JP2014077810A - Test device and reaction device - Google Patents

Test device and reaction device Download PDF

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JP2014077810A
JP2014077810A JP2014020890A JP2014020890A JP2014077810A JP 2014077810 A JP2014077810 A JP 2014077810A JP 2014020890 A JP2014020890 A JP 2014020890A JP 2014020890 A JP2014020890 A JP 2014020890A JP 2014077810 A JP2014077810 A JP 2014077810A
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test
reaction
test solution
liquid
test device
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JP5831566B2 (en
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Kusunoki Higashino
楠 東野
Yasuhiro Santo
康博 山東
Kenichi Miyata
謙一 宮田
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Konica Minolta Inc
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Abstract

PROBLEM TO BE SOLVED: To provide a test device and a reaction device capable of increasing the reaction efficiency using a conventional size of a fine flow channel.SOLUTION: The test device includes; a fine flow channel 11 which has, in its part, a reaction section 12 including a reactant which reacts with a test substance dispersed in a test solution fixed therein; and a uniformizing means 28 that operates the test solution to uniformize the concentration distribution of the test substance in the test solution located at least at one of one side and the other side of the fine flow channel 11. The fine flow channel 11 allows the test solution to flow therein repeatedly plural times. The uniformizing means 28 is provided to reservoirs 21 and 22 of the test solution, which has a capacity larger than the volume of the test solution located at least at one of the one side and the other side of the fine flow channel 11.

Description

本発明は、試験デバイス及び反応装置、特に、抗原などの試験物質を含む試験液を微細流路で送液し、試験物質を抗体などの反応物質に反応させるための試験デバイス及び反応装置に関する。   The present invention relates to a test device and a reaction apparatus, and more particularly to a test device and a reaction apparatus for feeding a test liquid containing a test substance such as an antigen through a fine channel and reacting the test substance with a reaction substance such as an antibody.

従来、血漿中に含まれる各種抗原を抗体に反応させるための微細流路を備えた試験デバイスは、図９に示すように、微細流路５０の底部に反応物質が固定された反応部５１が設けられ、試験物質Ｔが分散された試験液を微細流路５０の一方から他方に（矢印Ａ参照）送液するように構成されている。反応部５１では試験物質が固相化面の近傍でしか反応しないので、微細流路５０の上部を流れる試験物質Ｔは反応に寄与せず、微細流路５０をそのまま通過してしまうため、反応効率が悪いという問題点を有していた。   Conventionally, a test device having a fine channel for reacting various antigens contained in plasma with an antibody has a reaction part 51 in which a reactant is fixed to the bottom of a fine channel 50 as shown in FIG. A test solution in which the test substance T is dispersed is provided from one side of the fine channel 50 to the other (see arrow A). Since the test substance reacts only in the vicinity of the solid phase in the reaction part 51, the test substance T flowing above the fine channel 50 does not contribute to the reaction and passes through the fine channel 50 as it is. It had the problem of poor efficiency.

その対策として、試験液を微細流路で往復させることで、未反応の試験物質を再度反応部を通過させて反応効率を上げる方法が考えられる。例えば、特許文献１には、ピペットなどの送液手段により試験液を反応部に往復送液することが記載されている。特許文献２には、液体を可逆的かつ制御可能に流すシステム及び方法が記載されている。   As a countermeasure, it is conceivable to increase the reaction efficiency by allowing the unreacted test substance to pass through the reaction part again by reciprocating the test solution through the fine flow path. For example, Patent Document 1 describes that a test solution is sent back and forth to a reaction part by a solution feeding means such as a pipette. Patent Document 2 describes a system and method for flowing a liquid reversibly and controllably.

しかし、前記往復送液方法を用いても以下のような問題点が残されている。即ち、試験物質を反応部に近付けて反応効率を上げるには、微細流路の深さは送液に支障を及ぼさない範囲でできるだけ浅いことが望ましく、概ね１ｍｍ以下が望ましい。また、試験液の流速は、微細流路内の送液圧力が過度に上昇するのを防ぐために、数十ｍｍ／ｓｅｃ以下に抑えることが好ましい。このような送液系においてはレイノルズ数が低いために流れが層流になり、試験液を往復させても反応物質は試験液中ではほとんど混合されず、微細流路の上部を流れた試験物質は往復させても常に流路上部を繰り返して流れるだけであり、何度往復させても反応に寄与しないのである。   However, the following problems remain even when the reciprocating liquid feeding method is used. That is, in order to increase the reaction efficiency by bringing the test substance close to the reaction part, it is desirable that the depth of the fine channel is as shallow as possible within a range that does not interfere with the liquid feeding, and is generally about 1 mm or less. Further, the flow rate of the test solution is preferably suppressed to several tens mm / sec or less in order to prevent the liquid feeding pressure in the fine channel from excessively rising. In such a liquid delivery system, the flow is laminar because the Reynolds number is low, and even when the test solution is reciprocated, the reactants are hardly mixed in the test solution, and the test material that has flowed through the top of the microchannel Even if it reciprocates, it always flows repeatedly in the upper part of the flow path, and it does not contribute to the reaction no matter how many times it reciprocates.

