JP5071272B2 - Liquid channel device - Google Patents

Liquid channel device

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JP5071272B2
JP5071272B2 JP2008167005A JP2008167005A JP5071272B2 JP 5071272 B2 JP5071272 B2 JP 5071272B2 JP 2008167005 A JP2008167005 A JP 2008167005A JP 2008167005 A JP2008167005 A JP 2008167005A JP 5071272 B2 JP5071272 B2 JP 5071272B2
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liquid
tank
flow path
adhesive layer
sample
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JP2010008190A (en
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茂 高橋
正明 櫻井
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Fujikura Kasei Co Ltd
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Fujikura Kasei Co Ltd
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Priority to US13/934,320 priority patent/US9283562B2/en
Priority to US13/934,314 priority patent/US9579653B2/en
Priority to US13/934,310 priority patent/US9283561B2/en
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本発明は、例えば血液中の抗原の検出、分析などに好適に使用される平板状の液体流路装置に関する。   The present invention relates to a flat liquid channel device that is suitably used for detecting and analyzing antigens in blood, for example.

近年、医療分野、環境分野などでは、液体試料中の微量成分の検出、分析が頻繁に行われており、その際、例えば医療分野では、基板に流路が形成されたマイクロチップと呼ばれる液体流路装置が使用される場合が多い。
例えば特許文献1には、マイクロチップに形成された液体流路内で、抗体を含有する試薬と血液とを混合、反応させた後、該マイクロチップごと検出装置に供して、抗原抗体反応を検出する技術が記載されている。また、例えば特許文献2には、回転可能なディスクの半径方向に流路を複数形成し、この流路の一部にあらかじめ抗体を固定しておき、その後、流路に体液を流通させることによって、抗原抗体反応により体液中の抗原を抗体に捕捉させるディスク状の液体流路装置が開示されている。
特開2007−139500号公報 特開平05−005741号公報
In recent years, detection and analysis of trace components in a liquid sample are frequently performed in the medical field, the environmental field, and the like. In this case, for example, in the medical field, a liquid flow called a microchip having a channel formed on a substrate is used. Road equipment is often used.
For example, in Patent Document 1, an antibody-containing reagent and blood are mixed and reacted in a liquid channel formed in a microchip, and then the whole microchip is provided to a detection device to detect an antigen-antibody reaction. The technology to do is described. Further, for example, in Patent Document 2, a plurality of flow paths are formed in the radial direction of a rotatable disk, antibodies are fixed in advance in a part of the flow paths, and then body fluid is circulated through the flow paths. A disc-shaped liquid channel device is disclosed in which an antigen in a body fluid is captured by an antibody by an antigen-antibody reaction.
JP 2007-139500 A JP 05-005741 A

しかしながら、このような従来の液体流路装置では、液体流路を閉止したり開通させたりすることができず、目的の成分の検出、分析に不都合が生じることがあった。   However, in such a conventional liquid channel device, the liquid channel cannot be closed or opened, which may cause inconvenience in detection and analysis of the target component.

本発明の目的は、簡便に液体流路を閉止状態から開通状態にできる液体流路装置を低コストで提供することである。   An object of the present invention is to provide a liquid flow path device that can easily change a liquid flow path from a closed state to an open state at a low cost.

本発明の液体流路装置は、基板の少なくとも片面に、試料および試薬の少なくとも一方からなる液体が流通する液体流路が形成され、前記基板の前記液体流路が形成された流路形成面には蓋板が積層した液体流路装置であって、前記液体流路の一部を閉止状態から開通状態にする開通手段を有し、前記蓋板は、該蓋板の表面を構成する第1基材層と、該第1基材層の内側に形成された強粘着層と、該強粘着層の内側に形成された第2基材層と、該第2基材層の内側に形成され、前記流路形成面に粘着する弱粘着層とを有し、前記開通手段では、前記液体流路に第1凸部が形成され、該第1凸部の頂部と前記弱粘着層とが粘着し、かつ、前記強粘着層と前記第2基材層とが離間していることを特徴とする。
液体流路装置は、前記液体流路の一部を開通状態から閉止状態にする閉止手段をさらに有し、前記閉止手段では、前記液体流路に第2凸部が形成され、該第2凸部の頂部と前記弱粘着層とが離間し、かつ、前記強粘着層と前記第2基材層との間にはスペーサ部材が介在し、該スペーサ部材と前記強粘着層とが粘着していることが好ましい。
前記液体流路には、一定量の液体を計量する計量槽が設けられ、少なくとも該計量槽の上流には前記閉止手段が設けられ、下流には前記開通手段が設けられていることが好ましい。
前記計量槽には、前記一定量を超えた液体をオーバーフローさせるオーバーフロー手段が設けられていることが好ましい。
In the liquid channel device of the present invention, a liquid channel through which a liquid composed of at least one of a sample and a reagent flows is formed on at least one surface of the substrate, and the channel forming surface on which the liquid channel of the substrate is formed Is a liquid flow path device in which a cover plate is laminated, and has an opening means for bringing a part of the liquid flow path from a closed state to an open state, and the cover plate forms a first surface of the cover plate. A base material layer, a strong adhesive layer formed inside the first base material layer, a second base material layer formed inside the strong adhesive layer, and formed inside the second base material layer. A weak adhesive layer that adheres to the flow path forming surface, and in the opening means, a first convex portion is formed in the liquid flow channel, and the top of the first convex portion and the weak adhesive layer adhere to each other. In addition, the strong adhesion layer and the second base material layer are separated from each other.
The liquid channel device further includes a closing unit that changes a part of the liquid channel from an open state to a closed state, and the closing unit includes a second convex portion formed in the liquid channel. The top of the part and the weak adhesive layer are separated from each other, and a spacer member is interposed between the strong adhesive layer and the second base material layer, and the spacer member and the strong adhesive layer adhere to each other. Preferably it is.
It is preferable that a measuring tank for measuring a certain amount of liquid is provided in the liquid flow path, the closing means is provided at least upstream of the measuring tank, and the opening means is provided downstream.
It is preferable that the weighing tank is provided with overflow means for overflowing the liquid exceeding the certain amount.

本発明によれば、簡便に液体流路を閉止状態から開通状態にできる液体流路装置を低コストで提供できる。   ADVANTAGE OF THE INVENTION According to this invention, the liquid flow path apparatus which can make a liquid flow path from a closed state to an open state simply can be provided at low cost.

以下、本発明について詳細に説明する。
図1は本発明の液体流路装置の一実施形態例を概略的に示す平面透視図、図2は図1の液体流路装置の一部を拡大した平面透視図、図3は図2のI−I’線に沿う断面図である。
この液体流路装置10Aは、平板からなる四角形の基板11Aの片面に、試料および試薬の少なくとも一方からなる液体が流通する溝状の液体流路12と、液体流路12の端部や途中において液体が溜まる複数(この例では9)の液槽(14a〜14i)とが形成され、基板11Aの液体流路12が形成された側の流路形成面12aに蓋板13が積層して構成されたものである。この液体流路装置10Aにおいては、図1中の上端部側が上方に、下端部側が下方に位置するように立てた場合には、液体流路12の上流側の端部から下流側の端部に向けて矢印F方向に試料が重力により流通し、その途中で試料に対して各種の処理や試薬との混合がなされ、各種検出、分析に供される測定液とされる。
Hereinafter, the present invention will be described in detail.
FIG. 1 is a plan perspective view schematically showing an embodiment of the liquid flow path device of the present invention, FIG. 2 is a plan perspective view in which a part of the liquid flow path device of FIG. 1 is enlarged, and FIG. It is sectional drawing which follows the II 'line.
This liquid flow path device 10A includes a groove-shaped liquid flow path 12 through which a liquid consisting of at least one of a sample and a reagent flows on one side of a flat substrate 11A made of a flat plate, and an end portion or a middle of the liquid flow path 12 A plurality (9 in this example) of liquid reservoirs (14a to 14i) in which liquid is accumulated is formed, and the cover plate 13 is laminated on the flow path forming surface 12a on the side where the liquid flow path 12 of the substrate 11A is formed. It has been done. In this liquid channel device 10A, when the upper end side in FIG. 1 is positioned upward and the lower end side is positioned downward, the end portion on the downstream side from the upstream end portion of the liquid channel 12 is provided. The sample flows in the direction of the arrow F toward the arrow F by gravity, and the sample is mixed with various treatments and reagents in the middle of the sample and used as a measurement solution for various detections and analyses.

