JP5838418B2 - Microreactor - Google Patents

Description

  The present invention relates to a microreactor that is easy to assay.

  A microreactor has grooves and recesses of several microns to several hundred microns inside, and a micro fluid is allowed to flow inside the microreactor to perform various biochemical reactions, antibody reactions, electrochemical reactions, synthetic reactions, analytical chemical reactions, etc. It is a device.

A microreactor having such a fine flow path is manufactured by superimposing a lid on a base body having grooves and recesses opened on the surface in order to form a fluid flow path, a reaction microspace, etc. (patent) Reference 1).
In addition, when forming a three-dimensional flow path, one or more intermediate bodies formed with grooves or flow paths penetrating in the vertical direction are stacked on the base body having grooves or recesses, and further on The lid body is manufactured by overlapping (Patent Document 2).
Even when the lid is directly superimposed on the base body, even when the lid is superimposed on the base body via the intermediate body, the base body and the intermediate body Positioning with high accuracy is important, and it is also necessary to prevent the cross-sectional shape of the flow path and the reaction space capacity from changing when the lids are overlapped.

  When optically detecting the reaction system, such as fluorescence, the base body and lid with fine flow paths are made of a light-transmitting material. The positioning of was difficult.

  Patent Document 3 discloses a position detection mechanism using positioning marks in paragraph (0034) of the same publication, but it is not provided in association with the fluid supply port and discharge port of the lid, and positioning during the assay is not always easy.

Japanese Patent No. 4347736 Japanese National Patent Publication No. 10-503708 JP 2007-307644 A

  It is an object of the present invention to provide a microreactor that can be easily assayed and has excellent cross-sectional accuracy and sealing properties such as flow paths and reaction spaces.

Microreactor according to the onset Ming, includes a base body having a micro flow path opened to the surface, and a lid superimposing directly or via an intermediate on the base body, the base body supply recess of the fluid and It has a discharge recess and a positioning mark in the supply recess and the discharge recess, and the lid body has a fluid supply port and a discharge port penetrating in the vertical direction. It is possible to align and overlap each positioning mark provided in the supply recess and the discharge recess provided in the base body.
Here, the supply port is for supplying a fluid into the microreactor, and is not limited to one depending on the use of the microreactor, and may have a plurality of supply ports for each of a plurality of different raw fluids. There may be multiple outlets.
When there are a plurality of supply ports and / or discharge ports, it is only necessary that the marks for positioning at least one of the supply ports and the discharge ports be provided in the supply recesses and the discharge recesses of the base body.

The present invention includes a translucent base body having a micro-channel that is open on the surface, and a lid body that is superimposed on the base body directly or via an intermediate body, the base body being a fluid supply recess. and has a discharge recess, the lid has an outlet extending through corresponding to the discharge recess in the inlet and the base body penetrating corresponding to the supply recess of the base body, in the case with an intermediate body, the The intermediate body has a fluid inflow port that matches the supply port of the lid and an outflow port that matches the discharge port of the lid, and holds the lower holding body and the lid for placing and holding the base body has a retainer, the lower holding member has a positioning mark for positioning the discharge recess and supply recess of the base body, wherein the retainer is connected to the tube corresponding to the inlet and outlet of the lid a connecting member for the coupler are then screwed into retainer Both have a tube insertion hole with a conical side surface with an enlarged diameter on the distal end side, and the distal end portion of the tube inserted into the insertion hole of the coupling tool has a truncated cone shape with an enlarged diameter on the distal end side, thereby tightening the coupling tool. Seal adjustment is possible for the lid, and the base body is placed so that the position of the supply recess and the discharge recess is aligned with the positioning mark of the lower holding part, and the supply port and the discharge port of the lid are placed thereon. It is preferable to overlap the positioning mark and fix the presser to the lower holding body from above.

In the present invention, the lid body is preferably softer than the base body and the intermediate body and has a hardness in the range of 60 to 95.
Here, the hardness indicates a measured value with a durometer type A defined in JIS K6253.
If the hardness of the lid is too low, deformation will be large when pressed to the base body side, the sealing performance will be reduced, or a part of the back surface of the lid will enter the flow channel groove provided in the base body etc. Accuracy is reduced.
Further, if the lid body is too hard, it is difficult to ensure the sealing pressure of the flow path portion, and if the lid body is pressed too strongly, the base body and the like may be deformed.
Examples of the material of the lid having such a hardness range include soft vinyl chloride, polyurethane, an ethylene-vinyl acetate copolymer, a blend material of a polypyropylene resin and an elastomer, and the like.
Depending on the application of the microreactor, a material having affinity for proteins, cells and the like is preferable.

It may be used together means attached to the case of forming the present invention flow path superposed lid directly or via an intermediate base material in such a lower holder for placing holding the base member If a presser for pressing the lid from the upper side is provided, not only the alignment of the base body and the lid but also an external system can be easily connected.
Moreover, when fixing a pressing tool to a lower holding body, the positioning mechanism of a pressing tool and a lower holding body can also be provided.