なお、レイノルズ数とは、流体力学の分野で一般的に使われる指標値であり、その値が概ね２０００を超えると乱流となるが、それ以下である場合は層流となることが知られている。溶媒が水系であり、流路の寸法、流速が前記の場合、レイノルズ数は概ね１００以下であり、層流になるので、特別な工夫を講じない限り、反応効率は上昇しないのである。   The Reynolds number is an index value generally used in the field of fluid dynamics. When the value exceeds 2000, turbulent flow occurs. However, when the value is less than that, laminar flow is known. ing. In the case where the solvent is an aqueous system and the flow path dimensions and flow rates are as described above, the Reynolds number is approximately 100 or less, and the flow becomes laminar. Therefore, unless special measures are taken, the reaction efficiency does not increase.

特開２００６−９０７１７号公報JP 2006-90717 A 特表２００２−５４０４０５号公報Special table 2002-540405 gazette

そこで、本発明の目的は、微細流路のサイズは従来のままで反応効率を向上させることのできる試験デバイス及び反応装置を提供することにある。   Accordingly, an object of the present invention is to provide a test device and a reaction apparatus that can improve the reaction efficiency while maintaining the conventional size of the fine channel.

以上の目的を達成するため、本発明の第１の形態である試験デバイスは、
試験液中に分散された試験物質と反応し得る反応物質が固定化された反応部をその一部に有する微細流路と、
前記微細流路の一方側及び他方側の少なくとも一方に、前記試験液中における試験物質の濃度分布を均一化するように試験液を動作させる均一化手段と、
を備え、
前記微細流路は試験液が複数回繰り返して流通されるように使用され、
前記均一化手段は、前記微細流路の一方側及び他方側の少なくとも一方において、前記試験液の液量以上の容積を有する試験液の貯留部に備えられていること、
を特徴とする。 In order to achieve the above object, a test device according to the first aspect of the present invention includes:
A fine channel having, in part, a reaction part in which a reactive substance capable of reacting with a test substance dispersed in a test solution is fixed;
Homogenizing means for operating the test solution so that the concentration distribution of the test substance in the test solution is made uniform on at least one of the one side and the other side of the fine channel;
With
The fine channel is used so that the test solution is repeatedly circulated a plurality of times,
The homogenizing means is provided in a test liquid storage section having a volume equal to or larger than the liquid volume of the test liquid on at least one of the one side and the other side of the fine flow path;
It is characterized by.

本発明の第２の形態である反応装置は、
前記試験デバイスと、
前記微細流路に前記試験液を複数回繰り返して流通させるための送液手段と、
を備え、
前記送液手段は前記試験液を往復送液するものであること、
を特徴とする。 The reaction apparatus according to the second aspect of the present invention is:
The test device;
A liquid feeding means for allowing the test liquid to flow through the fine channel repeatedly a plurality of times;
With
The liquid feeding means is for reciprocating the test liquid;
It is characterized by.

なお、本発明において、「試験液中における試験物質の濃度分布を均一化するように試験液を動作させる」とは、必ずしも完全に均一化することを意味するのではなく、均一化する方向に試験液を動作させることを意味する。   In the present invention, “operating the test solution so that the concentration distribution of the test substance in the test solution is made uniform” does not necessarily mean that the test solution is made uniform, but in the direction of making it uniform. It means that the test solution is operated.

本発明によれば、微細流路の一方側及び他方側の少なくとも一方において、試験液中での試験物質の濃度分布を均一化させるため、試験液を複数回繰り返して流通させることで試験物質が反応する割合が増加し、反応効率が向上する。   According to the present invention, in order to make the concentration distribution of the test substance in the test liquid uniform on at least one of the one side and the other side of the fine flow path, the test substance can be distributed by repeatedly circulating the test liquid several times. The reaction rate increases and the reaction efficiency is improved.

第１実施例である試験デバイスを示す断面図である。It is sectional drawing which shows the test device which is 1st Example. 第２実施例である試験デバイスを示す断面図である。It is sectional drawing which shows the test device which is 2nd Example. 第３実施例である試験デバイスを示す断面図である。It is sectional drawing which shows the test device which is 3rd Example. 第３実施例に使用されているポンプを示す正面図である。It is a front view which shows the pump currently used for 3rd Example. 第４実施例である試験デバイスを示す断面図である。It is sectional drawing which shows the test device which is 4th Example. 第４実施例に用いられている螺旋状溝部を示す断面図である。It is sectional drawing which shows the spiral groove part used for 4th Example. 第５実施例である試験デバイスを示す断面図である。It is sectional drawing which shows the test device which is 5th Example. 第６実施例である試験デバイスを示す断面図である。It is sectional drawing which shows the test device which is 6th Example. 従来における試験液の送液状態を示す説明図である。It is explanatory drawing which shows the liquid feeding state of the test liquid in the past.