すなわち、液体流路12の上流側の端部には、投入された試料が溜まる試料投入槽14aが設けられ、この試料投入槽14aの下流には、試料投入槽14aから流通してきた試料に対してろ過処理が施される図示略のフィルタが内蔵されたろ過槽14bが設けられている。
ろ過槽14bの下流には、ろ過処理された試料を一定量計量する計量槽14cが設けられている。この例の計量槽14cには、オーバーフロー流路12bとその下流に設けられた廃液槽14dとからなるオーバーフロー手段が備えられている。そのため、計量槽14cで一定量を超えた試料はオーバーフローしてオーバーフロー流路12bを流れ、廃液槽14dに流入し、その結果、計量槽14cでは、一定量の試料が計量できるようになっている。
That is, at the upstream end of the liquid flow path 12, a sample loading tank 14a in which the loaded sample is stored is provided, and downstream of the sample loading tank 14a, the sample flowing from the sample loading tank 14a is provided. A filtration tank 14b containing a filter (not shown) to be filtered is provided.
A measuring tank 14c for measuring a fixed amount of the filtered sample is provided downstream of the filtering tank 14b. The measuring tank 14c of this example is provided with overflow means comprising an overflow channel 12b and a waste liquid tank 14d provided downstream thereof. Therefore, the sample exceeding a certain amount in the measuring tank 14c overflows and flows through the overflow channel 12b and flows into the waste liquid tank 14d. As a result, the measuring tank 14c can measure a certain amount of sample. .

計量槽14cの下流には、計量槽14cで計量された試料と、あらかじめ第1試薬槽14eに所定量封入されている液体の第1試薬とが混合される第1混合槽14fが設けられ、第1混合槽14fの下流には、第1混合槽14fで調製された中間調製液と、あらかじめ第2試薬槽14gに所定量封入されている液体の第2試薬とが混合される第2混合槽14hが設けられている。
そして、第2混合槽14hの下流(液体流路12の下流側の端部)には測定槽14iが設けられ、第2混合槽14hで調製された測定液がここに貯留され、図示略の検出分析手段により、各種成分の検出や分析がなされるようになっている。
なお、各液槽には、大気と連通する図示略の連通孔が設けられている。
Downstream of the measuring tank 14c, a first mixing tank 14f is provided in which the sample weighed in the measuring tank 14c and the liquid first reagent previously sealed in the first reagent tank 14e are mixed. Downstream of the first mixing tank 14f is a second mixing in which the intermediate preparation liquid prepared in the first mixing tank 14f and the liquid second reagent sealed in a predetermined amount in the second reagent tank 14g are mixed. A tank 14h is provided.
A measurement tank 14i is provided downstream of the second mixing tank 14h (the end on the downstream side of the liquid flow path 12), and the measurement liquid prepared in the second mixing tank 14h is stored here, and is not illustrated. Detection and analysis means detect and analyze various components.
Each liquid tank is provided with a communication hole (not shown) that communicates with the atmosphere.

また、この液体流路装置10Aの蓋板13は、図3に示すように、蓋板13の表面を構成する第1基材層13aと、第1基材層13aの内側に形成された強粘着層13bと、強粘着層13bの内側に形成された第2基材層13cと、第2基材層13cの内側に形成され、流路形成面12aに粘着する弱粘着層13dとを有して構成されている。
第1基材層13aは、表面側から垂直方向(第1基材層13aと垂直に交差する方向)の荷重が加えられた場合には撓み、その後、荷重が取り去られた場合には元に戻る復元力を有する材料からなっている。一方、第2基材層13cは、同様の荷重により容易に撓み、荷重を取り去っても復元しない、すなわち容易に塑性変形する材料からなっている。また、強粘着層13bの粘着力は、弱粘着層13dよりも大きく形成されている。
Further, as shown in FIG. 3, the lid plate 13 of the liquid channel device 10A includes a first base material layer 13a constituting the surface of the lid plate 13 and a strong member formed on the inner side of the first base material layer 13a. An adhesive layer 13b, a second base material layer 13c formed inside the strong adhesive layer 13b, and a weak adhesive layer 13d formed inside the second base material layer 13c and sticking to the flow path forming surface 12a are provided. Configured.
The first base material layer 13a bends when a load in the vertical direction (a direction perpendicular to the first base material layer 13a) is applied from the surface side, and then returns to the original when the load is removed. It is made of a material having a restoring force to return to On the other hand, the second base material layer 13c is made of a material that is easily bent by the same load and does not recover even when the load is removed, that is, easily plastically deformed. Moreover, the adhesive force of the strong adhesion layer 13b is formed larger than the weak adhesion layer 13d.

また、この液体流路装置10Aは、液体流路12の一部を閉止状態から開通状態にする開通手段S1〜S7と、開通状態から閉止状態にする閉止手段T1とを有している。
この例では、開通手段S1〜S7は、試料投入槽14aとろ過槽14bとの間、ろ過槽14bと計量槽14cとの間、計量槽14cと第1混合槽14fとの間、第1混合槽14fと第2混合槽14hとの間、第1試薬槽14eと第1混合槽14fとの間、第2試薬槽14gと第2混合槽14hとの間、第2混合槽14hと測定槽14iとの間の各液体流路12にそれぞれ1ずつ設けられている。
一方、閉止手段T1は、ろ過槽14bと計量槽14cとの間の液体流路12において、開通手段S2よりも下流側に設けられている。
Further, the liquid flow path device 10A includes opening means S1 to S7 for bringing a part of the liquid flow path 12 from the closed state to the open state, and a closing means T1 for changing the open state to the closed state.
In this example, the opening means S1 to S7 include the first mixing tank 14a and the filtering tank 14b, the filtering tank 14b and the measuring tank 14c, the measuring tank 14c and the first mixing tank 14f, Between the tank 14f and the second mixing tank 14h, between the first reagent tank 14e and the first mixing tank 14f, between the second reagent tank 14g and the second mixing tank 14h, and between the second mixing tank 14h and the measuring tank One is provided in each liquid flow path 12 between 14i.
On the other hand, the closing means T1 is provided downstream of the opening means S2 in the liquid channel 12 between the filtration tank 14b and the measuring tank 14c.

そして、各開通手段S1〜S7においては、図3のS1およびS2を例示して説明すると、液体流路12に第1凸部15が形成され、この第1凸部15の頂部15aと弱粘着層13dとが粘着し、かつ、強粘着層13bと第2基材層13cとが離間している。
よって、各開通手段S1〜S7における液体流路12は、第1凸部15とこれの頂部15aに粘着した弱粘着層13dとにより閉じられ、通常時は閉止状態となっている。ところが、図4に開通手段S1を例に挙げて示すように、この開通手段S1おける第1基材層13aを表面側から矢印Aで示すように押圧して、第1基材層13aに垂直方向の荷重を加えた場合には、図4(a)に示すように、第1基材層13aが撓み、第1基材層13aの内側の強粘着層13bが第2基材層13cに粘着する。そして、その後に荷重を取り去ると、図4(b)に示すように、第1基材層13aはその復元力により元の状態に復元し、その際、第1基材層13aの内側に粘着した強粘着層13bと、強粘着層13bに粘着し、容易に塑性変形可能な第2基材層13cと、第2基材層13cの内側に粘着した弱粘着層13dも第1基材層13aの復元に追従し、持ち上がる。その結果、第1凸部15の頂部15aと弱粘着層13dとの間が新たに離間し、ここを液体が流通できるようになる。
このように開通手段S1〜S7においては、蓋板13を表面側から押圧して垂直方向の荷重を加えた後、この荷重を取り去る押圧操作によって、元々は粘着していた第1凸部15の頂部15aと弱粘着層13dとの間が離間し、その結果、この部分の液体流路12が閉止状態から開通状態となる。
And in each opening means S1-S7, if S1 and S2 of FIG. 3 are illustrated and demonstrated, the 1st convex part 15 will be formed in the liquid flow path 12, and the top part 15a of this 1st convex part 15 and weak adhesion The layer 13d is adhered, and the strong adhesion layer 13b and the second base material layer 13c are separated from each other.
Therefore, the liquid flow path 12 in each of the opening means S1 to S7 is closed by the first convex portion 15 and the weak adhesive layer 13d adhered to the top portion 15a, and is normally closed. However, as shown in FIG. 4 taking the opening means S1 as an example, the first base material layer 13a in the opening means S1 is pressed from the surface side as indicated by the arrow A, and is perpendicular to the first base material layer 13a. When a load in the direction is applied, as shown in FIG. 4A, the first base material layer 13a bends, and the strong adhesive layer 13b inside the first base material layer 13a becomes the second base material layer 13c. Stick. Then, when the load is removed thereafter, as shown in FIG. 4B, the first base material layer 13a is restored to its original state by its restoring force, and at that time, the first base material layer 13a is adhered to the inside of the first base material layer 13a. The strong adhesion layer 13b, the second substrate layer 13c that adheres to the strong adhesion layer 13b and can be easily plastically deformed, and the weak adhesion layer 13d that adheres to the inside of the second substrate layer 13c are also the first substrate layer. Follows the recovery of 13a and lifts. As a result, the top portion 15a of the first convex portion 15 and the weak adhesive layer 13d are newly separated from each other, and the liquid can flow therethrough.
In this way, in the opening means S1 to S7, after pressing the cover plate 13 from the surface side and applying a load in the vertical direction, by the pressing operation to remove this load, the first convex portion 15 that was originally adhered is removed. The top portion 15a and the weak adhesive layer 13d are separated from each other, and as a result, the liquid flow path 12 in this portion is changed from the closed state to the open state.

