JP7303623B2 - inspection tool - Google Patents

Description

TECHNICAL FIELD The present invention relates to a test tool including a substrate provided with a flow path through which fluid is sent.

2. Description of the Related Art Conventionally, various test tools have been proposed that include a substrate provided with a channel such as a microchannel through which a fluid is sent. Methods of performing blood tests, genetic tests, and the like by controlling liquid feeding and reactions of various specimens or samples using such test tools are being studied.

By the way, a liquid flowing through a microchannel generally produces a stable laminar flow. Therefore, when mixing a plurality of liquids in a microchannel, there is a problem that the efficiency of mixing decreases.

Therefore, for example, Patent Document 1 below discloses a microfluidic device in which a mixing channel is provided in the middle of a microchannel for reliably and efficiently mixing a plurality of fluids that are moved and fed. It is In Patent Literature 1, the mixing channel has a portion that protrudes on one side of the substrate and a portion that protrudes on the other side of the substrate. In addition, the portion protruding on one surface side and the portion protruding on the other surface side are arranged line-symmetrically in the liquid feeding direction, and are positioned to completely overlap in the liquid feeding direction. is provided in

JP 2016-097353 A

However, even in the case of providing a mixing channel as in Patent Document 1, the accuracy of mixing is still insufficient.

In addition, the present inventors have found that if they try to increase the efficiency of mixing by generating turbulence under a laminar flow such as a microchannel, liquid residue may occur. It was found that a problem arises in that the sensitivity of the measurement decreases in the analysis.

SUMMARY OF THE INVENTION An object of the present invention is to provide a test tool that can reliably mix a plurality of liquids and that is less likely to leave residual liquids.

A test tool according to the present invention includes a substrate provided with a flow channel for feeding a fluid, a mixing flow channel for mixing a plurality of liquids in the middle of the flow channel, and the mixing a flow channel having a first flow channel portion enlarged on one surface side of the substrate and a second flow channel portion enlarged on the other surface side of the substrate; in the direction in which the first channel portion and the second channel portion partially overlap, and the first channel portion with respect to the entire length of the first channel portion The length ratio L1 of the part where the flow path part and the second flow path part overlap, and the first flow path part and the second flow path part with respect to the entire length of the second flow path part 2 of the length ratio L2 of the part where the channel part overlaps, the smaller ratio L is 0.05 or more and 0.7 or less, and the surface area of the entire mixing channel The ratio (S/V) of S to the volume V of the entire mixing channel is 4 or less.

In a specific aspect of the inspection tool according to the present invention, the substrate has a first main surface and a second main surface that face each other, and connects the first main surface and the second main surface, It has a first side surface and a second side surface that are opposed to each other, the first flow path part is enlarged toward the first side surface, and the second flow path part is widened to the second side surface. is enlarged to the lateral side of the

In another specific aspect of the test tool according to the present invention, the first flow path section and the second flow path section are alternately provided in the direction in which the flow path extends.

In still another specific aspect of the test tool according to the present invention, the total number of the first flow path section and the second flow path section is two or more.

In still another specific aspect of the inspection tool according to the present invention, the ratio L is 0.1 or more and 0.5 or less.

In still another specific aspect of the test tool according to the present invention, the channel is a microchannel.

ADVANTAGE OF THE INVENTION According to this invention, the test|inspection tool which can mix several liquids reliably, and is hard to produce a liquid residue can be provided.

FIG. 1 is a schematic perspective view showing a microchip according to one embodiment of the present invention. FIG. 2 is a schematic plan view for explaining the channel structure of the microchip according to one embodiment of the present invention. FIG. 3 is a schematic plan view showing an enlarged mixing channel in the microchip according to one embodiment of the present invention. FIG. 4 is a schematic plan view showing an enlarged mixing channel in the first modified example of the microchip according to one embodiment of the present invention. FIG. 5 is a schematic plan view showing an enlarged mixing channel in a second modification of the microchip according to one embodiment of the present invention. FIG. 6 is a schematic plan view for explaining each dimension of the mixing channel in the microchip according to one embodiment of the present invention. FIG. 7 is a schematic plan view showing an enlarged mixing channel of a microchip of a comparative example.

