脂被覆を燃焼させて除去する方法が知られている。この方法によると、被覆は被覆端面がキャピラリ長手方向の中心軸に概略直角になって除去される。しかし、燃焼によって被覆を除去する方法ではキャピラリ表面に燃えかすが残るため、燃焼後に燃えかすを拭い取る必要があり、その際に石英管を傷付けてしまうことがある。また、燃焼によって樹脂被覆が除去された部分と樹脂被覆が残っている部分との境界では通常、被覆のめくれあがりが起き、複数本のキャピラリを被覆外径基準で整列させると、配列精度が劣化し安定した品質を確保することができない。更に、熱の制御が難しく、高温過ぎるとガラス管の曲がりや、熱歪みの蓄積による折損が多くなる等の問題がある。   As a method for removing the coating at the photodetection portion of the capillary, a method for removing the coating by burning the resin coating with a flame such as a torch or a lighter is known. According to this method, the coating is removed with the coated end face approximately perpendicular to the central axis in the longitudinal direction of the capillary. However, in the method of removing the coating by combustion, there is a residue left on the capillary surface, and therefore it is necessary to wipe off the residue after the combustion, which may damage the quartz tube. Also, the coating is usually turned up at the boundary between the part where the resin coating is removed by combustion and the part where the resin coating remains, and if multiple capillaries are aligned based on the outer diameter of the coating, the alignment accuracy deteriorates. However, stable quality cannot be ensured. Furthermore, control of heat is difficult, and if the temperature is too high, there are problems such as bending of the glass tube and increased breakage due to accumulation of thermal strain.

そのため、被覆除去の新しい方法として、キャピラリアレイの光検出部となる領域を反応室の内部空間に囲い、反応室にオゾンを含む反応性ガスを流し込むと共にその中に囲まれた部分のキャピラリ及び反応性ガスを加熱することで、反応性ガス中に含まれるオゾンを分解して酸素ラジカルを作り出し、反応室内部に位置する樹脂被覆を酸素ラジカルとの酸化反応によりガス状物質に変えて除去する方法が案出された（特願2000-269218号）。   For this reason, as a new method for removing the coating, the region that becomes the light detection portion of the capillary array is surrounded by the internal space of the reaction chamber, and a reactive gas containing ozone is poured into the reaction chamber, and the capillary and reaction in the portion surrounded by it By heating the reactive gas to decompose ozone contained in the reactive gas to produce oxygen radicals, and to remove the resin coating located inside the reaction chamber into a gaseous substance by oxidation reaction with the oxygen radicals Has been devised (Japanese Patent Application No. 2000-269218).

この方法で樹脂被覆を除去したとき、樹脂が除去されて石英管が剥き出しになっている部分と樹脂被覆が通常の状態で残っている部分との境界領域において被覆厚さの変化に伴い生じる被覆表面の傾斜の角度は、キャピラリの長手方向中心軸となす角度で通常５度から２０度程度であり、キャピラリの外周方向に部分的に被覆の除去むら等が発生しても、最大でも７０度以下である。この方法によると、キャピラリ母材の石英管に影響を及ぼすことなく、必要な部分のみ狭い範囲を限定してきれいに樹脂被覆を除去することが可能となる。   When the resin coating is removed by this method, the coating that occurs due to the change in coating thickness in the boundary region between the portion where the resin is removed and the quartz tube is exposed and the portion where the resin coating remains in the normal state The angle of the surface inclination is usually about 5 to 20 degrees as the angle with the central axis in the longitudinal direction of the capillary, and even if uneven coating removal occurs partially in the outer peripheral direction of the capillary, it is at most 70 degrees. It is as follows. According to this method, it is possible to cleanly remove the resin coating by limiting a narrow range only in a necessary portion without affecting the quartz tube of the capillary base material.

