JP5446597B2 - Liquid channel device and manufacturing method thereof - Google Patents

Description

  The present invention relates to a plate-like liquid flow path device suitably used for detecting and analyzing antigens in blood, for example, and a method for producing the same.

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

        However, in such a conventional liquid channel device, a part of the liquid channel cannot be changed from the closed state to the open state, which may cause inconvenience in detection and analysis of the target component.

        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.

In the liquid channel device of the present invention, a liquid channel in which a liquid circulates and at least one liquid tank in which the liquid is accumulated are formed on at least one surface of the substrate, and the liquid channel and the liquid tank of the substrate are formed. Is a liquid flow path device in which a cover plate is laminated on the flow path forming surface formed with
An opening means for opening a part of the liquid flow path from a closed state to an open state;
The opening means includes a sealing plug that is disposed in the part of the liquid flow path and is plastically deformed by an operation of pressing the lid plate or the bottom of the liquid flow path from the outside to make the open state. Features.
It is preferable that a peeling process is applied to a portion of the lid plate or the bottom portion of the liquid channel that is in contact with the sealing plug.
The method for manufacturing a liquid channel device of the present invention is a method for manufacturing the liquid channel device,
A first step of forming the liquid flow path and the liquid tank on the substrate; a second step of forming the sealing plug on the part of the liquid flow path; and the flow path forming surface of the substrate. A third step of laminating the lid plate,
In the first step, after forming the upper part of the liquid tank and the liquid flow path in the sheet constituting the inner layer of the substrate, and forming the lower part of the liquid tank in the sheet constituting the intermediate layer of the substrate, The sheet constituting the inner layer, the sheet constituting the intermediate layer, and the sheet constituting the outer layer of the substrate are sequentially laminated.
In the second step, it is preferable that the sealing plug is formed by a method of applying a sealing plug forming material for forming the sealing plug to the part of the liquid channel.

  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.

It is a schematic plan perspective view showing the liquid channel device of the present invention. FIG. 2 is an enlarged plan perspective view of a part of the liquid channel device in FIG. 1. It is sectional drawing which follows the I-I 'line of FIG. In the liquid channel device of FIG. 1, it is a figure explaining a mode that an opening means act | operates, Comprising: (a) Sectional drawing which shows the state which added the load to the sealing plug, (b) The state which removed the load It is sectional drawing shown. It is sectional drawing which follows the II-II 'line | wire of FIG. In the liquid flow path device of FIG. 1, it is a figure explaining a mode that a closing means act | operates, Comprising: (a) Sectional drawing and (b) top view which show the state which extruded the sealing material. It is process drawing which illustrates the manufacturing method of the liquid flow-path apparatus of FIG. 1 typically.

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 10 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 rectangular substrate 11 made of a flat plate, and an end portion or a middle of the liquid flow path 12. A plurality of (9 in this example) liquid tanks (14a to 14i) in which liquid is accumulated are formed, and the lid plate 13 is laminated on the flow path forming surface 12a on the side where the liquid flow path 12 of the substrate 11 is formed. It has been done. In this liquid channel device 10, when it is erected so that the upper end side in FIG. 1 is located at the upper side and the lower end side is located at the lower side, the downstream side from the upstream end of the liquid channel 12 is provided. The sample circulates in the direction of arrow F toward the end by gravity, and the sample is mixed with various treatments and reagents in the middle of the sample to prepare a measurement solution for various detections and analyses.

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 an overflow means comprising an overflow channel 12d 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 12d and flows into the waste liquid tank 14d. As a result, the measuring tank 14c can measure a certain amount of sample. .

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 can be opened and closed and communicates with the atmosphere as necessary.

As shown in FIG. 3, the substrate 11 of the liquid flow path device 10 includes three layers: an outer layer 11a, an intermediate layer 11b stacked on the inner side, and an inner layer 11c stacked on the inner side.
In the inner layer 11c, an upper portion (portion on the lid plate 13 side of the liquid tank) of the liquid tank (only the sample charging tank 14a and the filtration tank 14b are shown in FIG. 3) and the liquid flow path 12 are formed.
In the intermediate layer 11b, a lower part of the liquid tank (a part on the bottom side of the liquid tank other than the upper part) is formed. Further, in the intermediate layer 11 b, the surface on the inner layer 11 c side constitutes the bottom portion 12 b of the liquid channel 12.
The outer layer 11a is disposed on the outermost side of the substrate 11, and the surface on the intermediate layer 11b side constitutes the bottom of the liquid tank.