Hereinafter, the present invention will be clarified by describing specific embodiments of the present invention with reference to the drawings.

It should be noted that each embodiment described herein is exemplary and that partial permutations or combinations of configurations are possible between different embodiments.

In one embodiment below, a microchip having a microchannel will be described as an example of the test tool of the present invention. However, the test tool according to the present invention is not limited to such microchips, and can be applied to chips having channels of normal dimensions. In addition, the inspection tool in the present invention is not limited only to inspection, but is used in a broad concept including analysis tools used for various analyses.

FIG. 1 is a schematic perspective view showing a microchip according to one embodiment of the present invention. As shown in FIG. 1, the microchip 1 has a rectangular plate-like substrate 2 . However, the shape of the substrate 2 is not particularly limited, and may be disc-shaped, for example.

The substrate 2 has a first major surface 2a and a second major surface 2b facing each other. The substrate 2 also has a first side 2c and a second side 2d that face each other. The first side surface 2c and the second side surface 2d connect the first main surface 2a and the second main surface 2b.

The substrate 2 has a substrate body 3 , a first cover layer 4 provided to cover the upper surface of the substrate body 3 , and a second cover layer 5 laminated on the lower surface side of the substrate body 3 . The first cover layer 4 is provided on the first main surface 2a side. The second cover layer 5 is provided on the second main surface 2b side. Note that the laminated structure is not particularly limited.

The material forming the substrate body 3 is not particularly limited, but synthetic resin, for example, can be used. Although the synthetic resin is not particularly limited, it is preferably a thermoplastic resin. Among others, for example, cycloolefin polymer, cycloolefin copolymer, polycarbonate, polymethyl methacrylate, or polypropylene can be used as the thermoplastic resin. These may be used individually by 1 type, and may use multiple types together.

The substrate main body 3 is preferably made of the thermoplastic resin molded body. The molding method is not particularly limited, and known molding methods can be used. Examples of molding methods include injection molding, injection compression molding, gas-assisted injection molding, extrusion molding, multi-layer extrusion molding, rotational molding, heat press molding, blow molding, and foam molding. Among them, injection molding is preferable.

The first cover layer 4 and the second cover layer 5 can be made of, for example, a flexible material such as a resin film. As the resin film, for example, a thermoplastic resin such as cycloolefin polymer, cycloolefin copolymer, polycarbonate, polymethyl methacrylate, or polypropylene can be used. These may be used individually by 1 type, and may use multiple types together. In addition, in the present invention, the substrate main body 3 and the cover layer may be configured integrally.

Also, the first cover layer 4 and the second cover layer 5 may be made of an elastic member. Although the elastic member is not particularly limited, it is preferably an elastomer.

A method for bonding the first cover layer 4 and the second cover layer 5 to the substrate body 3 is not particularly limited, and a known lamination method can be used. Lamination methods include, for example, methods such as press crimping and roll lamination. Although lamination conditions are not particularly limited, it is preferable to laminate at a temperature of 50° C. or less, for example. Moreover, it is preferable to laminate at a pressure of 10 MPa or less. By laminating under such conditions, embedding of the first cover layer 4 and the second cover layer 5 in the flow path can be made more difficult to occur.

FIG. 2 is a schematic plan view for explaining the channel structure of the microchip according to one embodiment of the present invention. Moreover, FIG. 3 is a schematic plan view showing an enlarged mixing channel in the microchip according to one embodiment of the present invention.

Inside the substrate 2, there is provided a channel through which a fluid is sent. Here, the channel is the microchannel 10 . The channel may be a channel having a larger cross-sectional area than the microchannel 10 instead of the microchannel 10 . However, it is preferably the microchannel 10 . As a result, various analyzes and inspections can be performed with a very small amount of sample.

By the way, the microchannel 10 is a minute channel that produces a micro effect when transporting a fluid. In such a microchannel 10, the liquid is strongly affected by surface tension and behaves differently from liquid flowing through a normal large-sized channel.