一方、キャピラリアレイの光検出部は、キャピラリ内部に蛍光試料が存在しない状態でレーザ光を照射しても発光しないことが必要である（蛍光試料が存在しないときの発光を、以下では外面発光という）。しかし、上述の酸化反応によって樹脂被覆を除去して形成した光検出部は外面発光が観察される場合があり、外面発光が観察されるキャピラリではＳ/Ｎ比が低下し検出感度が落ちることが分かった。本発明の目的は、キャピラリアレイの光検出部に関し、数本のキャピラリを精度良く整列させることができ、外面発光を低減できるキャピラリアレイを提供することである。   On the other hand, the light detection part of the capillary array needs to emit no light even if it is irradiated with laser light in the absence of the fluorescent sample inside the capillary (light emission when there is no fluorescent sample is hereinafter referred to as outer surface light emission). ). However, the light detection part formed by removing the resin coating by the above-described oxidation reaction may observe the outer surface light emission, and the S / N ratio is lowered and the detection sensitivity is lowered in the capillary where the outer surface light emission is observed. I understood. An object of the present invention is to provide a capillary array capable of aligning several capillaries with high accuracy and reducing external light emission, with respect to a photodetection section of the capillary array.

本発明者らは、外面発光の原因を解明すべく鋭意研究を重ねた。外面発光の原因として当初は、被覆の除去残り、ゴミ、光検出部と反対側からの反射光、散乱光などを想定した。これらの原因に基づく外面発光は、確実な被覆除去、ゴミ付着防止、検出部と反対方向からの反射防止などである程度低減可能である。しかし、それらの対策を施してもまだ発光値が高いことがある。   The inventors of the present invention have intensively studied to elucidate the cause of external light emission. Initially, the cause of external light emission was assumed to be unremoved coating residue, dust, reflected light from the side opposite to the light detection unit, scattered light, and the like. External light emission based on these causes can be reduced to some extent by reliable coating removal, dust adhesion prevention, reflection prevention from the direction opposite to the detection unit, and the like. However, even if these measures are taken, the emission value may still be high.

そこで、さらに研究を重ねたところ、被覆が除去されている部分と被覆が除去されていない部分との境界部分を発光しない黒いペンなどで塗布すると、外面発光が低減することを確認した。これにより、外面発光を低減するには、それ自体蛍光発光性を有する境界部分のポリイミド樹脂を黒色化等により蛍光を発しないようにすることが有効であることが判明した。   As a result of further research, it was confirmed that when the boundary between the part where the coating was removed and the part where the coating was not removed was applied with a black pen or the like that does not emit light, the external light emission was reduced. As a result, it has been found that in order to reduce the light emission from the outer surface, it is effective to prevent the fluorescent resin from emitting fluorescence by blackening or the like in the polyimide resin at the boundary portion that itself has fluorescence.

図１と図２を参照して、本発明者らが解明した外面発光の発生機構とその抑制方法について説明する。図１は、被覆を除去したキャピラリから外面発光が発生する様子を説明する図である。被覆除去された溶融石英管９の表面には僅かに付着した異物３９が存在している。矢印のように励起用のレーザ光３３を照射するとして、この異物３９は蛍光を発しないのでレーザ光３３が当たったとしても問題ない。しかし、その異物３９で散乱された散乱光４１が被覆除去されていない部分のポリイミド樹脂１０に当たる。するとポリイミド樹脂１０は蛍光を発するので、その蛍光４０が検出器（図示せず）に到達し、外面発光として検出される。図２は、外面発光抑制手段を設けたキャピラリの説明図である。ポリイミド被覆が除去された部分と除去されていない部分の境界は、ヒータで焦がすなどして黒くして非反射部４２を形成している。異物３９に励起レーザ光３３が当たると、異物からの散乱光４１は非反射部４２に当たるが、ポリイミド樹脂１０に直接当たることはない。このように非反射部４２で励起光をガードしているためポリイミド樹脂１０からの蛍光発光を防止できる。   With reference to FIG. 1 and FIG. 2, the generation | occurrence | production mechanism of the outer surface light emission which the present inventors clarified and the suppression method are demonstrated. FIG. 1 is a diagram for explaining a state in which external light emission occurs from a capillary from which a coating has been removed. A slightly adhered foreign matter 39 is present on the surface of the fused quartz tube 9 from which the coating has been removed. If the laser beam 33 for excitation is irradiated as indicated by the arrow, the foreign matter 39 does not emit fluorescence, so there is no problem even if the laser beam 33 hits. However, the scattered light 41 scattered by the foreign matter 39 hits a portion of the polyimide resin 10 where the coating is not removed. Then, since the polyimide resin 10 emits fluorescence, the fluorescence 40 reaches a detector (not shown) and is detected as external emission. FIG. 2 is an explanatory diagram of a capillary provided with outer surface light emission suppression means. The non-reflective portion 42 is formed by blackening the boundary between the portion where the polyimide coating is removed and the portion where the polyimide coating is not removed by, for example, scorching with a heater. When the excitation laser beam 33 hits the foreign matter 39, the scattered light 41 from the foreign matter hits the non-reflecting portion 42 but does not hit the polyimide resin 10 directly. In this way, since the excitation light is guarded by the non-reflecting portion 42, fluorescence emission from the polyimide resin 10 can be prevented.