以下、本発明に係る試験デバイス及び反応装置の実施例について、添付図面を参照して説明する。なお、各図面において、同一部材、部分に関しては同じ符号を付し、重複する説明は省略する。   Embodiments of a test device and a reaction apparatus according to the present invention will be described below with reference to the accompanying drawings. In addition, in each drawing, the same code | symbol is attached | subjected regarding the same member and part, and the overlapping description is abbreviate | omitted.

（第１実施例、図１参照）
第１実施例である試験デバイス１０Ａは、図１に示すように、微細流路１１の一方側に第１の貯留部２１を設け、他方側に第２の貯留部２２を設け、第２の貯留部２２の一端に連通する廃液溜め２３と空気注入・排出口２４を設けたものである。空気注入・排出口２４には空気ポンプ３０が接続されている。貯留部２１，２２は送液される試験液（図１でクロスハッチングで示す）の液量以上の容積を有している。本第１実施例において、試験デバイス１０Ａに空気ポンプ３０を加えたものを反応装置と称する。 (See the first embodiment, FIG. 1)
As shown in FIG. 1, the test device 10A according to the first embodiment is provided with a first reservoir 21 on one side of the microchannel 11 and a second reservoir 22 on the other side. A waste liquid reservoir 23 communicating with one end of the reservoir 22 and an air inlet / outlet 24 are provided. An air pump 30 is connected to the air inlet / outlet 24. The reservoirs 21 and 22 have a volume equal to or larger than the amount of the test liquid to be fed (indicated by cross hatching in FIG. 1). In the first embodiment, the test device 10A to which the air pump 30 is added is referred to as a reactor.

微細流路１１の一部には、試験液中に分散された試験物質と反応し得る反応物質が固定化された反応部１２が設けられている。第１の貯留部２１の側壁部には振動子２８が貼着されている。この振動子２８は第１の貯留部２１に溜められた試験液を、試験物質の濃度を均一化するように攪拌・混合させるためのものである。例えば、ＰＺＴ（チタン酸ジルコン酸鉛）を材料とした圧電アクチュエータを好適に用いることができる。   A part of the microchannel 11 is provided with a reaction section 12 on which a reactive substance capable of reacting with a test substance dispersed in a test solution is fixed. A vibrator 28 is attached to the side wall portion of the first storage portion 21. The vibrator 28 is for agitating and mixing the test solution stored in the first storage unit 21 so that the concentration of the test substance is uniform. For example, a piezoelectric actuator made of PZT (lead zirconate titanate) can be preferably used.

試験液としては、例えば、生体から採取された血液を遠心分離して得られた血漿を用いる。この場合、試験液に含まれる試験物質は、血液中に存在する各種抗原である。反応部に固定化された反応物質とは、抗原に対して特異的に反応し得る抗体である。   As the test solution, for example, plasma obtained by centrifuging blood collected from a living body is used. In this case, the test substance contained in the test solution is various antigens present in the blood. The reactive substance immobilized in the reaction part is an antibody that can specifically react with an antigen.

第１実施例である試験デバイス１０Ａにおいて、試験液はまず貯留部２１に注入され、空気ポンプ３０を駆動することによって、空気圧で図１（Ａ）の状態から図１（Ｂ）に示すように、貯留部２２に向かって送液され、さらに、図１（Ａ）の状態に逆方向に送液される。即ち、試験液は微細流路１１を往復送液されて反応部１２を複数回繰り返して流通され、これにて抗原が抗体と反応する。試験液が貯留部２１に溜められている間に、振動子２８を動作させ、試験液中における抗原の濃度分布を均一化するように試験液を攪拌・混合させる。   In the test device 10A according to the first embodiment, the test solution is first injected into the reservoir 21, and the air pump 30 is driven so that the air pressure is changed from the state of FIG. 1 (A) to the state shown in FIG. 1 (B). Then, the liquid is fed toward the storage unit 22 and further fed in the reverse direction to the state shown in FIG. That is, the test solution is reciprocated through the fine channel 11 and is circulated through the reaction unit 12 a plurality of times, whereby the antigen reacts with the antibody. While the test liquid is stored in the storage unit 21, the vibrator 28 is operated to stir and mix the test liquid so that the antigen concentration distribution in the test liquid is uniform.

本第１実施例によれば、微細流路１１の一方に設けた貯留部２１において試験液中での抗原の濃度分布を均一化させ、試験液を複数回繰り返して流通させることで抗原が反応部１２の抗体に反応する割合が増加し、反応効率が向上する。   According to the first embodiment, the antigen reacts by making the concentration distribution of the antigen in the test solution uniform in the reservoir 21 provided on one side of the microchannel 11 and repeatedly circulating the test solution multiple times. The rate of reaction with the antibody of part 12 increases, and the reaction efficiency is improved.

