Fluid control device, and examination device

Abstract

To achieve a fluid control device that is affected by an internal fluid action to self-open a flow path, even if an operation for opening the fluid path is not performed from outside.SOLUTION: A fluid control device 11 comprises: a first flow path 20 that has a flow path groove 21 formed on one surface of a substrate 10, and a sheathing material covering the flow path groove 21; a second flow path 30 that fluid-communicates with the first flow path 20 in at least one of a lateral face and bottom surface of the flow path groove 21; and an outflow port 40 that fluid-communicates with a connection part X of the first flow path 20 and the second flow path 30. The first flow path 20 has the flow path groove 21 of which a surface has any one of hydrophobicity or hydrophilicity, and a surface on a flow path groove side of the sheathing material has a second property serving as other of the hydrophobicity or hydrophilicity. The second flow path 30 has a guidance unit 32A that has the second property, and guides the fluid introduced to the second flow path 30 to the connection part X. When the fluid is introduced to the second flow path 30, the fluid guided by the guidance unit 32A forms a droplet in the connection part X.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a fluid control device and an inspection device. [Background technology]

[0002] Microfluidic devices are known that perform biochemical measurements and chemical synthesis by flowing fluids through channels formed on a substrate. In particular, microanalysis devices and microreaction devices fabricated using microfabrication technology are preferred for their miniaturization, portability, small sample volumes, small reagent volumes, small waste volumes, and speed.

[0003] In such microchannel chips, various valve mechanisms for opening and closing channels have been proposed. For example, Japanese Patent Laid-Open No. 2005-308200 (Patent Document 1) discloses a microvalve mechanism that includes a fluidic element chip in which at least a portion of the upper part of a microchannel is made of an elastic material, and a pressure control port provided upright on the elastic material portion of the fluidic element chip, and that opens and closes the channel by supplying and discharging pressure via the pressure control port.

[0004] Microchannel chips used as part of testing devices have also been proposed. For example, International Publication No. 2012 / 060186 (Patent Document 2) discloses a microchannel chip comprising a resin substrate having a channel groove on one surface and a resin film bonded to the resin substrate so as to cover the channel groove. This microchannel chip is fabricated by bonding a substrate having a channel groove and a covering material covering the channel, and is used as part of a testing device capable of performing genetic analysis using polymerase chain reaction (PCR) or electrophoresis. In the testing device described above, first, target DNA in a sample is amplified (gene amplification) by PCR-based genetic analysis (PCR method) in the reaction chamber of the microchip. Then, the target substance contained in the product solution is optically detected in a detection region connected to the reaction chamber via a microchannel.

[0005] Meanwhile, in recent years, test kits using nucleic acid amplification have become commercially available as a rapid diagnostic method for viruses and bacteria, including the novel coronavirus. The nucleic acid amplification method involves the following steps: (1) creating a nucleic acid amplification reagent that acts to amplify part of the viral gene, and then adding a specimen (saliva, nasopharyngeal swab, etc.) to the nucleic acid amplification reagent; (2) using the nucleic acid amplification reagent to carry out an amplification reaction of the viral gene (nucleic acid) in the specimen; (3) detecting the viral gene that has been amplified tens of thousands of times by the reaction with the nucleic acid amplification reagent. PCR is also a type of nucleic acid amplification method. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Laid-Open No. 2005-308200 [Patent Document 2] International Publication No. 2012 / 060186 Summary of the Invention [Problem to be solved by the invention]

[0007] The microvalve mechanism of Patent Document 1 opens and closes by deforming a microchannel by supplying and discharging pressure from a pressing body provided in a pressure control port, and requires control from outside the microchannel when opening and closing the valve. Therefore, when applied to a testing device, for example, an external control device is required, making it difficult to form a testing device like the above-mentioned test kit.

[0008] In the testing device of Patent Document 2, the sample reacted in the reaction chamber is sent to the detection section by a micropump connected to a microchip, and the target substance is detected by an optical detection section. However, when the pre-reaction sample is introduced, the reacted sample naturally flows into the detection section, and the detection section is not able to detect the target substance. Furthermore, in the above-mentioned test kits, the gene (nucleic acid) amplification reaction of the collected sample in step (2) is usually carried out in a container by an operator while measuring the reaction time, and in many cases, the operator then supplies the reacted sample liquid from the container to the detection section using a pipette or the like. Such test kits also cannot detect the target substance by themselves by simply introducing the pre-reaction sample, and require the operator's effort.

[0009] Therefore, there is a need for a fluid control device that can automatically open a channel at the appropriate timing in response to the action of the fluid inside the microchannel chip, without requiring external operation when opening the channel.Furthermore, the realization of this fluid control device is also needed for a testing device that can automatically detect a post-reaction sample simply by introducing the pre-reaction sample. [Means for solving the problem]

[0010] The fluid control device according to the present invention comprises: a first flow path having a flow path groove formed on one surface of a substrate and a coating material covering the flow path groove; a second flow path fluidically connected to the first flow path on at least one of a side surface and a bottom surface of the flow path groove; and an outlet fluidically connected to a connection portion between the first flow path and the second flow path, wherein the first flow path has a surface of the flow path groove that has a first property being either hydrophobic or hydrophilic, and a surface of the coating material facing the flow path groove that has a second property being the other of hydrophobic and hydrophilic, and the second flow path has the second property and has a guide portion that guides a fluid introduced into the second flow path to the connection portion, and when the fluid is introduced into the second flow path, the fluid guided by the guide portion forms droplets at the connection portion.

[0011] The testing device according to the present invention is an testing device comprising a fluid control section that, when a fluid and a specimen are introduced, causes at least the specimen to flow out, and a detection section that can detect the specimen that has flowed out from the fluid control section, wherein the fluid control section comprises: a first flow path having a flow path groove formed on at least one surface of a substrate and a coating material that covers the flow path groove; a second flow path that is fluidically connected to the first flow path on at least one of a side surface and a bottom surface of the flow path groove; a fluid inlet that is fluidically connected to the first flow path and through which the fluid is introduced; a specimen inlet that is fluidically connected to the second flow path and through which the specimen is introduced; and an outlet that is fluidically connected from a connection portion between the first flow path and the second flow path and that guides the specimen. The first flow path has a surface of the flow path groove that has a first property, being either hydrophobic or hydrophilic, and a surface of the coating material facing the flow path groove that has a second property, being the other of hydrophobic and hydrophilic; the second flow path has the second property and has a guide section that guides the specimen introduced into the second flow path to the connection section; when the specimen is introduced into the specimen inlet, the specimen guided by the guide section forms droplets at the connection section; when the fluid is introduced into the fluid inlet and the fluid comes into contact with the droplets at the connection section, at least the specimen flows out from the outlet; and the detection section is fluidically connected to the outlet.