The liquid flow path device 10 includes opening means S1 to S7 that make part of the liquid flow path 12 open from the closed state, and closing means T1 that changes the open state from the closed 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.

As illustrated in FIG. 3 exemplifying S1 and S2, the opening means S1 to S7 are arranged in the liquid channel 12 so as to block a part of the liquid channel 12, and seal the liquid flow. These portions are formed by a resin sealing plug 15 that closes this portion. The sealing plug 15 is made of a resin that can be plastically deformed, and is plastically deformed by pressing the lid plate 13 of the portion where the sealing plug 15 is disposed from the outside, so that the liquid channel 12 is closed. Set to open state.
Specifically, as shown in FIG. 4 taking the opening means S1 as an example, a load is applied by pressing the sealing plug 15 constituting the opening means S1 from the outside of the cover plate 13 as indicated by an arrow A. In this case, as shown in FIG. 4A, the cover plate 13 is bent, and the sealing plug 15 in contact with the cover plate 13 is crushed and plastically deformed flat. Then, when the load is removed thereafter, as shown in FIG. 4B, the cover plate 13 is restored to its original state by its restoring force, but the sealing plug 15 remains flat and does not restore. As a result, the sealing plug 15 and the cover plate 13 are newly separated from each other so that liquid can flow therethrough.
Thus, in the opening means S1 to S7, the sealing plug 15 is pressed from the outside of the cover plate 13 and a load is applied. As a result, the liquid flow path 12 in this portion is changed from the closed state to the open state.

On the other hand, as shown in FIG. 5, the closing means T1 of the liquid flow path device 10 includes a sealing material supply tank 16 branched from the liquid flow path 12 and formed on the substrate 11, and the sealing material supply tank. 16 and a paste-like sealing material 17 filled in 16.
As shown in the sectional view of FIG. 6A and the plan view of FIG. 6B, the sealing material 17 is sealed by an operation of pressing the lid plate 13 corresponding to the sealing material supply tank 16 from the outside. Through the supply path 18 that connects the material supply tank 16 and the liquid flow path 12, it is pushed out to the liquid flow path 12, and the portion is changed from the open state to the closed state.
Specifically, when a cover plate 13 corresponding to the sealing material supply tank 16 is pressed from the outside as indicated by an arrow B and a load is applied, the cover plate 13 bends. As a result, as indicated by an arrow C, the sealing material 17 filled in the sealing material supply tank 16 is pushed out to the liquid flow path 12 through the supply path 18. As a result, the liquid flow path 12 is blocked by the extruded sealing material 17, and the liquid cannot flow through this portion.

As a specific method for preparing a measurement liquid using such a liquid channel device 10, first, the liquid channel device 10 is positioned so that the sample introduction tank 14 a side is located above and the measurement tank 14 i side is located below. Therefore, the liquid is likely to flow 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 introduction tank 14a and the filtration tank 14b, that is, the sealing plug 15 is pressed from the outside of the cover plate 13 to be plastically deformed, and the liquid flow path 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 an operator pressing with a finger, or a predetermined position may be pressed using a pressing device in which the pressing position is programmed in advance as XY coordinates. Good.

Next, after the filtration treatment is performed in the filtration tank 14b, the sealing plug 15 of the opening means S2 provided between the filtration tank 14b and the measuring tank 14c is also plastically deformed, and the liquid flow path 12 of this part is obtained. Is opened, and 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, and the liquid flow path 12 of this portion is operated. Is closed. Specifically, a portion of the cover plate 13 corresponding to the sealing material supply tank 16 is pressed as indicated by an arrow B to apply a load, and the sealing material 17 filled in the sealing material supply tank 16 is liquid. It pushes out to the flow path 12, and the liquid flow path 12 of this part is obstruct | occluded.
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.