また、貯留部２１，２２の容積はいずれも試験液の流量以上に設定されているため、試験液の全量が微細流路１１を流れるように往復送液させても、試験液が貯留部２１，２２から漏れ出るおそれはない。さらに、貯留部２１の底部は「お椀形」とされ、かつ、上部の開口面積は広い目に設定されている。これにて、振動子２８によって振動を与えられた試験液が動きやすくなり、攪拌効率が高くなる。貯留部２１の上部の開口面積は、試験液と同じ体積の球を想定し、該球の平面投影面積を基準として、概ね、該投影面積の１／１０倍以上とすれば、開口面積を広くした効果が現れる。   In addition, since the volumes of the reservoirs 21 and 22 are both set to be equal to or higher than the flow rate of the test solution, the test solution is stored in the reservoir 21 even when the total amount of the test solution is fed back and forth so as to flow through the fine channel 11. , 22 will not leak. Furthermore, the bottom part of the storage part 21 is set to be a bowl shape, and the upper opening area is set to be wide. As a result, the test liquid that is vibrated by the vibrator 28 can move easily, and the stirring efficiency is increased. The opening area of the upper part of the reservoir 21 is assumed to be a sphere having the same volume as the test solution, and if the projected area is approximately 1/10 times or more of the projected area on the basis of the planar projected area of the sphere, the opening area is increased. Effects appear.

なお、振動子２８の振動周波数は任意であるが、試験液の共振周波数又はそれに近い周波数であることが攪拌効率化の点で好ましい。試験液の共振周波数は、液量によっても変化することが予測されるため、送液による貯留部２１内の液量の増減に合わせて振動子２８の駆動周波数を変更することが好ましい。あるいは、駆動周波数を任意にスウィープさせることによって、間欠的に共振モードとし、試験液のランダムな動きを誘発して抗原の混合を促進することもできる。   The vibration frequency of the vibrator 28 is arbitrary, but is preferably the resonance frequency of the test liquid or a frequency close thereto from the viewpoint of increasing the stirring efficiency. Since the resonance frequency of the test liquid is predicted to change depending on the liquid volume, it is preferable to change the driving frequency of the vibrator 28 in accordance with the increase or decrease of the liquid volume in the storage unit 21 due to liquid feeding. Alternatively, by arbitrarily sweeping the drive frequency, it is possible to intermittently enter the resonance mode and induce random movement of the test solution to promote mixing of antigens.

試験液を所定回数だけ往復送液した後は、試験液を空気ポンプ３０で吸引し、廃液溜め２３に捨てる。そして、貯留部２１に洗浄液を滴下し、該洗浄液を空気ポンプ３０で微細流路１１に吸引送液して反応部１２に残った未反応の抗原を除去する。その後、反応部１２の面の光学的特性の変化を図示しない検出器で検出することによって、抗原と抗体の免疫反応を測定する。なお、この種の免疫反応の測定は周知であり、詳細な説明は省略する。   After the test solution is reciprocated a predetermined number of times, the test solution is sucked with the air pump 30 and discarded into the waste liquid reservoir 23. Then, a cleaning solution is dropped into the storage unit 21, and the cleaning solution is sucked and fed to the fine channel 11 by the air pump 30 to remove unreacted antigen remaining in the reaction unit 12. Thereafter, the change in the optical characteristics of the surface of the reaction unit 12 is detected by a detector (not shown) to measure the immune reaction between the antigen and the antibody. The measurement of this type of immune reaction is well known and will not be described in detail.

（第２実施例、図２参照）
第２実施例である試験デバイス１０Ｂは、図２に示すように、試験デバイス１０Ｂの一部に貯留部２１に隣接した共鳴エリア（空洞）２５を設けたものである。他の構成は前記第１実施例と同様である。第２実施例の作用効果は第１実施例と同様であり、特に、共鳴エリア２５を設けることで、振動子２８による共振振動を増幅させ、試験液の攪拌混合効率を高めることができる。 (See the second embodiment, FIG. 2)
As shown in FIG. 2, the test device 10B according to the second embodiment is provided with a resonance area (cavity) 25 adjacent to the storage portion 21 in a part of the test device 10B. Other configurations are the same as those of the first embodiment. The operational effect of the second embodiment is the same as that of the first embodiment. In particular, by providing the resonance area 25, the resonance vibration by the vibrator 28 can be amplified and the stirring and mixing efficiency of the test liquid can be increased.

（第３実施例、図３及び図４参照）
第３実施例である試験デバイス１０Ｃは、図３に示すように、前記空気ポンプ３０に代えて、蠕動式のチューブポンプ３５を設けたものである。このチューブポンプ３５は、図４に示すように、複数のローラ３６を中央部のローラ３７によって回転（自転）させ、壁部３５ａとローラ３６との間に挟み込まれたチューブ３８内の試験液を回転（自転）方向に送液するものである。 (Refer to the third embodiment, FIGS. 3 and 4)
As shown in FIG. 3, the test device 10 </ b> C according to the third embodiment is provided with a peristaltic tube pump 35 instead of the air pump 30. As shown in FIG. 4, the tube pump 35 rotates (spins) a plurality of rollers 36 by a roller 37 at the center, and the test solution in the tube 38 sandwiched between the wall 35 a and the roller 36 is supplied. Liquid is fed in the rotation (spinning) direction.