一方、閉止手段T1においては、図3に示すように、液体流路12に第2凸部16が形成され、この第2凸部16の頂部16aと弱粘着層13dとは離間し、かつ、強粘着層13bと第2基材層13cとの間にはスペーサ部材17が介在し、スペーサ部材17と強粘着層13bとが粘着している。
よって、閉止手段Tにおける液体流路12では、第2凸部16の頂部16aと弱粘着層13dとの間が離間して流路が保たれ、通常時は開通状態となっている。ところが、図5(a)に示すように、閉止手段T1における第1基材層13aを表面側から矢印Bで示すように押圧して、第1基材層13aに垂直方向の荷重を加えた場合には、第1基材層13aが撓み、その結果、蓋板13の最内層の弱粘着層13dが第2凸部16の頂部16aに粘着する。そして、その後に荷重を取り去ると、図5(b)に示すように、第1基材層13aはその復元力により元の状態に復元し、その際、第1基材層13aの内側に粘着した強粘着層13bと、強粘着層13bに粘着したスペーサ部材17は、第1基材層13aの復元に追従して持ち上がる。一方、スペーサ部材17と第2基材層13cとの間は粘着していないとともに、第2基材層13cは容易に塑性変形可能であるために、ここで荷重を取り去っても、第2基材層13cと弱粘着層13dは第1基材層13aの復元には追従しない。その結果、第2凸部16の頂部16aと弱粘着層13dとは粘着した状態となって液体流路12を閉止し、液体はここを流通できなくなる。
このように閉止手段T1においては、蓋板13を表面側から押圧して垂直方向の荷重を加えた後、この荷重を取り去る押圧操作によって、元々は離間していた第2凸部16の頂部16aと弱粘着層13dとの間が粘着して閉塞し、その結果、この部分の液体流路12が開通状態から閉止状態となる。
On the other hand, in the closing means T1, as shown in FIG. 3, a second convex portion 16 is formed in the liquid flow path 12, and the top portion 16a of the second convex portion 16 and the weak adhesive layer 13d are separated from each other, and A spacer member 17 is interposed between the strong adhesion layer 13b and the second base material layer 13c, and the spacer member 17 and the strong adhesion layer 13b are adhered.
Therefore, in the liquid flow path 12 in the closing means T, the top part 16a of the second convex part 16 and the weak adhesive layer 13d are separated from each other to maintain the flow path, and are normally open. However, as shown to Fig.5 (a), the 1st base material layer 13a in the closure means T1 was pressed from the surface side as shown by arrow B, and the load of the perpendicular direction was added to the 1st base material layer 13a. In this case, the first base material layer 13 a bends, and as a result, the innermost weak adhesive layer 13 d of the cover plate 13 adheres to the top 16 a of the second convex portion 16. Then, when the load is removed thereafter, as shown in FIG. 5B, the first base material layer 13a is restored to its original state by its restoring force, and at that time, the first base material layer 13a is adhered to the inside of the first base material layer 13a. The strong adhesive layer 13b and the spacer member 17 adhered to the strong adhesive layer 13b are lifted following the restoration of the first base material layer 13a. On the other hand, the spacer member 17 is not adhered between the second base material layer 13c and the second base material layer 13c can be easily plastically deformed. The material layer 13c and the weak adhesive layer 13d do not follow the restoration of the first base material layer 13a. As a result, the top portion 16a of the second convex portion 16 and the weak adhesive layer 13d are in an adhesive state, and the liquid channel 12 is closed, so that the liquid cannot flow therethrough.
As described above, in the closing means T1, the top plate 16a of the second convex portion 16 that was originally separated by pressing the cover plate 13 from the surface side and applying a load in the vertical direction and then removing the load. And the weak adhesive layer 13d are adhered and closed, and as a result, the liquid flow path 12 in this portion is changed from the open state to the closed state.

この液体流路装置10Aを用いて、測定液を調製する具体的な方法としては、まず、この液体流路装置10Aを試料投入槽14a側が上方に、測定槽14i側が下方に位置するように立てて、液体が重力によって上流側から下流側に流れやすい状態とする。
ついで、試料をシリンジなどにサンプリングし、このシリンジの針を試料投入槽14aに対応する部分の蓋板13に突き刺して、試料投入槽14aに試料を注入する。その後、試料投入槽14aとろ過槽14bとの間に設けられた開通手段S1を上述の押圧操作、すなわち、第1基材層13aを表面側から押圧して荷重を加えた後、取り去る操作で作動させ、この部分の液体流路12を開通状態とし、試料を重力によりろ過槽14bまで導入する。
この際、押圧操作は、作業者が指で第1基材層13aを表面側から押す手動により行ってもよいし、押圧位置がXY座標としてあらかじめプログラムされている押圧装置などを使用して、所定の位置を押すようにしてもよい。
As a specific method for preparing the measurement liquid using the liquid channel device 10A, first, the liquid channel device 10A is set up so that the sample introduction tank 14a side is located above and the measurement tank 14i side is located below. Thus, the liquid easily flows from the upstream side to the downstream side by gravity.
Next, the sample is sampled in a syringe or the like, and the needle of this syringe is pierced into the cover plate 13 corresponding to the sample loading tank 14a to inject the sample into the sample loading tank 14a. Thereafter, the opening means S1 provided between the sample charging tank 14a and the filtration tank 14b is pressed as described above, that is, the first base material layer 13a is pressed from the surface side to add a load, and then removed. The liquid channel 12 in this portion is opened, and the sample is introduced to the filtration tank 14b by gravity.
At this time, the pressing operation may be performed manually by the operator manually pressing the first base material layer 13a from the surface side with a finger, or the pressing position is pre-programmed as XY coordinates, You may make it push a predetermined position.

ついで、ろ過槽14bでろ過処理がなされた後、ろ過槽14bと計量槽14cとの間に設けられた開通手段S2を押圧操作で作動させて、この部分の液体流路12を開通状態とし、試料を重力により計量槽14cに導入する。
ついで、計量槽14cにおいて、導入された液体がオーバーフローし始めたことを確認後、ろ過槽14bと計量槽14cとの間に設けられた閉止手段T1を押圧操作で作動させて、この部分の液体流路12を閉止状態とする。このようにして、計量槽14cに上流側からの液体がさらに流入するのを停止させてから、計量槽14cの下流に設けられた開通手段S3を作動させて、計量槽14cで計量された試料を第1混合槽14fに導入する。
Next, after the filtration treatment is performed in the filtration tank 14b, the opening means S2 provided between the filtration tank 14b and the measuring tank 14c is operated by pressing operation, and the liquid flow path 12 of this portion is opened, The sample is introduced into the weighing tank 14c by gravity.
Then, after confirming that the introduced liquid has started to overflow in the measuring tank 14c, the closing means T1 provided between the filtration tank 14b and the measuring tank 14c is operated by a pressing operation, and the liquid in this portion The flow path 12 is closed. In this way, after stopping the further flow of the liquid from the upstream side into the measuring tank 14c, the opening means S3 provided downstream of the measuring tank 14c is operated, and the sample measured in the measuring tank 14c. Is introduced into the first mixing tank 14f.

こうして計量後の試料を第1混合槽14fに導入する一方で、第1試薬槽14eと第1混合槽14fとの間の開通手段S4を押圧操作で作動させて第1試薬を第1混合槽14fに導入し、試料と第1試薬とを第1混合槽14fにおいて混合し、中間調製液を調製する。
ついで、第1混合槽14fと第2混合槽14hとの間の開通手段S5を押圧操作で作動させて第1混合槽14fで調製された中間調製液を第2混合槽14hに導入する一方で、第2試薬槽14gと第2混合槽14hとの間の開通手段S6を押圧操作で作動させて第2試薬を第2混合槽14hに導入し、中間調製液と第2試薬とを第2混合槽14hにおいて混合し、測定液を調製する。
ついで、第2混合槽14hと測定槽14iとの間の開通手段S7を作動させ、第2混合槽14hで調製された測定液を測定槽14iに導入する。
そして、測定槽14iに測定液を導入した後、この液体流路装置10Aごと検出分析手段に供し、目的成分の検出や測定を行う。
In this way, while the sample after weighing is introduced into the first mixing tank 14f, the opening means S4 between the first reagent tank 14e and the first mixing tank 14f is operated by a pressing operation so that the first reagent is put into the first mixing tank 14f. The sample is introduced into 14f, and the sample and the first reagent are mixed in the first mixing tank 14f to prepare an intermediate preparation solution.
Next, while the opening means S5 between the first mixing tank 14f and the second mixing tank 14h is operated by a pressing operation, the intermediate preparation liquid prepared in the first mixing tank 14f is introduced into the second mixing tank 14h. Then, the opening means S6 between the second reagent tank 14g and the second mixing tank 14h is operated by a pressing operation to introduce the second reagent into the second mixing tank 14h, and the intermediate preparation solution and the second reagent are secondly added. Mix in the mixing tank 14h to prepare a measurement solution.
Next, the opening means S7 between the second mixing tank 14h and the measuring tank 14i is operated, and the measuring solution prepared in the second mixing tank 14h is introduced into the measuring tank 14i.
And after introduce | transducing a measurement liquid into the measurement tank 14i, it uses for a detection analysis means with this liquid flow path apparatus 10A, and a target component is detected and measured.