The cross-sectional shape and size of the microchannel 10 are not particularly limited as long as the channel produces the above micro effect. For example, when a pump or gravity is used to flow a fluid through the microchannel 10, from the viewpoint of reducing the channel resistance, when the cross-sectional shape of the microchannel 10 is generally rectangular (including square), , the dimension of the smaller side is preferably 20 μm or more, more preferably 50 μm or more, and even more preferably 100 μm or more. From the viewpoint of further miniaturization of the microfluidic device using the microchip 1, the dimension of the smaller side is preferably 5 mm or less, more preferably 1 mm or less, and even more preferably 500 μm or less.

Further, when the cross-sectional shape of the microchannel 10 is generally circular, the diameter (minor axis in the case of an ellipse) is preferably 20 μm or more, more preferably 50 μm or more, and even more preferably 100 μm or more. From the viewpoint of further miniaturization of the microfluidic device, the diameter (in the case of an ellipse, the minor axis) is preferably 5 mm or less, more preferably 1 mm or less, and even more preferably 500 μm or less.

On the other hand, for example, in order to effectively utilize capillary action when flowing a fluid through the microchannel 10, if the cross-sectional shape of the microchannel 10 is approximately rectangular (including square), the smaller side is preferably 5 μm or more, more preferably 10 μm or more, and even more preferably 20 μm or more. Also, the dimension of the smaller side is preferably 200 μm or less, more preferably 100 μm or less.

In this embodiment, a first liquid reservoir 11 , a second liquid reservoir 12 , a third liquid reservoir 13 , and a mixing channel 14 are provided in the middle of the microchannel 10 . More specifically, in the microchannel 10, a first liquid storage section 11, a second liquid storage section 12, and a third liquid storage section 13 are provided from the upstream side. A mixing channel 14 is provided downstream of the third liquid storage section 13 . A downstream channel 17 is provided further downstream of the mixing channel 14 . The first to third liquid storage units 11 to 13 and the mixing channel 14 may be directly connected to each other, or may be provided via a connecting microchannel or other space. . In this embodiment, the first to third liquid reservoirs 11 to 13 and the mixing channel 14 are connected to each other via connecting microchannels.

The first to third liquid storage units 11 to 13 are spaces in which liquids such as liquid reagents and solvents are stored before being fed into the mixing channel 14, respectively. When three liquid storage units are provided as in this embodiment, three types of liquid can be stored. However, in the present invention, the number of liquid reservoirs provided in the microchannel 10 is not particularly limited. Also, the liquid storage unit may not be provided.

In this embodiment, the mixing channel 14 is a channel for mixing three types of liquids sent from the first to third liquid storage units 11-13. However, the mixing channel 14 may be any channel that mixes two or more liquids, and the types of liquids to be mixed are not particularly limited.

As shown in FIG. 3 , the mixing channel 14 has a first channel portion 15 and a second channel portion 16 . The first flow path portion 15 is a concave portion whose flow path is enlarged toward the first side surface 2c. The second flow path portion 16 is a concave portion whose flow path is enlarged toward the second side surface 2d. However, in the present invention, the first flow path portion 15 is a concave portion in which the flow path is enlarged toward the first main surface 2a side, and the second flow path portion 16 flows toward the second main surface 2b side. The channel may be an enlarged recess. It is sufficient that the first channel portion 15 is a concave portion with a channel enlarged on one surface side, and the second channel portion 16 is a concave portion with a channel enlarged on the other surface side.

In this embodiment, the two first flow path portions 15 and the two second flow path portions 16 are provided alternately in order from the first flow path portion 15 . However, it suffices that at least one pair of the first flow path portion 15 and the second flow path portion 16 are provided adjacent to each other, and all the first flow path portions 15 and the second flow path portions 16 are not necessarily arranged alternately. does not need to be set in From the viewpoint of mixing a plurality of liquids more accurately in the mixing channel 14, it is preferable that the first channel portions 15 and the second channel portions 16 are alternately provided.

In addition, as shown in FIG. 3, in the present embodiment, the planar shapes of the first channel portion 15 and the second channel portion 16 are semicircular. However, like the mixing channel 14A in the first modified example shown in FIG. 4, the planar shapes of the first channel portion 15A and the second channel portion 16A may each be semi-elliptical. Like the mixing channel 14B in the second modified example shown in FIG. 5, the planar shapes of the first channel portion 15B and the second channel portion 16B may each be a polygonal concave portion. The semicircular, semielliptical, and polygonal shapes may be substantially semicircular, semielliptical, and polygonal, respectively. The planar shape of the path portion 16 is not particularly limited.