試験デバイス１０Ｃには、振動子２８を設けた貯留部２１と反応部１２を含む微細流路１１が設けられている。チューブ３８の一端は貯留部２１に臨み、他端は微細流路１１の他端開口部２６に接続されている。このチューブポンプ３５によって試験液は、貯留部２１から微細流路１１を繰り返して循環送液され、振動子２８による共振振動で貯留部２１において試験液中での抗原の濃度分布が均一化され、抗原が反応部１２の抗体に反応する割合が増加し、反応効率が向上する。特に、この循環送液方式は、液量が比較的多いときに有効である。   The test device 10 </ b> C is provided with a fine channel 11 including a storage unit 21 provided with a vibrator 28 and a reaction unit 12. One end of the tube 38 faces the storage portion 21, and the other end is connected to the other end opening 26 of the microchannel 11. The tube pump 35 repeatedly circulates the test liquid from the reservoir 21 through the fine flow path 11, and the concentration distribution of the antigen in the test liquid is made uniform in the reservoir 21 by the resonance vibration by the vibrator 28. The rate at which the antigen reacts with the antibody in the reaction part 12 increases, and the reaction efficiency improves. In particular, this circulating liquid feeding method is effective when the amount of liquid is relatively large.

なお、前記チューブポンプ３５は、扱きポンプ、ペリスタルティック（peristaltic）ポンプ、蠕動ポンプなど種々の名称で呼ばれることもある。   The tube pump 35 may be called by various names such as a handling pump, a peristaltic pump, and a peristaltic pump.

（第４実施例、図５及び図６参照）
第４実施例である試験デバイス１０Ｄは、図５に示すように、第１の貯留部２１の内壁面に螺旋状の溝部４１を設けたものである。他の構成は前記第１実施例と同様である。第１実施例で説明したように、試験液は貯留部２１，２２間を往復送液され、貯留部２１の螺旋状の溝部４１を通過することで回転攪拌されて混合され、試験液中での抗原の濃度分布が均一化される。貯留部２１の上部の開口面積は、溝部４１による試験液の攪拌混合が生じやすいように、広い目に設定されることが好ましい。試験液と同じ体積の球を想定し、該球の平面投影面積を基準として、概ね、該投影面積の１／１０倍以上の開口面積とすれば効果的である。 (Refer to the fourth embodiment, FIGS. 5 and 6)
As shown in FIG. 5, the test device 10 </ b> D according to the fourth embodiment is provided with a spiral groove 41 on the inner wall surface of the first reservoir 21. Other configurations are the same as those of the first embodiment. As explained in the first embodiment, the test liquid is reciprocated between the reservoirs 21 and 22, and is passed through the spiral groove 41 of the reservoir 21 so as to be rotationally stirred and mixed. The antigen concentration distribution is uniformized. It is preferable that the opening area of the upper part of the storage part 21 is set to a wide eye so that the stirring and mixing of the test solution by the groove part 41 can easily occur. It is effective to assume a sphere having the same volume as that of the test liquid and to set the opening area to be approximately 1/10 or more of the projected area on the basis of the planar projected area of the sphere.

螺旋状溝部４１を構成する板部材は図６に示す形状をなしており、溝部４１の段数は任意である。試験液の回転混合を効率よく行うために、溝部４１の幅寸法Ｄ１、（外径Ｄ２−内径Ｄ３）／２、は溝部４１の高さＨより大きく設定することが好ましい。これにて、試験液が溝部４１より内側の貫通穴部分４２を通過する場合の流路抵抗より、溝部４１を通過する場合の流路抵抗が小さくなるため、試験液が溝部４１を通過しやすくなり、試験液の回転混合効果が向上する。   The plate member constituting the spiral groove 41 has the shape shown in FIG. 6, and the number of steps of the groove 41 is arbitrary. In order to efficiently rotate and mix the test solution, it is preferable to set the width dimension D1 of the groove portion 41, (outer diameter D2−inner diameter D3) / 2, to be larger than the height H of the groove portion 41. As a result, the flow resistance when the test solution passes through the groove 41 is smaller than the flow resistance when the test solution passes through the through-hole portion 42 inside the groove 41, so that the test solution easily passes through the groove 41. Thus, the rotational mixing effect of the test solution is improved.

なお、図６において、溝部４１を構成する板部材の断面形状は矩形形状であるが、下方に傾斜させたり、角部に丸みを付けることにより、試験液の通過後の液残りを低減させることができる。   In FIG. 6, the cross-sectional shape of the plate member constituting the groove portion 41 is a rectangular shape. However, by reducing the liquid residue after passing the test solution by inclining downward or rounding the corner portion, Can do.