このような液体流通装置10Aによれば、液体流路12を閉止状態から開通状態にする開通手段S1〜S7と、開通状態から閉止状態にする閉止手段T1とを有するため、液体流路12中の液体の流れを制御でき、その結果、精度の高い検出や分析を短時間で行うことができる。
例えば、この例では、計量槽14cの上流には閉止手段T1が設けられ、下流には開通手段S3が設けられている。そのため、計量槽14cで試料を短時間で正確に計量して、第1混合槽14fに導入することができる。ここで仮に、計量槽14cの下流に開通手段S3が設けられておらず、この部分の液体流路12が常に開通した状態であると、計量中であっても計量槽14cから試料が連続的に流出してしまい、試料を一定量溜めることができず、計量自体が不可能となる。また、計量槽14cの上流に閉止手段T1が設けられていない場合には、ろ過槽14bを経た試料の全量が計量槽14cに完全に流入し終わってから、計量槽14cと第1混合槽14fの間の開通手段S3を作動させて、計量された試料を第1混合槽14fに導入する必要がある。この場合、試料が特に血液などの粘性を有した液体であると、ろ過槽14bを経た試料の全量が完全に計量槽14cに流入し終わるまでに時間を要し、短時間での計量が困難となる。その点、この例のように、計量槽14cの上流間に閉止手段T1が設けられていると、ろ過槽14bを経た試料の全量が計量槽14cに完全に流入し終わらなくても、計量槽14cにおいて試料がオーバーフローし始めた時点で閉止手段T1を作動させて、計量槽14cへの試料のさらなる流入を停止することができ、短時間での正確な計量が可能となる。
According to such a liquid circulation device 10 </ b> A, the liquid flow passage 12 has the opening means S <b> 1 to S <b> 7 for changing the liquid flow path 12 from the closed state to the open state and the closing means T <b> 1 for changing the open state to the closed state. As a result, highly accurate detection and analysis can be performed in a short time.
For example, in this example, closing means T1 is provided upstream of the weighing tank 14c, and opening means S3 is provided downstream. Therefore, the sample can be accurately weighed in a short time in the weighing tank 14c and introduced into the first mixing tank 14f. Here, if the opening means S3 is not provided downstream of the measuring tank 14c, and the liquid flow path 12 in this portion is always open, the sample continuously from the measuring tank 14c even during measurement. The sample cannot be collected in a certain amount, and measurement itself is impossible. In addition, when the closing means T1 is not provided upstream of the measuring tank 14c, after the entire amount of the sample that has passed through the filtration tank 14b has completely flowed into the measuring tank 14c, the measuring tank 14c and the first mixing tank 14f. It is necessary to introduce the weighed sample into the first mixing tank 14f by actuating the opening means S3 between the two. In this case, if the sample is a liquid having viscosity such as blood, it takes time until the entire amount of the sample passing through the filtration tank 14b completely flows into the measuring tank 14c, and it is difficult to measure in a short time. It becomes. In this respect, if the closing means T1 is provided between the upstream of the measuring tank 14c as in this example, even if the entire amount of the sample passing through the filtration tank 14b does not completely flow into the measuring tank 14c, the measuring tank When the sample starts to overflow in 14c, the closing means T1 can be operated to stop further inflow of the sample into the measuring tank 14c, and accurate measurement can be performed in a short time.

また、この例では、第1混合槽14fと第2混合槽14hとの間に開通手段S5が設けられ、第2混合槽14hと測定槽14iとの間に開通手段S7が設けられている。そのため、第1混合槽14fおよび第2混合槽14hにおいて、目的の混合や反応が十分に進行してから、これら開通手段S5、S7を開通させ、中間調製液や測定液をそれぞれ第2混合槽14hや測定槽14iに導入することができる。よって、混合や反応が不十分なことに起因する検出や分析の精度低下を防止することができる。   In this example, an opening means S5 is provided between the first mixing tank 14f and the second mixing tank 14h, and an opening means S7 is provided between the second mixing tank 14h and the measurement tank 14i. Therefore, in the first mixing tank 14f and the second mixing tank 14h, after the target mixing and reaction have sufficiently progressed, the opening means S5 and S7 are opened, and the intermediate preparation liquid and the measurement liquid are respectively supplied to the second mixing tank. 14h and the measuring tank 14i. Therefore, it is possible to prevent a decrease in detection and analysis accuracy due to insufficient mixing and reaction.

さらに、この例では、第1試薬槽14eと第1混合槽14fとの間、第2試薬槽14gと第2混合槽14hとの間にも開通手段S4、S6が設けられているため、所望の時点でこれらを開通させて、あらかじめ第1試薬槽14eおよび第2試薬槽14gにそれぞれ封入されている第1試薬および第2試薬を第1混合槽14fや第2混合槽14hに流入させることができる。仮に開通手段S4、S6が設けられていない場合には、液体流路装置10Aの保管時などに、第1試薬および第2試薬が下流側に流れ始めてしまうおそれがある。   Furthermore, in this example, since the opening means S4 and S6 are provided between the first reagent tank 14e and the first mixing tank 14f and between the second reagent tank 14g and the second mixing tank 14h, it is desirable. These are opened at the point of time, and the first reagent and the second reagent previously sealed in the first reagent tank 14e and the second reagent tank 14g, respectively, are caused to flow into the first mixing tank 14f and the second mixing tank 14h. Can do. If the opening means S4 and S6 are not provided, the first reagent and the second reagent may start to flow downstream when the liquid channel device 10A is stored.

また、この例の液体流路装置10Aの開通手段S1〜S7および閉止手段T1は、液体流路12に形成された第1凸部15および第2凸部16と蓋板13とが組み合わされた構成であるため、液体流路12を開通したり閉止したりするための別部材を新たに用意する必要がなく、低コストであるとともに構成もシンプルである。また、開通および閉止の操作も簡便な押圧操作のみで、操作性にも優れる。   Further, the opening means S1 to S7 and the closing means T1 of the liquid channel device 10A of this example are a combination of the first convex portion 15 and the second convex portion 16 formed in the liquid channel 12 and the lid plate 13. Since it is a structure, it is not necessary to prepare another member for opening and closing the liquid flow path 12, and it is low-cost and the structure is also simple. In addition, the opening and closing operations can be performed only by a simple pressing operation, and the operability is excellent.

図6は 本発明の液体流路装置の他の一実施形態例を示すものであって、この液体流路装置10Bは、扇状の平板からなる基板11Bの片面に、先に説明した液体流路装置10Aと同様に、試料および試薬の少なくとも一方からなる液体が流通する溝状の液体流路12と、液体流路12の端部や途中において液体が溜まる複数の液槽(14a、14e〜14h、14J、14k、14m)とが形成され、基板11の液体流路12が形成された側の流路形成面12aに蓋板13が積層して構成されたものである。この液体流路装置10Bにおいては、図6中の上端部側を中心に回転させた場合には、液体流路12の上流側の端部から下流側の端部に向けて矢印F’方向に試料が遠心力により流通し、その途中で試料に対して各種の処理や試薬との混合がなされ、測定液とされる。   FIG. 6 shows another embodiment of the liquid flow path device of the present invention. This liquid flow path device 10B has a liquid flow path described above on one side of a substrate 11B made of a fan-shaped flat plate. Similarly to the apparatus 10A, a groove-like liquid channel 12 through which a liquid consisting of at least one of a sample and a reagent flows, and a plurality of liquid tanks (14a, 14e to 14h) in which the liquid is accumulated at the end or in the middle of the liquid channel 12 14J, 14k, 14m), and the cover plate 13 is laminated on the flow path forming surface 12a of the substrate 11 on the side where the liquid flow path 12 is formed. In this liquid flow path device 10B, when rotated about the upper end side in FIG. 6, the direction from the upstream end to the downstream end of the liquid flow path 12 in the direction of arrow F ′ The sample is circulated by centrifugal force, and the sample is mixed with various treatments and reagents in the middle of the sample to obtain a measurement solution.