[0012] According to the fluid control device and fluid control unit of this configuration, a fluid (analyte) introduced into the second flow path forms droplets at the connection between the first and second flow paths, and when the fluid introduced into the first flow path comes into contact with the droplets, the fluid (analyte) remaining in the second flow path flows out through the outlet. In this way, the fluid control device and fluid control unit of the present invention can open the second flow path by the action of the fluid introduced into the first flow path, so no external opening operation is required to open the second flow path. Therefore, in a testing device employing the fluid control unit of this configuration, when a pre-reaction sample is introduced, the post-reaction sample naturally flows out to the detection unit, allowing the sample to be detected.

[0013] Preferred embodiments of the present invention will be described below, but the scope of the present invention is not limited to the preferred embodiments described below.

[0014] In the fluid control device of the present invention, the second flow path has a second flow path groove formed on the surface of the substrate opposite to the flow path groove of the first flow path, and a second coating material covering the second flow path groove, and it is preferable that the second coating material at least partially overlaps the connection portion in a planar view of the substrate.

[0015] According to this configuration, the second covering material can guide the fluid introduced into the second flow path to the connection portion.

[0016] In the fluid control device according to the present invention, it is preferable that the surface of the second covering material on the side of the second flow channel serves as the guide portion.

[0017] According to this configuration, the surface of the second covering material on the side of the second flow channel can guide the fluid introduced into the second flow channel to the connecting portion.

[0018] In the fluid control device according to the present invention, it is preferable that the first flow path has a larger pipeline resistance than the second flow path.

[0019] According to this configuration, when the fluid that has passed through the first flow path comes into contact with the droplet formed at the connecting portion, at least the fluid that has been introduced into the second flow path can flow out from the outlet.

[0020] The fluid control device according to the present invention further comprises a first fluid inlet that is fluidly connected to the first flow path and through which a first fluid is introduced, and a second fluid inlet that is fluidly connected to the second flow path and through which a second fluid is introduced, and it is preferable that the length of the first flow path from the first fluid inlet to the connecting portion is greater than the length of the second flow path from the second fluid inlet to the connecting portion.

[0021] According to this configuration, when a fluid introduced into the first fluid inlet and passing through the first flow path comes into contact with a droplet formed at the connection portion, at least the fluid introduced into the second fluid inlet can flow out from the outlet.

[0022] In the testing device according to the present invention, it is preferable that the flow channel of the first flow channel has a section with a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm, and that when the fluid and the sample are introduced, at least the sample flows out after a predetermined time.

[0023] According to this configuration, the variation in flow velocity of the fluid introduced into the first flow path is easily suppressed, and the predetermined time can be measured based on the time it takes for the fluid to pass through the first flow path.

[0024] Further features and advantages of the present invention will become more apparent from the following description of exemplary and non-limiting embodiments, which is given with reference to the drawings. [Brief explanation of the drawings]

[0025] [Figure 1] FIG. 1 is a plan view showing an inspection device according to an embodiment of the present invention; [Figure 2] Enlarged view of the main part of Figure 1 [Figure 3] Enlarged view of the main part of Figure 2 taken along the III-III cross section [Figure 4] A diagram showing the state in which the sample is introduced in FIG. [Figure 5] Enlarged view of the VV cross section of Figure 4 [Figure 6] FIG. 5 is a diagram showing the state in which the specimen flows out from the outlet in FIG. 4. [Figure 7] Cross-sectional view of the inspection device shown in Figure 1 along the line VII-VII [Figure 8] Enlarged view of the main part of the inspection device in Figure 1 taken along the VIII-VIII cross section [Figure 9] FIG. 2 is a plan view showing an example of an inspection result obtained by the inspection device of FIG. 1; [Figure 10] FIG. 10 is an enlarged cross-sectional view of a main part of an inspection device according to another embodiment of the present invention. [Figure 11]FIG. 11 is a diagram showing a state in which a sample is introduced into the testing device of FIG. 10. [Figure 12] FIG. 10 is an enlarged cross-sectional view of a main part of an inspection device according to another embodiment of the present invention. [Figure 13] FIG. 13 is a diagram showing a state in which a sample is introduced into the testing device of FIG. 12. [Figure 14] FIG. 10 is an enlarged cross-sectional view of a main part of an inspection device according to another embodiment of the present invention. [Figure 15] FIG. 15 is a diagram showing a state in which a sample is introduced into the testing device of FIG. 14. [Figure 16] FIG. 10 is an enlarged cross-sectional view of a main part of an inspection device according to another embodiment of the present invention. [Figure 17] FIG. 17 is a diagram showing a state in which a sample is introduced into the testing device of FIG. 16. DETAILED DESCRIPTION OF THE INVENTION

[0026] An inspection device 1 as a first embodiment of an inspection device according to the present invention and a fluid control unit 11 in the inspection device 1 as a first embodiment of a fluid control device according to the present invention will be described with reference to FIGS.

[0027] [Inspection equipment overview] The testing device 1 according to this embodiment is used as a test kit for testing infectious diseases caused by, for example, viruses, bacteria, etc., and, as shown in FIG. 1, includes a fluid control unit 11 and a detection unit 50 capable of detecting the sample liquid flowing out of the fluid control unit 11. The testing device 1 is configured such that, when sample liquid 18 containing a reaction reagent and a sample is introduced into sample inlet 33 and fluid 19 is introduced into fluid inlet 23, after a period of time, for example, several minutes or more, the reacted sample liquid 18 flows out of outlet 40 on its own, as shown in FIG. 6, and the sample (target substance) in sample liquid 18 is detected by detection unit 50. In this specification, the terms "sample" and "sample liquid" are used regardless of whether they refer to before or after the reaction or the extent of the reaction.