本発明は、上記のような外面発光の原因究明に基づいてなされたもので、キャピラリの一部のポリイミド樹脂被覆を面ヒータで熱を加えて変色させ、その一部をＯ3ガスを含む反応性ガスとの反応で被覆を除去し、被覆除去部と非除去部の境界の樹脂表面をなだらかにすることを特徴とする。 The present invention has been made on the basis of the above-described investigation of the cause of external light emission. A part of the capillary resin resin coating is discolored by applying heat with a surface heater, and a part of the reaction contains O 3 gas. It is characterized in that the coating is removed by reaction with a reactive gas and the resin surface at the boundary between the coating removal portion and the non-removal portion is smoothed.

すなわち、本発明によるキャピラリアレイ・ユニットは、複数のキャピラリと、複数のキャピラリを長さ方向の途中で整列保持し当該整列保持した複数のキャピラリに光照射するための開口とキャピラリから発せられた発光を取り出すための開口とを備えるウインドウユニットとを含むキャピラリアレイ・ユニットにおいて、複数のキャピラリは外周に樹脂被覆が施され、ウインドウユニットに整列保持された部分で所定長さだけ樹脂被覆が剥がされ、樹脂被覆が剥がされた部分と剥がされない部分との境界領域で樹脂表面がなだらかに接続され、境界領域に残っている樹脂及び境界領域に続く所定長さの樹脂被覆が黒化していることを特徴とする。樹脂被覆が剥がされた部分と剥がされない部分との境界領域で樹脂表面がなだらかに接続されるとは、樹脂被覆が剥がされた部分と剥がされない部分との境界領域に残っている樹脂の表面がキャピラリの長手方向となす傾斜角度が７０度以下であることを意味する。樹脂の黒化は樹脂をヒータ等で加熱したことによるものであることが製造工程の簡素化の点から好ましい。   That is, the capillary array unit according to the present invention includes a plurality of capillaries, an opening for aligning and maintaining the plurality of capillaries in the middle of the length direction, and light emission emitted from the capillaries. In a capillary array unit including a window unit having an opening for taking out a plurality of capillaries, a plurality of capillaries are coated with a resin coating on the outer periphery, and the resin coating is peeled off by a predetermined length at a portion aligned and held in the window unit, The resin surface is gently connected at the boundary region between the part where the resin coating is peeled off and the part where the resin coating is not peeled off, and the resin remaining in the boundary region and the resin coating of a predetermined length following the boundary region are blackened And When the resin surface is gently connected at the boundary area between the part where the resin coating is peeled off and the part where the resin coating is not peeled off, the surface of the resin remaining in the boundary area between the part where the resin coating is peeled off and the part where the resin coating is not peeled off It means that the inclination angle formed with the longitudinal direction of the capillary is 70 degrees or less. The blackening of the resin is preferably caused by heating the resin with a heater or the like from the viewpoint of simplifying the manufacturing process.

本発明によるキャピラリアレイ・ユニットの製造方法は、ポリイミド樹脂で被覆した複数のキャピラリを相互に固定してキャピラリアレイとするステップと、キャピラリアレイの長手方向の一部をヒータで加熱して黒化させるステップと、黒化した長手方向の領域中の一部を更にＯ3ガスを含む反応性ガスと反応させて被覆を除去するステップとを含むことを特徴とする。 A method for manufacturing a capillary array unit according to the present invention includes a step of fixing a plurality of capillaries coated with polyimide resin to each other to form a capillary array, and heating a part of the capillary array in the longitudinal direction with a heater to blacken the capillary array unit. And a step of reacting a part of the blackened longitudinal region with a reactive gas containing O 3 gas to remove the coating.

