JP2005257283A - Microchip - Google Patents

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JP2005257283A
JP2005257283A JP2004065062A JP2004065062A JP2005257283A JP 2005257283 A JP2005257283 A JP 2005257283A JP 2004065062 A JP2004065062 A JP 2004065062A JP 2004065062 A JP2004065062 A JP 2004065062A JP 2005257283 A JP2005257283 A JP 2005257283A
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substrate
pdms
silicon oxide
oxide film
microchip
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Kimiya Takasugi
公哉 高杉
Toshio Yoshida
敏雄 吉田
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FLUIDWARE TECHNOLOGIES KK
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a microchip capable making it permanently bond to a polydimenthylsiloxane (PDMS) substrate, even if synthetic resin substrate is used, as a counter substrate in place of glass substrate. <P>SOLUTION: In the microchip composed of the PDMS substrate, having at least fine flow channel formed thereto and the counter substrate bonded to the fine flow channel forming surface of the PDMS substrate, the counter substrate is formed of synthetic resin other than PDMS, and a silicon oxide film is formed on the laminating surface of the counter substrate. The counter substrate is bonded to the PDMS substrate via the silicon oxide film. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

本発明はポリジメチルシロキサン(PDMS)とその他の合成樹脂基板とからなるマイクロチップ及び該マイクロチップの製造方法に関する。   The present invention relates to a microchip comprising polydimethylsiloxane (PDMS) and another synthetic resin substrate, and a method for producing the microchip.

最近、マイクロスケール・トータル・アナリシス・システムズ(μTAS)又はラブ・オン・チップ(Lab-on-Chip)などの名称で知られるように、基板内にマイクロチャネルや反応容器及びポートなどの微細構造を設け、該微細構造内で物質の化学反応、合成、精製、抽出、生成及び/又は分析など各種の操作を行うように構成されたマイクロデバイスが提案され、一部実用化されている。このような目的のために製作された、基板内にマイクロチャネル、ポート及び反応容器などの微細構造を有する構造物は総称して「マイクロチップ」又は「マイクロ流体デバイス」と呼ばれる。マイクロチップは遺伝子解析、臨床診断、薬物スクリーニングなどの化学、生化学、薬学、医学、獣医学分野のみならず、化学工業、環境計測などの幅広い用途に使用できる。常用サイズの同種の装置に比べて、マイクロチップは(1)サンプル及び試薬の使用量が著しく少ない、(2)分析時間が短い、(3)感度が高い、(4)現場に携帯し、その場で分析できる、及び(5)使い捨てできるなどの利点を有する。   Microstructures such as microchannels, reaction vessels, and ports have been built into the substrate as is known recently under the name of Microscale Total Analysis Systems (μTAS) or Lab-on-Chip (Lab-on-Chip). A microdevice configured to perform various operations such as chemical reaction, synthesis, purification, extraction, generation and / or analysis of a substance within the microstructure has been proposed and partially put into practical use. Structures manufactured for this purpose and having a microstructure such as microchannels, ports and reaction vessels in the substrate are collectively referred to as “microchips” or “microfluidic devices”. Microchips can be used in a wide range of applications such as chemical industry and environmental measurement as well as chemical, biochemical, pharmaceutical, medical, and veterinary fields such as gene analysis, clinical diagnosis, and drug screening. Compared with the same type of equipment of the common size, the microchip is (1) significantly less sample and reagent usage, (2) shorter analysis time, (3) higher sensitivity, (4) carried on-site, It can be analyzed in the field and (5) can be disposable.

従来のマイクロチップ100は、例えば、図7A及びBに示されるように、第1の基板101に少なくとも1本のマイクロチャネル102が形成されており、このマイクロチャネル102の少なくとも一端には入出力ポート103,104が形成されており、基板101の下面側に対面基板105が接着されている。この対面基板105の存在により、ポート103,104及びマイクロチャネル102の底部が封止される。入出力ポート103,104の主な用途は、(a)試薬や検体サンプルの注入(分注)、(b)廃液や生成物の取り出し、(c)気体圧力の供給(主に、送液のための正圧や負圧の印加)、(d)大気開放(送液時に発生する内圧の分散や、反応で生じたガスの解放)及び(e)密閉(液体の蒸発防止や故意に内圧を発生させる目的のため)などである。   In the conventional microchip 100, for example, as shown in FIGS. 7A and 7B, at least one microchannel 102 is formed on a first substrate 101, and an input / output port is provided on at least one end of the microchannel 102. 103 and 104 are formed, and the facing substrate 105 is bonded to the lower surface side of the substrate 101. Due to the presence of the facing substrate 105, the ports 103 and 104 and the bottom of the microchannel 102 are sealed. The main uses of the input / output ports 103 and 104 are (a) injection of reagents and specimen samples (dispensing), (b) removal of waste liquid and products, and (c) supply of gas pressure (mainly for liquid feeding (D) Release to the atmosphere (dispersion of internal pressure generated during liquid delivery, release of gas generated by reaction) and (e) Sealing (preventing liquid evaporation and deliberately reducing internal pressure) For the purpose of generating).