Thus, while the sample after weighing is introduced into the first mixing tank 14f, the opening stopper S4 between the first reagent tank 14e and the first mixing tank 14f is also plastically deformed in the same manner. The reagent is introduced into the first mixing tank 14f, and the sample and the first reagent are mixed in the first mixing tank 14f to prepare an intermediate preparation solution.
Next, also for the opening means S5 between the first mixing tank 14f and the second mixing tank 14h, the intermediate preparation liquid prepared in the first mixing tank 14f by similarly plastically deforming the sealing plug is used as the second mixing tank. 14h. On the other hand, for the opening means S6 between the second reagent tank 14g and the second mixing tank 14h, the sealing reagent is similarly plastically deformed to introduce the second reagent into the second mixing tank 14h. Then, the intermediate preparation solution and the second reagent are mixed in the second mixing tank 14h to prepare a measurement solution.
Next, also for the opening means S7 between the second mixing tank 14h and the measuring tank 14i, the sealing plug is similarly plastically deformed, and the measuring liquid 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 10, and a target component is detected and measured.
In the process of preparing the measurement liquid in this way, it is possible to facilitate the flow of the liquid or to accurately determine the flow rate by appropriately opening and closing communication holes (not shown) provided in each liquid tank as necessary. The flow of the liquid may be controlled, for example, by improving the flow rate.

According to such a liquid flow path device 10, the liquid flow path 12 includes the opening means S <b> 1 to S <b> 7 that bring the liquid flow path 12 from the closed state to the open state and the closing means T <b> 1 that turns the liquid flow path 12 from the open state to the closed state. The flow of the liquid inside can be controlled, and 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 regard, as in this example, when the closing means T1 is provided on the upstream side of the measuring tank 14c, the measuring tank can be used even if the entire amount of the sample passing through the filtration tank 14b does not completely flow into the measuring tank 14c. 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.

  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.

  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 10 is stored.

  Further, the opening means S1 to S7 and the closing means T1 of the liquid channel device 10 of this example have a simple configuration and can be formed at low cost. Therefore, the liquid channel device 10 can be a disposable type. In addition, the opening and closing operations can be performed only by a simple pressing operation, and the operability is excellent.

  Such a liquid flow path device 10 includes a first step of forming a liquid flow path 12, a liquid tank, a sealing material supply tank 16, and a supply path 18 on a substrate 11, and a predetermined liquid flow path 12. A second step of forming the sealing plug 15 and a third step of laminating the cover plate 13 on the flow path forming surface 12a on the substrate 11 where the liquid flow path 12 and the like are formed. Can be manufactured.

Hereinafter, the manufacturing process of the liquid channel device 10 will be described with reference to FIG. 7 schematically showing the manufacturing process of the liquid channel device 10.
In the first step, first, a roll (roll) 20 of a sheet 11c ′ constituting the inner layer 11c of the substrate 11, a roll 21 of the sheet 11b ′ constituting the intermediate layer 11b, and a sheet constituting the outer layer 11a. 11a 'winding material 22 is prepared.
Next, the sheet 11c ′ is continuously supplied from the wound material 20 of the sheet 11c ′ constituting the inner layer 11c, and a portion corresponding to the liquid flow path 12 is punched out linearly by the punching machine 23a. The part corresponding to the upper part of each liquid tank, such as 14c, is punched into a hole shape. Further, since the liquid flow path device 10 includes a supply path 18 formed by branching from a part of the liquid flow path 12 and a sealing material supply tank 16, the supply path 18 is provided in the sheet 11c ′. The portions corresponding to the sealing material supply tank 16 are also punched into shapes corresponding thereto.
On the other hand, the sheet 11b ′ is continuously supplied from the wound material 21 of the sheet 11b ′ constituting the intermediate layer 11b, and holes corresponding to the lower portions of the liquid tanks such as the measuring tank 14c are opened by the punching machine 23b. Punch into a shape.

Next, the sheet 11a ′ is continuously supplied from the wound product 22 of the sheet 11a ′ constituting the outer layer 11a. And the board | substrate 11 is manufactured by laminating | stacking each sheet | seat 11a ', 11b', 11c 'sequentially.
Here, the sheets 11a ′, 11b ′, and 11c ′ are preferably bonded by an adhesive supplied from an unillustrated adhesive supply device, but depending on the material of the sheets 11a ′, 11b ′, and 11c ′. May be bonded together by heat fusion or the like. Furthermore, you may use the sheet | seat etc. which apply | coated the adhesive or the adhesive agent beforehand.

