JP4954386B2 - Microchip liquid-liquid interface reaction method by applying electric field or magnetic field and microchip for the same - Google Patents
Microchip liquid-liquid interface reaction method by applying electric field or magnetic field and microchip for the same Download PDFInfo
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【０００１】
【発明の属する技術分野】
この出願の発明は、電場または磁場印加によるマイクロチップ液液界面反応方法とそのためのマイクロチップに関するものである。
【０００２】
【従来の技術と発明の課題】
従来より、マイクロチップに形成した微細流路（マイクロチャンネル）において化学反応を行うことが提案されてきている。この出願の発明者らによっても、このようなマイクロチップ上での化学反応について、高効率での化学合成や高精度での分析等を可能とすることが見出され、たとえば、錯体形成反応、溶媒抽出、免疫反応、酵素反応、イオン対抽出などのさまざまな化学反応系としてマイクロチップに集積化することが提案されている。
【０００３】
そして、発明者らによるこれらの提案は、マイクロチップ上の流路という微小空間での液液界面反応とその制御についての多面的観点からの検討により得られた新規な知見に基づいている。
【０００４】
このような検討の過程において、発明者らは、微小空間での液液界面反応をより高度に制御するための方策を探索してきた。液液界面方法における反応基質の反応部位の位置や立体配置を自在に選択制御できるのであれば、反応効率を飛躍的に向上させることや、不斉合成、立体選択的合成も可能になると期待されるからである。
【０００５】
この出願の発明は、以上のとおりの背景よりなされたものであって、マイクロチップ上の流路における液液界面反応をより高度に選択制御することのできる新しい技術手段を提供することを課題としている。
【０００６】
【課題を解決するための手段】
この出願の発明は、上記の課題を解決するものとして、第１には、マイクロチップ流路における液液界面反応において、液液界面に電場または磁場を印加することを特徴とする電場または磁場印加によるマイクロチップ液液界面反応方法を提供する。また、第２には、上記第１のマイクロチップ液液界面反応方法であって、液液界面が形成されて反応が進行する流路で、マイクロチップの上下間に電場または磁場を印加することを特徴とする電場または磁場印加によるマイクロチップ液液界面反応方法を提供する。
【０００７】
そして、この出願の発明は、第３には、上記第１または２のマイクロチップ液液界面反応方法であって、液液界面が形成される流路への各試薬の導入路でマイクロチップの上下間に電場または磁場を印加することを特徴とするマイクロチップ液液界面反応方法を提供する。
【０００８】
また、この出願の発明は、第４には、上記の反応方法のためのマイクロチップであって、電場を形成するマイクロ電極または磁場を形成するマイクロマグネットもしくはマイクロコイルが配設されていることを特徴とするマイクロチップを提供する。
【０００９】
【発明の実施の形態】
この出願の発明は上記のとおりの特徴をもつものであるが、以下にその実施の形態について説明する。
【００１０】
添付した図面の図１は、この発明の方法とそのためのマイクロチップの要部について概要を例示した平面図であって、この例においては、試薬Ａと試薬Ｂとの液液界面反応を行うための流路（マイクロチャンネル）（１）において、たとえばマイクロチップの上下にマイクロ電極を配設することによって、液液界面に平行に電場が印加されるようにしている。また、この例においては、試薬Ａと試薬Ｂの導入のための流路（２Ａ）（２Ｂ）にも同様にマイクロ電極を配設して電場が印加されるようにしている。
【００１１】
液液界面が形成されて反応が進行する流路（１）での電場の印加によって、反応の選択性が高められることになる。試薬導入のための流路（２Ａ）（２Ｂ）においては、試薬の分極化等のために適宜に電場が印加されてよいが、このような電場の印加は必ずしも必要ではない。
【００１２】
もちろん、電場の印加は、必要に応じて、試薬の導入路（２Ａ）（２Ｂ）の少くともいずれかのみで行うようにしてもよい。
【００１３】
電場の印加によって、反応試薬の活性基や活性種の空間配置、分布が変更、制御され、反応の選択性が高められる。マイクロチップ上の流路という微小空間という特性によって、小さな外部電位で大きな電場を、効率的に、しかも方向を均一に印加することができる。同様にして、電場に代えてマイクロマグネットやマイクロコイルを配設して磁場印加可能としたマイクロチップにおいても、磁場感応性の選択的な反応が進行することになる。
【００１４】
電場や磁場の印加による反応においては、反応生成物をマイクロチップから容易回収できることはいうまでもなく、チップ上で多段反応を構成してもよいし、流路において、光学顕微鏡、特にこの出願の発明者らが提案している熱レンズ顕微鏡等の手段によって非接触で分析することもできる。
【００１５】
そこで、以下に実施例を示し、さらに詳しく発明の実施の形態について説明する。もちろん、以下の例によって発明が限定されることはない。
【００１６】
【実施例】