マイクロチップの材質や構造及び製造方法は例えば、特許文献1及び特許文献2などに開示されている。その中で、第1の基板の形成用素材としてエラストマータイプのシリコン樹脂であるポリジメチルシロキサン(PDMS)を用いたことを特徴とする一連のマイクロチップが開発されている。PDMSはチャネルなどの微細構造を有するマスター(鋳型)に対する良好なモールド転写性や透明性、耐薬品生、生体適合性などを有し、マイクロチップの構成部材として特に優れた特徴を有している。   The material, structure, and manufacturing method of the microchip are disclosed in, for example, Patent Document 1 and Patent Document 2. Among them, a series of microchips characterized by using polydimethylsiloxane (PDMS), which is an elastomer type silicon resin, as a material for forming the first substrate has been developed. PDMS has excellent mold transferability and transparency, chemical resistance, biocompatibility, etc. for a master (mold) having a fine structure such as a channel, and has particularly excellent characteristics as a component of a microchip. .

PDMS製マイクロチップの製造上の更なる利点は、PDMS基板と対面基板との貼り合わせに、いわゆる恒久接着(パーマネント・ボンディング)が利用できることである。第1の基板と対面基板との貼り合わせにおいては、チャネルなどの微細構造を損なうことなく、かつ、微細構造を良好に封止しなければならない。従って、一般的な接着剤を用いた貼り合わせは行うことができない。PDMS基板の恒久接着では、貼り合わせ面を適宜酸素プラズマなどによる表面改質処理した後、両方の基板の貼り合わせ面を密着して重ね合わせ、一定時間放置することで、容易に接着が行えるものである。   A further advantage in the manufacture of PDMS microchips is that so-called permanent bonding can be used for bonding the PDMS substrate and the facing substrate. In bonding the first substrate and the facing substrate, the fine structure must be well sealed without damaging the fine structure such as a channel. Therefore, it is not possible to perform bonding using a general adhesive. In permanent bonding of PDMS substrates, the bonding surfaces can be easily bonded by subjecting the bonding surfaces to appropriate surface modification treatment using oxygen plasma, etc., and then bonding and bonding the bonding surfaces of both substrates and leaving them to stand for a certain period of time. It is.

従来、PDMS基板と恒久接着するものは、PDMS基板同士かガラス基板だけであった。対面基板としてPDMS基板を恒久接着させても、機械的強度が弱いために、取り扱いに問題があった。また、PDMSは比較的高価であり、対面基板の材料としてPDMSを使用すると、マイクロチップ全体のコストアップを招くこととなる。一方、ガラス基板は機械的強度が高いので、取り扱い性の点では問題が無かった。しかし、ガラスからなる対面基板を有するPDMS製マイクロチップは次のような問題点を有している。(1)使用済みマイクロチップの廃棄を行う際、恒久接着したガラス基板からPDMS基板を引き剥がすことは非常に困難であり、各基板の分別廃棄が困難である;(2)ガラス基板は検出器などの装置に設置する場合、位置決め部分との接触が何度も起こると割れる恐れがあり、割れたガラスは鋭利な刃物と同様で、人体に怪我を及ぼし易い。従って、ガラス基板を恒久接着したマイクロチップは、取り扱いに十分な注意が必要である;(3)ガラスを厚くするため、石英ガラスなどのマイクロチップを搭載することは困難であった。なぜなら、一般市場で使用されている石英ガラス等のチップの流路を形成するシート厚は、50μm〜100μmで、この厚さをベースに検出器の光軸を設定しているのが一般的であるためである;(4)ガラス基板への機械加工が困難で高価である。PDMS基板の他に、対面基板としてのガラス基板へもチップ方向を示したり、装置への誤挿入防止のためのオリエンテーション・フラットとしての切り欠きやノッチ、装置内への装着時の位置決め用スプロケットホールやピン・突起、光学読取位置基準マーク、ハンドリング用ノブ、製品番号や型式の刻印、検査情報などを記録保存したICタグの埋め込みなど、各種の要件を盛り込む必要性が出てくる。このような観点から考察すると、ドリル穴加工や切削加工などの機械加工が行い難いガラスは必ずしも好ましい材料であるとは言えない。(5)ガラスは一般的に量産性が無い。ガラスは一部に低融点でモールド成形が行えるものが出てきたが、量産性や製造コスト面では合成樹脂の射出成形などと比較すると著しく見劣りがする;(6)ガラス基板は一般的に材料費が高い。ガラスは原料単価が高いばかりか、板材としての単価も高い;(7)ガラス基板は重量が重い。PDMS基板の比重は水とほぼ同等であるのに対し、ガラス基板はその2倍以上である。マイクロチップを一枚一枚扱う場合に、その重さは問題とはならないが、量産して大量に保存・輸送する場合には相当な重量となる。   Conventionally, the only thing permanently bonded to the PDMS substrate is between the PDMS substrates or the glass substrate. Even if a PDMS substrate is permanently bonded as a facing substrate, there is a problem in handling due to weak mechanical strength. Also, PDMS is relatively expensive. If PDMS is used as a material for the facing substrate, the cost of the entire microchip is increased. On the other hand, since the glass substrate has high mechanical strength, there was no problem in terms of handling. However, a PDMS microchip having a facing substrate made of glass has the following problems. (1) When disposing of used microchips, it is very difficult to peel off the PDMS substrate from the permanently bonded glass substrate, and it is difficult to dispose of each substrate separately; (2) The glass substrate is a detector When it is installed in a device such as the above, there is a risk of breaking if contact with the positioning portion occurs many times, and the broken glass is similar to a sharp blade, and easily injures the human body. Therefore, a microchip with a glass substrate permanently bonded needs to be handled with care; (3) it is difficult to mount a microchip such as quartz glass in order to increase the thickness of the glass. This is because the thickness of the sheet forming the flow path of the quartz glass or the like used in the general market is 50 μm to 100 μm, and the optical axis of the detector is generally set based on this thickness. (4) It is difficult and expensive to machine into a glass substrate. In addition to the PDMS substrate, the glass substrate as the facing substrate also indicates the chip direction, the notch or notch as an orientation flat to prevent erroneous insertion into the device, and a sprocket hole for positioning when mounted in the device There is a need to incorporate various requirements such as embedment of IC tags that record and store information such as pins, protrusions, optical reading position reference marks, handling knobs, product numbers and model markings, and inspection information. From this point of view, glass that is difficult to perform machining such as drilling and cutting is not necessarily a preferable material. (5) Glass is generally not mass-productive. Some glass can be molded with a low melting point, but it is significantly inferior to synthetic resin injection molding in terms of mass productivity and manufacturing cost; (6) Glass substrates are generally materials Expensive. Glass is not only expensive, but also expensive as a plate; (7) Glass substrates are heavy. The specific gravity of the PDMS substrate is almost the same as that of water, whereas the glass substrate is more than twice that of water. When handling microchips one by one, the weight is not a problem, but when mass-producing and storing and transporting in large quantities, it becomes a considerable weight.