As described above, as the first step, the sheets 11a ′, 11b ′, and 11c ′ are supplied from the rolls 20, 21, and 22, and the sheets 11b ′ and 11c ′ are each punched into a predetermined shape. When the step of sequentially laminating and adhering the sheets 11a ′, 11b ′, and 11c ′ is employed, a large number of substrates 11 in which the liquid channel 12 and the liquid tank are formed can be continuously produced. Such a method is a method in which a liquid tank or a liquid channel is formed on each substrate made of a single flat plate by, for example, photolithography or cutting, and a substrate in which the liquid tank or the liquid channel is formed is injection molded. Compared with the method of forming by, etc., the manufacturing cost is low, simple and mass production is possible, which is industrially suitable.
The method of punching the sheets 11b ′ and 11c ′ into a predetermined shape to form the liquid flow path 12 and the liquid tank is low in cost and excellent in productivity, but other methods (laser processing, knife, etc. are used). The sheet 11b ′, 11c ′ may be opened in a predetermined shape by cutting, heat processing, etc.) to form the liquid flow path 12, the liquid tank, and the like.

  In this example, the substrate 11 of the liquid flow path device 10 is composed of three layers of the outer layer 11a, the intermediate layer 11b, and the inner layer 11c. However, the substrate 11 is composed of two layers of the outer layer 11a and the inner layer 11c. It may be done. In that case, the liquid flow path 12, the liquid tank, the supply path 18, and the sealing material supply tank 16 are formed in the sheet 11c 'forming the inner layer 11c. In this case, the formed liquid flow path 12 and the depth of the liquid tank are the same.

As materials of the sheets 11a ′, 11b ′, 11c ′ constituting the outer layer 11a, the intermediate layer 11b, and the inner layer 11c of the substrate 11, styrene resin, acrylic resin, polycarbonate resin, vinyl chloride resin, PEN resin, polyester resin, epoxy Examples thereof include resins such as resin, phenol resin, ABS resin, polypropylene resin, and fiber reinforced plastic. Among these, styrene resin, acrylic resin, polycarbonate resin, vinyl chloride resin, PEN resin, and polyester resin are preferable because they are transparent and the state of the liquid flowing through the liquid flow path 12 can be visually observed.
In this embodiment, since a wound product of resin is used as the substrate 11 and a suitable manufacturing method of the liquid flow path device 10 at that time is described, the sheet material is made of resin in this way. Illustrated. However, there is no particular limitation on the manufacturing method. For example, when it is required to stably support the liquid flow path device, a transparent material other than a resin such as glass is used for the substrate, and this is subjected to a cutting process. It is also possible to form a liquid channel, a liquid tank, and the like by applying a method such as the above.

The thickness of each of the sheets 11a ′, 11b ′, and 11c ′ can be set as appropriate. However, in the case of the liquid channel device 10 shown in the drawing, the thickness of the sheet 11c ′ that forms the inner layer 11c is the liquid to be formed. The sum of the thicknesses of the sheet 11c ′ forming the inner layer 11c and the sheet 11b ′ forming the intermediate layer 11b corresponds to the depth of the flow path 12, and corresponds to the total depth of the liquid tank. Therefore, the thicknesses of the sheet 11b ′ and the sheet 11c ′ are determined in consideration of the depth required for the liquid tank and the liquid channel 12.
Specifically, the thickness of the sheet 11b ′ is preferably 25 to 500 μm, and the thickness of the sheet 11c ′ is preferably 10 to 300 μm.
Further, in this example (in the case where the lid plate 13 is pressed), the thickness of the sheet 11a ′ is preferably 50 μm or more, and more preferably 100 to 1000 μm. Works well.
There are no particular restrictions on the width of the liquid flow path 12, the volume and shape of each liquid tank and the sealing material supply tank 16, and can be set as appropriate. For example, the width of the liquid channel 12 is preferably 25 to 2000 μm, more preferably 500 to 2000 μm, and the volume of the liquid tank is preferably 50 to 50000 μl, more preferably 100 to 1000 μl.
However, the waste liquid tank 14d and the like do not have a particularly suitable volume, and can be freely designed according to the function of each liquid tank.

