Clocking device, clocking method, fluid control device, dilution device, and inspection device

Abstract

A clocking device 10 comprises: a flow path groove 12 that is formed on at least one surface of a substrate 11; a coating material that covers the flow path groove 12; and a fluid introduction port 14 that communicates with the flow path groove 12. The flow path groove 12 has a section with a width of 0.8-2.0 mm and a depth of 70-100 μm. The clocking device can measure a prescribed time by a required time until a fluid that is introduced into the introduction port 14 reaches a prescribed end point G that is located downstream of the flow path groove 12.

Description

Timing device, timing method, fluid control device, dilution device and inspection device

[0001] The present invention relates to a timing device, a timing method, a fluid control device, a dilution device, and an inspection device.

[0002] Flow channel devices are known that perform biochemical measurements or chemical synthesis by providing a flow channel on a substrate and flowing a fluid through the channel. In particular, microanalysis devices and microreaction devices fabricated using microfabrication techniques are preferred for their miniaturization, portability, small sample volumes, small reagent volumes, small waste volumes, and speed.

[0003] For example, International Publication No. 2012 / 060186 (Patent Document 1) 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, target DNA in a sample is first amplified (gene amplification) by PCR-based genetic analysis (PCR method) in a reaction chamber of the microchip. Then, a target substance contained in the product solution is optically detected in a detection region connected to the reaction chamber via a microchannel.

[0004] Meanwhile, in recent years, test kits using nucleic acid amplification have become commercially available as a rapid diagnostic method for viruses and bacteria, such as the novel coronavirus. Nucleic acid amplification involves the following steps: (1) preparing a nucleic acid amplification reagent that acts to amplify a portion of the viral gene, and adding a specimen (saliva, nasopharyngeal swab, etc.) to the nucleic acid amplification reagent; (2) amplifying the viral gene (nucleic acid) in the specimen using the nucleic acid amplification reagent to obtain an amplification reaction solution; (3) detecting the viral gene (gene amplification product) that has been amplified tens of thousands of times by the reaction with the nucleic acid amplification reagent from the amplification reaction solution. The PCR method mentioned above is also a type of nucleic acid amplification method.

[0005] Furthermore, various valve mechanisms for opening and closing the flow channel in such a microchannel chip have been proposed. For example, Japanese Patent Laid-Open Publication No. 2005-308200 (Patent Document 2) 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 flow channel by supplying and discharging pressure via the pressure control port.

[0006] Furthermore, techniques for performing operations required for sample detection on such microfluidic devices have been proposed. For example, Japanese Patent Laid-Open Publication No. 2006-266974 (Patent Document 3) proposes a test chip having, on the upper surface of a substrate, a sample reservoir for storing a liquid sample, a diluent injector into which a diluent is injected, a mixing pot for merging the liquid sample and the diluent, a flow path extending from the sample reservoir and the diluent injector to the mixing pot, and a microflow path through which a diluted sample flows from the mixing pot, the area of ​​the substrate including the mixing pot, the flow path, and the microflow path being covered from the upper side with a membrane, and the mixing pot houses a rotor having a magnetic body therein that rotates in response to changes in a magnetic field, and a dilution device on which the test chip is mounted for diluting a sample.

[0007] International Publication No. 2012 / 060186 Japanese Patent Application Laid-Open No. 2005-308200 Japanese Patent Application Laid-Open No. 2006-266974

[0008] The gene (nucleic acid) amplification reaction in the sample in step (2) requires a predetermined reaction time, typically set between 10 and 60 minutes. If this predetermined reaction time is not observed by the user of the testing device, accurate test results may not be obtained. Furthermore, the testing device of Patent Document 1 only performs amplification and detection of target DNA in the microchannel chip, and is not capable of measuring the reaction time.

[0009] Therefore, a flow path device capable of measuring a predetermined time is desired.

[0010] Furthermore, in the testing device of Patent Document 1, 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 a 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 performed in a container by an operator while measuring the reaction time, and then the operator often 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 a pre-reaction sample, and require the operator's effort.

[0011] The microvalve mechanism of Patent Document 2 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.

[0012] 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.

[0013] Furthermore, in the test device of Patent Document 1, the sample reacted in the reaction chamber is sent to the detection section by a micropump connected to a microchip, which requires an external pump and tends to make the device complex. In the test kit using the nucleic acid amplification method described above, a high sample concentration is desirable in the amplification reaction stage (2) above, but if the viscosity, concentration, etc. of the amplification reaction solution (3) above is too high, it may be difficult to detect the gene amplification product in the detection section. However, adding a step of diluting the amplification reaction solution to properties (viscosity, concentration, etc.) suitable for detection may make the test complicated, even though the test kit is in the form of a test kit.

[0014] Therefore, there is a demand for a fluid control device that can autonomously dilute one fluid with another fluid in a microchannel chip, and for a testing device to which this device is applied.

[0015] Furthermore, in test kits using the above-mentioned nucleic acid amplification method, a high sample concentration is desirable at the amplification reaction stage (2) above, and the amplification reaction solution (3) above is desirably diluted to optimal properties (viscosity, concentration, etc.) for detecting gene amplification products. On the other hand, the test chip of Patent Document 1 injects a reagent containing a fluorescent labeling substance into a diluted sample on the test chip, and analyzes the sample components by fluorescent detection; it does not react the collected sample with a reaction reagent to obtain an amplification reaction solution, as in the nucleic acid amplification method, and then dilutes it. Furthermore, the test chip of Patent Document 1 requires an external stirring mechanism to stir the tiny rotor in the mixing pod, which can easily make the device complex.

[0016] Therefore, there is a demand for a dilution device that includes at least a part of a microchannel chip and that can dilute a specimen after reacting it with a reaction reagent, etc., and a testing device that employs the dilution device.

[0017] [Timekeeping device, timekeeping method, and first inspection device] In order to achieve the above object, a characteristic configuration of a timekeeping device according to the present invention is that it comprises a flow channel formed on at least one surface of a substrate, a coating material covering the flow channel, and a fluid inlet port communicating with the flow channel, wherein the flow channel has a section that is 0.8 to 2.0 mm wide and 70 to 100 μm deep, and is capable of measuring a predetermined time based on the time required for the fluid introduced into the inlet to reach a predetermined destination located downstream of the flow channel.

[0018] Furthermore, in order to achieve the above-mentioned object, a characteristic configuration of the timing method according to the present invention is a timing method using a timing device comprising: a flow channel formed on at least one surface of a substrate; a coating material covering the flow channel; and a fluid inlet communicating with the flow channel, the flow channel having a section with a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm, wherein measurement of a predetermined time period begins when the fluid is introduced into the inlet, and the elapse of the predetermined time period is determined when the fluid reaches a predetermined end point located downstream of the flow channel.

[0019] As a result of extensive research, the inventors discovered that in a flow channel device including a flow channel groove formed on at least one surface of a substrate, a coating material covering the flow channel groove, and a fluid inlet port communicating with the flow channel groove, variation in the flow rate of a fluid introduced into the flow channel can be suppressed by defining the flow channel groove within a specific range of width 0.8 to 2.0 mm and depth 70 to 100 μm. With these configurations, the flow channel groove has a section with a width and depth within a specific range, thereby suppressing variation in flow rate. Therefore, measurement of a predetermined time period can be initiated when a fluid is introduced into the inlet port of the flow channel device, and the elapse of the predetermined time period can be determined when the fluid reaches a predetermined destination downstream of the flow channel.

[0020] a detection unit capable of detecting the analyte that has flowed out from the timing unit; and a flow channel formed on at least one surface of a substrate; a coating material covering the flow channel; a fluid receiving portion that communicates with the flow channel and into which the fluid is introduced; a sample receiving portion that communicates with the flow channel and into which the sample is introduced; and an outlet located downstream of the flow channel and from which at least the analyte flows out, the flow channel having a section that is 0.8 to 2.0 mm wide and 70 to 100 μm deep; and when the fluid is introduced into the fluid receiving portion and the sample is introduced into the sample receiving portion, at least the analyte flows out from the outlet after the predetermined time; and the detection unit is fluidically connected to the outlet, and the predetermined time is limited by the time required for the fluid introduced into the fluid receiving portion to reach a predetermined destination located downstream of the flow channel.

[0021] According to this configuration, the timing unit has a section of a flow channel that is 0.8 to 2.0 mm wide and 70 to 100 μm deep, and the detection unit automatically detects the sample that flows out of the timing unit, so the reaction time of the sample can be made approximately constant, and the testing accuracy of the testing device can be improved.

[0022] Preferred embodiments of the timing device, timing method, and first testing device according to the present invention will be described below. However, the scope of the present invention is not limited to the preferred embodiments described below.

[0023] In one aspect, the timing device according to the present invention is preferably configured so that the required time is within an allowable error of ±5% of the predetermined time.

[0024] According to this configuration, the timing device of the present invention can measure a predetermined time with almost accuracy.

[0025] In one aspect of the timepiece according to the present invention, it is preferable that a portion of at least one of the flow channel and the covering material that comes into contact with the fluid passing through the flow channel is hydrophilic.

[0026] According to this configuration, it is not necessary to make all of the portions of the flow channel that come into contact with the fluid passing through the flow channel hydrophilic; instead, it is sufficient to make at least one of the flow channel and the coating material hydrophilic, which can facilitate the formation of the flow channel. That is, if the substrate on which the flow channel is formed is made of a hydrophobic resin, the coating material can be made hydrophilic. If the surface of the flow channel is hydrophilic, the coating material can be hydrophobic. Conventionally, the surface of the flow channel on a substrate made of a hydrophobic resin is subjected to a hydrophilic treatment such as plasma treatment and then covered with a hydrophobic coating material. However, if a coating material that is more hydrophilic than the original coating material is used, it is not necessary to perform a hydrophilic treatment such as plasma treatment on the surface of the flow channel, which can simplify the process of forming the flow channel.