このため、PDMS基板からなるマイクロチップの対面基板としてガラスに代えて、合成樹脂製の基板の使用が試みられた。しかし、PDMS基板と合成樹脂基板は恒久接着させることが困難である。貼り合わせ面を表面改質処理してからPDMS基板と合成樹脂基板を貼り合わせると一時的に接着させることはできるが、数時間経過後には剥がれてしまい、実用にはならなかった。また、合成樹脂基板はガラス基板に比べて表面改質処理に対する耐性が低く、恒久接着のために必要な表面改質処理を好適に行うことができないなどの問題点も存在する。PDMS基板と合成樹脂基板との界面に接着剤を介在させれば、両基板を強固に接着させることはできるが、使用した接着剤が微細流路などを閉塞したり、試薬やサンプルなどにも悪影響を及ぼすことがあった。   For this reason, it has been attempted to use a synthetic resin substrate instead of glass as the facing substrate of the microchip made of the PDMS substrate. However, it is difficult to permanently bond the PDMS substrate and the synthetic resin substrate. When the PDMS substrate and the synthetic resin substrate are bonded together after the surface to be bonded is surface-modified, they can be temporarily bonded to each other, but they are peeled off after a few hours and have not become practical. In addition, the synthetic resin substrate has a lower resistance to the surface modification treatment than the glass substrate, and there is a problem that the surface modification treatment necessary for permanent adhesion cannot be suitably performed. If an adhesive is interposed at the interface between the PDMS substrate and the synthetic resin substrate, the two substrates can be firmly bonded. However, the used adhesive can block the fine flow path, and can also be used for reagents and samples. There was an adverse effect.

特開2000−27813号公報JP 2000-27813 A 特開2001−157855号公報JP 2001-157855 A

従って、本発明の目的はガラス基板に代えて、合成樹脂基板を対面基板として使用してもPDMS基板と恒久接着させることができるマイクロチップを提供することである。   Accordingly, an object of the present invention is to provide a microchip that can be permanently bonded to a PDMS substrate even when a synthetic resin substrate is used as a facing substrate instead of a glass substrate.

前記課題を解決するための手段は、第1に、少なくとも微細流路が形成されたポリジメチルシロキサン(PDMS)基板と、該PDMS基板の微細流路形成面に接着された対面基板とからなるマイクロチップにおいて、前記対面基板がPDMS以外の合成樹脂から形成されており、前記対面基板の貼り合わせ面には酸化シリコン膜が成膜されており、該対面基板が酸化シリコン膜を介して前記PDMS基板と接着されていることを特徴とするマイクロチップである。
前記課題を解決するための手段は、第2に、前記対面基板がポリカーボネート(PC)、ポリメチルメタクリレート(PMMA)、ポリエチレンテレフタレート(PET)、ポリスチレン(PS)、ポリエチレン(PS)及びポリアクリロニトリル(PAN)からなる群から選択される材料から形成されており、前記酸化シリコン膜の膜厚が1nm〜100nmの範囲内であることを特徴とする前記第1のマイクロチップである。
前記課題を解決するための手段は、第3に、前記対面基板がポリカーボネート(PC)又はポリメチルメタクリレート(PMMA)から形成されており、前記酸化シリコン膜の膜厚が10nm〜40nmの範囲内であることを特徴とする前記第2ののマイクロチップである。
前記課題を解決するための手段は、第4に、少なくとも微細流路が形成されたポリジメチルシロキサン(PDMS)基板と、該PDMS基板の微細流路形成面に接着された対面基板とからなるマイクロチップの製造方法において、
(a)PDMS以外の合成樹脂から形成された対面基板の一方の表面に酸化シリコン膜を成膜するステップと、
(b)少なくとも微細流路が形成されたPDMS基板を準備するステップと、
(c)前記酸化シリコン膜付き対面基板とPDMS基板の各貼り合わせ面を表面改質処理するステップと、
(d)表面改質処理された酸化シリコン膜付き対面基板を、該酸化シリコン膜を介して、表面改質処理されたPDMS基板の微細流路形成面に接着させるステップとからなることを特徴とするマイクロチップの製造方法である。
前記課題を解決するための手段は、第5に、前記対面基板がポリカーボネート(PC)、ポリメチルメタクリレート(PMMA)、ポリエチレンテレフタレート(PET)、ポリスチレン(PS)、ポリエチレン(PS)及びポリアクリロニトリル(PAN)からなる群から選択される材料から形成されており、前記酸化シリコン膜はスパッタ法により、1nm〜100nmの範囲内の膜厚に成膜されることを特徴とする前記第4のマイクロチップの製造方法である。
Means for solving the above-mentioned problem is as follows. First, a micro-layer comprising a polydimethylsiloxane (PDMS) substrate having at least a fine channel formed thereon, and a facing substrate bonded to the fine channel forming surface of the PDMS substrate. In the chip, the facing substrate is formed of a synthetic resin other than PDMS, a silicon oxide film is formed on a bonding surface of the facing substrate, and the facing substrate is interposed between the PDMS substrate and the silicon oxide film. It is a microchip characterized by being bonded.
Secondly, the means for solving the problem is that the facing substrate is polycarbonate (PC), polymethyl methacrylate (PMMA), polyethylene terephthalate (PET), polystyrene (PS), polyethylene (PS) and polyacrylonitrile (PAN). The first microchip is characterized in that the silicon oxide film has a thickness in the range of 1 nm to 100 nm.
Thirdly, the means for solving the problem is that the facing substrate is made of polycarbonate (PC) or polymethyl methacrylate (PMMA), and the thickness of the silicon oxide film is within a range of 10 nm to 40 nm. The second microchip is characterized in that the second microchip is provided.
Fourth, the means for solving the above-mentioned problem is a micro-structure comprising at least a polydimethylsiloxane (PDMS) substrate on which a fine channel is formed, and a facing substrate bonded to the fine channel forming surface of the PDMS substrate. In the chip manufacturing method,
(a) depositing a silicon oxide film on one surface of a facing substrate formed from a synthetic resin other than PDMS;
(b) preparing a PDMS substrate having at least a fine channel formed thereon;
(c) surface modification treatment of each bonding surface of the facing substrate with the silicon oxide film and the PDMS substrate;
(d) the step of adhering the surface-modified surface-facing substrate with the silicon oxide film to the surface of the surface-modified PDMS substrate on which the microchannel is formed through the silicon oxide film. This is a method for manufacturing a microchip.
Fifth, the means for solving the above-mentioned problem is that the facing substrate is polycarbonate (PC), polymethyl methacrylate (PMMA), polyethylene terephthalate (PET), polystyrene (PS), polyethylene (PS) and polyacrylonitrile (PAN). And the silicon oxide film is formed to a thickness in the range of 1 nm to 100 nm by a sputtering method. It is a manufacturing method.