In the microreactor according to the present invention, since the positioning marks are formed in the supply recess and the discharge recess of the fluid in the base body, the supply port and the discharge port of the lid can be overlapped on the positioning mark while visually aligning with each other. .
Moreover, if the base body is made of a light-transmitting material and a positioning mark is provided on the lower holding body on which the base body is placed, the base body and the lid body can be overlapped according to the positioning mark, Furthermore, the assay becomes easier.

The structural example of the microreactor which concerns on this invention is shown. 1 shows an assay procedure of a microreactor according to the present invention, where (a) is a lower holding body, (b) is a state in which a base body is placed on the lower holding body, and (c) is a lid placed on the base body. Indicates the state. (A) shows a state in which the presser is stacked on the lid, (b) shows a state in which the presser is fixed to the lower holding body, and (c) shows a state in which the tube is seal-connected. The assay status of the microreactor is shown. (A) is AA sectional view, (b) shows the elements on larger scale of a discharge port part.

The present invention provides a supply recess (supply section) for a fluid required for a base body in order to facilitate positioning of a base body having a micro-channel with a fine structure opened on the surface and a lid body to be overlaid on the base body. ) And the discharge recess (discharge portion) are provided with a positioning mark, and the positioning mark is aligned with the supply port (corresponding to the supply recess of the base body) and the discharge port (corresponding to the discharge recess of the base body). It is characterized in that it can be positioned by overlapping.
In this case, in addition to forming a two-dimensional flow path, in the case of forming a flow path having a three-dimensional structure as disclosed in Patent Document 2, the fluid flow to be matched with the supply port and the discharge port of the lid One or more intermediate bodies having an inlet and an outlet can be sandwiched between the base body and the lid body.

In the present invention, when the base body is made of a light-transmitting material and a positioning mark is marked on the lower holding body on which the base body is placed, the assay is further facilitated.
Hereinafter, a configuration example will be described based on the drawings.

FIG. 1 shows a configuration example of a microreactor according to the present invention, and FIGS. 2 to 4 show the assay procedure.
FIG. 5 shows a cross-sectional view.
In this embodiment, when the reactor is manufactured by superimposing the lid body 20 on the base body 10 having the microchannel, the base body 10 is placed on the lower holding body 30 and the lid body 20 is placed thereon. This is an example of an assay in which the presser 40 is fixed to the lower holding body 30 so as to be pressed by the presser 40 to which the tubes 61a and 61b are connected.
The microreactor has one or more fluid supply ports and one or more discharge ports through which the supplied fluid is discharged to the outside after a predetermined reaction.
Although there are many cases where there are a plurality of supply ports and discharge ports depending on the use and function of the microreactor, this embodiment will be schematically described in the case of one fluid supply port and one discharge port, and the flow path unit 13 is also a linear example. I will explain it.

The lower holding body 30 has a flat portion on which the base body 10 is placed, and the positioning marks M ₁ and M ₂ are marked on the flat portion.
The positioning mark is intended to determine the placement of the base body 10, and can be positioned by various detection means such as optical and electrical as well as optical, but a mark that can be visually observed is preferable.
If there are at least two positioning marks, the coordinates in the XY directions are determined.
The present embodiment is an example having a positioning mark M ₁ for determining the position of the fluid supply recess 11 and a positioning mark M ₂ for determining the position of the discharge recess 12.
As shown in FIG. 2B, the base body 10 has translucency, and is placed so that the supply recess 11 and the discharge recess 12 overlap the positioning marks M ₁ and M ₂ , and in this state, the lower holder 30 The base body 10 is fixed by the band 53 via the mounting female screw portions 52a and 52b provided on the base plate.
Next, as shown in FIG. 2C, the penetrating supply port 21 and the discharge port 22 provided in the lid 20 are aligned so as to overlap the positioning marks M ₁ and M ₂ , respectively, and overlap the base body 10.
Next, as shown in FIG. 3, the presser 40 in which the tubes 61 a and 61 b are connected by the connectors 62 and 63 is overlapped on the lid 20.
At this time, guide pins 31a to 31a standing on the lower holding body 30 with reference to the positioning marks M ₁ and M ₂ so that the tips of the tubes 61a and 61b are positioned at the supply port 21 and the discharge port 22 of the lid 20, respectively. Positioning is performed by a combination of 31d and guide holes 41a to 41d provided in the presser 40.
In addition, as long as the pressing tool 40 and the lower holding body 30 can be positioned with respect to each other, there is no particular limitation as long as one has a convex portion and a pin, and the other has a concave portion and a hole.
In this state, as shown in FIG. 3 (b), screw-like fixtures 51 a to 51 d are inserted into the through holes 42 a to 42 d provided in the presser 40 and provided to the lower holding body 30, so that the mounting holes 32 a made up of screw portions are provided. Screw and fix to ~ 32d.
The couplers 62, 63 are tubes 61a, 61b that are inserted into the insertion holes 62a, 62b, and the lower ends of the tubes 61a, 61b are truncated conical seals whose diameters are expanded downward, as shown in FIG. As shown in c), when the male threaded portions 62b and 63b of the connector are tightened, they are pressed and sealed on the conical side surfaces of the distal ends of the insertion holes 62a and 62b.