Returning to FIG. 3, in the present embodiment, in the X direction along the direction in which the microchannel 2 extends, the portion where the first channel portion 15 and the second channel portion 16 partially overlap (overlap) have. In this embodiment, in the X direction, the smaller ratio L of the ratio L1 and the ratio L2 is 0.05 or more and 0.7 or less. In addition, the ratio L1 is the ratio of the length of the part where the first flow path part 15 and the second flow path part 16 partially overlap with respect to the length of the entire first flow path part 15 (partial overlap length of the portion where the first channel portion 15 is formed/length of the entire first flow path portion 15). In addition, the ratio L2 is the ratio of the length of the part where the first flow path part 15 and the second flow path part 16 partially overlap to the length of the entire second flow path part 16 (partial overlap length of the portion where the second channel portion 16 is formed/length of the entire second flow path portion 16).

This is explained in more detail below with reference to FIG.

As shown in FIG. 6, in the X direction, a first end portion 15a of the first channel portion 15 overlapping the second channel portion 16 and a second end portion 15b of the other side is the length of the entire first channel portion 15 . On the other hand, in the X direction, a straight line connecting a first end portion 16a of the second flow channel portion 16 overlapping the first flow channel portion 15 and a second end portion 16b on the other side. The length is the length of the entire second channel portion 16 .

A straight line passing through the center of the microchannel 10 in the width direction and along the direction in which the microchannel 10 extends is defined as a straight line X1. Let P be the intersection of the straight line X1 and a perpendicular drawn from the first end portion 15a of the first flow path portion 15 to the straight line X1. Let Q be the intersection of the straight line X1 and a perpendicular drawn from the first end portion 16a of the second flow path portion 16 to the straight line X1. The distance between the intersection point P and the intersection point Q is the length of the portion where the first channel portion 15 and the second channel portion 16 partially overlap.

Each dimension of the first channel portion 15 and the second channel portion 16 passes through the center of gravity of the microchannel 10 and is the largest surface of the microchip 1 (for example, in the present embodiment, the first main We will ask for a plane parallel to plane 2a). Further, when the first flow channel portion 15 and the second flow channel portion 16 have a depth, the dimension of the surface at which the first flow channel portion 15 and the second flow channel portion 16 are the largest in the depth direction shall be sought.

In the present embodiment, the length of the part where the first flow path part 15 and the second flow path part 16 partially overlap with respect to the length of the entire first flow path part 15 obtained in this way and the ratio L2 of the length of the portion where the first flow path portion 15 and the second flow path portion 16 partially overlap with respect to the entire length of the second flow path portion 16, whichever is smaller The ratio L of one is 0.05 or more and 0.7 or less.

Also, the ratio (S/V) of the surface area S of the entire mixing flow path 14 to the volume V of the entire mixing flow path 14 is 4 or less.

The present inventors have found that by setting the ratio L and the ratio (S/V) within the above ranges, it is possible to reliably mix a plurality of liquids in the mixing flow path 14, and moreover, it is possible to make liquid residues less likely to occur. rice field.

In the present invention, it is sufficient that at least one set of adjacent first channel portion 15 and second channel portion 16 satisfies the above ranges of the ratio L and the ratio (S/V). However, from the viewpoint of more reliably mixing a plurality of liquids and making liquid residue less likely to occur, the ratio L and the ratio (S/V) satisfy the above ranges. is preferably 2 or more, more preferably 3 or more, preferably 20 or less, more preferably 10 or less. It should be noted that other flow paths whose ratio L and ratio (S/V) do not satisfy the above ranges may be further connected.

In the present invention, the ratio L is preferably 0.1 or more, more preferably 0.15 or more, preferably 0.5 or less, and more preferably 0.4 or less. When the ratio L is within the above range, the plurality of liquids can be mixed more reliably, and liquid residue can be made more difficult to occur.

Also, the ratio (S/V) is 4 or less, preferably 3 or less. When the ratio (S/V) is equal to or less than the above upper limit, the plurality of liquids can be mixed more reliably, and moreover, liquid residue can be made more difficult to occur. Although the ratio (S/V) is preferably as small as possible, the lower limit of the ratio (S/V) can be set to 1, for example.