本発明のマイクロチップによれば、酸化シリコン膜を介して合成樹脂製対面基板とPDMS基板を貼り合わせると、両基板を恒久接着させることができる。これにより、従来のガラス製対面基板を使用することに伴う前記(1)〜(7)の欠点は全て解消される。   According to the microchip of the present invention, when the synthetic resin facing substrate and the PDMS substrate are bonded together via the silicon oxide film, the two substrates can be permanently bonded. As a result, all the disadvantages (1) to (7) associated with the use of the conventional glass facing substrate are eliminated.

以下、図面を参照しながら本発明の好ましい実施態様について具体的に説明する。図1は本発明によるマイクロチップ1の一例の概要断面図である。本発明のマイクロチップ1におけるPDMS基板3には微細流路5とこの微細流路に連通し、かつ、大気に開放したポート7及び9が形成されている。このような微細流路及びポートの形成方法自体は前記特許文献1及び特許文献2などに記載されており、これ以上の説明は特に必要ないであろう。また、言うまでもなく、PDMS基板3には図示された微細流路5及びポート7,9の他に、必要に応じて、反応容器、逆止弁、マイクロポンプなど種々の構成要素を形成することができる。また、PDMS基板3は図示された単層に限らず、2枚以上を積層させた多層構造のPDMS基板も使用できる。   Hereinafter, preferred embodiments of the present invention will be specifically described with reference to the drawings. FIG. 1 is a schematic sectional view of an example of a microchip 1 according to the present invention. The PDMS substrate 3 in the microchip 1 of the present invention is formed with a fine channel 5 and ports 7 and 9 communicating with the fine channel and open to the atmosphere. The method of forming such a fine flow path and port itself is described in Patent Document 1 and Patent Document 2, etc., and no further explanation is necessary. Needless to say, various components such as a reaction vessel, a check valve, and a micropump may be formed on the PDMS substrate 3 as necessary in addition to the illustrated fine channel 5 and ports 7 and 9. it can. Further, the PDMS substrate 3 is not limited to the illustrated single layer, and a PDMS substrate having a multilayer structure in which two or more layers are laminated can also be used.

本発明によるマイクロチップ1では対面基板11として、合成樹脂製基板を使用する。この合成樹脂製対面基板11は透明であることが好ましい。PDMS基板は透明であり、対面基板が透明であれば、光学的検出装置などを使用することが可能になる。しかし、場合により不透明な対面基板を使用することもできる。このような対面基板形成用の合成樹脂としては、ポリカーボネート(PC)、ポリメチルメタクリレート(PMMA)、ポリエチレンテレフタレート(PET)、ポリスチレン(PS)、ポリエチレン(PS)、ポリアクリロニトリル(PAN)などが好適に使用される。これらの合成樹脂はフィルム状〜シート状の何れの形態でも使用できる。例えば、合成樹脂製対面基板11は50μm程度の厚さを有するフィルムから厚さ100μm〜1mm程度のシートであることができる。   In the microchip 1 according to the present invention, a synthetic resin substrate is used as the facing substrate 11. The synthetic resin facing substrate 11 is preferably transparent. If the PDMS substrate is transparent and the facing substrate is transparent, an optical detection device or the like can be used. However, in some cases, an opaque facing substrate can be used. As such a synthetic resin for forming the facing substrate, polycarbonate (PC), polymethyl methacrylate (PMMA), polyethylene terephthalate (PET), polystyrene (PS), polyethylene (PS), polyacrylonitrile (PAN) and the like are preferable. used. These synthetic resins can be used in any form of film to sheet. For example, the synthetic resin facing substrate 11 may be a sheet having a thickness of about 100 μm to 1 mm from a film having a thickness of about 50 μm.