[0028] [Configuration of fluid control unit] As shown in FIG. 1 , fluid control unit 11 (an example of a fluid control device) includes first flow path 20, second flow path 30, and outlet 40 fluidly connected to connection portion X between first flow path 20 and second flow path 30. Fluid control unit 11 releases sample liquid 18 (an example of a second fluid and a sample) introduced into and remaining in second flow path 30 and sample inlet 33 by the action of fluid 19 (an example of a first fluid) introduced into first flow path 20, causing the sample liquid to flow out of outlet 40. In other words, fluid control unit 11 functions as a passive valve that opens second flow path 30 in response to the action of fluid 19.

[0029] The fluid control unit 11 includes a fluid inlet 23 (an example of a first fluid inlet) that is fluidly connected to the upstream side of the first flow channel 20 and through which the fluid 19 is introduced, and a sample inlet 33 (an example of a second fluid inlet) that is fluidly connected to the upstream side of the second flow channel 30 and through which the sample liquid 18 is introduced. As shown in FIG. 1 , the fluid inlet 23 and the sample inlet 33 are provided at separate locations on the substrate 10. In this embodiment, a connection portion X between the first flow channel 20 and the second flow channel 30 is located downstream of the first flow channel 20 and the second flow channel 30.

[0030] Next, each part constituting the fluid control section 11 will be described in detail.

[0031] As shown in FIG. 3, the first flow path 20 has a first flow path groove 21 formed so as to open on one surface of the substrate 10 (the lower surface in FIG. 3), and a first covering material 22 covering the first flow path groove 21.

[0032] In this embodiment, as shown in FIG. 1 , the first flow channel 21 (21A, 21B) extends in a meandering manner on the substrate 10 in the length direction (flow direction). Specifically, the first flow channel 21 (21A, 21B) has five parallel straight sections and four arc-shaped curved sections connecting the five straight sections. With this configuration, the fluid 19 introduced into the fluid inlet 23 makes four U-turns on the substrate 10 and reaches the connection point X over a predetermined time period ranging from several minutes to several tens of minutes (e.g., 5 to 60 minutes). As described above, the first flow channel 20 of this embodiment is a timing flow channel capable of measuring a predetermined time. The details of the first flow channel 21 (21A, 21B) that constitutes this timing flow channel will be described later. The first flow channel 21 is set to have a width of 0.8 to 2.0 mm and a depth of 0.02 to 1 mm, for example.

[0033] In this embodiment, the substrate 10 is made of a hydrophobic resin, and the surfaces (side surface 21D and top surface 21E) of the first flow channel 21 in the first flow channel 20 are hydrophobic (first property). The bottom surface of the first flow channel 21 is disposed above and facing downward on the substrate 10 when the testing device 1 is in use, as shown in FIG. 3, forming the top surface. Therefore, in the following description, this will be referred to as the top surface 21E. The resin component constituting the substrate 10 is not particularly limited, but in this embodiment, it is selected from one or more hydrophobic resins selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl(meth)acrylate, and polyethylene terephthalate. The resin constituting the substrate 10 is preferably one that has either heat resistance or transparency, or both.

[0034] The surface of the first covering material 22 covering the first flow channel 21 is hydrophilic (second property). The first covering material 22 may have at least the surface on the first flow channel 21 side hydrophilic. In this embodiment, a hydrophilic resin film, such as a hydrophilic acrylic resin, is used. The resin constituting the first covering material 22 is preferably one that has either heat resistance or transparency, or both. A hydrophilic portion may be provided by applying a hydrophilic coating to a covering material made of a hydrophobic resin, or the surface may be made hydrophilic by subjecting the covering material made of a hydrophobic resin to a hydrophilic treatment such as plasma treatment. In this embodiment, the first covering material 22 covers the entire back surface (lower surface in FIG. 3 ) of the substrate 10, including the first flow channel 21.

[0035] The thickness of the first covering material 22 is not particularly limited, but can be, for example, 0.05 mm to 2 mm. When the thickness is 0.05 mm or more, wrinkles are less likely to occur during bonding, and the first flow channel 21 can be easily sealed. Furthermore, when the thickness is 2 mm or less, good conformability to the irregularities of the substrate 10 can be easily obtained.

[0036] The bonding between the first covering material 22 and the substrate 10 may be performed by providing an adhesive layer on the first covering material 22 side to serve as a bonding layer with the substrate 10, by bonding the substrate 10 and the covering material with an adhesive or the like, or by compressing the substrate 10 and the first covering material 22 by thermocompression bonding.

[0037] The second flow path 30 in this embodiment has a second flow path groove 31 formed so as to open to the surface of the substrate 10 opposite to the first flow path groove 21 (the upper surface in Figure 3), and a second covering material 32 covering the second flow path groove 31.

[0038] In this embodiment, the second flow channel 31 is a linear groove that is shallower and shorter than the first flow channel 21B. Specifically, the length of the second flow channel 31 is set so that the length of the first flow channel 20 from the outlet of the fluid inlet 23 to the connection part X (referred to as flow channel length M1, not shown) is longer than the length of the second flow channel 30 from the outlet of the specimen inlet 33 to the connection part X (referred to as flow channel length M2) (FIGS. 1 and 2). In this embodiment, the flow channel length M1 is set sufficiently long, for example, to be 10 times or more longer than the flow channel length M2.

[0039] The width and depth of the second flow channel 31 are not particularly limited, but in this embodiment, the width is set to be in the range of 0.8 to 2.0 mm, and the depth is set to be in the range of 0.1 to 0.4 mm, for example.

[0040] Since the second flow channel 31 is formed on the same substrate 10 as the first flow channel 21, the surfaces (side surface 31D and bottom surface 31E) of the second flow channel 31 are hydrophobic (first property). In this embodiment, the second covering material 32 uses the same hydrophilic resin film as the first covering material 22, and the surface 32A of the second covering material 32 is hydrophilic (second property).