図２に示したとおりのマイクロチップは７×３ｃｍ、厚さ１．４ｍｍ、チャネル幅２５０μｍ、深さ１００μｍとし、導入された有機相溶液と水相溶液はＹ字状に合流しチャネルに沿った平面状の液−液界面を形成するようにした。チップの上下に電極を取り付け直流電源によって０〜１７００Ｖ／ｃｍ（０〜２５０Ｖ）の電場を液−液界面に対して平行に印加するようにした。このマイクロチャネル中にレゾルシノール誘導体酢酸エチル溶液とｐ−ニトロペンゼンジアゾニウムテトラフルオロボレート水溶液を導入しジアゾカップリング反応を行った。平面状液−液界面を形成させた場合と、比較のため２相を１つの導入口から導入してランダムに混合し、平面状の液−液界面を形成させなかった場合についてそれぞれ反応を行った。合成収率は反応液の酢酸エチル相を採取してＨＰＬＣで評価した。
【００１７】
反応基質に４−エチルレゾルシノールを用いた結果、主生成物の収率が、平面状界面が形成していない場合では約１％でほぼ一定であるが、平面状界面の形成時では電場強度に依存して１．０６％から１．４４％にまで上昇するという、収率向上効果を見出した。また５−メチルレゾルシノールを基質として行ったときには１０．４７％から１３．５５％まで上昇した。この理由として、まずは電場印加による温度上昇の可能性を考え、電場印加時の温度変化を熱電対を用いて測定したが、これは誤差の範囲内であることが確認できた。このことから、電場印加による試薬の分子配向や濃度勾配の形成等によるものと考えられる。この結果は、マイクロチップ中に形成される比界面積が大きく、かつ方向の規制された液−液界面が、電場による反応制御に適用可能であることを示しており、位置・立体選択的合成反応等への展開が期待できる。
【００１８】
【発明の効果】
以上詳しく説明したとおり、この出願の発明によって、マイクロチップ上での液液界面反応がより高度に選択的に制御可能となる。
【図面の簡単な説明】
【図１】この発明の方法とそのためのマイクロチップの構成を例示した要部平面図である。
【図２】実施例について例示した概要斜視図である。[0001]
BACKGROUND OF THE INVENTION
The invention of this application relates to a microchip liquid-liquid interface reaction method by applying an electric field or a magnetic field and a microchip therefor.
[0002]
[Prior art and problems of the invention]
Conventionally, it has been proposed to perform a chemical reaction in a fine channel (microchannel) formed in a microchip. The inventors of this application have also found that chemical reaction on such a microchip enables chemical synthesis with high efficiency, analysis with high accuracy, etc., for example, complex formation reaction, It has been proposed to integrate microchips as various chemical reaction systems such as solvent extraction, immune reaction, enzyme reaction, and ion pair extraction.
[0003]
And these proposals by the inventors are based on new knowledge obtained by examination from various viewpoints about the liquid-liquid interface reaction in the micro space called the flow path on the microchip and its control.
[0004]
In the course of such studies, the inventors have searched for a measure for controlling the liquid-liquid interface reaction in a minute space to a higher degree. If the position and configuration of the reaction substrate in the liquid-liquid interface method can be freely selected and controlled, it is expected that reaction efficiency will be dramatically improved, and asymmetric synthesis and stereoselective synthesis will be possible. This is because that.
[0005]
The invention of this application has been made based on the background as described above, and has as its object to provide a new technical means capable of selecting and controlling the liquid-liquid interface reaction in the channel on the microchip to a higher degree. Yes.