[0027] In one aspect of the timepiece according to the present invention, the flow channel preferably further has another section that is deeper than the section.

[0028] According to this configuration, the flow velocity can be reduced by the other deeper sections, and a long measurement time can be measured without increasing the dimensions of the device. Therefore, a long time (for example, 10 to 30 minutes) can be set as the predetermined time.

[0029] In one aspect of the first testing device according to the present invention, the timing unit is provided with a sample liquid inlet that serves as the fluid receiving unit and sample receiving unit, into which sample liquid containing the fluid and the sample is introduced, and it is preferable that the predetermined destination point is the outlet.

[0030] According to this configuration, since the sample liquid is used in the timing section, it is easy to make the testing device have a simple configuration.

[0031] In one aspect of the first testing device according to the present invention, the timing unit is provided with a fluid inlet located upstream of the outlet and serving as the fluid receiving unit, and a sample inlet located downstream of the fluid inlet and serving as the sample receiving unit that is fluidically connected to the outlet, and it is preferable that the predetermined destination point is the sample inlet.

[0032] According to this configuration, when the viscosity of the sample liquid is particularly high, the fluid inlet and the sample inlet can be separated, and another fluid with low viscosity (e.g., water, buffer solution, etc.) can be used in the timing unit. The testing device of the present invention is not easily affected by viscosity, etc., and the sample liquid can be used in the timing unit, but the time measurement accuracy can be further improved by introducing a timing fluid into the fluid inlet. The sample can be reacted separately in the sample inlet downstream of the fluid inlet, and finally, at least the sample can be configured to flow out from the outlet.

[0033] In one aspect of the first testing device according to the present invention, at least a part of a cross section of the outlet in the outflow direction of the sample is preferably hydrophilic.

[0034] According to this configuration, the sample flowing out from the outlet is quickly introduced into the detection section from the outlet, thereby reducing the gap between the time required after the fluid and sample are introduced as measured by the timing section and the time until the sample is actually detected in the detection section.

[0035] [First Fluid Control Device and Second Inspection Device] A first 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.

[0036] A second testing device according to the present invention is a testing device comprising a fluid control section that, when a fluid and a sample are introduced, causes at least the sample to flow out, and a detection section that can detect the sample 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 sample inlet that is fluidically connected to the second flow path and through which the sample 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 sample. 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, and when the specimen is introduced into the specimen inlet, the specimen guided by the guide section forms droplets at the connection section, and 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 in fluid communication with the outlet.

[0037] According to the first 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 the second 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.

[0038] Preferred embodiments of the first fluid control device and the second testing device according to the present invention will be described below, although the scope of the present invention is not limited to the preferred embodiments described below.

[0039] In the first 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.

[0040] According to this configuration, the second covering material can guide the fluid introduced into the second flow path to the connection portion.

[0041] In the first 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.

[0042] 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.

[0043] In the first 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.

[0044] 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.

[0045] The first 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.

[0046] 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.

[0047] In the second 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.

[0048] 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.

[0049] [Second Fluid Control Device and Third Inspection Device] The second fluid control device according to the present invention is a fluid control device on a microchip that discharges both an introduced first fluid and a second fluid, and is characterized by comprising: a main 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; an outlet that is fluidically connected downstream of the main flow path and that guides both the first fluid and the second fluid; a first reservoir and a second reservoir that are fluidically connected to the main flow path and in which the first fluid and the second fluid are stored, respectively; a first fluid control mechanism that controls the discharge of the first fluid from the first reservoir; and a second fluid control mechanism that controls the discharge of the second fluid from the second reservoir.

[0050] According to this configuration, the microchip is provided with a first reservoir and a second reservoir in which a first fluid and a second fluid are stored, respectively, a first fluid control mechanism that controls the outflow of the first fluid from the first reservoir, and a second fluid control mechanism that controls the outflow of the second fluid from the second reservoir, so that two types of fluid with small volumes can be caused to flow out together, and one fluid can be used to dilute the other fluid.

[0051] Furthermore, a third testing device according to the present invention is a testing device comprising, on a microchip, a fluid control section that discharges both introduced specimen and dilution solvent, and a detection section that can detect the specimen that has discharged from the fluid control section, wherein the fluid control section comprises: a main flow path having a flow groove formed on at least one surface of a substrate and a coating material that covers the flow groove; an outlet that is fluidically connected downstream of the main flow path and that guides both the specimen and the dilution solvent; a first reservoir and a second reservoir that are fluidically connected to the main flow path and in which the dilution solvent and the specimen are stored, respectively; a first fluid control mechanism that controls the discharge of the dilution solvent from the first reservoir; and a second fluid control mechanism that controls the discharge of the specimen from the second reservoir, wherein the detection section is fluidically connected to the outlet.

[0052] According to this configuration, the microchip includes a first reservoir and a second reservoir for storing a dilution solvent and a sample, respectively, a first fluid control mechanism for controlling the outflow of the dilution solvent from the first reservoir, and a second fluid control mechanism for controlling the outflow of the sample from the second reservoir. This allows both the dilution solvent and the sample to flow out together, allowing the sample to be diluted with the dilution solvent. Furthermore, a grace period can be set before the sample and the dilution solvent mix in the second reservoir. This allows the sample to react with the reaction reagent in the second reservoir and then be diluted with the dilution solvent in the first reservoir. This allows the sample concentration to be increased during the nucleic acid amplification reaction between the sample and the reaction reagent, and the sample liquid to be diluted to optimal properties (viscosity, concentration, etc.) for detection before detecting the sample (gene amplification product) after the reaction.

[0053] Preferred embodiments of the second fluid control device and the third testing device according to the present invention will be described below, although the scope of the present invention is not limited to the preferred embodiments described below.

[0054] In the second fluid control device of the present invention, it is preferable that the first reservoir and the second reservoir have a predetermined volume ratio, one is located upstream and the other downstream in the main flow path, the outlet, the first reservoir and the second reservoir each have a through hole formed in the substrate, and a coating material covering the lower opening of the through hole serves as the bottom, and the first fluid and the second fluid both flow out at the predetermined volume ratio.

[0055] According to this configuration, both the first fluid and the second fluid tend to flow out at a volume ratio corresponding to the volume ratio of the first reservoir and the second reservoir.

[0056] In the second fluid control device according to the present invention, it is preferable that one of the first reservoir and the second reservoir is configured to protrude above the substrate, and that the one reservoir is greater in height than the other.

[0057] With this configuration, the first fluid in the first reservoir and the second fluid in the second reservoir, whichever has a higher liquid level, flows out preferentially to the outlet based on the difference in potential energy (difference in potential head).When the liquid levels of the two fluids become the same, the other fluid in the other reservoir flows out simultaneously with the first fluid, making it easy to enable the first and second fluids to flow out sequentially.

[0058] In the second fluid control device of the present invention, it is preferable that the height of the second reservoir is greater than the height of the first reservoir, and the connecting portion between the second reservoir and the main flow path is located closer to the outlet than the connecting portion between the first reservoir and the main flow path.

[0059] According to this configuration, based on the potential energy difference (difference in potential head) between the first fluid in the first reservoir and the second fluid in the second reservoir, the second fluid in the second reservoir flows out to the outlet until the liquid levels of the first fluid and the second fluid become the same, and when the liquid levels become the same, the first fluid in the first reservoir also flows out at the same time, which facilitates sequential outflow, in which the second fluid flows out first and then the first fluid flows out later. For example, if a diluent solvent is introduced into the first reservoir as the first fluid and an analyte is introduced into the second reservoir as the second fluid, the analyte with a higher concentration can flow out to the outlet first, followed by the diluent solvent, which facilitates a configuration in which the diluent solvent washes away the analyte with a higher concentration.

[0060] In a second fluid control device according to the present invention, the first reservoir and the second reservoir have a predetermined volume ratio, the main flow path has a branch point, a first branch path fluidly connected to the first reservoir between the branch point and the outlet, and a second branch path fluidly connected to the second reservoir between the branch point and the outlet, and the flow path length from the branch point to the connecting portion between the first reservoir and the first branch path is different from the flow path length from the branch point to the connecting portion between the second reservoir and the second branch path, and it is preferable that the first fluid and the second fluid both flow out at the predetermined volume ratio.

[0061] According to this configuration, by branching the main flow path and making the flow path lengths from the branching point to each communicating portion different, the first fluid and the second fluid can be caused to flow out at different times.

[0062] A second fluid control device according to the present invention includes a first communication passage that fluidly connects the main flow passage and the first reservoir, and a second communication passage that fluidly connects the main flow passage and the second reservoir, the main flow passage being in fluid communication with the first communication passage and the second communication passage at at least one of a side surface and a bottom surface of the flow passage groove of the main flow passage, the first fluid control mechanism including a first guide portion that guides the first fluid introduced into the first reservoir to a first connecting portion between the main flow passage and the first communication passage, the first guide portion having a first property that is either hydrophobic or hydrophilic, and a surface of the coating material facing the flow passage groove having a second property that is the other of hydrophobic and hydrophilic, the first communication passage having the second property, and a first connecting portion that connects the first fluid introduced into the first reservoir and the first communication passage, the first connecting portion being configured to connect ... The guided first fluid forms first droplets at the first connection portion, thereby controlling the outflow of the first fluid from the first reservoir, and the second fluid control mechanism preferably has the main flow path such that the surface of the flow groove has a first property that is either hydrophobic or hydrophilic, the surface of the coating material on the flow groove side has a second property that is the other of hydrophobic and hydrophilic, the second communicating path has the second property, and has a second guide portion that guides the second fluid introduced into the second reservoir to a second connecting portion between the main flow path and the second communicating path, and when the second fluid is introduced into the second reservoir, the second fluid guided by the second guide portion forms second droplets at the second connecting portion, thereby controlling the outflow of the second fluid from the second reservoir.