[0041] The specimen liquid 18 used in the testing device 1 of this embodiment is an aqueous solution containing a reaction reagent and a specimen, and an aqueous solution such as water or a buffer solution is used as the fluid 19 introduced into the fluid inlet 23. Because the specimen liquid 18 and the fluid 19 are both hydrophilic liquids, the fluid 19 is repelled by the surface of the first flow channel 21 in the first flow channel 20 and exhibits the property of wetting and spreading on the surface of the first coating material 22. Similarly, the specimen liquid 18 is repelled by the surface of the first flow channel 21 and the surface of the second flow channel 31 in the second flow channel 30 and exhibits the property of wetting and spreading on the surfaces of the first coating material 22 and the second coating material 32.

[0042] Therefore, when fluid 19 is introduced into first flow channel 20 from fluid inlet 23, fluid 19 flows along the hydrophilic surface of first covering material 22 and into first flow channel 20. Similarly, when specimen liquid 18 is introduced into second flow channel 30 from specimen inlet 33, specimen liquid 18 flows along hydrophilic surface 32A of second covering material 32 and into second flow channel 30.

[0043] The first covering material 22 and the second covering material 32 may be different in material, thickness, etc., as long as their surfaces are hydrophilic. Furthermore, the method for bonding the substrate 10 to the second covering material 32 may be different from the method for bonding the substrate 10 to the first covering material 22. In this embodiment, since the area of ​​the second covering material 32 is smaller than the area of ​​the first covering material 22, the first covering material 22 may be bonded by thermocompression bonding, and the second covering material 32 may be bonded by an adhesive layer or bonding layer.

[0044] 3, the first flow path 20 and the second flow path 30 are fluidly connected to each other by partially intersecting the flow path grooves 21, 31 at the connection portion X. In this embodiment, the first flow path 20 intersects with the second flow path 30 at a substantially right angle on the downstream side of the fifth straight section of the first flow path 20.

[0045] In this embodiment, the thickness of the substrate 10 is approximately 0.7 mm. The depth D2 of the first flow path groove 21B is approximately 0.6 mm, and the depth D3 of the second flow path groove 31 is approximately 0.15 mm, so that the first flow path 20 and the second flow path 30 overlap by approximately 0.05 mm in the depth direction. With this configuration, a through hole is formed in the substrate 10 at the connection portion X, and the first covering material 22 and the second covering material 32 are located on both sides of the through hole.

[0046] The second covering material 32 is disposed at least at a location covering the second flow channel 31 of the second flow channel 30 on the surface of the substrate 10 opposite to the first covering material 22. In this embodiment, the second covering material 32 is disposed so as to overlap the connection portion X in a plan view of the substrate 10. The second covering material 32 may extend so as to protrude from the second flow channel 31 toward the sample inlet 33.

[0047] Fluid inlet 23 is a through-hole formed in substrate 10, and although there are no limitations on its shape or size as long as it can introduce fluid 19 into first flow channel 20, in this embodiment it is cylindrical with a diameter of 2 to 5 mm (for example, a diameter of 4 mm). The top of fluid inlet 23 is open, and the bottom is covered with first covering material 22 extending from first flow channel 20.

[0048] Like the fluid inlet 23, the sample inlet 33 is a through-hole formed in the substrate 10. The shape and size of the sample inlet 33 are not limited as long as it allows the sample liquid 18 to be introduced into the second flow channel 30. In this embodiment, the sample inlet 33 is cylindrical and has a diameter of 2 to 5 mm (e.g., 4 mm). The sample inlet 33 is also open at the top and covered at the bottom with the first coating material 22. In this embodiment, a reaction reagent is introduced into the sample inlet 33 along with the sample, and the sample inlet 33 is used as a reaction vessel for promoting a reaction of the sample (e.g., a nucleic acid amplification reaction). Therefore, the sample inlet 33 is maintained at a constant temperature (e.g., a predetermined temperature between 25 and 65°C) so that the reaction can be carried out at a constant temperature. The sample inlet 33 can be maintained or heated by placing the entire testing device 1 in a thermostatic bath or room, or by placing a heating device such as a heater in contact with the underside of the sample inlet 33.

[0049] The outlet 40 indicates a region downstream from the connection portion X, and includes a downstream portion including the end of the first flow channel 20, and a notch 40A that is in fluid communication with the end of the first flow channel 20. The notch 40A opens on one side of the substrate 10, penetrates the substrate 10 in the thickness direction, and has a detection unit 50 attached thereto. The sidewall of the notch 40A is hydrophobic, similar to the substrate 10. The open lower surface of the notch 40A is covered with a hydrophilic first coating material 22 that extends from the first flow channel 20.

[0050] The outer shape and size of the substrate 10 can be set appropriately taking into consideration ease of handling, etc. For example, if the substrate is quadrilateral (square or rectangle), each side preferably has a length of 10 mm or more and 200 mm or less, and more preferably 10 mm or more and 100 mm or less. The outer shape of the substrate 10 is not particularly limited, and may be other polygonal, circular, elliptical, or the like. The thickness of the substrate 10 is also not particularly limited, and may be, for example, 5 to 20 mm.

[0051] The resin substrate 10 can be produced by a resin molding process technique, such as injection molding, transfer molding, or extrusion molding.

[0052] In this embodiment, the first property is hydrophobic and the second property is hydrophilic. However, the first property is a property that prevents the fluid used from wetting and spreading (i.e., a repelling property), and the second property is a property that the fluid used spreads and wetting, and the degree and physical value of the property are not particularly limited. In this embodiment, the surface of the substrate 10, which is hydrophobic (first property), has a contact angle with water of, for example, 60° or more and 100° or less. The lower limit of the contact angle of the substrate 10 with water is preferably 70° or more, and more preferably 80° or more. The upper limit of the contact angle of the substrate 10 with water is preferably 95° or less, and more preferably 90° or less. Furthermore, the surfaces of the first coating material 22 and the second coating material 32, which are hydrophilic (second property), have a contact angle with water of, for example, 0° or more and 40° or less. The upper limit of the contact angle of the first coating material 22 and the second coating material 32 is preferably 20° or less, and more preferably 10° or less. The contact angle with water in this embodiment is a value measured at 25°C using a commercially available contact angle meter.

[0053] The fluid control unit 11 according to this embodiment has a fluid control function of automatically causing a reacted sample to flow out when an unreacted sample is introduced, and also has a timing function of measuring a predetermined reaction time for the sample introduced into the sample inlet 33 to react with a reaction reagent. This is because the time (required time) for the fluid 19 to flow through the first flow channel 21 is restricted to a preset time (predetermined time). Next, the configuration of the first flow channel 21 related to the timing function of the first flow channel 20 will be described with reference to FIGS. 7 and 8.