[0006]
[Means for Solving the Problems]
In order to solve the above problems, the invention of this application firstly applies an electric field or a magnetic field, wherein an electric field or a magnetic field is applied to a liquid-liquid interface in a liquid-liquid interface reaction in a microchip channel. A microchip liquid-liquid interface reaction method is provided. Second, in the first microchip liquid-liquid interface reaction method, an electric field or a magnetic field is applied between the upper and lower sides of the microchip in a flow path in which the liquid-liquid interface is formed and the reaction proceeds. A microchip liquid-liquid interface reaction method by applying an electric field or a magnetic field is provided.
[0007]
Third, the invention of this application is the above-described first or second microchip liquid-liquid interface reaction method, wherein each reagent is introduced into a flow path where a liquid-liquid interface is formed . Provided is a microchip liquid-liquid interface reaction method characterized by applying an electric field or a magnetic field between upper and lower sides .
[0008]
The invention of this application is, fourthly, a microchip for the above reaction method, wherein a microelectrode for forming an electric field or a micromagnet or a microcoil for forming a magnetic field is provided. A featured microchip is provided.
[0009]
DETAILED DESCRIPTION OF THE INVENTION
The invention of this application has the features as described above, and an embodiment thereof will be described below.
[0010]
FIG. 1 of the accompanying drawings is a plan view illustrating an outline of the main part of the method of the present invention and the microchip for the method. In this example, a liquid-liquid interface reaction between the reagent A and the reagent B is performed. In this flow path (microchannel) (1), for example, by arranging microelectrodes above and below the microchip, an electric field is applied in parallel to the liquid-liquid interface. In this example, the microelectrodes are similarly disposed in the flow paths (2A) and (2B) for introducing the reagent A and the reagent B so that an electric field is applied.
[0011]
The selectivity of the reaction is enhanced by the application of an electric field in the flow path (1) where the liquid-liquid interface is formed and the reaction proceeds. In the flow paths (2A) and (2B) for introducing the reagent, an electric field may be appropriately applied for the polarization of the reagent and the like, but such an electric field is not necessarily applied.
[0012]
Of course, the electric field may be applied through at least one of the reagent introduction paths (2A) and (2B) as required.
[0013]
By applying an electric field, the spatial arrangement and distribution of the active groups and active species of the reaction reagent are changed and controlled, and the selectivity of the reaction is enhanced. A large electric field with a small external potential can be applied efficiently and uniformly in a direction due to a characteristic of a micro space called a flow path on a microchip. Similarly, in a microchip in which a micromagnet or microcoil is provided instead of an electric field and a magnetic field can be applied, a magnetic field sensitive selective reaction proceeds.
[0014]
In the reaction by applying an electric field or a magnetic field, it is needless to say that the reaction product can be easily recovered from the microchip, and a multistage reaction may be configured on the chip. Non-contact analysis can also be performed by means such as a thermal lens microscope proposed by the inventors.
[0015]
Therefore, examples will be shown below, and the embodiments of the invention will be described in more detail. Of course, the invention is not limited by the following examples.
[0016]
【Example】
The microchip as shown in FIG. 2 has a size of 7 × 3 cm, a thickness of 1.4 mm, a channel width of 250 μm, and a depth of 100 μm, and the introduced organic phase solution and aqueous phase solution merge in a Y shape and follow the channel. A flat liquid-liquid interface was formed. Electrodes were attached to the top and bottom of the chip, and an electric field of 0 to 1700 V / cm (0 to 250 V) was applied in parallel to the liquid-liquid interface by a DC power source. A resorcinol derivative ethyl acetate solution and a p-nitrobenzene diazonium tetrafluoroborate aqueous solution were introduced into the microchannel to carry out a diazo coupling reaction. For the case where a planar liquid-liquid interface is formed and for comparison, two phases are introduced from one inlet and mixed randomly, and the planar liquid-liquid interface is not formed. It was. The synthesis yield was evaluated by HPLC after collecting the ethyl acetate phase of the reaction solution.