[0063] According to this configuration, the first fluid control mechanism and the second fluid control mechanism are configured to utilize surface tension as described above, so it is possible to realize a fluid control mechanism in which the first fluid and the second fluid autonomously mix.

[0064] A third testing device according to the present invention preferably includes a communication passage that fluidly connects the main flow path and the first reservoir, the main flow path being fluidly connected to the communication passage at at least one of the side and bottom surfaces of the flow channel, and the first fluid control mechanism is configured such that the surface of the main flow channel has a first property that is either hydrophobic or hydrophilic, and the surface of the coating material facing the flow channel has a second property that is the other of hydrophobic and hydrophilic, the communication passage having the second property, and a guide section that guides either the specimen or the dilution solvent introduced into the first reservoir to a connection portion between the main flow path and the communication passage, and when either the specimen or the dilution solvent is introduced into the first reservoir, the specimen or the dilution solvent guided by the guide section forms droplets at the connection portion, thereby controlling the outflow of either the specimen or the dilution solvent from the first reservoir.

[0065] According to this configuration, the first fluid control mechanism and the second fluid control mechanism are configured to utilize surface tension as described above, so that a fluid control mechanism can be realized in which the sample and dilution solvent are mixed autonomously.

[0066] In a third testing device according to the present invention, the flow channel of the main flow channel has a regulated section in which the time required for the fluid to pass through is regulated, and the device is equipped with a fluid inlet that is fluidically connected to the flow channel of the main flow channel and introduces the fluid, and when the fluid, the dilution solvent, and the specimen are introduced into the fluid inlet, the first reservoir, and the second reservoir, respectively, it is preferable that the fluid contacts the droplet at the connection portion, and after a predetermined time, the specimen and the dilution solvent flow out together.

[0067] According to this configuration, the flow channel of the main flow channel has a regulated section in which the time required for the fluid to pass through is regulated, so that the analyte and the diluent solvent can both flow out after a predetermined time, making it easier to flow out the analyte that has reacted for a predetermined time together with the diluent solvent.

[0068] In the third inspection device according to the present invention, it is preferable that the restricted section includes a section in which the flow channel has a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm.

[0069] According to this configuration, by including the above section in the restriction section, it is possible to reduce the variation in the time required for the fluid to pass through.

[0070] [Dilution device and fourth testing device] A dilution device according to the present invention includes a dilution liquid outlet section that discharges at least a diluent when a fluid is introduced therein, and a specimen dilution section that receives a specimen and dilutes the specimen with the diluent discharged from the diluent outlet section, wherein the diluent outlet section includes a flow channel formed on at least one surface of a substrate, a coating material that covers the flow channel, a fluid receiving section that communicates with the flow channel and into which the fluid is introduced, a diluent receiving section that communicates with the flow channel and into which the diluent is introduced, a fluid control mechanism that controls the discharge of the diluent from the diluent receiving section, and an outlet that is located downstream of the flow channel and through which at least the diluent discharges, wherein the dilution device is configured such that when the fluid is introduced into the fluid receiving section and the diluent is introduced into the diluent receiving section, at least the diluent discharges from the outlet, and the specimen dilution section is configured such that when a mixture of the diluent and the specimen reaches a predetermined liquid level, the specimen dilution section dilutes the specimen to a predetermined ratio.

[0071] a fluid receiving section communicating with the flow channel and into which the fluid is introduced; a diluent receiving section communicating with the flow channel and into which the diluent is introduced; a fluid control mechanism for controlling the outflow of the diluent from the diluent receiving section; and an outlet located downstream of the flow channel and through which at least the diluent flows; wherein the fluid is introduced into the fluid receiving section and the diluent is introduced into the diluent receiving section, and the diluent is introduced into the diluent receiving section; and wherein the specimen dilution section is configured so that when the fluid is introduced into the fluid receiving section and the diluent is introduced into the diluent receiving section, at least the diluent flows out of the outlet; and the specimen dilution section is configured so that when the mixed liquid of the diluent and the specimen reaches or exceeds a predetermined liquid level, the mixed liquid reaches the detection section.

[0072] According to these configurations, the microchannel chip is provided with at least a diluent outlet, and the diluent flowing out from the diluent outlet dilutes the specimen in the specimen dilution section, allowing a grace period before the specimen and the diluent mix together, and allowing the specimen to react with the reaction reagent in advance in the specimen dilution section. Furthermore, because the specimen liquid containing the specimen does not pass through the fluid control mechanism, the properties of the specimen that can be used are not limited by the fluid control mechanism.

[0073] According to the fourth testing device of the present invention, a sample liquid diluted to a predetermined dilution rate or more can be introduced into the detection unit, making it easier to detect the sample in the detection unit.

[0074] Preferred embodiments of the dilution device and the fourth testing device according to the present invention will be described below, but the scope of the present invention is not limited to the preferred embodiments described below.

[0075] In the dilution device of the present invention, it is preferable that the flow path groove has a regulated section in which the time required for the fluid to pass through is regulated, and that when the fluid and the diluent are introduced, at least the diluent flows out after a predetermined time.

[0076] According to this configuration, the flow channel has a regulated section in which the time required for the fluid to pass through is regulated, so that the diluent can flow out after a predetermined time.

[0077] In the dilution device according to the present invention, it is preferable that the regulated section includes a section in which the flow channel has a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm.

[0078] According to this configuration, by having a section within the above range, it is possible to reduce the variation in the time required for the fluid to pass through the regulated section.

[0079] In the dilution device according to the present invention, it is preferable that the substrate is erected so that the outflow direction downstream of the flow channel faces downward.

[0080] This configuration makes it easier to quickly discharge the diluent from the outlet.

[0081] In the dilution device according to the present invention, it is preferable that the diluent receiving portion is formed in the shape of a pocket on at least one surface of the base plate.

[0082] According to this configuration, the diluent receiving portion is formed in a pocket shape, which makes it easy to increase the volume of the diluent and to easily hold the diluent when the substrate is placed upright.

[0083] In the dilution device of the present invention, the dilution liquid outflow section comprises a first flow path formed by the flow path groove and the covering material, and a second flow path fluidly connected to the dilution liquid receiving section and fluidly connected to at least one of the side surface and bottom surface of the first flow path, and the fluid control mechanism is configured so that the surface of the first flow path has a first property which is either hydrophobic or hydrophilic, the surface of the covering material of the first flow path facing the flow path groove has a second property which is the other of hydrophobic and hydrophilic, and the second flow path has the second property, and has a guide section that guides the dilution liquid introduced into the dilution liquid receiving section to a connection portion between the first flow path and the second flow path, and when the dilution liquid is introduced into the dilution liquid receiving section, the dilution liquid guided by the guide section forms droplets at the connection portion.

[0084] According to this configuration, an autonomously diluting device can be realized.

[0085] In the dilution device of the present invention, the diluent outlet portion is preferably configured such that the fluid is the diluent, and the diluent reservoir serves as both the fluid receiving portion and the diluent receiving portion, and the diluent reservoir is fluidically connected to each of the first flow path and the second flow path, and when the diluent is introduced from the diluent reservoir into the first flow path, the diluent that flows out from the diluent reservoir through the second flow path flows out from the outlet.

[0086] According to this configuration, the fluid is a diluent, and one reservoir can serve as both the fluid receiving portion and the diluent receiving portion, making it easy to make a simple and compact device.

[0087] According to the fourth testing device of the present invention, it is preferable that the specimen dilution unit includes at least a part of the substrate, the detection unit is housed in a through-hole formed in the substrate or a recess formed on at least one surface of the substrate, and at least one surface of the substrate further includes a detection flow channel connecting the specimen dilution unit and the detection unit, and the mixed liquid in the specimen dilution unit flows out to the detection unit via the detection flow channel.

[0088] This configuration makes it easy to mount the specimen dilution unit and the detection unit on one substrate.

[0089] 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.