[0054] The fluid control unit 11 according to this embodiment has a characteristic configuration related to the timing function, in that the first flow path 20 includes a first section L1 (not shown). In this embodiment, the first section L1 starts from a starting point S and extends to a point P midway along the fifth straight section of the first flow path 20. In the first section L1, the first flow path groove 21A has a width W1 of 0.8 to 2.0 mm and a depth D1 of 0.07 to 0.10 mm (70 to 100 μm). Setting the width W1 and depth D1 of the first flow path groove 21 within this range can suppress variations in the flow velocity of the fluid flowing through the flow path.

[0055] The width W1 of the first flow channel 21A is preferably 0.8 to 1.5 mm, and more preferably 0.9 to 1.2 mm. The depth D1 of the first flow channel 21A is preferably 0.09 to 0.10 mm, and more preferably 0.095 to 0.100 mm.

[0056] In this embodiment, the cross-sectional shape of the first flow channel 21A is quadrangular (particularly rectangular), but the shape is not limited thereto. The cross-sectional shape of the first flow channel 21 may be trapezoidal or semicircular, and in particular, if the cross-sectional shape of the first flow channel 21 is a trapezoid in which the side on the opening side (the side of the first covering material 22) is larger than the side at the groove bottom of the first flow channel 21, the first flow channel 21 can be easily manufactured using a mold. In the case of such a shape, the width W1 and depth D1 of the first flow channel 21 refer to the maximum width and maximum depth of the first flow channel 21.

[0057] In this embodiment, a second section L2 is provided adjacent to the first section L1 and has a depth greater than that of the first flow channel 21A in the first section L1. In this embodiment, the depth D2 of the flow channel 12B in the second section L2 is set to 2 to 10 times (6 times in this embodiment) the depth W1 of the first flow channel 12A in the first section. The width W2 of the first flow channel 21B in the second section is set to be the same as the width W1 of the first flow channel 21A in the first section. By providing the second section L2, the flow rate can be reduced, allowing for long measurement times without increasing the dimensions of the device. Therefore, a long time (for example, 10 to 30 minutes) can be set as the predetermined time.

[0058] Point P, which is the transition point from first flow channel 21A in first section L1 to first flow channel 21B in second section L2, has inclined surface 21C as shown in FIG. 8 . In this embodiment, the angle θ between top surface 21E of first flow channel 21B and inclined surface 21C is 100°. At point P, first flow channel 21A in first section L1 suddenly expands from depth D1 to depth D2 of first flow channel 21B in second section L2. This is a so-called sudden expansion pipe, and when fluid 19 enters first flow channel 21B, the flow of fluid 19 cannot immediately follow the flow channel shape and draws in the surrounding fluid 19, forming a vortex at the sudden expansion portion. This vortex is a flow that remains in place, resulting in pressure loss. However, in this embodiment, this pressure loss is utilized to reduce the fluid flow velocity. The angle θ formed between the top surface 21E of the first flow channel 21B and the inclined surface 21C is not particularly limited, but is preferably 95° to 105°.

[0059] The ratio of the lengths of the first section L1 and the second section L2 (length of L1: length of L2) is not particularly limited, but is preferably 9:1 to 5:5. With such a ratio, the effect of suppressing time variations in the first section L1 can be easily obtained.

[0060] In this embodiment, the time required for fluid 19 to reach connection part X after being introduced into fluid inlet 23 is within an allowable error of, for example, ±5% of the predetermined time. In the above-described fluid control part 11, the time required for at least specimen liquid 18 to flow out of outlet 40 after fluid 19 is introduced into fluid inlet 23 and specimen liquid 18 is introduced into specimen inlet 33 is within an allowable error of, for example, ±5% of the predetermined time.

[0061] In this embodiment, the first flow path 20 is configured to have a higher conduit resistance than the second flow path 30. The conduit resistance of a flow path is determined by various conditions, and generally, when the first flow path 20 is longer, has a higher friction coefficient, is narrower, or has a higher flow rate than the second flow path 30, the first flow path 20 will have a higher conduit resistance than the second flow path 30. In this embodiment, as described above, the flow path length M1 from the fluid inlet 23 to the connection part X is sufficiently longer than the flow path length M2 from the specimen inlet 33 to the connection part X, and the conduit resistance of the first flow path 20 is greater than the conduit resistance of the second flow path 30.

[0062] [Detection section] In the testing device 1, the detection unit 50 is attached to a notch 40A in an outlet 40 provided in the substrate 10. In the testing device 1, the detection unit 50 is fluidically connected to the outlet 40 of the fluid control unit 11. A hydrophilic first coating material 22 provided on the underside of the outlet 40 guides the sample liquid 18 to the detection unit 50, enabling detection of the sample in the sample liquid flowing out of the outlet 40. While the fluid 19 passes through the first flow path 20 for a predetermined time, a reaction such as a nucleic acid amplification reaction of the sample progresses in the sample liquid 18 with a reaction reagent. The fluid control unit 11 allows the sample after the predetermined reaction time to flow into the detection unit 50. Therefore, the detection unit 50 can detect the sample (target substance) after the reaction. The detection unit 50 can be a detection unit of a commercially available test kit for immunochromatography or the like. In this embodiment, a detection unit using chromatography paper with a conjugate pad (e.g., a nucleic acid chromatography strip) is used. If the detection unit 50 uses chromatography paper with a conjugate pad, the time and effort required for adding a developing solution can be eliminated.

[0063] [Inspection method using inspection equipment] Next, an inspection method using the inspection device 1 will be described in relation to the functions and actions of each part of the inspection device 1.

[0064] The specimen liquid 18 and the fluid 19 are prepared in advance. The specimen liquid 18 is, for example, a mixture of a specimen, such as saliva or a nasopharyngeal swab collected from a human or animal, and a reaction reagent, such as a nucleic acid amplification reagent. The fluid 19 is a fluid control fluid for causing the specimen liquid 18 remaining in the second flow path 30 and the specimen inlet 33 to flow out the outlet 40, and also serves as a timing fluid for measuring a predetermined time by flowing through the first flow path 20. For this reason, the fluid 19 is a liquid with small viscosity variation, such as water or a buffer solution, and it has been confirmed in advance that the time required for the fluid 19 introduced into the fluid inlet 23 to reach the connection part X is within a tolerance of ±5% of the predetermined time. Both the specimen liquid 18 and the fluid 19 are hydrophilic.