Next, a second step of forming the sealing plug 15 is performed in a part of the liquid flow path 12 formed in the substrate 11 in the first step described above, that is, in each position where the opening means S1 to S7 are provided.
In the second step, a sealing plug forming material for forming the sealing plug 15 is formed at a predetermined position in the liquid channel 12 of the substrate 11 that is continuously supplied by a printing machine (for example, a screen printing machine), a dispenser. The sealing plug 15 is formed by a coating method using a coating device 24a such as a coater (roll coater, knife coater, etc.).

The sealing plug forming material is not limited as long as it does not interact with the liquid flowing through the liquid flow path 12 and reliably closes the liquid in the closed state and is plastically deformed by pressing. And a resin composition containing a plastic component, a filler, and a solvent. And when using a dispenser as the coating device 24a, the viscosity of the resin composition is preferably 30 to 500 dPa · s, and when using a screen printer or the like, the viscosity of the resin composition is 50 to 500 dPa · s. Is preferred.
The resin component preferably has a glass transition temperature of −10 ° C. or less and a mass average molecular weight of 30 from the viewpoints of sealing ability and its stability, non-eluting property, applicability (printability, dispensing property, etc.). Ten thousand or less resins are preferably used. Examples of the resin include epoxy resins, polyester resins, chlorine resins, acrylic resins, ester resins such as phthalic acid, and the like, and one or more resins can be used.
As the plastic component, a plasticizer having a glass transition temperature of 30 ° C. or lower is preferably used. Examples of the plasticizer include thermoplastic resins having a low melting point such as hard resin resins, epoxy resins, and polyester resins. One or more plasticizers can be used.

The filler is blended to adjust the viscosity of the sealing plug forming material and the sealing plug forming property, and examples thereof include precipitated barium sulfate, talc, acicular silicon oxide, and hollow beads. One or more can be used.
Among these, sealing plugs formed from resin compositions containing hollow beads (made of glass, resin, etc.) are not only plastically deformed when pressed, but the hollow beads are broken and broken. This reduces the bulk. Therefore, according to the sealing plug containing hollow beads in this way, when pressed and crushed, it can be deformed more flatly and in a state of opening, the liquid can flow more easily.
The solvent is blended in order to adjust the viscosity of the sealing plug forming material, and an appropriate organic solvent is used. In addition, as long as the sealing plug forming material can be applied by printing or the like without containing a solvent, it may not contain a solvent, and preferably contains no solvent.

  As described above, according to the method of applying the sealing plug forming material by the printing method, the dispenser method, the coater method, etc., the sealing plug 15 can be continuously and efficiently formed at a predetermined position.

In the second step, the sealing material supply tank 16 constituting the closing means T1 is filled with the paste-like sealing material 17 by the coating device 24b. Also in this case, according to the method of applying the sealing material 17 by the above-described printing method, dispensing method, coater method, etc., the sealing material 17 can be filled in a predetermined position continuously and efficiently.
The paste-like sealing material 17 may be any material that does not interact with the liquid flowing through the liquid flow path 12 and can be extruded to close the liquid flow path 12. For example, a resin component and a plastic component For example, a resin composition containing a filler and having a viscosity of 30 to 500 dPa · s is preferably used. Moreover, finally, a resin composition having an elongation percentage of 500% or more is preferable.
The resin component preferably has a glass transition temperature of −40 ° C. or less and a mass average molecular weight of 50,000 from the viewpoints of coating properties (printability, dispensing properties, etc.), fluidity, sealing ability and stability thereof. The following resins are preferably used. Examples of the resin include epoxy resins, polyester resins, chlorine resins, acrylic resins, ester resins such as phthalic acid, and the like, and one or more resins can be used.
As the plastic component, a plasticizer having a glass transition temperature of 30 ° C. or lower is preferably used. Examples of the plasticizer include thermoplastic resins having a low melting point such as hard resin resins, epoxy resins, and polyester resins. One or more plasticizers can be used.
The filler is blended to adjust the viscosity of the sealing material 17 and to form a shape that easily closes the liquid channel 12 when the sealing material 17 is pushed out to the liquid channel 12. Fiber pieces, extender pigments, thixotropic imparting agents, and the like can be used. For example, fumed silica such as Aerosil (trade name, manufactured by Nippon Aerosil Co., Ltd.), precipitated barium sulfate, and talc are preferably used.