[0090] 1A is a plan view showing a testing device according to a first embodiment of the present invention; FIG. 1B is a II-II cross-sectional view of the testing device of FIG. 1; FIG. 1C is a III-III cross-sectional view of the testing device of FIG. 1A is an enlarged view of a main part of the testing device at IV-IV cross section in FIG. 1A is a plan view showing the test results of the testing device of FIG. 1A is a plan view showing a testing device according to a second embodiment of the present invention; FIG. 6A is an enlarged view of a main part of the testing device of FIG. 6A is an enlarged view of a main part explaining the testing device of FIG. 6 in detail; FIG. 8B is a IX-IX cross-sectional view of FIG. 8C is a diagram showing a state in which a sample liquid has been introduced in FIG. 8; FIG. 10B is a XI-XI cross-sectional view of FIG. 10C is a diagram showing a state in which a sample liquid has flowed out of an outlet in FIG. 8A is a plan view showing a timing device used in Test Examples 1 to 4; 26 is a diagram showing a state where a sample has been introduced; an enlarged view of a main part in the XIX-XIX cross section of FIG. 18; a diagram showing a state where a sample has flowed out of the outlet in FIG. 18; an XXI-XXI cross section of the inspection device in FIG. 15; an enlarged view of a main part in the XXII-XXII cross section of the inspection device in FIG. 15; a plan view showing an example of an inspection result in the inspection device in FIG. 15; an enlarged view of a main sectional part of the inspection device according to the fourth embodiment of the present invention; a diagram showing a state where a sample has been introduced in the inspection device in FIG. 24; an enlarged view of a main sectional part of the inspection device according to the fifth embodiment of the present invention; a diagram showing a state where a sample has been introduced in the inspection device in FIG. 26; an enlarged view of a main sectional part of the inspection device according to the sixth embodiment of the present invention; a diagram showing a state where a sample has been introduced in the inspection device in FIG. 28; an enlarged view of a main sectional part of the inspection device according to the seventh embodiment of the present invention;Figures showing the state with the specimen introduced, Plan view showing the inspection apparatus according to the eighth embodiment of the present invention, Cross-sectional view taken along line A-A of the inspection apparatus in FIG. 32, Enlarged view of the main part of the cross-section taken along line B-B of the inspection apparatus in FIG. 32, Enlarged view of the main part in FIG. 32, Cross-sectional view taken along line C-C of FIG. 35, Plan view for explaining the usage state of the inspection apparatus in FIG. 32, Cross-sectional view taken along line D-D of FIG. 37, Plan view for explaining the usage state of the inspection apparatus in FIG. 32, Plan view for explaining the usage state of the inspection apparatus in FIG. 32, Cross-sectional view taken along line F-F of FIG. 40, Plan view for explaining the usage state of the inspection apparatus in FIG. 32, Plan view for explaining the usage state of the inspection apparatus in FIG. 32, Cross-sectional view showing the transition of the liquid surface heights of the dilution solvent reservoir (first reservoir) and the specimen liquid reservoir (second reservoir) during the use of the inspection apparatus in FIG. 32, Plan view showing the inspection apparatus according to the ninth embodiment of the present invention, Enlarged view of the main part of the cross-section taken along line I-I of FIG. 45, Cross-sectional view showing the transition of the liquid surface heights of the dilution solvent reservoir (first reservoir) and the specimen liquid reservoir (second reservoir) during the use of the inspection apparatus in FIG. 45, Plan view showing the inspection apparatus according to the tenth embodiment of the present invention, Plan view for explaining the usage state of the inspection apparatus in FIG. 48, Plan view for explaining the usage state of the inspection apparatus in FIG. 48, Plan view for explaining the usage state of the inspection apparatus in FIG. 48, Cross-sectional view showing the transition of the liquid surface heights of (first reservoir) and the specimen liquid reservoir (second reservoir) during the use of the inspection apparatus in FIG. 48, Figure showing an example of other connection parts in the fluid control section (fluid control apparatus) of the present invention, Enlarged view of the main part of the cross-section taken along line M-M of FIG. 53, In the fluid control section (fluid control apparatus) of the present invention,FIG. showing an example of another connection part, enlarged view of the main part of the N-N line cross-section of FIG. 55, front view showing an inspection apparatus according to the eleventh embodiment of the present invention, right side view of the inspection apparatus of FIG. 57, schematic view for explaining an inspection apparatus according to the eleventh embodiment of the present invention, schematic view for explaining an inspection apparatus according to the eleventh embodiment of the present invention, schematic view for explaining an inspection apparatus according to the eleventh embodiment of the present invention, front view showing the substrate of the inspection apparatus of FIG. 57, perspective view showing a pocket-shaped member related to the inspection apparatus of FIG. 57, B-B line cross-section view of FIG. 62, C-C line cross-section view of FIG. 62, enlarged view of the main part of the D-D line cross-section of FIG. 62, view for explaining the fluid control mechanism of an inspection apparatus according to the eleventh embodiment of the present invention, enlarged view of the main part of the E-E line cross-section of FIG. 67, view for explaining the fluid control mechanism of an inspection apparatus according to the eleventh embodiment of the present invention, enlarged view of the main part of the F-F cross-section of FIG. 69, view for explaining the fluid control mechanism of an inspection apparatus according to the eleventh embodiment of the present invention, perspective view of a modified inspection apparatus according to the eleventh embodiment of the present invention, enlarged view of the main part of the G-G cross-section of the inspection apparatus of FIG. 72, perspective view showing a diluent outflow part and a specimen dilution part of an inspection apparatus according to the twelfth embodiment of the present invention, enlarged view of the main part of the H-H cross-section of the inspection apparatus of FIG. 74, view for explaining the state where the diluent has flowed in in FIG. 75, view for explaining the usage method of an inspection apparatus according to the thirteenth embodiment of the present invention, schematic view for explaining an inspection apparatus according to the thirteenth embodiment of the present invention, schematic view for explaining an inspection apparatus according to the thirteenth embodiment of the present invention, schematic view for explaining an inspection apparatus according to the thirteenth embodiment of the present invention, schematic view for explaining an inspection apparatus according to the thirteenth embodiment of the present invention, schematic view for explaining an inspection apparatus according to the thirteenth embodiment of the present invention, view showing an example of another connection part in the fluid control mechanism of the present invention, enlarged view of the main part of the I-I cross-section of FIG. 83, view showing an example of another connection part in the fluid control mechanism of the present invention, enlarged view of the main part of the J-J cross-section of FIG. 85

[0091] 1. First Embodiment <Testing Device 1> A testing device 1 according to a first embodiment of the present invention will be described with reference to FIGS. 1 to 5. The testing device 1 includes a timing unit 10 and a detection unit 20 capable of detecting sample liquid flowing out from the timing unit 10. The testing device 1 is used, for example, as a test kit for testing infectious diseases caused by viruses, bacteria, etc., and is configured so that when a sample liquid containing a reaction reagent and a sample is introduced into the sample liquid inlet 14, the sample (target substance) after a reaction occurs is detected by the detection unit 20 after a predetermined time. The testing device 1 according to this embodiment is used with the side where the sample liquid inlet 14 and outlet 15 open (the front side in FIG. 1 ) on the upper side, and the side where the covering material 13 is laminated (the rear side in FIG. 1 ) on the lower side. In the following description, when referring to the orientation of the testing device 1, this refers to the up-down direction based on the orientation in which the testing device 1 is placed so that the covering material 13 is in contact with the ground (the orientation shown in FIGS. 2, 3, and 4 ). Furthermore, when referring to the horizontal direction of the testing device 1, this refers to the direction perpendicular to the above-mentioned vertical direction (i.e., the left-right direction in Figures 2, 3, and 4, or the direction perpendicular to the paper surface). The depth direction is also the same as the vertical direction. In the first and second embodiments, the terms "specimen" and "specimen liquid" are used regardless of whether the reaction is before or after or the degree of progress of the reaction.

[0092] The timing unit 10 (an example of a timing device) has a function of measuring a predetermined reaction time for the reaction between the sample and the reaction reagent, because the time (required time) for the sample liquid containing the fluid and the sample to flow through the flow channel 12 is regulated to a preset time (predetermined time).

[0093] 2, the timing unit 10 includes a flow channel 12 formed on one surface of a substrate 11, a covering material 13 covering the flow channel 12, and a sample liquid inlet 14 (an example of an inlet) communicating with the flow channel 12. The space formed by the flow channel 12 and the covering material 13 forms a flow channel through which a fluid passes.

[0094] In this embodiment, the substrate 11 has a through-hole at one end of the flow channel 12 that communicates with the flow channel 12 and passes through the substrate 11. As shown in Fig. 2, the through-hole located upstream of the flow channel 12 is a sample liquid inlet 14. Meanwhile, the other end of the flow channel 12 has a notch that passes through the substrate 11. The notch located downstream of the flow channel 12 is a sample liquid outlet 15. The outlet 15 is in fluid communication with the detection unit 20.

[0095] The flow channel 12 has a first section L1 having a width W1 of 0.8 to 2.0 mm and a depth D1 of 70 to 100 μm. If the width W1 and depth D1 of the flow channel 12 are within these ranges, variation in the flow rate of the sample liquid flowing through the flow channel can be suppressed.

[0096] The analyte liquid inlet 14 serves as a fluid receiving section and analyte receiving section into which the analyte liquid containing the fluid and the analyte is introduced. The timer 10 is configured such that when the analyte liquid containing the pre-reacted analyte and the fluid is introduced into the analyte liquid inlet 14, the flow rate is regulated by the first section L1, and after a predetermined time, the analyte liquid containing the reacted analyte flows out of the outlet 15. That is, the length of the flow channel 12 is set so that the predetermined time can be measured from the time required for the analyte liquid introduced into the analyte liquid inlet 14 to reach the outlet 15 (an example of a predetermined destination). In this embodiment, the outlet portion of the analyte liquid inlet 14 is the starting point S, and the inlet portion of the outlet 15 is the destination point G. The shape and size of the analyte liquid inlet 14 are not limited as long as it allows the analyte liquid containing the fluid and the analyte to be introduced into the flow channel 12. In this embodiment, the analyte liquid inlet 14 is a circular hole with a diameter of 2 to 5 mm (e.g., 4 mm). The top of the analyte liquid inlet 14 is open, and the bottom is covered with the same covering material 13 that covers the flow channel 12.

[0097] The width W1 of the flow channel 12 is preferably 0.8 to 1.5 mm, and more preferably 0.9 to 1.2 mm. The depth D1 of the flow channel 12 is preferably 90 to 100 μm, and more preferably 95 to 100 μm.

[0098] In this embodiment, the cross-sectional shape of the flow channel 12 is quadrangular (particularly rectangular), but the shape is not limited thereto. The cross-sectional shape of the flow channel 12 may be trapezoidal or semicircular, and in particular, if the cross-sectional shape of the flow channel 12 is a trapezoid in which the side on the opening side (the side of the covering material 13) is larger than the side on the groove bottom of the flow channel 12, the flow channel 12 can be easily manufactured using a mold. In such a shape, the width W1 and depth D1 of the flow channel 12 described above refer to the maximum width and maximum depth of the flow channel 12.

[0099] In this embodiment, flow channel 12 constituting the flow channel has five parallel straight sections and four arc-shaped curved sections connecting the five straight sections. The sample liquid introduced into sample liquid inlet 14 is configured to make four U-turns on the substrate before reaching outlet 15.