本発明によるマイクロチップ1の最大の特徴は、PDMS基板3と合成樹脂製対面基板11との界面に酸化シリコン(SiO)膜13が存在することである。この酸化シリコン膜13は合成樹脂製対面基板11の貼り合わせ面側に形成される。酸化シリコン膜13は常用の真空蒸着法,イオンプレーテイング法,スパッタ法,常圧CVD法、減圧CVD法及びプラズマCVD法等の気相成長法により形成することができる。スパッタ法は膜厚均一性が優れており、基板温度が上がらないこと、ターゲットの組成通りの蒸着膜が得られるなどの利点があるので、合成樹脂基板への酸化シリコン膜はスパッタ法で成膜することが好ましい。このような気相成長法自体は当業者に周知であり、特に説明する必要はないであろう。 The greatest feature of the microchip 1 according to the present invention is that a silicon oxide (SiO 2 ) film 13 exists at the interface between the PDMS substrate 3 and the synthetic resin facing substrate 11. This silicon oxide film 13 is formed on the bonding surface side of the synthetic resin facing substrate 11. The silicon oxide film 13 can be formed by a vapor deposition method such as a conventional vacuum deposition method, an ion plating method, a sputtering method, an atmospheric pressure CVD method, a low pressure CVD method, and a plasma CVD method. The sputtering method has excellent film thickness uniformity, and there are advantages such as that the substrate temperature does not increase and a vapor deposition film according to the composition of the target can be obtained. Therefore, the silicon oxide film on the synthetic resin substrate is formed by the sputtering method. It is preferable to do. Such a vapor deposition method itself is well known to those skilled in the art and need not be described in particular.

この酸化シリコン膜13の膜厚は一般的に、1nm〜100nmの範囲内である。酸化シリコン膜13の膜厚が1nm未満では均一な厚さの酸化シリコン膜を形成するのが非常に困難となるばかりか、PDMS基板3と合成樹脂製対面基板11とを恒久接着させる効果が不十分となる。一方、酸化シリコン膜13の膜厚が100nm超になると、PDMS基板3と合成樹脂製対面基板11とを恒久接着させる効果が飽和し、成膜コストが上がるだけで不経済となるばかりか、光透過性に悪影響を及ぼすので好ましくない。酸化シリコン膜の膜厚は10nm〜40nmの範囲内であることが一層好ましい。この範囲内の膜厚であれば、PDMS基板3と合成樹脂製対面基板11とを恒久接着させるのに十分であるばかり、光透過性にも殆ど悪影響を及ぼさない。   The thickness of the silicon oxide film 13 is generally in the range of 1 nm to 100 nm. If the thickness of the silicon oxide film 13 is less than 1 nm, it becomes very difficult to form a silicon oxide film having a uniform thickness, and the effect of permanently bonding the PDMS substrate 3 and the synthetic resin facing substrate 11 is ineffective. It will be enough. On the other hand, when the film thickness of the silicon oxide film 13 exceeds 100 nm, the effect of permanently bonding the PDMS substrate 3 and the synthetic resin facing substrate 11 is saturated, and not only the film formation cost increases, but also it becomes uneconomical. This is undesirable because it adversely affects permeability. The thickness of the silicon oxide film is more preferably in the range of 10 nm to 40 nm. A film thickness within this range is sufficient to permanently bond the PDMS substrate 3 and the synthetic resin facing substrate 11 and has almost no adverse effect on light transmission.

合成樹脂製対面基板を酸化シリコン膜を介してPDMS基板と接合させると、従来のガラス基板と同等な恒久接着が得られることが発見され、本発明はこの知見に基づき完成された。しかし、酸化シリコン膜を介してPDMS基板と合成樹脂製対面基板を接合させると恒久接着が得られる正確なメカニズムは未だ解明されていない。想像の範囲内であるが、酸化シリコン膜のシリコン原子とPDMS基板のシリコン原子との間で何らかの結合が生成されるために恒久接着するものと思われる。   When a synthetic resin facing substrate was bonded to a PDMS substrate via a silicon oxide film, it was discovered that permanent adhesion equivalent to that of a conventional glass substrate was obtained, and the present invention was completed based on this finding. However, the exact mechanism by which the permanent adhesion is obtained when the PDMS substrate and the synthetic resin facing substrate are bonded via the silicon oxide film has not yet been elucidated. Although it is within the range of imagination, it is considered that a certain bond is generated between the silicon atom of the silicon oxide film and the silicon atom of the PDMS substrate, so that the permanent adhesion occurs.