（第５実施例、図７参照）
第５実施例である試験デバイス１０Ｅは、図７に示すように、第１の貯留部２１の内壁面に設けた螺旋状の溝部４３を構成する板部材の断面形状を、内側に細いテーパ形状としたものである。他の構成や作用効果は、前記第１実施例及び前記第４実施例と同様である。 (Refer to the fifth embodiment, FIG. 7)
As shown in FIG. 7, the test device 10E according to the fifth embodiment has a cross-sectional shape of the plate member that forms the spiral groove 43 provided on the inner wall surface of the first storage portion 21, and a narrow taper shape on the inside. It is what. Other configurations and operational effects are the same as those of the first and fourth embodiments.

（第６実施例、図８参照）
第６実施例である試験デバイス１０Ｆは、図８に示すように、第１の貯留部２１の内壁面に螺旋状の階段部４４を設けたものである。他の構成は前記第１実施例と同様である。本第６実施例では、貯留部２１において螺旋状の階段部４４にて試験液が回転攪拌されて混合され、試験液中での抗原の濃度分布が均一化される。 (See the sixth embodiment, FIG. 8)
As shown in FIG. 8, the test device 10 </ b> F according to the sixth embodiment is provided with a spiral staircase 44 on the inner wall surface of the first reservoir 21. Other configurations are the same as those of the first embodiment. In the sixth embodiment, the test solution is rotationally stirred and mixed in the spiral staircase 44 in the storage unit 21, and the antigen concentration distribution in the test solution is made uniform.

（他の実施例）
なお、本発明に係る試験デバイス及び反応装置は前記実施例に限定するものではなく、その要旨の範囲内で種々に変更できる。以下に、前記実施例に記載した以外の種々の実施例について説明する。 (Other examples)
In addition, the test device and reaction apparatus which concern on this invention are not limited to the said Example, It can change variously within the range of the summary. Various embodiments other than those described in the above embodiments will be described below.

特に、反応部での反応については、前記抗原と抗体の免疫反応以外に種々の反応であってもよい。但し、抗原と抗体の免疫反応の場合は、抗原の分子サイズが比較的大きくて自発的な拡散をしにくい特性を持っているため、本発明のように、積極的に濃度分布を均一化するように試験液を動作させることは非常に有効である。   In particular, the reaction in the reaction part may be various reactions other than the immune reaction between the antigen and the antibody. However, in the case of an immune reaction between an antigen and an antibody, since the molecular size of the antigen is relatively large and has the property of preventing spontaneous diffusion, the concentration distribution is actively made uniform as in the present invention. It is very effective to operate the test solution.

試験液に振動を与える振動子は、試験デバイス自体に貼着したものではなく、外部から圧電アクチュエータ、電磁アクチュエータなどを押し付ける形態であってもよい。また、振動子は第２の貯留部に設けてもよく、第１及び第２の貯留部の両方に設けてもよい。振動子は、部分的に振動を与えるのではなく、試験デバイスを全体的に振動させるものであってもよい。   The vibrator that applies vibration to the test solution is not attached to the test device itself, and may be a form in which a piezoelectric actuator, an electromagnetic actuator, or the like is pressed from the outside. Further, the vibrator may be provided in the second storage part, or may be provided in both the first and second storage parts. The vibrator may be one that vibrates the test device as a whole rather than partially vibrating it.

反応の検出方法についても、光学的特性の検出以外に、電気的特性などの検出や、着色状態を目視で検出する方法であってもよい。検出手段は反応装置に含まれていてもよく、反応装置とは別の装置として構成されていてもよい。光学的な検出を補助するために、レンズ、導波路、プリズムなどが試験デバイスに組み込まれていてもよい。   The reaction detection method may be a method of detecting electrical characteristics or the like, or a method of visually detecting a colored state, in addition to the detection of optical characteristics. The detection means may be included in the reaction apparatus, or may be configured as an apparatus different from the reaction apparatus. Lenses, waveguides, prisms, etc. may be incorporated into the test device to assist in optical detection.

また、検出効率を上げるために、蛍光体などの標識物質を用いてもよい。即ち、固定化された抗体（固相抗体）と抗原の免疫反応の場合、別途、抗原に対して特異的に反応し得る標識用の抗体（標識抗体）を蛍光体で予め修飾しておいたものを用いてもよい。   In order to increase the detection efficiency, a labeling substance such as a phosphor may be used. That is, in the case of an immune reaction between an immobilized antibody (solid phase antibody) and an antigen, a labeling antibody (labeled antibody) that can react specifically with the antigen is previously modified with a phosphor. A thing may be used.