The lengths in the X direction of the first channel portion 15 and the second channel portion 16 can be, for example, 0.3 mm or more and 20 mm or less, respectively. The thicknesses of the first channel portion 15 and the second channel portion 16 can be, for example, 0.1 mm or more and 20 mm or less, respectively.

When the planar shapes of the first channel portion 15 and the second channel portion 16 are semicircular, the radii thereof can be, for example, 0.3 mm or more and 20 mm or less, respectively. When the planar shapes of the first channel portion 15 and the second channel portion 16 are semi-elliptical, the short diameters can be, for example, 0.3 mm or more and 20 mm or less, respectively. In addition, the major diameter can be the length in the X direction of the first channel portion 15 and the second channel portion 16, respectively. In addition, when the planar shape of the first channel portion 15 and the second channel portion 16 is a polygonal concave portion, the distance from the vertex farthest away from the microchannel 10 to the main channel of the microchannel 10 The lengths can be, for example, ≧0.3 mm and ≦20 mm, respectively. In addition, each dimension such as the radius of the first channel portion 15 and the second channel portion 16 may have the same length or may have different lengths.

The surface area S of the entire mixing channel 14 can be, for example, 5 mm ² or more and 3000 mm ² or less. In addition, the volume V of the entire mixing channel 14 can be, for example, 3 μL or more and 1000 μL or less. In this case, the unit of the ratio S/V can also be expressed as (mm ² /μL).

In the present invention, the liquid to be sent inside the microchannel 10 can be sent by a liquid sending means provided inside or outside the microchip 1 . The liquid sending means is not particularly limited, and examples thereof include a micropump. Specifically, means for sending liquid to the mixing channel 14 and the downstream channel 17 on the further downstream side by using a micropump to send liquid, air, or a predetermined gas into the microchannel 10 is mentioned. In this case, the micropump may be provided inside the microchip 1 or may be provided outside the microchip 1 . By such means, the liquid is sent to the mixing channel 14 and the downstream channel 17 further downstream.

Further, as another liquid sending means, there is a gas generating member arranged in a space connected to the upstream side of the microchannel 10 . A gas generating member is a member that generates gas by an external force such as light or heat. By applying an external force to the gas generating member at a predetermined timing, gas can be generated and the gas can be fed into the microchannel 10 . Thereby, the liquid can be sent to the mixing channel 14 side. Examples of gas generating members include gas generating tapes.

Hereinafter, the present invention will be clarified by giving specific examples and comparative examples of the present invention. In addition, the present invention is not limited to the following examples.

(Examples 1-22, Comparative Examples 1-9 , 11-16 )
In Examples 1 to 22 and Comparative Examples 1 to 9 and 11 to 16, test chips were produced as follows.

A cycloolefin polymer (manufactured by Nippon Zeon Co., Ltd., trade name "1420R") was used as a material for the substrate, and a substrate having recesses was produced by injection molding this polymer. In addition, a resin film (“Zeonor Film ZF14-188 (cycloolefin polymer)” (film thickness: 0.188 mm) manufactured by Nippon Zeon Co., Ltd.) is superimposed on the substrate surface and heat-sealed to form a flow as shown in FIG. A microchip provided with a channel structure was obtained. The heat-sealing conditions were as follows: the press plate temperature on the substrate side was 60° C., the press temperature on the resin film side was 190° C., the press pressure was 60 kg/cm ² , and the press time was 10 seconds. Each dimension of the mixing channel 14 is as shown in Tables 1 to 4 below. In each of Examples 1 to 22 and Comparative Examples 1 to 9 and 11 to 16, one first channel portion and one second channel portion are formed, and the total number of channel portions is two. is one. Further, in Examples 1 to 20 and Comparative Examples 1 to 9 and 11 to 16, semicircular first channel portions 15 and second channel portions 16 as shown in FIG. 3 were formed. In Example 21, a semi-elliptical first channel portion 15A and a second channel portion 16A were formed as shown in FIG. In Example 22, the first channel portion 15B and the second channel portion 16B, which are polygonal recesses as shown in FIG. 5, were formed. Further, in Comparative Examples 6 to 9, the first channel portion 15 and the second channel portion 16 that completely overlap in the liquid feeding direction X were formed. In Comparative Example 11 , as shown in FIG. 7, the first channel portion 105 and the second channel portion 106 that do not completely overlap in the liquid feeding direction X were formed.