Since the microreactor according to the present invention is characterized in that the flow path is formed by overlapping the lid body directly or via an intermediate body with the base body, the hardness of the resin for molding the lid body is the hardness of the base body. Softer is better.
This is because if the lid body is harder than the base body, it is difficult to seal the flow path portion of the base body, or if the cover body is pressed hard, the cross-sectional shape of the flow path is deformed.
Further, if the lid is too soft, the lid is deformed and enters the channel of the base body, and the channel cross-sectional area becomes smaller than a predetermined value.
Then, the base and the lid were made as a trial and the overlapping state was examined.

先のベース体に上記サンプルの蓋体を図１〜図５に示すように重ね合せ、固定具５１ａ〜５１ｄを用いてネジ固定した。
その結果、実施例１〜５の蓋体は、流路幅１０，３０，５０，１００μｍのいずれのベース体にあっても所定の流路が得られたが、比較例１１の硬度５５の蓋体は、幅１００μｍの流路を有するベース体に対して約１０μｍ程の深さまで蓋体が喰い込んでいた。
また、比較例１２の硬度９８の蓋体はベース体との密着が不充分で液漏れが生じるサンプルが一部に発生した。
このことから蓋体の硬度はＡタイプで６０〜９５の範囲が好ましい。 First, the base body was manufactured as follows.
80 parts by weight of n-butyl acrylate (manufactured by Wako Pure Chemical Industries), 40 parts by weight of diethylene glycol dimethacrylate (Blenmer PDE-100, manufactured by Nippon Oil & Fats) and 20 parts by weight of Parapet SA-NW201 (manufactured by Kuraray) are mixed. 1.2 parts by weight of Ciba DAROCUR 1173 (manufactured by Ciba Specialty Chemicals, 2-hydroxy-2-methyl-1-phenyl-propan-1-one) was added as a polymerization initiator, and this mixture formed a fine channel. It was injected into a silicon mold and UV cured.
Evaluation samples having flow paths with a depth of 30 μm and widths of 10, 30, 50, and 100 μm on the surface were prepared by releasing the cured resin from various prototype molds.
In addition, when the surface hardness was measured in a portion without a flow path, the hardness was 65 according to JIS K6253 type D.
Next, a plate-shaped lid having a thickness of about 1 mm was formed.

As shown in FIGS. 1 to 5, the above-described sample lid body was overlaid on the previous base body, and was fixed with screws using fixtures 51 a to 51 d.
As a result, the lids of Examples 1 to 5 had a predetermined flow path regardless of the base body having a flow path width of 10, 30, 50, or 100 μm. The body was bitten by a lid to a depth of about 10 μm with respect to a base body having a channel having a width of 100 μm.
In addition, the lid of Comparative Example 12 having a hardness of 98 had some samples in which the close contact with the base body was insufficient and liquid leakage occurred.
From this, the hardness of the lid is preferably in the range of 60 to 95 for the A type.

10 base body 11 supplied recess 12 discharge recess 13 flow path portion 20 the lid 21 feed port 22 discharge port 30 the lower holding member 31c guide pin 32a mounting hole 40 retainer 61a tube 62 connector _{M 1} positioning mark

Claims (1)

A translucent base body having a micro-channel opened on the surface, and a lid body that is superposed on the base body directly or via an intermediate body,
The base body has a fluid supply recess and a discharge recess, and the lid body has a supply port penetrating and corresponding to the supply recess of the base body, and a drain port penetrating and corresponding to the discharge recess of the base body,
In the case of having an intermediate body, the intermediate body has an inflow port for fluid that matches the supply port of the lid and an outflow port that matches with the discharge port of the lid,
A lower holding body for placing and holding the base body and a presser for pressing the lid;
The lower holding body has a positioning mark for positioning the supply recess and the discharge recess of the base body,
The presser has a connector for connecting a tube corresponding to the supply port and the discharge port of the lid,
The connector is screwed to the presser and has a tube insertion hole with a conical side surface whose diameter is enlarged on the tip side, and a distal end portion of the tube inserted into the insertion hole of the connector is a cone whose diameter is enlarged on the tip side. Due to the trapezoidal shape, it is possible to adjust the seal with respect to the lid body by tightening the connector,
The base body is placed so that the position of the supply concave portion and the discharge concave portion is aligned with the positioning mark of the lower holding portion, and the supply port and the discharge port of the lid are overlapped with the positioning mark on the base body, A microreactor characterized in that a presser is fixed to a lower holding body.

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