本発明による電気泳動装置用キャピラリの製造方法は、ポリイミド樹脂で被覆したキャピラリの長手方向の一部をヒータで加熱して黒化させるステップと、黒化した長手方向の領域中の一部を更にＯ3ガスを含む反応性ガスと反応させて被覆を除去するステップとを含むことを特徴とする。 The method for manufacturing a capillary for an electrophoresis apparatus according to the present invention comprises a step of heating a part of the capillary covered with polyimide resin in the longitudinal direction with a heater to blacken, and a part of the blackened longitudinal region further Reacting with a reactive gas containing O 3 gas to remove the coating.

本発明によれば、外面発光を低減することが可能で、Ｓ/Ｎ比の向上を達成できる。   According to the present invention, it is possible to reduce outer surface light emission and achieve an improvement in the S / N ratio.

以下、図面を参照して本発明の実施の形態を説明する。図３は、本発明によるキャピラリアレイ・ユニット１６の説明図である。キャピラリアレイを構成する１本１本のキャピラリ１は、外径が０．１〜０．７ｍｍ、内径が０．０２〜０．５ｍｍで、外被はポリイミド樹脂コーテイングされている。キャピラリ自体は石英パイプであり複数本（数本から数１０本が一般的である）のキャピラリを配列してキャピラリアレイを構成する。キャピラリアレイ・ユニット１６は、蛍光標識されたＤＮＡサンプル等が入った試料容器から電気泳動でキャピラリにサンプルを取り込むロードヘッダ３１、ロードヘッダ３１のサンプル番号順にキャピラリ１を配列固定する検知部（ウインドウユニット）２９、複数本のキャピラリを束ねて接着したキャピラリヘッド３０を備える。ロードヘッダ３１から突出する試料注入端には、キャピラリに泳動電圧を印加するための中空電極３２が設けられている。検知部（ウインドウユニット）２９は、整列保持したキャピラリアレイに側方から光照射するための開口４とキャピラリから発せられた発光を取り出すための開口６とを備える。   Embodiments of the present invention will be described below with reference to the drawings. FIG. 3 is an explanatory diagram of the capillary array unit 16 according to the present invention. Each of the capillaries 1 constituting the capillary array has an outer diameter of 0.1 to 0.7 mm and an inner diameter of 0.02 to 0.5 mm, and the outer cover is coated with a polyimide resin. The capillaries themselves are quartz pipes, and a plurality of capillaries (generally several to several tens) are arranged to constitute a capillary array. The capillary array unit 16 includes a load header 31 that takes a sample into a capillary by electrophoresis from a sample container containing a fluorescently labeled DNA sample and the like, and a detection unit (window unit) that fixes the capillaries 1 in the order of the sample numbers of the load header 31 29) A capillary head 30 in which a plurality of capillaries are bundled and bonded is provided. A hollow electrode 32 for applying a migration voltage to the capillary is provided at the sample injection end protruding from the load header 31. The detection unit (window unit) 29 includes an opening 4 for irradiating light from the side to the aligned and held capillary array and an opening 6 for taking out light emitted from the capillary.

図４は、電気泳動システムを示す概略図である。図３に示したキャピラリアレイ・ユニット１６は、ロードヘッダ３１から突出した中空電極３２及びキャピラリ１の試料注入端が蛍光標識されたＤＮＡサンプルを入れた試料容器３４を複数入れたサンプルトレイに浸漬され、他端のキャピラリヘッド３０は緩衝液が入った緩衝液容器３６に耐圧気密で取り付けられる。緩衝液容器３６とロードヘッダ３１には高電圧電源１９から１５ｋＶ前後の高電圧印加され、キャピラリに注入された試料が電気泳動されて分離する。   FIG. 4 is a schematic diagram showing an electrophoresis system. In the capillary array unit 16 shown in FIG. 3, the hollow electrode 32 protruding from the load header 31 and the sample injection end of the capillary 1 are immersed in a sample tray containing a plurality of sample containers 34 containing a fluorescently labeled DNA sample. The capillary head 30 at the other end is attached to a buffer solution container 36 containing a buffer solution in a pressure-tight and air-tight manner. A high voltage of about 15 kV is applied to the buffer container 36 and the load header 31 from the high voltage power source 19, and the sample injected into the capillary is electrophoresed and separated.