すなわち、液体流路12の上流側の端部には、投入された試料が溜まる試料投入槽14aが設けられ、この試料投入槽14aの下流には、第1試薬槽14eからの第1試薬および第2試薬槽14gからの第2試薬と試料投入槽14aからの試料とが混合され、中間調製液が調製される第1混合槽14fが設けられている。
第1混合槽14fの下流には、第3試薬槽14jからの第3試薬および第4試薬槽14kからの第4試薬と第1混合槽14fからの中間調製液とが混合される第2混合槽14hが設けられている。
この例では、第2混合槽14hは測定槽としても作用し、第2混合槽14hで調製された測定液に対して、図示略の検出分析手段により、各種成分の検出や分析がなされるようになっている。
また、この例では、第2混合槽14hで測定された後の測定液を貯留しておく廃棄槽14mが形成されている。
なお、各液槽には、大気と連通する図示略の連通孔が設けられている。
That is, the upstream end of the liquid channel 12 is provided with a sample introduction tank 14a in which the introduced sample is stored, and the first reagent and the first reagent from the first reagent tank 14e are provided downstream of the sample introduction tank 14a. There is provided a first mixing tank 14f in which the second reagent from the second reagent tank 14g and the sample from the sample charging tank 14a are mixed to prepare an intermediate preparation liquid.
Downstream of the first mixing tank 14f is a second mixing in which the third reagent from the third reagent tank 14j, the fourth reagent from the fourth reagent tank 14k, and the intermediate preparation liquid from the first mixing tank 14f are mixed. A tank 14h is provided.
In this example, the second mixing tank 14h also acts as a measurement tank, and various components are detected and analyzed by a detection analysis unit (not shown) with respect to the measurement liquid prepared in the second mixing tank 14h. It has become.
In this example, a disposal tank 14m is formed for storing the measurement liquid after being measured in the second mixing tank 14h.
Each liquid tank is provided with a communication hole (not shown) that communicates with the atmosphere.

また、この液体流路装置10Bにおいても、蓋板13は上述の液体流路装置10Aの場合と同様の図3に示す構成、すなわち、蓋板13の表面を構成する第1基材層13aと、第1基材層13aの内側に形成された強粘着層13bと、強粘着層13bの内側に形成された第2基材層13cと、第2基材層13cの内側に形成され、流路形成面に粘着する弱粘着層13dとを有した構成になっている。  Also in this liquid channel device 10B, the lid plate 13 has the same configuration as shown in FIG. 3 as in the case of the above-described liquid channel device 10A, that is, the first base material layer 13a constituting the surface of the lid plate 13 and A strong adhesive layer 13b formed inside the first base material layer 13a, a second base material layer 13c formed inside the strong adhesive layer 13b, and formed inside the second base material layer 13c. It has a configuration having a weak adhesive layer 13d that adheres to the path forming surface.

また、試料投入槽14aと第1混合槽14fとの間、第1試料槽14eと第1混合層14fとの間、第2試料槽14gと第1混合槽14fとの間、第1混合槽14fと第2混合槽14hとの間、第3試料槽14jと第2混合層14hとの間、第4試料槽14kと第2混合槽14hとの間、第2混合槽14hと廃棄槽14mとの間には、液体流路12を閉止状態から開通状態とする開通手段S8〜S14が1つずつ設けられている。
一方、試料投入槽14aと第1混合槽14fとの間の液体流路12において、開通手段S8よりも下流側に、閉止手段T2が設けられている。
Further, between the sample charging tank 14a and the first mixing tank 14f, between the first sample tank 14e and the first mixing layer 14f, between the second sample tank 14g and the first mixing tank 14f, and between the first mixing tank 14f and the first mixing tank 14f. 14f and the second mixing tank 14h, the third sample tank 14j and the second mixing layer 14h, the fourth sample tank 14k and the second mixing tank 14h, the second mixing tank 14h and the disposal tank 14m. Are provided with one opening means S8 to S14 for bringing the liquid flow path 12 from the closed state to the open state.
On the other hand, in the liquid flow path 12 between the sample introduction tank 14a and the first mixing tank 14f, a closing means T2 is provided on the downstream side of the opening means S8.

そして、液体流路装置10Aの場合と同様に、各開通手段S8〜S14では、図3に示したように、液体流路12に第1凸部15が形成され、この第1凸部15の頂部15aと弱粘着層13dとが粘着し、かつ、強粘着層13bと第2基材層13cとが離間している。一方、閉止手段T2では、液体流路12に第2凸部16が形成され、この第2凸部16の頂部16aと弱粘着層13dとは離間し、かつ、強粘着層13bと第2基材層13cとの間にはスペーサ部材17が介在し、スペーサ部材17と強粘着層13bとが粘着している。   As in the case of the liquid channel device 10 </ b> A, in each of the opening means S <b> 8 to S <b> 14, as illustrated in FIG. 3, the first convex portion 15 is formed in the liquid channel 12. The top portion 15a and the weak adhesive layer 13d are adhered to each other, and the strong adhesive layer 13b and the second base material layer 13c are separated from each other. On the other hand, in the closing means T2, the second convex portion 16 is formed in the liquid channel 12, the top portion 16a of the second convex portion 16 and the weak adhesive layer 13d are separated from each other, and the strong adhesive layer 13b and the second base are formed. A spacer member 17 is interposed between the material layer 13c and the spacer member 17 and the strong adhesion layer 13b are adhered.

この液体流路装置10Bを用いて、測定液を調製する場合には、まず、この液体流路装置10Bを試料投入槽14a側が回転中心側に位置し、測定槽14i側が回転の外周側に位置するように遠心装置にセットする。
ついで、試料をシリンジなどにサンプリングし、このシリンジの針を試料投入槽14aに対応する部分の蓋板13に突き刺して、試料投入槽14aに試料を注入する。その後、遠心装置を作動させることによって、回転中心側から外周側に作用する遠心力が生じ、この遠心力により、液体が上流側から下流側に流れ始める。
ついで、試料投入槽14aと第1混合槽14fとの間に設けられた開通手段S8を液体流路装置10Aの場合と同様の押圧操作で作動させ、この部分の液体流路12を開通状態とし、試料を遠心力により第1混合槽14fに導入する。
When preparing a measurement liquid using the liquid channel device 10B, first, the liquid channel device 10B is positioned on the rotation center side on the sample loading tank 14a side, and the measurement tank 14i side is positioned on the outer peripheral side of the rotation. Set to centrifuge.
Next, the sample is sampled in a syringe or the like, and the needle of this syringe is pierced into the cover plate 13 corresponding to the sample loading tank 14a to inject the sample into the sample loading tank 14a. Thereafter, by operating the centrifugal device, a centrifugal force acting from the rotation center side to the outer peripheral side is generated, and by this centrifugal force, the liquid starts to flow from the upstream side to the downstream side.
Next, the opening means S8 provided between the sample charging tank 14a and the first mixing tank 14f is operated by the same pressing operation as in the liquid channel device 10A, and the liquid channel 12 in this part is opened. The sample is introduced into the first mixing tank 14f by centrifugal force.

こうして遠心力を生じさせながら、試料を第1混合槽14fに導入する一方で、第1試薬槽14eと第1混合槽14fとの間の開通手段S9を押圧操作で作動させて、あらかじめ封入されていた第1試薬を第1混合槽14fに導入し、ついで、第2試薬槽14eと第1混合槽14fとの間の開通手段S10を押圧操作で作動させて、あらかじめ封入されていた第2試薬も第1混合槽14fに導入し、試料と第1試薬と第2試薬とを第1混合槽14fにおいて混合する。
そして、この際に、必要に応じて、試料の全量が完全に第1混合槽14fに流入し終わる前に、閉止手段T2を作動させることによって、試料の第1混合槽14への過剰な流入を止めることもできる。
While the sample is introduced into the first mixing tank 14f while the centrifugal force is generated in this way, the opening means S9 between the first reagent tank 14e and the first mixing tank 14f is operated by a pressing operation, and is enclosed in advance. The first reagent which has been introduced is introduced into the first mixing tank 14f, and then the opening means S10 between the second reagent tank 14e and the first mixing tank 14f is operated by a pressing operation, so that the second sealed in advance The reagent is also introduced into the first mixing tank 14f, and the sample, the first reagent, and the second reagent are mixed in the first mixing tank 14f.
At this time, if necessary, before the entire amount of the sample completely flows into the first mixing tank 14f, the closing means T2 is operated, whereby the sample is excessively flowed into the first mixing tank 14. Can also be stopped.