  Thus, after apply | coating the sealing plug formation material and the sealing material 17 to a predetermined position, respectively, these are heat-dried as needed by the composition of the sealing plug formation material and the sealing material 17, etc. Steps not shown in the figure, such as a step of curing and a step of curing.

  Thereafter, in a third step, a sheet 13 ′ constituting the cover plate 13 is laminated on the flow path forming surface 12 a of the substrate 11 and bonded. In this case, it is preferable to continuously supply the sheet 13 ′ constituting the cover plate 13 from the wound product 25. Here, the substrate 11 and the sheet 13 'are preferably bonded by an adhesive supplied from an adhesive supply device (not shown). However, depending on these materials, the substrates 11 and the sheet 13' are bonded together by heat fusion or the like. May be. Thereby, the continuous body with which the several liquid flow-path apparatus 10 continued continuously can be manufactured.

  The continuous body of the liquid flow path device 10 manufactured in this way may be wound up as shown in FIG. 7 to be in the state of the wound product 26 or in a folded state. Moreover, you may be set as the single wafer type cut | disconnected one sheet at a time. In the case of the state of the wound product 26 or the folded state, a process of forming a line such as a perforation or a concave line between the liquid channel devices 10 may be performed. Thereby, it becomes easy to bend | fold between each liquid flow path apparatus 10, and can make it easy to fold the continuous body of the liquid flow path apparatus 10. FIG. Moreover, it can be made easy to separate into a single wafer type.

  The cover plate 13 bends when pressed and a load is applied as shown by an arrow A in FIG. 4, and is restored to its original state by its restoring force when the load is removed thereafter. Is. If it is such, there is no restriction | limiting in particular in the material and thickness of the cover board 13, As a material, for example, a styrene resin, an acrylic resin, a polycarbonate resin, a vinyl chloride resin, a PEN resin, a polyester resin, an epoxy resin And resins such as phenol resin, ABS resin, polypropylene resin, and fiber reinforced plastic. Among these, styrene resin, acrylic resin, polycarbonate resin, vinyl chloride resin, PEN resin, and polyester resin are preferable because they are transparent and the state of the liquid flowing through the liquid flow path 12 can be visually observed. A thickness of about 15 to 300 μm is preferable because it has flexibility and restoring force suitable for the cover plate 13.

  In addition, in the third step, before the lid plate 13 is laminated and bonded to the flow path forming surface 12a of the substrate 11, the part 13a in contact with the sealing plug 15 in the lid plate 13 contains a silicone component or the like. It is preferable to perform a peeling treatment in advance by applying an agent. When the peeling treatment is performed in this manner, the lid plate 13 and the sealing plug 15 can be quickly separated when the load indicated by the arrow A is removed (FIG. 4B), and the opening is easily performed. Can be in a state. On the other hand, it is preferable that the bottom portion 12b of the liquid flow path 12 in contact with the sealing plug 15 is previously subjected to an adhesion treatment by applying an adhesive or the like. If this is done, the sealing plug 15 is securely bonded to this portion, so that the sealing plug 15 can be attached to the lid plate 13 more smoothly as shown in FIG. Can be separated from the side.

In the above description, as shown in FIG. 4, as the sealing plug 15 constituting the opening means S <b> 1 to S <b> 7, the liquid channel 12 is opened by being plastically deformed by pressing from the outside of the lid plate 13. It was illustrated about what to make. However, it is good also as a form which carries out plastic deformation by operation which presses the bottom part 12b of the liquid flow path 12 of the part in which the sealing plug 15 is arrange | positioned from the outside. In that case, the outer layer 11a and the intermediate layer 11b constituting the substrate 11 bend when pressed and a load is applied, and return to the original state by the restoring force when the load is removed thereafter. It is necessary to be configured to restore. In this case (in the case of pressing the bottom 12b), the thickness of the sheet 11a ′ is preferably 10 to 300 μm, more preferably 15 to 200 μm.
In this case, it is preferable that the portion 13 a in contact with the sealing plug 15 in the lid plate 13 is subjected to an adhesion treatment, and the portion in contact with the sealing plug 15 in the bottom portion 12 b of the liquid flow path 12 is subjected to a peeling treatment. .
Similarly, in the above description, as shown in FIG. 6, the sealing material 17 is pushed out by the operation of pressing the lid plate 13 corresponding to the sealing material supply tank 16 from the outside, and the liquid flow path 12 is moved. It illustrated about the form to obstruct | occlude. However, the sealing material 17 may be pushed out by pressing the bottom portion 16a of the sealing material supply tank 16 from the outside. Even in that case, it is necessary that the outer layer 11a and the intermediate layer 11b constituting the substrate 11 be configured to bend when pressed and a load is applied.