レーザ光源２０は、ミラー２１、ビームスプリッタ２２、集光レンズ２３等からなる励起光学系によって検知部（ウインドウユニット）２９に励起光３３を照射する。励起光照射によってキャピラリ中を泳動している試料から発せられる信号光である蛍光３５は、第１レンズ２４、光学フィルタ及び像分割プリズム２５、及び第２レンズ２６を備える検出レンズ系を介してＣＣＤカメラ２７で検出される。検出された信号は、信号処理演算装置２８で演算処理される。   The laser light source 20 irradiates a detection unit (window unit) 29 with excitation light 33 by an excitation optical system including a mirror 21, a beam splitter 22, a condenser lens 23, and the like. Fluorescence 35, which is signal light emitted from the sample migrating in the capillary due to excitation light irradiation, is passed through the detection lens system including the first lens 24, the optical filter and image dividing prism 25, and the second lens 26. It is detected by the camera 27. The detected signal is arithmetically processed by the signal processing arithmetic unit 28.

図示の例の電気泳動システムは、電気泳動するＤＮＡや蛋白質の入ったキャピラリアレイの両側面からレーザ光を照射し、キャピラリのレンズ作用によってレーザ光を集光させることにより全てのキャピラリに励起光を照射し、各キャピラリからの蛍光を検出光学系によって検出する。   The electrophoresis system of the example shown in the figure irradiates laser light from both sides of the capillary array containing the DNA or protein to be electrophoresed, and condenses the laser light by the lens action of the capillary, so that excitation light is emitted to all capillaries. Irradiation is performed, and fluorescence from each capillary is detected by a detection optical system.

なお、レーザ光３３はキャピラリアレイの片側のみから照射させる構成でもよく、受光光学系も、図４に示す構成に限るものではない。また、キャピラリアレイを構成するキャピラリ１の本数は１６本に限るものではなく、キャピラリヘッド３０やロードヘッダ３１の構成などについても図４に示す構成に限るものではない。   The laser beam 33 may be irradiated from only one side of the capillary array, and the light receiving optical system is not limited to the configuration shown in FIG. Further, the number of capillaries 1 constituting the capillary array is not limited to 16, and the configuration of the capillary head 30 and the load header 31 is not limited to the configuration shown in FIG.

図５は、本発明によるキャピラリアレイ・ユニット１６の検知部（ウインドウユニット）２９の分解組立図である。検知部は図５に示すように、キャピラリ１、シリコン基板２、支持基板３などから構成される。シリコン基板２には、キャピラリ１の配列位置決め用としてＶ溝８が形成されている。キャピラリ１は、シリコン基板２のＶ溝８に収まるように配列され、その反対側から支持基板３により挟み込まれて固定される。   FIG. 5 is an exploded view of the detection unit (window unit) 29 of the capillary array unit 16 according to the present invention. As shown in FIG. 5, the detection unit includes a capillary 1, a silicon substrate 2, a support substrate 3, and the like. A V-groove 8 is formed in the silicon substrate 2 for positioning the capillaries 1. The capillaries 1 are arranged so as to fit in the V-grooves 8 of the silicon substrate 2 and are sandwiched and fixed by the support substrate 3 from the opposite side.