ついで、第1混合槽14fと第2混合槽14hとの間の開通手段S11を押圧操作で作動させて、第1混合槽14fで調製された中間調製液を第2混合槽14hに導入する一方で、第3試薬槽14gと第2混合槽14hとの間の開通手段S12と、第3試薬槽14gと第2混合槽14hとの間の開通手段S13とを押圧操作で作動させて、あらかじめ封入されていた第3試薬および第4試薬も第2混合槽14hに導入し、中間調製液と第3試薬と第4試薬とを第2混合槽14hにおいて混合する。
そして、この液体流路装置10Bごと検出分析手段に供し、第2混合槽で調製された測定液に対して、目的成分の検出や分析を行う。
検出や分析が終了した後には、開通手段S14を作動させて、測定後の測定液を廃棄槽14mへ廃棄することもできる。
Next, the opening means S11 between the first mixing tank 14f and the second mixing tank 14h is operated by a pressing operation, and the intermediate preparation liquid prepared in the first mixing tank 14f is introduced into the second mixing tank 14h. Then, the opening means S12 between the third reagent tank 14g and the second mixing tank 14h and the opening means S13 between the third reagent tank 14g and the second mixing tank 14h are actuated by pressing operation in advance. The sealed third reagent and fourth reagent are also introduced into the second mixing tank 14h, and the intermediate preparation liquid, the third reagent, and the fourth reagent are mixed in the second mixing tank 14h.
Then, the entire liquid flow path device 10B is provided for detection analysis means, and the target component is detected and analyzed for the measurement liquid prepared in the second mixing tank.
After the detection and analysis are completed, the opening means S14 can be operated to discard the measurement liquid after measurement into the waste tank 14m.

このような液体流通装置10Bによっても、液体流路12を閉止状態から開通状態にする開通手段S8〜S14と、開通状態から閉止状態にする閉止手段T2とを有するため、液体流路12中の液体の流れを制御でき、その結果、検出や分析を良好な精度で短時間に行うことができる。
また、開通手段S8〜S14および閉止手段T2も、低コストであるとともに構成もシンプルで、しかも、簡便な押圧操作のみで操作することができる。
Such a liquid circulation device 10B also includes the opening means S8 to S14 that bring the liquid flow path 12 from the closed state to the open state and the closing means T2 that turns the liquid flow path 12 from the open state to the closed state. The flow of the liquid can be controlled, and as a result, detection and analysis can be performed with good accuracy in a short time.
Further, the opening means S8 to S14 and the closing means T2 are low in cost and simple in configuration, and can be operated only by a simple pressing operation.

なお、この例の液体流路装置10Bの場合にも、開通手段S8〜S14および閉止手段T2における押圧操作を手動で行えるが、液体流路装置10Bの蓋板13の表面を圧接する圧接ディスクにより押圧すると、複数枚の液体流路装置10Bに対して、連続的に押圧操作ができ好ましい。
図7は、遠心装置の有する基盤20上に円形になるように並べられてセットされた複数枚(この例では6枚)の扇状(中心角α=60°)の液体流路装置10Bに対して、圧接ディスク21により押圧操作する方法を示したものである。この例の圧接ディスク21は、液体流路装置10Bを回転させる遠心装置の回転軸22から側方に延びたアーム23に軸設され、アーム23を中心として回転しながら、アーム23の長さ方向(液体流路装置の回転の半径方向)に沿って、液体流路装置10Bの回転中心側から外周側に向けて移動する。よって、遠心装置により液体流路装置10Bを回転させながら、圧接ディスク21をこのように移動させることによって、圧接ディスク21は円形に並べられた液体流路装置10B上を回転中心側から外周側に向けて相対的に渦巻き状に走査し、これら液体流路装置10Bに設けられた開通手段S8〜14および閉止手段T2を順次押圧操作することができる。
Also in the case of the liquid channel device 10B of this example, the pressing operation in the opening means S8 to S14 and the closing means T2 can be performed manually, but by a pressure contact disk that presses the surface of the lid plate 13 of the liquid channel device 10B. When pressed, a plurality of liquid flow path devices 10B can be continuously pressed, which is preferable.
FIG. 7 shows a plurality of (six in this example) fan-shaped (center angle α = 60 °) liquid channel device 10B arranged in a circular shape on a base plate 20 of the centrifugal device. The method of pressing with the press contact disk 21 is shown. The pressure contact disk 21 in this example is provided on an arm 23 extending laterally from a rotation shaft 22 of a centrifugal device that rotates the liquid flow path device 10B, and rotates in the length direction of the arm 23 while rotating around the arm 23. Along the (radial direction of rotation of the liquid flow path device), the liquid flow path device 10B moves from the rotation center side toward the outer peripheral side. Therefore, by moving the pressure contact disk 21 in this manner while rotating the liquid flow path device 10B by the centrifugal device, the pressure contact disk 21 moves on the liquid flow path device 10B arranged in a circle from the rotation center side to the outer peripheral side. Scanning relatively spirally toward each other, the opening means S8 to S14 and the closing means T2 provided in the liquid channel device 10B can be sequentially pressed.

なお、以上の説明では、液体流路装置10A、10Bの試料投入槽14aに試料を注入する方法として、シリンジの針を蓋板13に突き刺す方法を例示しているが、例えば、あらかじめ蓋板13に試料注入孔を形成しておき、そこから試料を注入してもよい。その場合、試料注入孔には保護テープを被せておき、シリンジを保護テープに突き刺すことで注入してもよいし、保護テープを剥がして試料注入孔にシリンジを挿入して注入してもよい。   In the above description, as a method of injecting a sample into the sample introduction tank 14a of the liquid flow path apparatuses 10A and 10B, a method of piercing the needle of the syringe into the cover plate 13 is exemplified. Alternatively, a sample injection hole may be formed, and the sample may be injected therefrom. In that case, the sample injection hole may be covered with a protective tape and injected by piercing the syringe with the protective tape, or the protective tape may be peeled off and the syringe inserted into the sample injection hole for injection.

以上説明した液体流路装置10A、10Bにおいて、液体流路12および液槽が形成される基板11A、11Bには、例えば、スチレン樹脂、アクリル樹脂、ポリカーボネート樹脂、塩化ビニル樹脂、PEN樹脂、ポリエステル樹脂、エポキシ樹脂、フェノール樹脂、ABS樹脂、ポリプロピレン樹脂、繊維強化プラスチックなどの樹脂板や、ガラス板が使用できる。これらのなかでも、透明であって、液体流路12を流通する液体の様子を基板11A、11B側から目視することができる点では、ガラス板や、スチレン樹脂、アクリル樹脂、ポリカーボネート樹脂、塩化ビニル樹脂、PEN樹脂、ポリエステル樹脂が好ましい。また、ガラス板よりも破損しにくく取扱性に優れる点では、樹脂板の方が好ましい。
基板11A、11Bの厚さには特に制限はなく、形成される液体流路12の深さなどに応じて決定されればよいが、通常0.5〜7mmである。
In the liquid flow path apparatuses 10A and 10B described above, the substrates 11A and 11B on which the liquid flow path 12 and the liquid tank are formed include, for example, styrene resin, acrylic resin, polycarbonate resin, vinyl chloride resin, PEN resin, and polyester resin. A resin plate such as an epoxy resin, a phenol resin, an ABS resin, a polypropylene resin, or a fiber reinforced plastic, or a glass plate can be used. Among these, a glass plate, a styrene resin, an acrylic resin, a polycarbonate resin, and vinyl chloride are transparent in that the state of the liquid flowing through the liquid flow path 12 can be visually observed from the side of the substrates 11A and 11B. Resins, PEN resins, and polyester resins are preferred. In addition, a resin plate is preferable in that it is less likely to break than a glass plate and has excellent handleability.
The thickness of the substrates 11A and 11B is not particularly limited, and may be determined according to the depth of the liquid channel 12 to be formed, but is usually 0.5 to 7 mm.

液体流路12や液槽は、基板11A、11Bの片面上に、例えばフォトリソグラフィ、射出成形、ブロー成形、接合形成、溶解形成、切削形成、機械加工などの技術により溝状に形成される。
液体流路12の断面形状(流れに対して垂直方向の断面)には特に制限はなく、例えば、半円形状、四角形状、逆三角形状などが挙げられる。液体流路12の幅や深さにも特に制限はなく、求められる液体の流量などに応じて決定されればよいが、幅および深さがそれぞれ10〜5000μmの範囲であれば、小さな流路抵抗で液体を流すことができ、かつ、流通させる液体の量も少量ですむ点で好ましい。
また、液体流路12には、液体を流れやすくするために、液体の種類に応じた表面処理を施すことが好ましい。このような表面処理としては、塗料の塗布処理、プラズマ処理、フレーム処置、薬品処理、生理活性処理、抗体処理などが挙げられる。さらに、液体流路12には、必要に応じて、邪魔板、攪拌板、突起を設けたり、分水形状を形成したりして、流通する液体が均一な混合状態となるようにしてもよい。
各液槽も、形状などには特に制限はなく、各液槽に要求される容積などに応じて適宜形成されればよい。
The liquid flow path 12 and the liquid tank are formed in a groove shape on one surface of the substrates 11A and 11B by techniques such as photolithography, injection molding, blow molding, bonding formation, dissolution formation, cutting formation, and machining.
There is no particular limitation on the cross-sectional shape of the liquid flow path 12 (the cross-section in the direction perpendicular to the flow), and examples thereof include a semicircular shape, a quadrangular shape, and an inverted triangular shape. The width and depth of the liquid channel 12 are not particularly limited and may be determined according to the required flow rate of the liquid. However, if the width and depth are in the range of 10 to 5000 μm, the small channel It is preferable in that a liquid can be flowed by resistance and a small amount of liquid can be circulated.
The liquid flow path 12 is preferably subjected to a surface treatment according to the type of liquid in order to facilitate the flow of the liquid. Examples of such surface treatment include coating application treatment, plasma treatment, flame treatment, chemical treatment, physiological activity treatment, and antibody treatment. Furthermore, the liquid flow path 12 may be provided with a baffle plate, a stirring plate, a protrusion, or formed with a water diverting shape, if necessary, so that the flowing liquid is in a uniform mixed state. .
Each liquid tank is not particularly limited in shape, and may be appropriately formed according to the volume required for each liquid tank.