[0100] In this embodiment, the first section L1 starts from the starting point S and extends to a point P midway along the fifth straight section. The first section L1 is followed by a second section L2 that is deeper than the flow channel grooves 12A in the first section L1. In this embodiment, the depth D2 of the flow channel grooves 12B in the second section L2 is set to 2 to 10 times (e.g., 6 times) the depth W1 of the flow channel grooves 12A in the first section. The width W2 of the flow channel grooves 12B in the second section is the same as the width W1 of the flow channel grooves 12A in the first section. The inclusion of the second section L2 effectively reduces the flow velocity, allowing a longer time to be set as a timer for measuring a predetermined time.

[0101] Point P, which marks the transition point from flow channel 12A in first section L1 to flow channel 12B in second section L2, has an inclined surface 12C as shown in FIG. 4 . In this embodiment, the angle θ of inclined surface 12C is 100°. Flow channel 12A in first section L1 suddenly expands from depth D1 to depth D2. This is a so-called sudden expansion pipe, and when the sample liquid enters flow channel 12B, the flow of the sample liquid cannot immediately follow the flow channel shape, and a vortex is formed at the sudden expansion section, drawing in the surrounding sample liquid. This vortex is a flow that remains in place, resulting in pressure loss. In this embodiment, this pressure loss is utilized to reduce the flow rate of the sample liquid. The angle θ of inclined surface 12C is not particularly limited, but is preferably 95° to 105°.

[0102] The ratio of the lengths of the first section L1 and the second section L2 (length of L1: length of L2) is preferably 9:1 to 5:5. With such a ratio, the effect of suppressing time variation in the first section L1 is easily achieved for the entire timing unit 10.

[0103] In this embodiment, the time required to pass through the timer unit 10 is set to be within a tolerance of ±5% of the predetermined time.

[0104] Next, the constituent materials of the timing unit 10 will be described.

[0105] The substrate 11 may be made of glass or resin, and the material is not particularly limited, but in this embodiment, a resin is used. The resin constituting the substrate 11 can be appropriately selected from those having excellent heat resistance and transparency. The substrate 11 can be made of a resin selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl (meth)acrylate, and polyethylene terephthalate. As will be described later, if the flow channel 12 is to be made hydrophilic, the flow channel 12 may be subjected to a hydrophilization treatment such as plasma treatment after being formed.

[0106] The outer shape and size of the substrate 11 can be set appropriately taking into consideration ease of handling, etc. For example, if the substrate is quadrilateral (square or rectangle), each side is preferably 10 mm to 200 mm, and more preferably 10 mm to 100 mm. The outer shape of the substrate 11 is not particularly limited, and may be other polygonal, circular, elliptical, or the like. The thickness of the substrate 11 is also not particularly limited, and may be, for example, 5 to 20 mm.

[0107] The resin substrate 11 can be produced by a resin molding process technique using a molding die, such as injection molding, transfer molding, or extrusion molding.

[0108] In this embodiment, a resin film is used as the covering material 13. It is preferable to appropriately select a resin that has excellent heat resistance and transparency as the resin that constitutes the covering material 13.

[0109] In this embodiment, the portion of at least one of the flow channel 12 and the covering material 13 that comes into contact with the fluid passing through the flow channel 12 is hydrophilic. In the portion that comes into contact with the fluid passing through the flow channel 12, both the flow channel 12 and the covering material 13 may be hydrophilic, only the flow channel 12 may be hydrophilic, or only the covering material 13 may be hydrophilic. Furthermore, the entire portion of the flow channel 12 and the covering material 13 that comes into contact with the fluid does not need to be hydrophilic, as long as the fluid can flow through the flow channel due to surface tension.

[0110] When the covering material 13 is made of a hydrophobic resin, the covering material 13 can be made of a resin selected from the group consisting of polycarbonate, cycloolefin copolymer, cycloolefin polymer, polymethylpentene, polystyrene, polymethyl(meth)acrylate, and polyethylene terephthalate. The resin that makes up the covering material 13 may be the same as or different from the resin that makes up the substrate 11.

[0111] When the covering material 13 is made of a hydrophilic resin, the covering material 13 can be made of, for example, a hydrophilic acrylic resin.

[0112] In addition, a hydrophilic portion may be provided by applying a hydrophilic coating to the coating material 13 made of a hydrophobic resin, or the coating material 13 made of a hydrophobic resin may be subjected to a hydrophilization treatment such as plasma treatment.

[0113] The thickness of the covering material 13 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 flow channel 12 can be easily sealed. Furthermore, when the thickness is 2 mm or less, good conformability to the irregularities of the substrate 11 can be easily obtained.

[0114] The substrate 11 and the covering material 13 are laminated so that the surface of the substrate 11 on which the flow channel 12 is formed is in contact with one surface of the covering material 13. The covering material 13 is bonded to the substrate 11 so as to cover the flow channel 12. The bonding between the substrate 11 and the covering material 13 may be performed by providing an adhesive layer on the covering material 13 side to serve as a bonding layer with the substrate 11, or by separately bonding the substrate 11 and the covering material 13 with an adhesive or the like, or by compressing the substrate 11 and the covering material 13 by thermocompression bonding. In this way, a flow channel is formed between the substrate 11 and the covering material 13.

[0115] [Detection Unit] The detection unit 20 is capable of detecting the sample flowing out from the timing unit 10 and is inserted directly into the outlet 15 provided on the substrate 11 for use. As the sample liquid passes through the timing unit 10, a reaction such as a nucleic acid amplification reaction progresses in the sample in the sample liquid. After a predetermined reaction time, the sample flows into the detection unit 20, and the post-reaction sample (target substance) is automatically detected in the detection unit 20. The detection unit 20 can be a detection unit from 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 20 uses chromatography paper with a conjugate pad, the addition of a developing solution is unnecessary and the sample liquid is absorbed, making it easy to prevent the sample liquid from flowing out of the detection unit 20.

[0116] In this embodiment, at least a portion of the cross section of the outlet 15 in the outflow direction of the sample liquid, which contacts the detection unit 20, is made hydrophilic. The hydrophilic coating material 13 that covers the flow channel 12 (12A, 12B) may be extended to the lower surface portion of the outlet 15, or the portion of the substrate 11 at the outlet 15 may be subjected to the hydrophilization treatment described above. In the former case, it is also preferable to cover the entire lower surface of the substrate 11 with the hydrophilic coating material 13.

[0117] <Testing Method Using Testing Device 1> Next, a testing method using the testing device 1 will be described. First, a sample liquid is introduced into the timing unit 10. The sample liquid is, for example, a sample such as saliva or a nasopharyngeal swab collected from a human or animal mixed with a reaction reagent such as a nucleic acid amplification reagent. After being introduced into the sample liquid inlet 14, the sample liquid flows out of the outlet after a predetermined time (e.g., a preset time such as 20 minutes) has elapsed and automatically flows into the detection unit 20, where the sample (target substance) is detected. The test result is confirmed by whether or not both detection lines C and T appear in the detection unit 20, as shown in FIG. 5 . The appearance of both detection lines C and T in the detection unit 20 indicates a positive result, while the appearance of only detection line C indicates a negative result.

[0118] According to the testing device 1, the sample liquid introduced into the timing unit 10 passes through the timing unit 10 over a predetermined time and is automatically introduced into the detection unit 20, thereby suppressing variations in test results due to variations in reaction time. Therefore, it is possible to improve the test accuracy while maintaining a test kit that allows for simple and quick detection.

[0119] 2. Second Embodiment Next, an inspection device 2 according to a second embodiment of the present invention will be described with reference to FIGS.

[0120] <<Testing Device 2>> Testing device 2 differs from testing device 1 in that the fluid receiving portion into which the fluid is introduced and the sample receiving portion into which the sample is introduced are provided separately in different locations on the substrate. Testing device 2 is useful when the viscosity of the sample liquid varies particularly greatly, and the fluid for which the predetermined time is measured in timing unit 30 and the sample liquid to be reacted in the reaction tank are separately located. Note that components that have the same functions as those in the previous embodiment and do not differ significantly in shape are assigned the same reference numerals.

[0121] 6, the timing unit 30 in the testing device 2 is located upstream of the outlet 35 and includes a fluid inlet 31 which is a fluid receiving unit, and a specimen inlet 32 ​​which is a specimen receiving unit which is located downstream of the fluid inlet 31 and is fluidly connected to the outlet 35. The specimen inlet 32 ​​is provided at a destination G in the timing unit 30 where a predetermined time is measured.

[0122] 7, in this embodiment, the specimen inlet 32 ​​is provided at a position on the substrate 11 that directly communicates with the outlet 35, and the flow channel 12, specimen inlet 32, and outlet 35 intersect at one location. In the testing device 2, this intersection (connection portion X) is the destination point G of the fluid. In addition, in the testing device 2, the outlet 35 refers to the portion downstream from the connection portion X.

[0123] The specimen inlet 32 ​​includes a specimen reaction chamber 33 in which a specimen reaction (e.g., a nucleic acid amplification reaction) proceeds, and a communication groove 34 that connects the specimen reaction chamber 33 to the flow channel 12B. Similar to the fluid inlet 31, the specimen reaction chamber 33 is formed as a through-hole in the substrate 11, and a hydrophilic coating material 13 extending from the underside of the flow channel 12 is located on its underside. The specimen reaction chamber 33 is maintained at a constant temperature (e.g., a predetermined temperature between 25 and 65°C) to allow the reaction to occur at a constant temperature. The specimen reaction chamber 33 can be maintained or heated by placing the entire testing device 2 in a thermostatic bath or room, or by placing a heater or other heating device in contact with only the underside of the specimen reaction chamber 33.

[0124] The testing device 2 is configured so that, when pre-reacted specimen liquid 18 containing a reaction reagent and a specimen is introduced into specimen reaction chamber 33 and fluid 19 is introduced into fluid inlet 31, after a period of time, for example, several minutes or more, the reacted specimen liquid 18 flows out of outlet 35 on its own, as shown in FIG. 12 , and the specimen (target substance) in specimen liquid 18 is detected by detection unit 20. That is, the timing unit 30 according to this embodiment has a timing function for measuring a predetermined reaction time for the specimen introduced into specimen reaction chamber 33 to react with the reaction reagent, and also has a fluid control function for automatically causing the reacted specimen to flow out when the pre-reacted specimen is introduced. The configuration of the timing unit 30 with the fluid control function will be described below.