[0065] First, fluid 19 is introduced into fluid inlet 23, and sample liquid 18 is introduced into sample inlet 33. The introduction of fluid 19 into fluid inlet 23 and the introduction of sample liquid 18 into sample inlet 33 are preferably simultaneous, but may be slightly different, and the order of introduction is not particularly limited. As shown in FIGS. 4 and 5 , the surface 32A of second coating material 32 in second flow path 30 serves as a guide, causing a portion of sample liquid 18 to flow out of sample inlet 33, fill the second flow path 30, and be guided to connection portion X. The sample liquid 18 then forms a droplet 18A at connection portion X. In this embodiment, droplet 18A spreads over surface 32A of second coating material 32 above connection portion X and is held on surface 32A of second coating material 32 in a state where it hangs down due to surface tension and gravity. At this time, droplet 18A does not contact first coating material 22. Even if droplet 18A comes into contact with side surface 21D and top surface 21E of first flow channel 21, or side surface 31D and bottom surface 31E of second flow channel 31, these surfaces are all hydrophobic, so droplet 18A does not wet and spread, but becomes a rounded droplet due to surface tension. This configuration can prevent specimen liquid 18 from flowing out of outlet 40 before droplet 18A comes into contact with fluid 19.

[0066] On the other hand, when fluid 19 is introduced into fluid inlet 23, it starts from starting point S and flows through first flow path 20 (20A, 20B) over a predetermined time (e.g., a preset time such as 20 minutes) until it reaches connecting portion X. As described above, first flow path 20 according to this embodiment has a timing function, and can regulate the predetermined time by the time required for passing through first flow path 20, and the reaction between the specimen in sample liquid 18 and the reaction reagent proceeds during this predetermined time.

[0067] Next, the fluid 19 that has passed through the first flow path 20 over a predetermined time period reaches the connection point X and comes into contact with the droplet 18A. As a result, at least the specimen liquid 18 flows out from the outlet 40, as shown in FIG. 6 . In this manner, the fluid 19 that has passed through the first flow path 20 acts to force the specimen liquid 18 that had remained in the second flow path 30 and the specimen inlet 33 to flow out from the outlet 40. The fluid 19 that has passed through the long first flow path 20 (20A, 20B) loses pressure (driving force) due to friction with the walls of the flow path before reaching the connection point X. Therefore, at the connection point X, the outflow of the specimen liquid 18 from the second flow path 30 takes priority over the outflow of the fluid 19 from the first flow path 20. At the connection point X where two flow paths are connected, the fluid that has passed through one flow path breaks the balance of the surface tension of the fluid in the other flow path, thereby opening the other flow path. Therefore, the fluid control unit 11 can also be called a "surface tension valve" that utilizes surface tension.

[0068] According to the fluid control unit 11 of this embodiment, specimen liquid 18 in second flow path 30 can be released to outlet 40 by the action of fluid 19 introduced into first flow path 20 formed in the same substrate 10, without performing an operation to open second flow path 30 from the outside. Furthermore, in the fluid control unit 11 of this embodiment, second covering material 32 at least partially overlaps connection portion X in a plan view of substrate 10, so that surface 32A of second covering material 32 can guide specimen liquid 18 to connection portion X. That is, in the fluid control unit 11, surface 32A of second covering material 32 in second flow path 30 serves as a guide that guides specimen liquid 18 to connection portion X.

[0069] The fluid control unit 11 according to this embodiment is configured such that the flow path length M1 of the first flow path 20 from the fluid inlet 23 to the connection portion X is greater than the flow path length M2 of the second flow path 30 from the sample inlet 33 to the connection portion X. The first flow path 20 has a greater conduit resistance than the second flow path 30. Therefore, when the fluid 19 passing through the first flow path 20 comes into contact with the droplet 18A of the sample liquid 18 formed at the connection portion X, the reacted sample liquid 18 naturally flows out of the outlet 40 and into the detection unit 50. The lower opening of the notch 40A of the outlet 40 is covered with the first coating material 22, which has a hydrophilic surface and extends from the first flow path 20, so that the hydrophilic sample liquid 18 can be quickly introduced into the chromatography paper with a conjugate pad in the detection unit 50. Through the above-described steps, the sample (target substance) can be detected in the detection unit 50.

[0070] The test result in the test device 1 is confirmed by whether or not both detection line C and detection line T appear in the detection unit 50, as shown in an example in Figure 9. If both detection line C and detection line T appear in the detection unit 50, it is positive, and if only detection line C appears, it is negative.

[0071] In the fluid control unit 11 of the testing device 1, when the fluid 19 reaches the connection part X, the specimen liquid 18 flows out of the outlet automatically. In this way, the fluid control unit 11 opens the second flow path 30 in response to the action of the fluid 19 and discharges the specimen liquid 18, without requiring external control to open the second flow path 30.

[0072] Furthermore, in the fluid control unit 11 according to this embodiment, the fluid 19 introduced into the fluid inlet 23 passes through the first flow path 20 over a predetermined time, and the first flow path 20 functions as a timer that measures the reaction time of the specimen liquid 18. Therefore, when the specimen liquid before reaction is introduced, the specimen liquid 18 that has reacted for a predetermined time can be introduced into the detection unit 50. This makes it possible to suppress variations in the test results due to variations in reaction time, and improve the test accuracy while providing a test kit in the form of one that allows for simple and quick detection.

[0073] In addition, in this embodiment, the second flow channel 30 crosses the first flow channel 20 in a plan view, so that in a microchannel device having fine flow channels, it is not necessary to precisely control the processing dimensions of the connection portion X between the first flow channel groove 21 and the second flow channel groove 31. This makes it easy to manufacture the fluid control unit 11.