各キャピラリ１は、ポリイミド樹脂被覆が除去され溶融石英管９が露出している部分と、樹脂被覆をヒータなどにより黒色化した非反射部４２と、通常の樹脂被覆された部分１０からなる。なお、図５に示すように、キャピラリ１はシリコン基板２において貫通窓６を形成した領域のポリイミド樹脂１０が除去されているが、ポリイミド樹脂１０を除去する領域はこれに限るものではない。また、キャピラリ１の被覆材としてはポリイミド樹脂に限る必要はなく、ポリイミド樹脂と同等の電気絶縁性、およびその他諸特性をもつ材料を用いてもよい。更に、基板２としてはシリコン基板に限る必要はなく、ガラス、金属、セラミックス、樹脂などを用いても構わない。   Each capillary 1 includes a portion where the polyimide resin coating is removed and the fused quartz tube 9 is exposed, a non-reflective portion 42 in which the resin coating is blackened by a heater or the like, and a normal resin-coated portion 10. As shown in FIG. 5, in the capillary 1, the polyimide resin 10 in the region where the through window 6 is formed in the silicon substrate 2 is removed, but the region from which the polyimide resin 10 is removed is not limited to this. Further, the covering material for the capillary 1 is not limited to the polyimide resin, and a material having the same electrical insulation and other characteristics as the polyimide resin may be used. Furthermore, the substrate 2 is not limited to a silicon substrate, and glass, metal, ceramics, resin, or the like may be used.

図６、図７、図８の工程図を参照して、本発明によるキャピラリアレイ・ユニットの検知部（ウインドウユニット）の作成方法の一例について説明する。ここで説明するのは、ヒータによる加熱処理によって樹脂被覆部分と被覆除去部分との境界部分及びそれに続く所定長の樹脂被覆領域のポリイミド樹脂を黒化する方法である。   With reference to the process charts of FIGS. 6, 7, and 8, an example of a method for creating the detection unit (window unit) of the capillary array unit according to the present invention will be described. The method described here is a method of blackening the polyimide resin in the boundary portion between the resin-coated portion and the coating-removed portion and the resin-covered region having a predetermined length following the heat treatment by the heater.

まず、図６に示すように、面ヒータ４７の上にキャピラリアレイを設置し、ある一定の温度になってから一定の時間熱を加え、面ヒータ４７上に設置された領域のポリイミド樹脂１０を黒化する。もちろんこの時には一本一本のキャピラリを個別に加熱処理してもよいし、アレイ上に整列した状態で複数本のキャピラリを同時に加熱処理してもかまわない。   First, as shown in FIG. 6, a capillary array is installed on the surface heater 47, heat is applied for a certain period of time after reaching a certain temperature, and the polyimide resin 10 in the region installed on the surface heater 47 is removed. Blacken. Of course, at this time, the individual capillaries may be individually heat-treated, or a plurality of capillaries may be simultaneously heat-treated while being aligned on the array.

その後、図７に示すように、Ｏ3ガスを含む反応性ガスとの酸化反応でポリイミド樹脂被覆を除去して溶融石英管９を露出させる。Ｏ3ガスを含む反応性ガスとの酸化反応を利用した被覆除去方法によると、被覆除去部と非除去部との境界１１をなだらかにすることができ、被覆のめくれあがりなどに起因するキャピラリ配列不良をなくすることができる。且つ被覆は、露出している溶融石英管９と接する領域まで黒くすることができる。 Thereafter, as shown in FIG. 7, the polyimide resin coating is removed by an oxidation reaction with a reactive gas containing O 3 gas to expose the fused quartz tube 9. According to the coating removal method using an oxidation reaction with a reactive gas containing O 3 gas, the boundary 11 between the coating removal portion and the non-removal portion can be smoothed, and the capillary array resulting from the coating turning up or the like Defects can be eliminated. In addition, the coating can be blackened to the area in contact with the exposed fused quartz tube 9.

そのあと、図８に示すように、ガラス基板３とシリコン基板２などでキャピラリを挟み込み検知部を構成する。この石英管露出部と樹脂被覆部の境界の黒化部４２が散乱光の反射を防止し、外面発光が低減する。なお、石英管露出部と樹脂被覆部の境界の黒化は、ペンのようなもので蛍光を発生しないインクを一本一本塗布することで形成してもよい。また、キャピラリ自体に黒いキャピラリを用いることで非反射部を設けてもよい。   Thereafter, as shown in FIG. 8, the capillary is sandwiched between the glass substrate 3 and the silicon substrate 2 to constitute a detection unit. The blackened portion 42 at the boundary between the exposed portion of the quartz tube and the resin coating portion prevents reflection of scattered light, thereby reducing external light emission. Note that the blackening of the boundary between the quartz tube exposed portion and the resin coating portion may be formed by applying ink such as a pen that does not generate fluorescence one by one. Further, a non-reflective portion may be provided by using a black capillary for the capillary itself.