[0125] 8 , the timing unit 30 with fluid control function includes a first flow path 120 having a flow path groove 12 and a coating material 13 (referred to as a first coating material 13 in this embodiment) covering the flow path groove 12, a second flow path 130 having a communication groove 34 and a second coating material 132 covering the communication groove 34, and an outlet 35 fluidly communicating with a connection portion X between the first flow path 120 and the second flow path 130. In detail, the second flow path 130 according to this embodiment includes a communication groove 34 formed to open on the surface of the substrate 11 opposite the flow path groove 12 (the upper surface in FIG. 9 ), and a second coating material 132 covering the communication groove 34. The timing unit 30 with fluid control function releases the sample liquid 18 introduced and remaining in the second flow path 130 and the sample reaction reservoir 33 by the action of the fluid 19 introduced into the first flow path 120, causing the sample liquid 18 to flow out of the outlet 35. In other words, the timing unit 30 having a fluid control function has a function of a passive valve that opens the second flow path 130 when acted upon by the fluid 19 .

[0126] In this embodiment, the flow channel 12 (12A, 12B) constituting the first flow channel 120 also has five parallel straight line sections and four arc-shaped curved line sections connecting the five straight line sections. With this configuration, the fluid 19 introduced into the fluid inlet 31 makes four U-turns on the substrate 11 and reaches the connection part X over a predetermined time period ranging from several minutes to several tens of minutes (e.g., 5 to 60 minutes). In this way, the first flow channel 120 of this embodiment is a timing flow channel capable of measuring a predetermined time, and the flow channel 12 (12A, 12B) constituting this timing flow channel has the same configuration as the flow channel 12 in the timing unit 10.

[0127] In this embodiment, the substrate 11 is formed from a hydrophobic resin, and the surfaces (side surface 12D and top surface 12E) of the flow channel 12 in the first flow channel 120 are hydrophobic (first property). Note that, when the testing device 2 is in use, the bottom surface of the flow channel 12 is positioned above and facing downward on the substrate 11, forming the top surface, as shown in FIG. 9 , and is therefore referred to as the top surface 12E in the following description. The resin component constituting the substrate 11 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 11 is preferably one that has either heat resistance or transparency, or both.

[0128] The surface of the first covering material 13 covering the flow channel 12 is hydrophilic (second property). The first covering material 13 may be hydrophilic at least on the surface facing the flow channel 12. In this embodiment, a hydrophilic resin film, such as a hydrophilic acrylic resin, is used. The resin constituting the first covering material 13 is preferably one that has either heat resistance or transparency, or both. A hydrophilic portion may be formed 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 13 covers the entire back surface (lower surface in FIG. 9 ) of the substrate 11, including the flow channel 12. The thickness of the first covering material 13 and the method of bonding the first covering material 13 to the substrate 11 are the same as those in the above-described embodiment.

[0129] In this embodiment, the communication groove 34 is a linear groove that is shallower and shorter than the flow path groove 12B. Specifically, the length of the communication groove 34 is set so that the length of the first flow path 120 from the outlet of the fluid inlet 31 to the connection portion X (referred to as flow path length M1, not shown) is longer than the length of the second flow path 130 from the outlet of the sample reaction tank 33 to the connection portion X (referred to as flow path length M2) ( FIG. 8 ). In this embodiment, the flow path length M1 is set sufficiently long, for example, 10 times or more longer than the flow path length M2.

[0130] The width and depth of the communication groove 34 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.

[0131] Since the communication groove 34 is formed on the same substrate 11 as the flow channel 12, the surfaces (side surface 34D and bottom surface 34E) of the communication groove 34 are hydrophobic (first property). In this embodiment, the second covering material 132 uses the same hydrophilic resin film as the first covering material 13, and the surface 132A of the second covering material 132 is hydrophilic (second property).

[0132] 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 31. Because the specimen liquid 18 and the fluid 19 are both hydrophilic liquids, the fluid 19 is repelled by the surface of the flow channel 12 in the first flow channel 120 and exhibits the property of wetting and spreading on the surface of the first coating material 13. Similarly, the specimen liquid 18 is repelled by the surface of the flow channel 12 and the surface of the communicating groove 34 in the second flow channel 130 and exhibits the property of wetting and spreading on the surfaces of the first coating material 13 and the second coating material 132.

[0133] Therefore, when fluid 19 is introduced into first flow path 120 from fluid inlet 31, fluid 19 flows along the hydrophilic surface of first covering material 13 and into first flow path 120. Similarly, when specimen liquid 18 is introduced into second flow path 130 from specimen reaction reservoir 33, specimen liquid 18 flows along surface 132A of second covering material 132, which is hydrophilic, and into second flow path 130.

[0134] The first covering material 13 and the second covering material 132 may be different in material, thickness, etc., as long as their surfaces are hydrophilic. Furthermore, the method for bonding the substrate 11 and the second covering material 132 may be different from the method for bonding the substrate 11 and the first covering material 13. In this embodiment, since the area of ​​the second covering material 132 is smaller than the area of ​​the first covering material 13, the first covering material 13 may be bonded by thermocompression bonding, and the second covering material 132 may be bonded by an adhesive layer or a bonding layer.

[0135] 9 , the first flow path 120 and the second flow path 130 are fluidly connected to each other by a portion of their flow path grooves (flow path groove 12B, communication groove 34) intersecting at a connection portion X. In this embodiment, the first flow path 120 intersects with the second flow path 130 at a substantially right angle on the downstream side of the fifth straight section of the first flow path 120.

[0136] In this embodiment, the thickness of the substrate 11 is approximately 0.7 mm. The depth D2 of the flow path groove 12B is approximately 0.6 mm, and the depth D3 of the communication groove 34 is approximately 0.15 mm, so that the first flow path 120 and the second flow path 130 overlap by approximately 0.05 mm in the depth direction. With this configuration, a through hole is formed in the substrate 11 at the connection portion X, and the first coating material 13 and the second coating material 132 are located on both sides of the through hole.

[0137] The second coating material 132 is disposed at least at a portion covering the communication groove 34 of the second flow channel 130 on the surface of the substrate 11 opposite to the first coating material 13. In this embodiment, the second coating material 132 is disposed so as to overlap the connection portion X in a plan view of the substrate 11. The second coating material 132 may extend so as to protrude from the communication groove 34 toward the specimen reaction chamber 33.

[0138] Fluid inlet 31 is a through-hole formed in substrate 11, and although there are no limitations on its shape or size as long as it can introduce fluid 19 into first flow channel 120, in this embodiment it is a circular hole with a diameter of 2 to 5 mm (for example, a diameter of 4 mm). The top of fluid inlet 31 is open, and the bottom is covered with first covering material 13 extending from first flow channel 120.

[0139] Like the fluid inlet 31, the specimen reaction vessel 33 is a through-hole formed in the substrate 11. The shape and size of the specimen reaction vessel 33 are not limited as long as it allows specimen liquid 18 to be introduced into the second flow channel 130; however, in this embodiment, the specimen reaction vessel 33 is a circular hole having a diameter of 2 to 5 mm (e.g., 4 mm). The specimen reaction vessel 33 also has an open top and a covered bottom with a first coating material 13. In this embodiment, a specimen and a reaction reagent are introduced into the specimen reaction vessel 33, and the specimen reaction vessel 33 is used as a reaction vessel for promoting a specimen reaction (e.g., a nucleic acid amplification reaction). Therefore, as described above, the specimen reaction vessel 33 is maintained at a constant temperature (e.g., a predetermined temperature between 25 and 65°C) to allow the reaction to occur at a constant temperature. The specimen reaction vessel 33 may be maintained or heated by placing the entire testing device 2 in a thermostatic bath or room, or by placing a heating device such as a heater in contact with the underside of the specimen reaction vessel 33.

[0140] As described above, the outlet 35 indicates the region downstream from the connection portion X, and includes a downstream portion including the end of the first flow path 120, and a notch 35A that is in fluid communication with the end of the first flow path 120. The notch 35A opens on one side of the substrate 11, penetrates the substrate 11 in the thickness direction, and is fitted with the detection unit 20. The sidewall of the notch 35A is hydrophobic, similar to the substrate 11. The open lower surface of the notch 35A is covered with a hydrophilic first coating material 13 that extends from the first flow path 120.

[0141] 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 properties are not particularly limited. In this embodiment, the surface of the substrate 11, 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 11 with water is preferably 70° or more, and more preferably 80° or more. The upper limit of the contact angle of the substrate 11 with water is preferably 95° or less, and more preferably 90° or less. Furthermore, the surfaces of the first coating material 13 and the second coating material 132, 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 13 and the second coating material 132 is preferably 20° or less, and more preferably 10° or less. In this embodiment, the contact angle with water is a value measured at 25°C using a commercially available contact angle meter.

[0142] In this embodiment, the first flow path 120 is configured to have a higher conduit resistance than the second flow path 130. The conduit resistance of a flow path is determined by various conditions, and generally, the conduit resistance of the first flow path 120 is higher than that of the second flow path 130 when the first flow path 120 is longer, has a higher coefficient of friction, is narrower, or has a higher flow rate than the second flow path 130. In this embodiment, as described above, the flow path length M1 from the fluid inlet 31 to the connection portion X is sufficiently longer than the flow path length M2 from the sample reaction reservoir 33 to the connection portion X, and the conduit resistance of the first flow path 120 is higher than the conduit resistance of the second flow path 130.