蓋板13の表面を構成する第1基材層13aは、その表面側から垂直方向の荷重を加えられた場合には撓み、その後、戻ろうとする復元力を有するものである。このような特性、すなわち、可撓性と復元力とを有する基材であれば、第1基材層13aとして使用でき、その材質や厚みには特に制限はないが、ポリエチレンテレフタレート(PET)、ポリエチレンナフタレート(PEN)、ポリカーボネート(PC)、ポリイミドなどからなる厚さ50〜500μmのフィルムであれば、第1基材層13aとして使用するのに適切な可撓性と復元力を有するため好ましい。   The first base material layer 13a constituting the surface of the cover plate 13 has a restoring force to bend and then return when a vertical load is applied from the surface side. If it is a base material having such characteristics, that is, flexibility and restoring force, it can be used as the first base material layer 13a, and its material and thickness are not particularly limited, but polyethylene terephthalate (PET), A film having a thickness of 50 to 500 μm made of polyethylene naphthalate (PEN), polycarbonate (PC), polyimide, or the like is preferable because it has flexibility and resilience appropriate for use as the first base material layer 13a. .

一方、第2基材層13cは、垂直方向の荷重により容易に撓むものであればよく、復元しないものがさらに好ましい。このような特性を有する基材であれば、第2基材層13cとして使用でき、その材質や厚みには特に制限はないが、アルミニウム箔、銅箔などの金属箔、紙、PET、PEN、PC、ポリイミドなどの樹脂からなる厚さ5〜50μmのフィルムであれば、第2基材層13cとして使用するのに好ましい。紙を使用する場合には、防水処理された紙が好ましく、金属箔を使用する場合には、防錆処理された金属箔が好ましい。   On the other hand, the 2nd base material layer 13c should just be easily bent by the load of a perpendicular direction, and the thing which does not restore | restore is still more preferable. If it is the base material which has such a characteristic, it can be used as the 2nd base material layer 13c, Although there is no restriction | limiting in particular in the material and thickness, Metal foil, such as aluminum foil and copper foil, paper, PET, PEN, A film having a thickness of 5 to 50 μm made of a resin such as PC or polyimide is preferable for use as the second base material layer 13c. When using paper, waterproof paper is preferable, and when using metal foil, rust-proof metal foil is preferable.

強粘着層13bおよび弱粘着層13dには、従来公知の粘着剤の中から第1基材層13aや第2基材層13cの材質などに応じて適宜選択することができるが、その際、強粘着層13bを形成する粘着剤の粘着力(粘着強度)は、弱粘着層13dを形成する粘着剤の粘着力よりも強いことが必要である。強粘着層13bを形成する粘着剤の粘着力が弱粘着層13dを形成する粘着剤の粘着力以下であると、開通手段S1〜S14において押圧操作をした場合でも、第1凸部15の頂部15aと弱粘着層13dとを離間させることができず、液体流路12を開通できなくなる。強粘着層13bを形成する粘着剤の粘着力は、弱粘着層13dを形成する粘着剤の粘着力よりも0.1N/cm以上大きいことが好ましい。さらには、0.1〜30N/cmの範囲で大きいことが好ましい。強粘着層13dを形成する粘着剤の粘着力が弱粘着層13dを形成する粘着剤の粘着力よりも0.1N/cm以上大きいと、開通手段S1〜S14を確実に作動させることができる。一方、粘着力の差が30N/cmを超えるようにこれらの粘着層を構成することは困難である。
また、そのうえで、強粘着層13bの粘着力を1〜30N/cmの範囲とし、弱粘着層13dの粘着力を0.05〜5N/cmの範囲とすることが好ましい。
The strong adhesive layer 13b and the weak adhesive layer 13d can be appropriately selected from conventionally known adhesives according to the material of the first base material layer 13a and the second base material layer 13c. The adhesive force (adhesive strength) of the adhesive forming the strong adhesive layer 13b needs to be stronger than the adhesive force of the adhesive forming the weak adhesive layer 13d. When the pressure-sensitive adhesive of the pressure-sensitive adhesive forming the strong pressure-sensitive adhesive layer 13b is equal to or lower than the pressure-sensitive adhesive of the pressure-sensitive adhesive forming the weak pressure-sensitive adhesive layer 13d, even when a pressing operation is performed in the opening means S1 to S14, 15a and the weak adhesion layer 13d cannot be separated, and the liquid flow path 12 cannot be opened. It is preferable that the adhesive strength of the adhesive forming the strong adhesive layer 13b is 0.1 N / cm or more larger than the adhesive strength of the adhesive forming the weak adhesive layer 13d. Furthermore, it is preferable that it is large in the range of 0.1-30 N / cm. When the adhesive force of the adhesive forming the strong adhesive layer 13d is 0.1 N / cm or more larger than the adhesive force of the adhesive forming the weak adhesive layer 13d, the opening means S1 to S14 can be operated reliably. On the other hand, it is difficult to configure these adhesive layers so that the difference in adhesive strength exceeds 30 N / cm.
Moreover, it is preferable that the adhesive force of the strong adhesive layer 13b is in the range of 1 to 30 N / cm and the adhesive force of the weak adhesive layer 13d is in the range of 0.05 to 5 N / cm.

強粘着層13bおよび弱粘着層13dに使用する粘着剤としては、例えば、アクリル系、ゴム系、ポリウレタン系、ポリエステル系、シリコン系などが挙げられる。これらのうち、例えば、強粘着層13bにはアクリル系、ゴム系などを使用し、さらに芯材として、不織布、ポリエステル繊維などを含ませてもよい。弱粘着層13dには、アクリル系、シリコン系のものを使用することが好ましい。強粘着層13bと弱粘着層13dとの粘着力の差を上述の好適な範囲とするためには、各粘着剤を構成する樹脂のガラス転移温度を適宜調整したり、粘着剤に粘着付与剤、硬化剤、芯材などの添加剤を加えたり、その添加量を調整したりする方法が挙げられる。
また、強粘着層および弱粘着層の厚さには制限はないが、通常、10〜1000μmである。
Examples of the adhesive used for the strong adhesive layer 13b and the weak adhesive layer 13d include acrylic, rubber-based, polyurethane-based, polyester-based, and silicon-based adhesives. Among these, for example, the strong adhesive layer 13b may be made of acrylic or rubber, and may further include a nonwoven fabric, polyester fiber, or the like as a core material. The weak adhesive layer 13d is preferably made of acrylic or silicon. In order to make the difference in adhesive strength between the strong adhesive layer 13b and the weak adhesive layer 13d within the above-mentioned preferable range, the glass transition temperature of the resin constituting each adhesive is appropriately adjusted, or the tackifier is added to the adhesive. And a method of adding additives such as a curing agent and a core material and adjusting the amount of the additive.
Moreover, although there is no restriction | limiting in the thickness of a strong adhesion layer and a weak adhesion layer, Usually, it is 10-1000 micrometers.

なお、ここで「粘着力」とは、JIS Z 0237のステンレス板に対する180度引きはがし粘着力のことである。   Here, “adhesive strength” refers to the adhesive strength that peels 180 degrees from a stainless steel plate of JIS Z 0237.

スペーサ部材17としては、PET、PEN、PC、アクリル樹脂、エポキシ樹脂、フェノール樹脂、ポリウレタン樹脂などの樹脂の他、紙なども使用できる。スペーサ部材17の厚みには特に制限はないが、50〜2000μmの範囲にすると、開通手段S1〜S14の作動前には、強粘着層13bと第2基材層13cとを確実に離間させておくことができ、一方、作動時には、強粘着層13bと第2基材層13cとを確実に粘着させることができる。   As the spacer member 17, paper, etc. can be used in addition to resins such as PET, PEN, PC, acrylic resin, epoxy resin, phenol resin, and polyurethane resin. Although there is no restriction | limiting in particular in the thickness of the spacer member 17, If it is set as the range of 50-2000 micrometers, before the opening means S1-S14 act | operates, the strong adhesion layer 13b and the 2nd base material layer 13c will be spaced apart reliably. On the other hand, at the time of operation, the strong adhesion layer 13b and the second base material layer 13c can be reliably adhered.