固相抗体と反応して反応部に捕捉された抗原に対して、さらに、前記標識抗体が含まれる溶液を送液することによって、反応部に捕捉された抗原に対して蛍光体を標識させることもできる。あるいは、予め蛍光体を修飾させた標識抗体を抗原と反応させて蛍光標識させた複合体を生成させ、該複合体を反応部に送液することによって固相抗体と抗原との反応を検出しやすくすることもできる。これらの標識抗体、あるいは、抗原と標識抗体とが反応した複合体を微細流路に送液する場合においても、複数回の送液途中に濃度を均一化することで反応効率の向上が期待できる。   The antigen captured by the reaction part after reacting with the solid phase antibody is further fed with a solution containing the labeled antibody so that the antigen captured by the reaction part is labeled with a fluorescent substance. You can also. Alternatively, a labeled antibody whose phosphor is modified in advance is reacted with an antigen to produce a fluorescently labeled complex, and the complex is sent to the reaction part to detect the reaction between the solid phase antibody and the antigen. It can also be made easier. Even when these labeled antibodies or a complex in which an antigen and labeled antibody are reacted are sent to a fine channel, the reaction efficiency can be expected to be improved by homogenizing the concentration during multiple times of feeding. .

濃度分布を均一化するように試験液を動作させる手段としては、以下の態様を採用してもよい。例えば、反応部を含む微細流路の上流側又は下流側の少なくとも一方にスターラー（磁気回転子）を入れておき、試験デバイスの外部で磁石を回転させたり、電磁石をオン／オフさせるなどの方法で磁場を変化させ、スターラーを回転させて試験液を攪拌してもよい。スターラーに代えて磁気ビーズを用いることもできる。   The following modes may be employed as means for operating the test solution so as to make the concentration distribution uniform. For example, a method in which a stirrer (magnetic rotator) is inserted in at least one of the upstream side or the downstream side of the micro flow path including the reaction part, and the magnet is rotated outside the test device, or the electromagnet is turned on / off. The test solution may be stirred by changing the magnetic field and rotating the stirrer. Magnetic beads can be used in place of the stirrer.

あるいは、反応部を含む微細流路の上流側又は下流側の少なくとも一方に、試験液よりも比重の大きいセラミック微粒子を入れておき、試験デバイスの外部から振動を与えることで試験液中で該微粒子を振動させてもよい。あるいは、反応部を含む微細流路の上流側又は下流側の少なくとも一方に電極を配置し、該電極に交流電圧を印加することで試験液中のイオン、その他の電気的特性を有する物質を振動させてもよい。該電極に交流電圧を印加したときに、抗原などの試験物質そのものが電気的な力によって試験液中を移動する現象を利用してもよい。   Alternatively, ceramic fine particles having a specific gravity larger than that of the test liquid are placed in at least one of the upstream side or the downstream side of the fine flow path including the reaction part, and the fine particles are contained in the test liquid by applying vibration from the outside of the test device. May be vibrated. Alternatively, an electrode is arranged on at least one of the upstream side or downstream side of the micro flow path including the reaction part, and an alternating voltage is applied to the electrode to vibrate ions or other substances having electrical characteristics in the test solution. You may let them. A phenomenon may be utilized in which when an AC voltage is applied to the electrode, a test substance such as an antigen moves in the test solution by an electric force.

以上のように、本発明は、微細流路を有する試験デバイス及び反応装置に有用であり、特に、反応効率が向上する点で優れている。   As described above, the present invention is useful for a test device and a reaction apparatus having a fine channel, and is particularly excellent in that the reaction efficiency is improved.

１０Ａ〜１０Ｆ…試験デバイス
１１…微細流路
１２…反応部
２１，２２…貯留部
２８…振動子
３０…空気ポンプ
３５…チューブポンプ
４１，４３…螺旋状溝部
４４…螺旋状階段部 DESCRIPTION OF SYMBOLS 10A-10F ... Test device 11 ... Fine flow path 12 ... Reaction part 21,22 ... Reservoir 28 ... Vibrator 30 ... Air pump 35 ... Tube pump 41, 43 ... Spiral groove part 44 ... Spiral step part

Claims (7)