[0143] In the timing unit 30 having a fluid control function according to this embodiment, the time required for at least the specimen liquid 18 to flow out of the outlet 35 after the fluid 19 is introduced into the fluid inlet 31 and the specimen liquid 18 is introduced into the specimen reaction tank 33 is configured to be within an allowable error of, for example, ±5% of the specified time.

[0144] <Testing Method Using Testing Apparatus 2> Next, a testing method using testing apparatus 2 will be described. Sample liquid 18 and fluid 19 are prepared in advance. In testing apparatus 2, sample liquid 18 is introduced into sample reaction reservoir 33 of sample inlet 32 ​​at the same time as fluid is introduced into fluid inlet 31. Sample liquid 18 is obtained by mixing a sample, such as saliva or a nasopharyngeal swab collected from a human or animal, with a reaction reagent, such as a nucleic acid amplification reagent. Introduction of fluid 19 into fluid inlet 31 and introduction of sample liquid 18 into sample reaction reservoir 33 are preferably simultaneous, but may be slightly out of sequence, and the order of introduction is not particularly limited.

[0145] A liquid with stable physical properties and small viscosity variation, such as water or a buffer solution, is introduced into the fluid inlet 31 as the fluid 19. The fluid 19 introduced into the fluid inlet 31 passes through the first flow path 120, and a predetermined time is measured. In this embodiment, the use of a timing fluid 19 facilitates further improvement in the accuracy of time measurement by the timing unit 30. It is preferable that the fluid 19 introduced into the fluid inlet 31 is one that has been confirmed in advance to have a time required to reach the connection portion X within an allowable error of ±5% of the predetermined time. The fluid 19 also functions as a fluid control fluid for causing the sample liquid 18 remaining in the second flow path 130 and the sample reaction chamber 33 to flow out to the outlet 35. Both the sample liquid 18 and the fluid 19 are hydrophilic.

[0146] While the fluid 19 is being measured for a predetermined time, a reaction (such as a nucleic acid amplification reaction) of the specimen in the specimen liquid 18 progresses in the specimen reaction chamber 33. If necessary, the entire testing device 2 or the specimen reaction chamber 33 is heated to, for example, 25 to 65°C. A portion of the specimen liquid 18 in which the reaction has progressed in the specimen reaction chamber 33 fills the second flow path 130 and extends from the second flow path 130 toward the connection portion X due to surface tension.

[0147] In this state, when the fluid 19 to be measured arrives at the connection part X, the sample liquid 18 that has come into contact with the fluid 19 flows out from the outlet 35 in priority to the fluid 19 that has passed through the timing unit 30. In this way, in the testing device 2 as well, the sample liquid 18 containing the sample flows out from the outlet 35 after a predetermined time, and the sample that has flowed out from the outlet 35 is detected by the detection unit 20.

[0148] Next, the testing method using the testing device 2 will be described in more detail in relation to the function and action of the timing unit 30 having a fluid control function in the testing device 2.

[0149] First, fluid 19 is introduced into fluid inlet 31, and then specimen liquid 18 is introduced into specimen reaction chamber 33. Then, as shown in FIGS. 10 and 11 , the surface 132A of second coating material 132 in second flow path 130 acts as a guide, causing a portion of specimen liquid 18 to flow out of specimen reaction chamber 33, fill second flow path 130, and be guided further to connection portion X. The specimen liquid 18 then forms droplet 18A at connection portion X. In this embodiment, droplet 18A wets and spreads on surface 132A of second coating material 132 above connection portion X, and is held on surface 132A of second coating material 132 in a state in which it hangs downward due to surface tension and gravity. At this time, droplet 18A does not come into contact with first coating material 13. Even if droplet 18A comes into contact with side surface 12D and top surface 12E of flow channel 12, or side surface 34D and bottom surface 34E of communication channel 34, these surfaces are all hydrophobic, so droplet 18A does not wet and spread, and instead becomes a rounded droplet due to surface tension. This configuration can prevent sample liquid 18 from flowing out of outlet 40 before droplet 18A comes into contact with fluid 19.

[0150] On the other hand, when fluid 19 is introduced into fluid inlet 31, it starts from starting point S and flows through first flow path 120 (120A, 120B) 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 120 according to this embodiment has a timing function, and can regulate the predetermined time by the time required for passing through first flow path 120, and the reaction between the specimen in specimen liquid 18 and the reaction reagent proceeds during this predetermined time.

[0151] Next, the fluid 19 that has passed through the first flow path 120 over a predetermined time reaches the connection portion X and comes into contact with the droplet 18A. Then, as shown in FIG. 12 , at least the specimen liquid 18 flows out from the outlet 35. In this manner, the fluid 19 that has passed through the first flow path 120 acts to cause the specimen liquid 18 that has remained in the second flow path 130 and the specimen reaction chamber 33 to flow out from the outlet 35. The fluid 19 that has passed through the long first flow path 120 (120A, 120B) loses pressure (propulsion force) due to friction with the wall surfaces within the flow path before reaching the connection portion X. Therefore, at the connection portion X, the outflow of the specimen liquid 18 from the second flow path 130 takes priority over the outflow of the fluid 19 from the first flow path 120. The timing unit 30 with a fluid control function can also be called a "surface tension valve" that utilizes surface tension, because at the connection part X where two flow paths are connected, a 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.

[0152] According to the timing unit 30 with fluid control function of this embodiment, the sample liquid 18 in the second flow path 130 can be released to the outlet 35 by the action of the fluid 19 introduced into the first flow path 120 formed in the same substrate 11, without requiring any external operation to open the second flow path 130. Furthermore, in the timing unit 30 with fluid control function of this embodiment, the second coating material 132 at least partially overlaps the connection portion X in a plan view of the substrate 11, so that the surface 132A of the second coating material 132 can guide the sample liquid 18 to the connection portion X. That is, in the timing unit 30 with fluid control function, the surface 132A of the second coating material 132 in the second flow path 130 serves as a guide that guides the sample liquid 18 to the connection portion X.

[0153] In the present embodiment, the timing unit 30 with fluid control function is configured such that the flow path length M1 of the first flow path 120 from the fluid inlet 31 to the connection portion X is greater than the flow path length M2 of the second flow path 130 from the sample reaction chamber 33 to the connection portion X, and the first flow path 120 has a greater conduit resistance than the second flow path 130. Therefore, when the fluid 19 passing through the first flow path 120 contacts the droplet 18A of the sample liquid 18 formed at the connection portion X, the reacted sample liquid 18 spontaneously flows out of the outlet 35 and into the detection unit 20. The lower opening of the notch 35A of the outlet 35 is covered with the first coating material 13 having a hydrophilic surface and extending from the first flow path 120, so that the hydrophilic sample liquid 18 can be quickly introduced into the chromatography paper with a conjugate pad in the detection unit 20. Through the above-described steps, the detection unit 20 can detect the sample (target substance).

[0154] In the timing unit 30 having a fluid control function of the testing device 2, the specimen liquid 18 flows out of the outlet automatically when the fluid 19 reaches the connection part X. In this way, the timing unit 30 having a fluid control function opens the second flow path 130 in response to the action of the fluid 19 and releases the specimen liquid 18, without requiring external control to open the second flow path 130.

[0155] Furthermore, in the timing unit 30 having a fluid control function according to this embodiment, the fluid 19 introduced into the fluid inlet 31 passes through the first flow path 120 over a predetermined time, and the first flow path 120 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 test results due to variations in reaction time, and improve test accuracy while providing a test kit in the form of one that is easy to use and enables detection in a short time.

[0156] Other embodiments of the timing device, timing method, and first inspection device according to the present invention will be described below. In the above embodiments, examples have been described in which the timing device and timing method are applied to the timing unit 10 of the inspection devices 1 and 2. However, the present invention is not limited to such a configuration, and the timing device and timing method may also be used as a timer device for measuring a predetermined time.

[0157] In the above embodiment, an example has been described in which the flow channel 12 includes the first section L1 and the second section L2 in this order from the starting point. However, the present invention is not limited to such a configuration, and the second section L2 may be provided before the first section L1, or the second section L2 may be sandwiched between first sections L1, or the first section L1 may be sandwiched between second sections L2, etc.

[0158] In the above embodiment, an example has been described in which the first section L1 is longer than the second section L2. However, the present invention is not limited to such a configuration, and the second section may be longer than the first section L1.

[0159] In the above embodiment, an example was described in which the second section L2 has the same width as the first section L1. However, this is not limited to such a configuration, and the width of the second section L2 may be larger than the width of the first section L1. For example, the width of the second section L2 may be two to four times the width of the first section L1.

[0160] In the above embodiment, the testing device 1 is described as being used as a test kit for testing infectious diseases caused by viruses, bacteria, etc. However, the testing device 1 is not limited to such a configuration and may be used for tests other than those described above.

[0161] In the above embodiment, the testing device 1 is described as being configured such that the side where the sample liquid inlet 14 and outlet 15 (the front side in FIG. 1 ) are located on the upper side, and the side where the coating material 13 is laminated (the rear side in FIG. 1 ) is located on the lower side. However, the arrangement of the timing device and testing device according to the present invention is not limited to this arrangement. For example, the substrate 11 may be tilted at a predetermined angle from the horizontal direction, or may be installed vertically. For example, the longitudinal direction of the substrate 11 may be vertically oriented so that the sample liquid inlet 14 is located at the upper position and the outlet 15 is located at the lower position.

[0162] Similarly, the testing device 2 according to the other embodiment described above has been described as being configured with the side where the fluid inlet 31, the sample inlet 32 ​​(sample reaction chamber 33), and the outlet 15 (the front side in FIG. 6 ) are located on the upper side, and the side where the coating material 13 is laminated (the rear side in FIG. 1 ) on the lower side. However, the arrangement of the timing device and testing device according to the present invention is not limited to this. For example, the substrate 11 may be tilted at a predetermined angle from the horizontal, or may be installed vertically. For example, the longitudinal direction of the substrate 11 may be vertical, with the fluid inlet 31 located at the upper position and the outlet 15 located at the lower position. In this case, a pocket-shaped member with an upward opening may be attached to the opening side of the sample reaction chamber 33 to increase the volume of the sample liquid 18. Alternatively, a fluid other than the sample liquid 18 may be stored in the sample reaction chamber 33.