In the illustrated liquid channel device 10, the liquid channel 12 is formed only on one side of the substrate 11, but the liquid channel 12 may be formed on both sides of the substrate 11.
Moreover, there is no restriction | limiting in the form of the communication hole which can be opened and closed provided as needed in each liquid tank, By inserting and removing a fitting type cap to the communication hole formed in the cover plate 13, a communication hole is made. The form which can be opened and closed may be used. Further, an opening means and a closing means having the same configuration as the opening means S1 to S7 and the closing means T1 provided in the liquid flow path 12 may be provided in the communication hole.
Moreover, you may provide a liquid feeding means in each liquid tank as needed. As a specific form of the liquid feeding means, the internal volume of the liquid tank is reduced by the operation of pressing the lid plate 13 corresponding to the liquid tank or the bottom of the liquid tank from the outside, and the inside of the liquid tank The liquid is discharged and sent to the downstream side. The liquid tank provided with such a liquid feeding means is preferably provided with a backflow prevention means such as a weir plate for preventing the backflow of the liquid to the upstream side.

In the above example, in order to circulate the liquid, the form using the action of gravity is shown, but the action of centrifugal force may be used. For example, the liquid channel device 10 is set in a centrifuge so that the sample introduction tank 14a side is located on the rotation center side and the measurement tank 14i side is located on the outer periphery side of the rotation. Centrifugal force acts from the upstream side of the flow path 12 to the downstream side, and as a result, the liquid may flow.
Further, when the liquid flow path device 10 is rotated and the liquid is circulated by utilizing the centrifugal force in this way, the pressing operation for operating the opening means S1 to S7 and the closing means T1 is performed by a pressure contact disk. Can also be used. The pressure contact disk presses a predetermined position while moving the surface of the cover plate 13 of the liquid flow path device 10 from the rotation center side toward the rotation outer peripheral side in the rotation radial direction.

  In addition to moving the liquid using gravity or centrifugal force, the liquid flow path 12, a part of the liquid tank, or both of them are heated to expand the air in the liquid flow path 12 or the liquid tank. In addition, an oxygen absorbent (such as iron powder that easily oxidizes) is sealed in a part of the liquid channel 12, and the inside of the liquid channel 12 is decompressed by absorbing oxygen in the liquid channel 12, A method of moving and distributing the liquid may be used in combination.

  In the above description, as a method of injecting the sample into the sample loading tank 14a, a method of piercing the needle of the syringe into the cover plate 13 is exemplified. For example, a sample injection hole is formed in the cover plate 13 in advance. Alternatively, 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.

There are no particular limitations on the sample and reagent through which the liquid channel device 10 is circulated, and any sample and reagent conventionally employed in the medical field, environmental field, and the like can be used in appropriate combination.
For example, in the medical field, examples of samples include blood (whole blood), plasma, serum, buffy coat, urine, feces, saliva, sputum, and other organisms, viruses, bacteria, molds, yeast, animal and plant cells, etc. Can be 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.
The liquid channel device 10 exemplified above includes a filtration tank 14b for performing a filtration process on the sample flowing from the sample insertion tank 14a downstream of the sample insertion tank 14a. Therefore, when such a liquid channel device 10 is used, for example, in the case where blood cells are removed from blood by filtration, a sample that conventionally had to be previously filtered by another filtration device is previously filtered. Without being supplied to the sample loading tank 14a of the liquid channel device 10 as it is.

The reagent is not particularly limited and may be appropriately selected depending on the target component. However, when an antigen present in a sample is captured and analyzed using an antigen-antibody reaction, a reagent containing an antibody against the antigen is preferable. .
In the above example, a reagent containing, for example, an antibody is sealed in the first reagent tank 14e or the second reagent tank 14g in advance, and these reagents and, for example, a sample containing an antigen are mixed in the first mixing tank. An example in which the antigen is captured by the antibody by mixing in 14f or the second mixing tank 14h is illustrated. However, the form in which the antigen is captured by the antibody is not limited to such a form. For example, the antibody or the magnetic bead carrying the antibody is fixed in the liquid tank of the liquid channel device 10 or in the middle of the liquid channel. Alternatively, an antigen in the sample may be captured by the antibody by circulating the sample therethrough. Next, an appropriate reagent is introduced from the sample introduction tank 14a by a syringe or the like, and the above-described liquid feeding means is also appropriately used as necessary to wash or denature the captured antigen. Analysis, growth (concentration increase), or separation can be performed to improve the analysis accuracy.