[0017]
As a result of using 4-ethylresorcinol as the reaction substrate, the yield of the main product is almost constant at about 1% when the planar interface is not formed, but the electric field strength is increased when the planar interface is formed. The yield increasing effect of increasing from 1.06% to 1.44% was found. Further, when 5-methylresorcinol was used as a substrate, it increased from 10.47% to 13.55%. As a reason for this, first, considering the possibility of temperature rise due to electric field application, the temperature change at the time of electric field application was measured using a thermocouple, and it was confirmed that this was within the error range. From this, it is considered that this is due to the molecular orientation of the reagent and the formation of a concentration gradient by applying an electric field. This result shows that the liquid-liquid interface with a large specific interface area formed in the microchip and whose direction is regulated can be applied to the reaction control by the electric field. The development to reaction etc. can be expected.
[0018]
【Effect of the invention】
As described in detail above, the invention of this application makes it possible to control the liquid-liquid interface reaction on the microchip more selectively.
[Brief description of the drawings]
FIG. 1 is a plan view of an essential part illustrating the method of the present invention and the configuration of a microchip for the method.
FIG. 2 is a schematic perspective view illustrating an example.
Claims (4)
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| JP2001136669A JP4954386B2 (en) | 2001-05-07 | 2001-05-07 | Microchip liquid-liquid interface reaction method by applying electric field or magnetic field and microchip for the same |
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| JP2001136669A JP4954386B2 (en) | 2001-05-07 | 2001-05-07 | Microchip liquid-liquid interface reaction method by applying electric field or magnetic field and microchip for the same |
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| WO2005009605A1 (en) * | 2003-07-24 | 2005-02-03 | Ryoichi Aogaki | Microreactor including magnetic barrier |
| JP2006187685A (en) | 2004-12-28 | 2006-07-20 | Fuji Xerox Co Ltd | Microstructure, microreactor, heat exchanger and manufacturing method of microstructure |
| JP2006187684A (en) | 2004-12-28 | 2006-07-20 | Fuji Xerox Co Ltd | Microfluid device |
| JP2007038047A (en) | 2005-07-29 | 2007-02-15 | Sumitomo Electric Ind Ltd | Microreacter |
| JP5092443B2 (en) * | 2007-02-20 | 2012-12-05 | 富士ゼロックス株式会社 | Microfluidic device, reaction apparatus, and reaction method |
| US9539511B2 (en) | 2011-03-08 | 2017-01-10 | Nintendo Co., Ltd. | Computer-readable storage medium, information processing system, and information processing method for operating objects in a virtual world based on orientation data related to an orientation of a device |
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| JPH0772146B2 (en) * | 1991-06-12 | 1995-08-02 | 工業技術院長 | Control method of chemical reaction |
| JPH11104487A (en) * | 1997-09-30 | 1999-04-20 | Shimadzu Corp | Chemical reaction device |
| JPH11104485A (en) * | 1997-10-03 | 1999-04-20 | Japan Science & Technology Corp | Promotion of dissolution of gas into liquid by magnetic field gradient |
| GB9723260D0 (en) * | 1997-11-05 | 1998-01-07 | British Nuclear Fuels Plc | A method of performing a chemical reaction |
| EP1174182A4 (en) * | 1999-02-18 | 2003-07-23 | Toyo Kohan Co Ltd | Micro-chip for chemical reaction |
| JP2000298079A (en) * | 1999-04-13 | 2000-10-24 | Kanagawa Acad Of Sci & Technol | Molecule transportation and extraction method |
| JP3417344B2 (en) * | 1999-05-26 | 2003-06-16 | 株式会社島津製作所 | Chemiluminescence detection method and microchip electrophoresis apparatus using the method |
| JP2001004628A (en) * | 1999-06-18 | 2001-01-12 | Kanagawa Acad Of Sci & Technol | Immunoassay and its method |
| JP3960806B2 (en) * | 2001-01-22 | 2007-08-15 | 独立行政法人科学技術振興機構 | Method for photo-substitution reaction of organic compounds |
| JP2002277478A (en) * | 2001-03-15 | 2002-09-25 | Kanagawa Acad Of Sci & Technol | Liquid-liquid interface segment flow method and segment analysis method |
| JP2002292275A (en) * | 2001-03-29 | 2002-10-08 | Kanagawa Acad Of Sci & Technol | Microchip pile-up type chemical reaction system |
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