[0074] Next, inspection devices 2 to 5 according to other embodiments of the present invention will be described with reference to Figures 9 to 16. The inspection devices 2 to 5 each include fluid control units 12 to 15 that are different from the fluid control unit 11 according to the first embodiment. More specifically, the connection portion X is different because each includes second flow paths 60, 70, 80, and 90 that are different from the second flow path 30 according to the first embodiment. Note that the same reference numerals are used to designate components that have the same functions as those in the previous embodiment and that are not significantly different in shape.

[0075] An inspection device 2 according to a second embodiment of the present invention will be described with reference to FIGS.

[0076] <Inspection device 2> As shown in FIG. 10 , the fluid control unit 12 of the testing device 2 shortens the downstream end of the second flow channel 61 of the second flow channel 60 so that it reaches a midpoint in the first flow channel 20. In this configuration, the volume of the connection portion X between the first flow channel 20 and the second flow channel 60 is small, but as shown in FIG. 11 , the second coating material 32 at least partially overlaps the connection portion X in a plan view of the substrate 10. Therefore, the second coating material 32 guides the sample liquid 18 to the connection portion X, and a droplet 18B can be formed at the connection portion X. Therefore, when the fluid 19 passing through the first flow channel 20 comes into contact with the droplet 18B of the sample liquid 18 at the connection portion X, the sample liquid 18 flows out from the outlet 40. Although the volume of the droplet 18B formed at the connection portion X in the fluid control unit 12 is smaller than that of the fluid control unit 11 of the first embodiment, the fluid control unit 12 has the same fluid control function as the fluid control unit 11.

[0077] Next, an inspection device 3 according to a third embodiment of the present invention will be described with reference to FIGS. <Inspection device 3> As shown in FIG. 12 , in the fluid control unit 13 of the testing device 3, the second flow channel 71 of the second flow channel 70 is formed shorter than in the second embodiment, and the second flow channel 70 communicates with the first flow channel 20 while abutting against the side surface of the first flow channel groove 21. In this configuration, the connection portion X between the first flow channel 20 and the second flow channel 60 is a surface perpendicular to the substrate 10, and the volume of the connection portion X is even smaller than in the second embodiment. However, as shown in FIG. 13 , the second coating material 32 at least partially overlaps the connection portion X in a plan view of the substrate 10. In this configuration, the second coating material 32 also guides the sample liquid 18 to the connection portion X, allowing a droplet 18C to form at the connection portion X. Therefore, when the fluid 19 passing through the first flow channel 20 comes into contact with the droplet 18C of the sample liquid 18 at the connection portion X, the sample liquid 18 flows out from the outlet 40. Although the fluid control section 13 can form droplets 18C at the connection portion X that are even smaller than those in the second embodiment, it has the same fluid control function as the fluid control section 11 in the first embodiment.

[0078] Next, an inspection device 4 according to a fourth embodiment of the present invention will be described with reference to FIGS. <Inspection device 4> In the fluid control unit 14 of the testing device 4, the downstream end of the second flow channel 81 extends to a position where it roughly overlaps with the inner side surface 21D of the first flow channel 21 in a planar view. Furthermore, the depth D4 of the second flow channel 80 is changed to approximately 0.1 mm. With this configuration, a through-hole is formed through the substrate 10 in the area where the first flow channel 20 and the second flow channel 30 overlap in a planar view. This allows the first flow channel 20 and the second flow channel 80 to communicate with each other. In this configuration, as shown in FIG. 15 , the second covering material 32 at least partially overlaps the connection portion X in a planar view of the substrate 10. The surface 32A of the second covering material 32 guides the sample liquid 18 to the connection portion X, allowing a droplet 18D to form over a large area at the connection portion X. Therefore, when the fluid 19 passing through the first flow channel 20 comes into contact with the droplet 18D of the sample liquid 18 at the connection portion X, the sample liquid 18 flows out of the outlet 40. The fluid control section 14 has a smaller depth than the second flow channel 31 of the fluid control section 11 of the first embodiment, but has the same fluid control function as the fluid control section 11 of the first embodiment.

[0079] Next, an inspection device 5 according to a fifth embodiment of the present invention will be described with reference to FIGS. <Inspection device 5> In the fluid control unit 15 of the testing device 5, a second flow path 90 is formed inside the substrate 10, and the second flow path 90 fluidly connects the side surface of the sample inlet 33 to the front side surface 21D of the first flow path groove 21 of the first flow path 20. The cross-sectional shape of the second flow path 30 in this embodiment is not limited and may be a polygonal shape such as a square, or may be a circle or an ellipse. The inner surface of the second flow path 90 is hydrophilically coated, and this hydrophilic coating serves as a guide portion. According to this configuration, the inner surface of the second flow path 90 is hydrophilic (second property), while the side surface 21D of the first flow path groove 21 of the first flow path 20 is hydrophobic (first property). Therefore, the sample liquid 18 introduced into the sample inlet 33 is guided to the connection portion X and forms a droplet 18E protruding in a meniscus shape from the connection portion X toward the side surface 21D of the first flow path groove 21. In this configuration, when fluid 19 passing through first flow path 20 comes into contact with droplet 18E of sample liquid 18 at connection portion X, sample liquid 18 flows out from outlet 40. Even if second covering material 32 is not provided as in fluid control unit 15 and a guide unit is provided in second flow path 90 by other means, the fluid control function is maintained similar to that of fluid control unit 11 of the first embodiment.

[0080] [Other embodiments] Other embodiments of the fluid control device and the inspection device according to the present invention will be described below. Note that the configurations disclosed in the following embodiments can be applied in combination with the configurations disclosed in other embodiments, as long as no contradiction occurs.

[0081] In the above embodiment, the sample liquid 18 and the fluid 19 are hydrophilic liquids, and the side surfaces 21D and 21E of the first flow channel 21 and the side surfaces 31D and 31E of the second flow channel 31 are hydrophobic (first property), while the surface 22A of the first covering material 22 and the surface 32A of the second covering material 32 are hydrophilic (second property). However, in the present invention, the first property is a property that prevents the fluid from wetting and spreading, and the second property is a property that allows the fluid to wetting and spreading. The relationship between hydrophobicity and hydrophilicity in the present invention can be reversed from that in the above embodiment. For example, when the sample liquid 18 and the fluid 19 are hydrophobic fluids such as organic solvents, the effects of the present invention can be achieved by making the side surfaces 21D and 21E of the first flow channel 21 and the side surfaces 31D and 31E of the second flow channel 31 hydrophilic (first property) and making the surface 22A of the first covering material 22 and the surface 32A of the second covering material 32 hydrophobic (second property). In this case, for example, the substrate 10 may be formed from a hydrophilic resin, and the first coating material 22 and the second coating material 32 may be formed from a hydrophobic resin film.