(evaluation)
measurement of mixing performance;
Each liquid shown in Table 1 was filled in the first to third liquid storage units 11 to 13 . Next, gas is generated by a micropump, and the gas is applied from the rear of each liquid to press the liquids filled in the first to third liquid storage units 11 to 13 into the mixing channel. 14 and mixed in the mixing channel 14 . After that, 5 μL of the liquid was collected from each of the leading portion and the trailing end of the liquid that passed through the mixing channel 14 and was sent to the downstream channel 17 , and used for the measurement of the refractive index. The refractive index was evaluated by the V-block method using a precision refractometer (KPR-3000 type) manufactured by Shimadzu Corporation.

A difference Δ in refractive index between the liquid head and the liquid tail was determined and evaluated according to the following evaluation criteria.

[Evaluation criteria]
◎ ... Δ = 0.001 or less ○ ... Δ = 0.001 or more and 0.01 or less × ... Δ = 0.01 or more and 0.1 or less

(liquid residue)
Each liquid shown in Table 1 was filled in the first to third liquid storage units 11 to 13 . Next, gas is generated by a micropump, and the gas is applied from the rear of each liquid to press the liquids filled in the first to third liquid storage units 11 to 13 into the mixing channel. 14 and mixed in the mixing channel 14 . After that, the amount of the liquid that passed through the mixing channel 14 and was sent to the downstream channel 17 was measured, and the remaining amount of liquid was obtained from the relationship with the amount of liquid sent by the following formula, and the following evaluation criteria were used. Evaluated the rest.

Remaining liquid amount (%) = 100 - (liquid amount measured in the downstream channel 17/liquid feeding amount) x 100

[Evaluation criteria]
〇 ... Remaining liquid amount is 0.1% or less × ... Remaining liquid amount is more than 0.1%

The results are shown in Tables 1 to 4 below.

Reference Signs List 1 Microchip 2 Substrates 2a, 2b First and second main surfaces 2c, 2d First and second side surfaces 3 Substrate bodies 4 and 5 First and second cover layers 10 Microflow Channels 11, 12, 13... First, second, third liquid storage parts 14, 14A, 14B... Mixing channels 15, 15A, 15B... First channel parts 15a, 16a... First end part 15b , 16b... second end portions 16, 16A, 16B... second channel portion 17... downstream channel

Claims (6)

A substrate provided with a flow path through which a fluid is sent,
A mixing channel for mixing a plurality of liquids is provided in the middle of the channel,
The mixing channel includes a first channel portion that is a concave portion that is enlarged on one surface side of the substrate, and a second channel portion that is a concave portion that is enlarged on the other surface side of the substrate. and
In the direction in which the flow path extends,
The first flow path portion and the second flow path portion have a partially overlapping portion,
A ratio L1 of the length of the part where the first flow path part and the second flow path part partially overlap with respect to the length of the entire first flow path part, and the second flow path part The ratio L2 of the length of the portion where the first channel portion and the second channel portion partially overlap with respect to the overall length, and the smaller ratio L is 0.05 or more and 0 .7 or less,
A test tool in which the ratio (S/V) of the surface area S of the entire mixing channel to the volume V of the entire mixing channel is 4 mm ² /μL or less (provided that the mixing channel is split into the channel and turbulent flow paths) . The substrate has a first main surface and a second main surface facing each other, and a first side surface and a second side surface connecting the first main surface and the second main surface, and facing each other. has
The first flow path portion is expanded toward the first side surface,
The inspection tool according to claim 1, wherein said second flow path portion is enlarged toward said second side surface. The inspection tool according to claim 1 or 2, wherein the first flow path section and the second flow path section are alternately provided in the extending direction of the flow path. The inspection tool according to any one of Claims 1 to 3, wherein the total number of said first channel portion and said second channel portion is two or more. The inspection tool according to any one of claims 1 to 4, wherein the ratio L is 0.1 or more and 0.5 or less. The test tool according to any one of claims 1 to 5, wherein the channel is a microchannel.

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