被覆を除去したキャピラリから外面発光が発生する様子を説明する図。The figure explaining a mode that outer surface light emission generate | occur | produces from the capillary which removed the coating | coated. 外面発光抑制手段を設けたキャピラリの説明図。Explanatory drawing of the capillary which provided the outer surface light emission suppression means. 本発明によるキャピラリアレイ・ユニットの説明図。Explanatory drawing of the capillary array unit by this invention. 電気泳動システムを示す概略図。Schematic which shows an electrophoresis system. 本発明によるキャピラリアレイ・ユニットの検知部（ウインドウユニット）の分解組立図。The exploded view of the detection part (window unit) of the capillary array unit by this invention. 本発明によるキャピラリアレイ・ユニットの検知部の作成方法を示す工程図。FIG. 5 is a process diagram illustrating a method for creating a detection unit of a capillary array unit according to the present invention. 本発明によるキャピラリアレイ・ユニットの検知部の作成方法を示す工程図。FIG. 5 is a process diagram illustrating a method for creating a detection unit of a capillary array unit according to the present invention. 本発明によるキャピラリアレイ・ユニットの検知部の作成方法を示す工程図。FIG. 5 is a process diagram illustrating a method for creating a detection unit of a capillary array unit according to the present invention.

符号の説明Explanation of symbols

１…キャピラリ、２…シリコン基板、３…ガラス基板、４…レーザ照射部、６…貫通窓、８…Ｖ溝、９…溶融石英管、１０…ポリイミド樹脂、１６…キャピラリアレイ・ユニット、１９…高電圧電源、２０…レーザ光源、２１…ミラー、２２…ビームスプリッタ、２３…集光レンズ、２４…第１レンズ、２５…光学フィルタ及び像分割プリズム、２６…第２レンズ、２７…ＣＣＤカメラ、２８…処理演算装置、２９…検知部、３０…キャピラリヘッド、３１…ロードヘッダ、３２…中空電極、３３…レーザ、３４…試料容器、３５…蛍光、３６…緩衝液溶器、３９…異物、４０…反射光、４１…散乱光、４２…非反射部、４７…面ヒータ DESCRIPTION OF SYMBOLS 1 ... Capillary, 2 ... Silicon substrate, 3 ... Glass substrate, 4 ... Laser irradiation part, 6 ... Through window, 8 ... V groove, 9 ... Fused quartz tube, 10 ... Polyimide resin, 16 ... Capillary array unit, 19 ... High voltage power source, 20 ... laser light source, 21 ... mirror, 22 ... beam splitter, 23 ... condensing lens, 24 ... first lens, 25 ... optical filter and image splitting prism, 26 ... second lens, 27 ... CCD camera, 28 ... Processing arithmetic unit, 29 ... detector, 30 ... capillary head, 31 ... load header, 32 ... hollow electrode, 33 ... laser, 34 ... sample container, 35 ... fluorescence, 36 ... buffer solution welder, 39 ... foreign matter, 40 ... reflected light, 41 ... scattered light, 42 ... non-reflective portion, 47 ... surface heater

Claims (6)