次に、本発明のマイクロチップ1の製造方法について説明する。先ず、合成樹脂製対面基板11を準備し、この基板の酸化シリコン膜成膜面を必要に応じて清浄にするための処理を行う。その後、この基板11を気相成長装置(例えば、スパッタ装置)内に入れ、清浄面上に酸化シリコン膜を所定の膜厚になるまで成長させ、気相成長装置から取り出す。次いで、予め微細流路5やポート7,9などが形成されたPDMS基板3と酸化シリコン膜が成膜された合成樹脂製対面基板11とをプラズマ装置内に入れ、酸素プラズマで表面処理する。表面改質処理は酸素雰囲気下でエキシマUV光を照射することにより行うこともできる。PDMSなどの基板表面の酸素プラズマ又はエキシマUV光による表面改質処理法の具体的内容は当業者に公知である。例えば、反応性イオンエッチング(RIE)装置による酸素プラズマ処理を例にとると、PDMS基板及び合成樹脂対面基板に対して、酸素雰囲気下において、数十W程度の出力で、数秒未満のプラズマ発生時間で処理すると好適な改質表面が得られる。処理後、PDMS基板3と合成樹脂製対面基板11を取り出し、PDMS基板3の微細流路形成面側と合成樹脂製対面基板11の酸化シリコン膜成膜面側とを接合させる。この際、注意すべきことは、PDMS基板3の微細流路形成面及び合成樹脂製対面基板11の酸化シリコン膜成膜面を絶対に擦らないことである。擦ると、表面に擦過傷が入り、恒久接着に悪影響が出る危険がある。また、両基板を接合させる際、必要に応じて加圧することもできる。   Next, the manufacturing method of the microchip 1 of this invention is demonstrated. First, a synthetic resin facing substrate 11 is prepared, and a process for cleaning the silicon oxide film forming surface of the substrate is performed as necessary. Thereafter, the substrate 11 is placed in a vapor phase growth apparatus (for example, a sputtering apparatus), and a silicon oxide film is grown on the clean surface to a predetermined thickness, and is taken out from the vapor phase growth apparatus. Next, the PDMS substrate 3 on which the fine flow path 5 and the ports 7 and 9 are formed in advance and the synthetic resin facing substrate 11 on which the silicon oxide film is formed are placed in a plasma apparatus and surface-treated with oxygen plasma. The surface modification treatment can also be performed by irradiating excimer UV light in an oxygen atmosphere. The specific contents of the surface modification treatment method using oxygen plasma or excimer UV light on the substrate surface such as PDMS are known to those skilled in the art. For example, taking an oxygen plasma treatment by a reactive ion etching (RIE) apparatus as an example, a plasma generation time of less than a few seconds with an output of about several tens W in an oxygen atmosphere with respect to a PDMS substrate and a synthetic resin facing substrate. To obtain a suitable modified surface. After the treatment, the PDMS substrate 3 and the synthetic resin facing substrate 11 are taken out, and the fine flow path forming surface side of the PDMS substrate 3 and the silicon oxide film forming surface side of the synthetic resin facing substrate 11 are bonded. At this time, it should be noted that the fine flow path forming surface of the PDMS substrate 3 and the silicon oxide film forming surface of the synthetic resin facing substrate 11 are never rubbed. Rubbing can cause scratches on the surface and adversely affect permanent adhesion. Moreover, when joining both board | substrates, it can also pressurize as needed.

(1)PDMS基板の作製
先ず、上面に微細流路などの原型となる微細構造を有するマスター(鋳型)を準備した。このような鋳型自体は公知慣用の光リソグラフィー技術により作製することができる。次いで、このマスターの上面をフルオロカーボン(CHF)の存在下で反応性イオンエッチング装置により処理し、離型膜を形成させた。この離型膜は後の工程でPDMS基板をマスターから剥離し易くするために必要である。離型膜形成後、このマスターの上面にPDMSプレポリマーと硬化剤を10:1の割合で混合し、脱気したPDMSプレポリマー混合液(米国のダウ・コーニング社製のSYLGARD 184 SILICONE ELASTOMER)をスピンコート法により塗布した。このマスターをオーブン中で65℃で4時間加熱し、塗布されたPDMSプレポリマー混合液を硬化させた。オーブンから取り出し、常温に戻るまで放置した後、硬化したPDMS基板をマスターから剥離した。厚さ1mmのPDMS基板が得られた。得られたPDMS基板について更に外形トリミング及び入出力ポートとなる穴開け加工を施して3cm×4cmのサイズのPDMS基板を作製した。
(2)対面基板の作製
厚さ1mmで5cm×6cmのサイズのポリカーボネート(PC)基板を準備した。このPC基板の表面に、スパッタ装置(徳田製作所(株)製CFS・12P・100)を用いて厚さ20nmの酸化シリコン膜を成膜させた。成膜条件は、到達圧力:7×10−4Pa、逆スパッタ(PC基板表面清浄化処理):300W/5分間(100%O使用)、ターゲット:SiO、雰囲気ガス:Ar30SCCM、圧力:0.2Pa、電力:RF1kW、プレスパッタ(シャッターを閉じた状態でスパッタを行い装置を安定化させる):5分間、スパッタ時間(シャッター開放時間):3分30秒間であった。
(3)表面改質処理
得られたPDMS基板と酸化シリコン膜付きPC基板を反応性イオンエッチング装置(サムコインターナショナル製コンパクトエッチャーモデルFA−1)内で酸素プラズマにより各貼り合わせ面の表面改質処理を行った。表面改質処理条件は酸素ガス流量26SCCM、チャンバー内圧力20Pa、RF出力25W、プラズマ発生時間0.8秒〜1秒間であった。
(4)貼り合わせ
PDMS基板と酸化シリコン膜付きPC基板を、反応性イオンエッチング装置から取り出し、PDMS基板の微細流路形成面と、PC基板の酸化シリコン膜面とを貼り合わせマイクロチップを完成させた。
(1) Production of PDMS substrate First, a master (mold) having a fine structure serving as a prototype such as a fine channel on the upper surface was prepared. Such a mold itself can be produced by a known and commonly used photolithography technique. Next, the upper surface of this master was treated with a reactive ion etching apparatus in the presence of fluorocarbon (CHF 3 ) to form a release film. This release film is necessary for facilitating peeling of the PDMS substrate from the master in a later step. After the release film is formed, PDMS prepolymer and curing agent are mixed at a ratio of 10: 1 on the upper surface of this master, and a degassed PDMS prepolymer mixture (SYLGARD 184 SILICONE ELASTOMER manufactured by Dow Corning, USA) The coating was performed by a spin coating method. The master was heated in an oven at 65 ° C. for 4 hours to cure the applied PDMS prepolymer mixture. After taking out from the oven and leaving to return to room temperature, the cured PDMS substrate was peeled off from the master. A PDMS substrate having a thickness of 1 mm was obtained. The obtained PDMS substrate was further trimmed in shape and punched to be an input / output port to prepare a PDMS substrate having a size of 3 cm × 4 cm.
(2) Production of facing substrate A polycarbonate (PC) substrate having a thickness of 1 mm and a size of 5 cm × 6 cm was prepared. A silicon oxide film having a thickness of 20 nm was formed on the surface of the PC substrate using a sputtering apparatus (CFS • 12P • 100 manufactured by Tokuda Manufacturing Co., Ltd.). Film formation conditions are ultimate pressure: 7 × 10 −4 Pa, reverse sputtering (PC substrate surface cleaning treatment): 300 W / 5 minutes (use of 100% O 2 ), target: SiO 2 , atmosphere gas: Ar30SCCM, pressure: 0.2 Pa, power: RF 1 kW, pre-sputtering (sputtering with the shutter closed to stabilize the apparatus): 5 minutes, sputtering time (shutter opening time): 3 minutes 30 seconds.
(3) Surface modification treatment The resulting PDMS substrate and PC substrate with a silicon oxide film were subjected to surface modification treatment of each bonded surface by oxygen plasma in a reactive ion etching apparatus (compact etcher model FA-1 manufactured by Samco International). Went. The surface modification treatment conditions were an oxygen gas flow rate of 26 SCCM, a chamber internal pressure of 20 Pa, an RF output of 25 W, and a plasma generation time of 0.8 seconds to 1 second.
(4) Bonding The PDMS substrate and the PC substrate with the silicon oxide film are taken out from the reactive ion etching apparatus, and the microchannel is completed by bonding the surface of the PDMS substrate with the fine flow path and the silicon oxide film surface of the PC substrate. It was.