[0082] The materials constituting each part described in the above embodiment are merely examples, and the materials of each part are not limited. For example, in the above embodiment, the substrate 10 is made of a hydrophobic resin, but it may be made of glass or resin, and the material is not particularly limited.

[0083] In the above embodiment, examples of connection portion X and droplets 18A to 18E have been described using inspection devices 1 to 5. However, in the present invention, the position, size, and shape of connection portion X and droplets are not limited as long as droplets are formed at connection portion X. For example, connection portion X may be located upstream of first flow path 20 as long as the function of the present invention is not impaired.

[0084] In the above embodiment, an example has been described in which the outflow of specimen liquid 18 from the second flow path takes precedence over fluid 19 from first flow path 20. However, in the present invention, it is sufficient that at least the specimen flows out to outlet 40, and fluid 19 may flow out to outlet 40 together with specimen liquid 18.

[0085] In the above embodiments, the test devices 1 to 5 are described as being used as test kits for testing infectious diseases caused by viruses, bacteria, etc. However, the test devices are not limited to such a configuration and may be used for tests other than those described above.

[0086] In the above embodiment, an example was described in which the fluid control device was applied as fluid control units 11-15 having a timing function of the inspection devices 1-5. However, the fluid control device is not limited to applications having a timing function, and the width, depth, length, etc. of the first flow channel 21 (21A, 21B) are not limited to the above-mentioned ranges. Furthermore, it is not necessary to have both the first section L1 and the second section L2. For example, in the above embodiment, an example was shown in which the depth of the first flow channel 21 changes before and after point P, but an embodiment in which the depth does not change is also possible.

[0087] The fluid control device of the present invention may be used as a fluid control device for a microchannel device for other applications that require the discharge of a fluid introduced into a channel, such as a chip for detecting water leaks and a device with a fixed-volume dispensing function.

[0088] Regarding other configurations, it should be understood that the embodiments disclosed in this specification are illustrative in all respects and that the scope of the present invention is not limited thereby. Those skilled in the art will easily understand that appropriate modifications are possible without departing from the spirit of the present invention. Therefore, other embodiments modified without departing from the spirit of the present invention are naturally included in the scope of the present invention. [Industrial Applicability]

[0089] The fluid control device according to the present invention can be used, for example, as a valve structure for opening a flow channel in a micro-channel device, and the testing device according to the present invention can be used, for example, as various test kits. [Explanation of symbols]

[0090] 1 to 5: Inspection equipment 10: Substrate 11 to 15: Fluid control unit (fluid control device) 18: Sample liquid (sample) 18A~18E: Droplet 19 :Fluid 20: First flow path 21: First flow channel 22: First coating material 23: Fluid inlet (first fluid inlet) 30: Second flow path 31: Second flow channel 32: Second coating material 32A: Surface of second covering material (guide part) 33: Sample inlet (second fluid inlet) 40: Outlet 50:Detection unit X: Connection part W: Width of flow channel D: Depth of flow channel

Claims

1. a first flow channel having a flow channel groove formed on one surface of a substrate and a coating material covering the flow channel; a second flow channel fluidly communicating with the first flow channel on at least one of a side surface and a bottom surface of the flow channel; an outlet in fluid communication with a connection portion of the first flow path and the second flow path; The first flow path is the surface of the flow channel has a first property of either hydrophobicity or hydrophilicity, the surface of the coating material on the side of the flow channel has a second property which is the other of the hydrophobicity and the hydrophilicity, The second flow path is a guide portion having the second property and guiding the fluid introduced into the second flow path to the connecting portion; When the fluid is introduced into the second flow path, the fluid guided by the guide portion forms droplets at the connecting portion.

2. the second flow path has a second flow path groove formed on a surface of the substrate opposite to the flow path groove of the first flow path, and a second coating material covering the second flow path groove, The fluid control device according to claim 1 , wherein the second coating material at least partially overlaps the connection portion in a plan view of the substrate.

3. The fluid control device according to claim 2 , wherein the surface of the second covering material on the side of the second flow channel serves as the guide portion.

4. 4. The fluid control device according to claim 1, wherein the first flow path has a larger pipeline resistance than the second flow path.

5. a first fluid inlet that is in fluid communication with the first flow path and through which a first fluid is introduced; a second fluid inlet that is fluidly connected to the second flow path and through which a second fluid is introduced; A fluid control device according to any one of claims 1 to 3, wherein the length of the first flow path from the first fluid inlet to the connecting portion is greater than the length of the second flow path from the second fluid inlet to the connecting portion.

6. A testing device comprising: a fluid control section that causes at least a specimen to flow out when a fluid and a specimen are introduced; and a detection section that can detect the specimen that has flowed out from the fluid control section, The fluid control unit a first flow channel having a flow channel groove formed on at least one surface of a substrate and a coating material covering the flow channel; a second flow channel fluidly communicating with the first flow channel on at least one of a side surface and a bottom surface of the flow channel; a fluid inlet port that is in fluid communication with the first flow path and through which the fluid is introduced; a sample inlet fluidly communicating with the second flow path and through which the sample is introduced; an outlet that is in fluid communication with a connection portion between the first flow channel and the second flow channel and that guides the sample; Equipped with The first flow path is the surface of the flow channel has a first property of either hydrophobicity or hydrophilicity, the surface of the coating material on the side of the flow channel has a second property which is the other of the hydrophobicity and the hydrophilicity, The second flow path is a guide portion having the second property and guiding the sample introduced into the second flow path to the connecting portion; When the sample is introduced into the sample inlet, the sample guided by the guide section forms droplets at the connection portion; the fluid is introduced into the fluid inlet, and when the fluid contacts the droplet at the connection portion, at least the sample flows out from the outlet; The detection unit is in fluid communication with the outlet.

7. 7. The testing device according to claim 6, wherein the flow channel of the first flow channel has a section having a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm, and when the fluid and the specimen are introduced, at least the specimen flows out after a predetermined time.

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