複数のキャピラリと、励起光が照射される前記複数のキャピラリを長さ方向の途中で整列保持する検知部とを含むキャピラリアレイ・ユニットであって、
前記複数のキャピラリは外周に樹脂被膜が施され、前記検知部に整列保持された部分で所定長さだけ前記樹脂被膜が剥がされ、前記樹脂被膜が剥がされた部分と剥がされない部分との境界領域に残っている樹脂及び前記境界領域に続く所定長さの樹脂被膜が黒化し、前記被膜樹脂の黒化は、蛍光を発しないインクを塗布することにより形成されたものであるキャピラリアレイ・ユニット。 A capillary array unit including a plurality of capillaries and a detection unit that holds the plurality of capillaries irradiated with excitation light in the middle of the length direction,
The plurality of capillaries are provided with a resin coating on the outer periphery, and the resin coating is peeled off by a predetermined length at a portion aligned and held by the detection unit, and a boundary region between a portion where the resin coating is peeled off and a portion where the resin coating is not peeled off And the resin coating of a predetermined length following the boundary region is blackened, and the blackening of the coating resin is formed by applying an ink that does not emit fluorescence. 石英管を樹脂により被覆し、石英管が剥き出しとなっている部分を含むキャピラリを含み、該石英管が剥き出しの部分にレーザ光が照射されるキャピラリアレイ・ユニットであって、
被膜が除去されている部分と被膜が除去されていない部分との境界部分の樹脂が、蛍光を発しないインクを塗布することにより黒化されているキャピラリアレイ・ユニット。 A capillary array unit in which a quartz tube is coated with a resin and includes a capillary including a portion where the quartz tube is exposed, and the portion where the quartz tube is exposed is irradiated with laser light,
A capillary array unit in which the resin at the boundary between the part from which the film has been removed and the part from which the film has not been removed is blackened by applying ink that does not emit fluorescence. 請求項２記載のキャピラリアレイ・ユニットであって、前記樹脂が、ポリイミド樹脂であるキャピラリアレイ・ユニット。   3. The capillary array unit according to claim 2, wherein the resin is a polyimide resin. 複数のキャピラリと、前記複数のキャピラリを長さ方向の途中で整列保持する検知部とを含むキャピラリアレイ・ユニットと、
前記キャピラリに注入された試料を電気泳動して分離する高電圧電源と、
前記検知部に励起光を照射する励起光学系と、
励起光照射によって前記キャピラリ中を泳動している試料から発せられる信号光を検出する受光光学系とを含むキャピラリアレイ電気泳動装置であって、
前記複数のキャピラリは外周に樹脂被膜が施され、前記検知部に整列保持された部分で所定長さだけ前記樹脂被膜が剥がされ、前記樹脂被膜が剥がされた部分と剥がされない部分との境界領域に残っている樹脂及び前記境界領域に続く所定長さの樹脂被膜が黒化し、前記被膜樹脂の黒化が、蛍光を発しないインクを塗布することにより形成されたものであるキャピラリアレイ電気泳動装置。 A capillary array unit including a plurality of capillaries and a detection unit that holds the plurality of capillaries aligned in the middle of the length direction;
A high voltage power source for electrophoresis and separation of the sample injected into the capillary;
An excitation optical system for irradiating the detection unit with excitation light;
A capillary array electrophoresis apparatus including a light receiving optical system that detects signal light emitted from a sample that is migrating in the capillary by irradiation with excitation light,
The plurality of capillaries are provided with a resin film on the outer periphery, and the resin film is peeled off by a predetermined length at a portion aligned and held by the detection unit, and a boundary region between a part where the resin film is peeled off and a part where the resin film is not peeled off A capillary array electrophoresis apparatus in which the resin remaining in the resin and the resin film of a predetermined length following the boundary region are blackened, and the blackening of the resin is formed by applying an ink that does not emit fluorescence . 石英管を樹脂により被覆し、該石英管が剥き出しとなっている部分を含むキャピラリと、
前記キャピラリに注入された試料を電気泳動して分離する高電圧電源と、
前記石英管が剥き出しの部分にレーザ光を照射する励起光学系と、
レーザ光の照射によって前記キャピラリ中を泳動している試料から発せられる蛍光を検出する受光光学系とを含むキャピラリアレイ電気泳動装置であって、
被膜が除去されている部分と被膜が除去されていない部分との境界部分の樹脂が、蛍光を発しないインクを塗布することにより黒化されている電気泳動装置。 A quartz tube covered with a resin, and a capillary including a portion where the quartz tube is exposed;
A high voltage power source for electrophoresis to separate the sample injected into the capillary;
An excitation optical system for irradiating the exposed portion of the quartz tube with laser light; and
A capillary array electrophoresis apparatus including a light receiving optical system that detects fluorescence emitted from a sample migrating in the capillary by laser light irradiation,
An electrophoretic device in which a resin at a boundary between a portion where a film is removed and a portion where a film is not removed is blackened by applying an ink that does not emit fluorescence. 請求項５記載の電気泳動装置であって、前記樹脂が、ポリイミド樹脂である電気泳動装置。   6. The electrophoresis apparatus according to claim 5, wherein the resin is a polyimide resin.
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