対面基板の材料をポリメチルメタクリレート(PMMA)としたこと、及び酸化シリコン膜の膜厚を40nmとし、スパッタ時間を7分間としたこと以外は実施例1と同じ条件及び方法によりマイクロチップを作製した。   A microchip was fabricated under the same conditions and method as in Example 1 except that the material of the facing substrate was polymethyl methacrylate (PMMA), the thickness of the silicon oxide film was 40 nm, and the sputtering time was 7 minutes. .

比較例1Comparative Example 1

対面基板の材料をガラスとし、このガラス基板に対して酸化シリコン膜を成膜しなかったこと以外は実施例1と同じ条件及び方法によりマイクロチップを作製した。   A microchip was manufactured under the same conditions and method as in Example 1 except that the material of the facing substrate was glass and a silicon oxide film was not formed on the glass substrate.

比較例2Comparative Example 2

対面基板の材料をPCとし、このPC基板に対して酸化シリコン膜を成膜しなかったこと以外は実施例1と同じ条件及び方法によりマイクロチップを作製した。   A microchip was manufactured under the same conditions and method as in Example 1 except that the material of the facing substrate was PC and no silicon oxide film was formed on the PC substrate.

前記実施例1〜2及び比較例1〜2でそれぞれ得られたマイクロチップを24時間大気中に放置した後、剥離試験を行った。剥離試験はPDMS基板と対面基板を指でそれぞれ掴み、引き剥がすことにより行った。その結果、実施例1、実施例2及び比較例1のマイクロチップでは、PDMS基板が引き千切れてしまうほどの強い接着強度を示したが、比較例2のマイクロチップではPDMS基板がPC対面基板から簡単に剥がれてしまった。これらの事実から、本発明によりPCやPMMAなどの合成樹脂基板でも酸化シリコン膜を介してPDMS基板と接合させれば、従来のガラス基板(比較例1)と同等の恒久接着が得られることが確認される。   The microchips obtained in Examples 1 and 2 and Comparative Examples 1 and 2 were left in the atmosphere for 24 hours, and then a peel test was performed. The peeling test was performed by holding the PDMS substrate and the facing substrate with fingers and peeling them off. As a result, the microchips of Example 1, Example 2 and Comparative Example 1 showed strong adhesive strength that would cause the PDMS substrate to tear, but in the microchip of Comparative Example 2, the PDMS substrate was a PC facing substrate. Easily peeled off. From these facts, even if a synthetic resin substrate such as PC or PMMA is bonded to a PDMS substrate through a silicon oxide film according to the present invention, permanent adhesion equivalent to that of a conventional glass substrate (Comparative Example 1) can be obtained. It is confirmed.

本発明の合成樹脂製対面基板と恒久接着されたPDMS基板からなるマイクロチップにより、例えば、市場にある既存のマイクロチップを使った電気泳動装置を検出器として使用でき、電極位置と検出位置を同一とし、中間流路を自由に設計したオリジナルなカスタムオーダーチップを、作ったらすぐ実験に供することが可能になる。このことより、日本及び諸外国でマイクロ流体チップを利用した様々な新製品開発は格段に加速されることが強く期待できる。   With the microchip comprising the PDMS substrate permanently bonded to the synthetic resin facing substrate of the present invention, for example, an electrophoretic device using an existing microchip on the market can be used as a detector, and the electrode position and the detection position are the same. As soon as an original custom order chip with a freely designed intermediate channel is made, it can be used for experiments. From this, it can be strongly expected that development of various new products using microfluidic chips in Japan and other countries will be greatly accelerated.