試験液中に分散された試験物質と反応し得る反応物質が固定化された反応部をその一部に有する微細流路と、
前記微細流路の一方側及び他方側の少なくとも一方に、前記試験液中における試験物質の濃度分布を均一化するように試験液を動作させる均一化手段と、
を備え、
前記微細流路は試験液が複数回繰り返して流通されるように使用され、
前記均一化手段は、前記微細流路の一方側及び他方側の少なくとも一方において、前記試験液の液量以上の容積を有する試験液の貯留部に備えられていること、
を特徴とする試験デバイス。 A fine channel having, in part, a reaction part in which a reactive substance capable of reacting with a test substance dispersed in a test solution is fixed;
Homogenizing means for operating the test solution so that the concentration distribution of the test substance in the test solution is made uniform on at least one of the one side and the other side of the fine channel;
With
The fine channel is used so that the test solution is repeatedly circulated a plurality of times,
The homogenizing means is provided in a test liquid storage section having a volume equal to or larger than the liquid volume of the test liquid on at least one of the one side and the other side of the fine flow path;
Test device characterized by. 前記均一化手段は、少なくとも一度前記反応部を通過して前記貯留部に送液された試験液を攪拌する手段であることを特徴とする請求項１に記載の試験デバイス。   2. The test device according to claim 1, wherein the homogenizing means is means for stirring the test solution that has passed through the reaction unit and sent to the storage unit at least once. 前記均一化手段は振動子であることを特徴とする請求項１又は請求項２に記載の試験デバイス。   The test device according to claim 1, wherein the uniformizing means is a vibrator. 前記均一化手段は螺旋状の溝部であることを特徴とする請求項１又は請求項２に記載の試験デバイス。   The test device according to claim 1, wherein the uniformizing means is a spiral groove. 前記均一化手段は螺旋状の階段部であることを特徴とする請求項１又は請求項２に記載の試験デバイス。   The test device according to claim 1, wherein the uniformizing means is a spiral stepped portion. 前記反応部での反応が抗原と抗体との免疫反応であることを特徴とする請求項１ないし請求項５のいずれかに記載の試験デバイス。   The test device according to claim 1, wherein the reaction in the reaction part is an immune reaction between an antigen and an antibody. 請求項１ないし請求項６のいずれかに記載の試験デバイスと、
前記微細流路に前記試験液を複数回繰り返して流通させるための送液手段と、
を備え、
前記送液手段は前記試験液を往復送液するものであること、
を特徴とする反応装置。 A test device according to any of claims 1 to 6;
A liquid feeding means for allowing the test liquid to flow through the fine channel repeatedly a plurality of times;
With
The liquid feeding means is for reciprocating the test liquid;
A reactor characterized by.
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Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002540405A (en) * 1999-03-22 2002-11-26 バイアコア アーベー Reversible flow conduit system
US20040028559A1 (en) * 2001-11-06 2004-02-12 Peter Schuck Sample delivery system with laminar mixing for microvolume biosensing
JP2004321063A (en) * 2003-04-24 2004-11-18 Yaskawa Electric Corp Microreactor
JP2005134372A (en) * 2003-10-06 2005-05-26 Matsushita Electric Ind Co Ltd Test substance measurement device
JP2005199245A (en) * 2004-01-19 2005-07-28 Dainippon Printing Co Ltd Micromixer and its production method
JP2006053091A (en) * 2004-08-13 2006-02-23 Alps Electric Co Ltd Plate
JP2006051459A (en) * 2004-08-13 2006-02-23 Hitachi Ltd Fluid control system
JP2006090717A (en) * 2004-09-21 2006-04-06 Fuji Photo Film Co Ltd Sensing method and device in utilizing attenuated total reflection, and immobilizing device
JP2006090985A (en) * 2004-09-27 2006-04-06 Fuji Photo Film Co Ltd Measuring apparatus utilizing total reflection attenuation and method therefor
JP2006142210A (en) * 2004-11-19 2006-06-08 Hitachi Maxell Ltd Microchip and fluid mixing method using the same
JP2007071711A (en) * 2005-09-07 2007-03-22 Fujifilm Corp Analytic chip
JP2008148677A (en) * 2006-12-16 2008-07-03 Fumito Arai Method for producing micromagnetic tool, and method for producing the micromagnetic tool device
JP2008212882A (en) * 2007-03-07 2008-09-18 Toyama Prefecture Micromixer

Patent Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002540405A (en) * 1999-03-22 2002-11-26 バイアコア アーベー Reversible flow conduit system
US20040028559A1 (en) * 2001-11-06 2004-02-12 Peter Schuck Sample delivery system with laminar mixing for microvolume biosensing
JP2004321063A (en) * 2003-04-24 2004-11-18 Yaskawa Electric Corp Microreactor
JP2005134372A (en) * 2003-10-06 2005-05-26 Matsushita Electric Ind Co Ltd Test substance measurement device
JP2005199245A (en) * 2004-01-19 2005-07-28 Dainippon Printing Co Ltd Micromixer and its production method
JP2006053091A (en) * 2004-08-13 2006-02-23 Alps Electric Co Ltd Plate
JP2006051459A (en) * 2004-08-13 2006-02-23 Hitachi Ltd Fluid control system
JP2006090717A (en) * 2004-09-21 2006-04-06 Fuji Photo Film Co Ltd Sensing method and device in utilizing attenuated total reflection, and immobilizing device
JP2006090985A (en) * 2004-09-27 2006-04-06 Fuji Photo Film Co Ltd Measuring apparatus utilizing total reflection attenuation and method therefor
JP2006142210A (en) * 2004-11-19 2006-06-08 Hitachi Maxell Ltd Microchip and fluid mixing method using the same
JP2007071711A (en) * 2005-09-07 2007-03-22 Fujifilm Corp Analytic chip
JP2008148677A (en) * 2006-12-16 2008-07-03 Fumito Arai Method for producing micromagnetic tool, and method for producing the micromagnetic tool device
JP2008212882A (en) * 2007-03-07 2008-09-18 Toyama Prefecture Micromixer

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