  Further, the reaction performed in the liquid channel device 10 is not limited to an antigen-antibody reaction, and various chemical reactions, PCR (polymerase chain reaction) for amplifying DNA, reaction for capturing a protein such as DNA, and the like can also be performed. A plurality of reactions may be combined, or some reaction may not necessarily be performed, for example, only the mixing process is performed in the liquid channel device 10. Thus, there is no limitation on the method of using the liquid flow path device 10.

  Moreover, in order to promote such various reactions or promote the flow of liquid, various treatments can be performed on the liquid channel 12 and the liquid tank. For example, various chemical treatments using acids, alkalis, etc., physical treatments using latex, fluorescent substances, etc., biochemical treatments using antigens, antibodies, DNA, etc. Surface treatment effects such as treatment and water repellent treatment can be obtained. In addition, coating treatment, plasma treatment, flame treatment, and the like may be performed. 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. . Further, the liquid flow path 12 and the liquid tank may be pressurized as necessary (pressure treatment) or decompressed (vacuum treatment).

Further, it is possible to put a colorant, a dye, a fluorescent agent, etc. in an appropriate liquid tank, and to color the sample that has reached it or to impart fluorescence to the sample.
In addition, the contents, procedures, and liquids of operations performed using the liquid flow path device 10 as needed at any location on the cover plate 13, the liquid flow path 12, the liquid tank, and the substrate 11 of the liquid flow path device 10. The name of the tank (for example, “weighing tank”) may be directly printed. Or you may stick the display sticker etc. which printed the content and procedure of operation, the name of a liquid tank, etc., or may provide the marking used as a certain mark. Further, for example, only a part of the cover plate 13 may be made transparent so that the portion becomes conspicuous.

  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 channel device 10. At that time, the liquid flow path device 10 may be heated or cooled as necessary.

DESCRIPTION OF SYMBOLS 10 Liquid flow-path apparatus 11 Board | substrate 11a Outer layer 11b Intermediate | middle layer 11c Inner layer 12 Liquid flow path 12a Flow path formation surface 13 Cover plate S1-S7 Opening means T1 Closing means 15 Sealing plug

Claims (3)

A flow path forming surface in which a liquid flow path through which liquid flows and at least one liquid tank in which the liquid accumulates are formed on at least one surface of the substrate, and the liquid flow path and the liquid tank of the substrate are formed. Is a liquid flow path device in which a cover plate is laminated,
An opening means for opening a part of the liquid flow path from a closed state to an open state;
The opening means is disposed in the part of the liquid flow path, and is formed of a sealing plug that is plastically deformed by an operation of pressing the lid plate or the bottom of the liquid flow path from the outside, and sets the open state.
The sealing plug is formed by application of a sealing plug forming material for forming the sealing plug, and the sealing plug forming material contains hollow beads that are broken by the pressing operation. A liquid flow path device.   The liquid channel device according to claim 1, wherein a peeling process is performed on a portion of the lid plate or a bottom portion of the liquid channel that contacts the sealing plug. It is a manufacturing method of the liquid channel device according to claim 1 or 2 ,
A first step of forming the liquid flow path and the liquid tank on the substrate; and the sealing plug forming material containing hollow beads broken by the pressing operation in the part of the liquid flow path. And a second step of forming the sealing plug by a method of applying, and a third step of laminating the lid plate on the flow path forming surface of the substrate,
In the first step, after forming the upper part of the liquid tank and the liquid flow path in the sheet constituting the inner layer of the substrate, and forming the lower part of the liquid tank in the sheet constituting the intermediate layer of the substrate, A method for manufacturing a liquid flow path device, comprising: sequentially laminating a sheet constituting the inner layer, a sheet constituting the intermediate layer, and a sheet constituting the outer layer of the substrate.

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