本発明によるマイクロチップの一例の概要断面図である。1 is a schematic cross-sectional view of an example of a microchip according to the present invention. (A)は従来のマイクロチップの一例の概要平面図であり、(B)は(A)におけるB−B線に沿った概要断面図である。(A) is an outline top view of an example of the conventional microchip, and (B) is an outline sectional view which met a BB line in (A).

符号の説明Explanation of symbols

1 本発明のマイクロチップ
3 PDMS基板
5 微細流路
7,9 ポート
11 合成樹脂製対面基板
13 酸化シリコン膜
DESCRIPTION OF SYMBOLS 1 Microchip of this invention 3 PDMS substrate 5 Fine flow path 7, 9 Port 11 Synthetic resin facing substrate 13 Silicon oxide film

Claims (5)

少なくとも微細流路が形成されたポリジメチルシロキサン(PDMS)基板と、該PDMS基板の微細流路形成面に接着された対面基板とからなるマイクロチップにおいて、
前記対面基板がPDMS以外の合成樹脂から形成されており、前記対面基板の貼り合わせ面には酸化シリコン膜が成膜されており、該対面基板が酸化シリコン膜を介して前記PDMS基板と接着されていることを特徴とするマイクロチップ。
In a microchip comprising at least a polydimethylsiloxane (PDMS) substrate having a fine channel formed thereon, and a facing substrate bonded to the fine channel forming surface of the PDMS substrate,
The facing substrate is made of a synthetic resin other than PDMS, a silicon oxide film is formed on the bonding surface of the facing substrate, and the facing substrate is bonded to the PDMS substrate via the silicon oxide film. A microchip characterized by
前記対面基板がポリカーボネート(PC)、ポリメチルメタクリレート(PMMA)、ポリエチレンテレフタレート(PET)、ポリスチレン(PS)、ポリエチレン(PS)及びポリアクリロニトリル(PAN)からなる群から選択される材料から形成されており、前記酸化シリコン膜の膜厚が1nm〜100nmの範囲内であることを特徴とする請求項1記載のマイクロチップ。 The facing substrate is made of a material selected from the group consisting of polycarbonate (PC), polymethyl methacrylate (PMMA), polyethylene terephthalate (PET), polystyrene (PS), polyethylene (PS) and polyacrylonitrile (PAN). 2. The microchip according to claim 1, wherein the silicon oxide film has a thickness in a range of 1 nm to 100 nm. 前記対面基板がポリカーボネート(PC)又はポリメチルメタクリレート(PMMA)から形成されており、前記酸化シリコン膜の膜厚が10nm〜40nmの範囲内であることを特徴とする請求項2記載のマイクロチップ。 3. The microchip according to claim 2, wherein the facing substrate is made of polycarbonate (PC) or polymethyl methacrylate (PMMA), and the thickness of the silicon oxide film is in the range of 10 nm to 40 nm. 少なくとも微細流路が形成されたポリジメチルシロキサン(PDMS)基板と、該PDMS基板の微細流路形成面に接着された対面基板とからなるマイクロチップの製造方法において、
(a)PDMS以外の合成樹脂から形成された対面基板の一方の表面に酸化シリコン膜を成膜するステップと、
(b)少なくとも微細流路が形成されたPDMS基板を準備するステップと、
(c)前記酸化シリコン膜付き対面基板とPDMS基板の各貼り合わせ面を表面改質処理するステップと、
(d)表面改質処理された酸化シリコン膜付き対面基板を、該酸化シリコン膜を介して、表面改質処理されたPDMS基板の微細流路形成面に接着させるステップとからなることを特徴とするマイクロチップの製造方法。
In a microchip manufacturing method comprising a polydimethylsiloxane (PDMS) substrate having at least a fine channel formed thereon, and a facing substrate bonded to the fine channel forming surface of the PDMS substrate,
(a) depositing a silicon oxide film on one surface of a facing substrate formed from a synthetic resin other than PDMS;
(b) preparing a PDMS substrate having at least a fine channel formed thereon;
(c) surface modification treatment of each bonding surface of the facing substrate with the silicon oxide film and the PDMS substrate;
(d) the step of adhering the surface-modified surface-facing substrate with the silicon oxide film to the surface of the surface-modified PDMS substrate on which the microchannel is formed through the silicon oxide film. A method for manufacturing a microchip.
前記対面基板がポリカーボネート(PC)、ポリメチルメタクリレート(PMMA)、ポリエチレンテレフタレート(PET)、ポリスチレン(PS)、ポリエチレン(PS)及びポリアクリロニトリル(PAN)からなる群から選択される材料から形成されており、前記酸化シリコン膜はスパッタ法により、1nm〜100nmの範囲内の膜厚に成膜されることを特徴とする請求項4記載のマイクロチップの製造方法。 The facing substrate is made of a material selected from the group consisting of polycarbonate (PC), polymethyl methacrylate (PMMA), polyethylene terephthalate (PET), polystyrene (PS), polyethylene (PS) and polyacrylonitrile (PAN). 5. The method of manufacturing a microchip according to claim 4, wherein the silicon oxide film is formed to a thickness within a range of 1 nm to 100 nm by a sputtering method.
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