なお、以上の説明においては、基板11A、11Bの片面のみに液体流路12が形成された液体流路装置10A、10Bを例示したが、基板11A、11Bの両面に液体流路12が形成されてもよい。
また、各液槽に設けられる連通孔は、液体流路装置11A、11Bの使用前には封止され、使用時に開通されることがコンタミネーション防止の点などから好ましい。よって、連通孔の手前に、液体流路12に設けられる開通手段S1〜14と同様の構成の開通手段を設けてもよい。
また、以上の説明においては、液体を流通させるために、液体流路装置10Aでは重力を利用し、液体流路装置10Bでは遠心力を利用した方法をそれぞれ説明したが、これらに限定されず、例えば、液体流路12の一部を加圧したり、液体流路12の一部を加熱して液体流路12内の空気を膨張させたり、液体流路12の一部に酸素吸収剤(酸化しやすい鉄粉など)を封入しておき、液体流路12内の酸素を吸収することで液体流路12内を減圧にしたりして、液体を移動させ、流通させる方法なども採用できる。または、液体流路12の一部ではなく、計量槽14を加圧、加熱、減圧してもよいし、場合によっては、液体流路12と計量槽14の両方を加圧、加熱、減圧してもよい。
In the above description, the liquid flow path devices 10A and 10B in which the liquid flow path 12 is formed only on one side of the substrates 11A and 11B are illustrated, but the liquid flow path 12 is formed on both sides of the substrates 11A and 11B. May be.
In addition, the communication holes provided in each liquid tank are preferably sealed before use of the liquid channel devices 11A and 11B and opened during use from the viewpoint of preventing contamination. Therefore, an opening means having the same configuration as the opening means S1 to 14 provided in the liquid channel 12 may be provided before the communication hole.
In the above description, in order to circulate the liquid, the liquid channel device 10A uses gravity and the liquid channel device 10B uses centrifugal force. However, the method is not limited thereto. For example, a part of the liquid channel 12 is pressurized, a part of the liquid channel 12 is heated to expand the air in the liquid channel 12, or an oxygen absorbent (oxidation agent) is added to a part of the liquid channel 12. It is also possible to employ a method in which a liquid is moved and circulated, for example, by enclosing an iron powder or the like that is easy to do and absorbing oxygen in the liquid channel 12 to reduce the pressure in the liquid channel 12. Alternatively, the measuring tank 14 may be pressurized, heated, or depressurized instead of a part of the liquid channel 12, or depending on the case, both the liquid channel 12 and the measuring tank 14 may be pressurized, heated, or depressurized. May be.

液体流路装置10A、10Bを流通させる試料および試薬としては、特に制限はなく、医療分野、環境分野などで従来より採用されている試料と試薬とを適宜組み合わせて使用することができる。例えば、医療分野おいては、試料として、血液(全血)、血漿、血清、バフィーコート、尿、糞便、唾液、喀痰などの生体由来のもの、ウィルス、細菌、カビ、酵母、動植物の細胞などが挙げられる。また、これらから単離したDNAまたはRNAを用いてもよいし、これらに対して何らかの前処理、希釈などが施されたものを試料としてもよい。試薬としては、試料中に存在する抗原を分析する場合には、それに対する抗体を含有する試薬が好ましい。
また、液体流路装置10A、10Bで調製された測定液の検出分析手段としては、従来公知の光学的手段、電気的手段などを適宜採用することができる。
There are no particular limitations on the sample and reagent through which the liquid flow path devices 10A and 10B are circulated, and a sample and a reagent that have been conventionally employed in the medical field, the environmental field, and the like can be used in appropriate combination. For example, in the medical field, samples (such as blood (whole blood), plasma, serum, buffy coat, urine, feces, saliva, sputum, etc.), viruses, bacteria, fungi, yeast, animal and plant cells, etc. Is mentioned. In addition, DNA or RNA isolated from these may be used, or a sample obtained by subjecting these to any pretreatment or dilution may be used. As a reagent, when an antigen present in a sample is analyzed, a reagent containing an antibody against the antigen is preferable.
Moreover, conventionally known optical means, electrical means, and the like can be appropriately employed as detection / analysis means for the measurement liquid prepared by the liquid flow path apparatuses 10A and 10B.

本発明の液体流路装置の一実施形態例を示す概略平面透視図である。It is a schematic plane perspective view showing an embodiment of the liquid channel device of the present invention. 図1の液体流路装置の一部を拡大した平面透視図である。FIG. 2 is an enlarged plan perspective view of a part of the liquid channel device in FIG. 1. 図2のI−I’線に沿う断面図である。It is sectional drawing which follows the I-I 'line of FIG. 開通手段が作動する様子を説明する説明図である。It is explanatory drawing explaining a mode that an opening means act | operates. 閉止手段が作動する様子を説明する説明図である。It is explanatory drawing explaining a mode that a closing means act | operates. 本発明の液体流路装置の他の一実施形態例を示す概略平面透視図である。It is a schematic plane perspective view which shows another example of embodiment of the liquid flow-path apparatus of this invention. 図6の液体流路装置の使用方法の一例を説明する概略説明図である。It is a schematic explanatory drawing explaining an example of the usage method of the liquid flow-path apparatus of FIG.

符号の説明Explanation of symbols

10A、10B 液体流路装置
11A、11B 基板
12 液体流路
12a 流路形成面
13 蓋板
13a 第1基材層
13b 強粘着層
13c 第2基材層
13d 弱粘着層
14c 計量槽
15 第1凸部
15a 第1凸部の頂部
16 第2凸部
16a 第2凸部の頂部
17 スペーサ部材
S1〜S14 開通手段
T1〜T2 閉止手段
10A, 10B Liquid channel device 11A, 11B Substrate 12 Liquid channel 12a Channel forming surface 13 Cover plate 13a First substrate layer 13b Strong adhesion layer 13c Second substrate layer 13d Weak adhesion layer 14c Weighing tank 15 First convex Part 15a Top part 16 of the first convex part Second convex part 16a Top part 17 of the second convex part Spacer members S1 to S14 Opening means T1 to T2 Closing means

Claims (4)

基板の少なくとも片面に、試料および試薬の少なくとも一方からなる液体が流通する液体流路が形成され、前記基板の前記液体流路が形成された流路形成面には蓋板が積層した液体流路装置であって、
前記液体流路の一部を閉止状態から開通状態にする開通手段を有し、
前記蓋板は、該蓋板の表面を構成する第1基材層と、該第1基材層の内側に形成された強粘着層と、該強粘着層の内側に形成された第2基材層と、該第2基材層の内側に形成され、前記流路形成面に粘着する弱粘着層とを有し、
前記開通手段では、前記液体流路に第1凸部が形成され、該第1凸部の頂部と前記弱粘着層とが粘着し、かつ、前記強粘着層と前記第2基材層とが離間していることを特徴とする液体流路装置。
A liquid channel in which a liquid channel including at least one of a sample and a reagent circulates is formed on at least one surface of the substrate, and a lid plate is laminated on the channel forming surface of the substrate on which the liquid channel is formed A device,
An opening means for opening a part of the liquid flow path from a closed state to an open state;
The lid plate includes a first base layer constituting the surface of the lid plate, a strong adhesive layer formed inside the first base layer, and a second base formed inside the strong adhesive layer. A material layer and a weak adhesive layer formed on the inner side of the second base material layer and sticking to the flow path forming surface;
In the opening means, a first convex portion is formed in the liquid flow path, a top portion of the first convex portion and the weak adhesive layer are adhered, and the strong adhesive layer and the second base material layer are bonded to each other. A liquid flow path device characterized by being spaced apart.
前記液体流路の一部を開通状態から閉止状態にする閉止手段をさらに有し、
前記閉止手段では、前記液体流路に第2凸部が形成され、該第2凸部の頂部と前記弱粘着層とが離間し、かつ、前記強粘着層と前記第2基材層との間にはスペーサ部材が介在し、該スペーサ部材と前記強粘着層とが粘着していることを特徴とする請求項1に記載の液体流路装置。
A closing means for closing a part of the liquid channel from an open state to a closed state;
In the closing means, a second convex portion is formed in the liquid flow path, a top portion of the second convex portion and the weak adhesive layer are separated from each other, and the strong adhesive layer and the second base material layer are separated from each other. The liquid channel device according to claim 1, wherein a spacer member is interposed between the spacer member and the strongly adhesive layer.
前記液体流路には、一定量の液体を計量する計量槽が設けられ、少なくとも該計量槽の上流には前記閉止手段が設けられ、下流には前記開通手段が設けられていることを特徴とする請求項2に記載の液体流路装置。   The liquid channel is provided with a measuring tank for measuring a certain amount of liquid, the closing means is provided at least upstream of the measuring tank, and the opening means is provided downstream. The liquid channel device according to claim 2. 前記計量槽には、前記一定量を超えた液体をオーバーフローさせるオーバーフロー手段が設けられていることを特徴とする請求項3に記載の液体流路装置。   The liquid channel device according to claim 3, wherein the weighing tank is provided with overflow means for overflowing the liquid exceeding the predetermined amount.
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