[0163] The timing unit 10 (timing device) of the inspection device 1 of this embodiment will be described in more detail below with reference to test examples. However, the scope of the present invention is not limited to the following test examples.

[0164] Test Example 1 (Preparation of a Timer) A 30 mm x 70 mm x 1 mm thick resin substrate made of cycloolefin polymer (COP) (ZEONOR (registered trademark) 1060R manufactured by Zeon Corporation) was cut to form a flow channel 12 shaped as shown in FIG. 13 , and 3 mm diameter through-holes serving as fluid inlets 14 (starting point S) and outlets 15 (end point G) at both ends of the flow channel 12. The length L3 of each flow channel 12 was 50 mm, and five flow channel 12 having the same width and depth were prepared on one substrate 11. Then, the surface of the substrate 11 on which the flow channel 12 was formed was subjected to a 10-minute plasma treatment (hydrophilization treatment). Next, the adhesive layer side of a PSA film (using an acrylic adhesive, 125 μm base layer, 7.5 μm adhesive layer) of the same size as the substrate was attached to the substrate so as to cover the flow channel, bonding the substrate and the PSA film to prepare a timer.

[0165] As shown in Table 1, Samples 1-1 to 1-8 were produced with different widths and depths of the flow channel grooves.

[0166] (Timing method) For each of the five flow channels, 15 μl of +40% sucrose buffer solution (50 mM Tris-HCl pH 8.0, 100 mM potassium acetate, 5 w / v % PEG-20000, 2 mM dithiothreitol, 40 w / v % sucrose) was introduced as a fluid into the inlet 14, which served as the starting point S, using a pipette, and at the same time, measurement was started with a stopwatch. When it was visually confirmed that the fluid had reached the end point G, the stopwatch was stopped and the time taken for the fluid to reach the end point G was measured.

[0167] The measurement times (seconds) along with the sizes of the flow channel grooves of Samples 1-1 to 1-8 are shown in Table 1. The standard deviation was calculated for the measurement times of the five samples.

[0168]

[0169] As shown in Table 1, samples 1-3, 1-4, 1-7, and 1-8, which have flow grooves with a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm, had a smaller standard deviation of the time it took for the liquid to flow through the first to fifth flow grooves, and the variation in the required time was smaller than that of the other samples.

[0170] Test Example 2 Samples 2-1 to 2-4 were prepared by varying the width of the flow channel as shown in Table 2 when the depth of the flow channel was set to 100 μm. As in Test Example 1, for each of the five flow channel grooves, 15 μl of +40% sucrose buffer solution (50 mM Tris-HCl pH 8.0, 100 mM potassium acetate, 5 w / v % PEG-20000, 2 mM dithiothreitol, 40 w / v % sucrose) was introduced as a fluid into the inlet 14, which served as the starting point S, using a pipette. At the same time, a stopwatch was started to measure the time (seconds) until the fluid reached the end point G. The results are shown in Table 2.

[0171]

[0172] As shown in Table 2, samples 2-3 and 2-4, in which the flow channel width was within the range of 0.8 to 2.0 mm and the depth was within the range of 70 to 100 μm, had a smaller standard deviation of the time it took for the fluid to flow through the first to fifth flow channel grooves, and the flow rate variation was smaller, compared to samples 2-1 and 2-2, which were outside the range.

[0173] Test Example 3 A timing device was fabricated in the same manner as in Test Example 1, except that the flow channel of the resin substrate was not subjected to plasma treatment and a hydrophilic film (using a hydrophilic acrylic adhesive) was used instead of the PSA film. That is, Test Example 3 differs from Test Example 1 in that the flow channel was hydrophobic and the covering material was hydrophilic.

[0174] Samples 3-1 to 3-4 were prepared with a channel width of 1.0 mm and depths varied as shown in Table 3. As in Test Example 1, for each of the five channel grooves, 15 μl of +40% sucrose buffer solution (50 mM Tris-HCl pH 8.0, 100 mM potassium acetate, 5 w / v% PEG-20000, 2 mM dithiothreitol, 40 w / v% sucrose) (viscosity at 25°C measured with a TV-100E viscometer: 9.382 mPa s) was introduced as a fluid into the inlet, which served as the starting point S, using a pipette. At the same time, a stopwatch was started to measure the time it took for the fluid to reach the end point G. The measured time (seconds) is shown in Table 3. The standard deviation was also calculated for the five measurement times.

[0175]

[0176] As shown in Table 3, samples 3-3 and 3-4, which had flow grooves with widths of 0.8 to 2.0 mm and depths of 70 to 100 μm, had smaller standard deviations in the time it took for the fluid to flow through the first to fifth flow grooves, and smaller variations in the required time, compared to samples 3-1 and 3-2. This indicates that even when the hydrophilic portions that come into contact with the fluid passing through the flow grooves are different, variations in the flow rate are small when the flow grooves are with widths of 0.8 to 2.0 mm and depths of 70 to 100 μm.

[0177] [Test Example 4] In the timing device of Test Example 3, the fluid introduced into the inlet serving as the starting point S was a sucrose buffer solution (50 mM Tris-HCl pH 8.0, 100 mM potassium acetate, 5 w / v% PEG-20000, 2 mM dithiothreitol) (viscosity at 25°C measured with a TV-100E viscometer: 4.510 mPa·s) for samples 4-1 to 4-4, and a 40% sucrose buffer solution (50 mM Tris-HCl pH 8.0, 100 mM potassium acetate, 5 w / v% PEG-20000, 2 mM dithiothreitol, 40 w / v% The time taken for the fluid to reach the end point G was measured using sucrose (viscosity at 25°C measured with a TV-100E viscometer: 9.382 mPa s). The measured times (seconds) for Samples 4-1 to 4-8 are shown in Table 4. The standard deviation was also calculated for the five measurement times.

[0178]

[0179] As shown in Table 4, even when the viscosity of the fluid changed, Samples 4-3, 4-4, 4-7, and 4-8, which had flow channel grooves with widths of 0.8 to 2.0 mm and depths of 70 to 100 μm, showed small variations in flow velocity.

[0180] [Test Example 5] In the timing device of Test Example 3, as shown in FIG. 14 , of the 50 mm long flow channel, section L4, which was 40 mm long from the starting point S, was a section (first section) with a flow channel width of 1.0 mm and a depth of 100 μm, and section L5 (second section) of the remaining 10 mm to the end point G had a depth changed as shown in Table 5. Between sections L4 and L5, an inclined surface with an angle θ of 100°, as shown in FIG. 4, was used. In Test Example 5, three flow channel grooves were created for each sample, and for each, 15 μl of Milli-Q (registered trademark) purified water was introduced as a fluid into the inlet 14, which was the starting point S, using a pipette. At the same time, a stopwatch was started to measure the time it took for the fluid to reach the end point G. The measured time (seconds) is shown in Table 5. The standard deviation was also calculated for the three measurement times.

[0181]

[0182] As shown in Table 5, Samples 5-2 to 5-6, which had a second section deeper than the first section, all had small variations in measurement time and were able to slow the flow rate. In particular, Samples 5-4 to 5-6, which had a second section four times deeper than the first section, were able to measure times more than twice as long as Sample 5-1, which had essentially only the first section. In particular, Sample 5-6, which had a second section six times deeper than the first section, measured times about four times longer.

[0183] Although the embodiments of the timing device, timing method, and first testing device have been described in detail above using test examples that are specific examples, the scope of the present invention is not limited to the specific embodiments described above. The embodiments disclosed in this specification are illustrative in all respects and can be modified as appropriate within the scope of the present invention.

[0184] The timing device of the present invention can be used as a timer for measuring a predetermined time, and also as a timing unit of a testing device in various test kits.

[0185] 3. Third Embodiment An inspection device 201 and a fluid control unit 211 in the inspection device 201 according to a third embodiment of the present invention will be described with reference to Figures 15 to 23. The third to seventh embodiments described below are examples of a second inspection device and a first fluid control device according to the present invention.

[0186] <<Overview of Testing Device 201>> Testing device 201 according to this embodiment is used as a test kit for testing for infectious diseases caused by, for example, viruses, bacteria, etc., and includes a fluid control unit 211 and a detection unit 250 capable of detecting sample liquid flowing out from fluid control unit 211, as shown in FIG. 15 . Testing device 201 is configured such that sample liquid 218 containing a reaction reagent and a sample is introduced into sample inlet 233, and fluid 219 is introduced into fluid inlet 223. After a period of time, for example, several minutes or more, reacted sample liquid 218 flows out of outlet 240, as shown in FIG. 20 , and the sample (target substance) in sample liquid 218 is detected by detection unit 250. In the third to seventh embodiments, the terms "sample" and "sample liquid" are used regardless of whether the reaction occurs before or after the reaction or regardless of the degree of progress of the reaction.

[0187] 15 , fluid control unit 211 (an example of a first fluid control device) includes first flow path 220, second flow path 230, and outlet 240 fluidically connected to connection portion X between first flow path 220 and second flow path 230. Fluid control unit 211 releases sample liquid 218 (an example of a second fluid and a sample) introduced into and remaining in second flow path 230 and sample inlet 233 by the action of fluid 219 (an example of a first fluid) introduced into first flow path 220, causing the sample liquid to flow out of outlet 240. In other words, fluid control unit 211 functions as a passive valve that opens second flow path 230 in response to the action of fluid 219.

[0188] The fluid control unit 211 includes a fluid inlet 223 (an example of a first fluid inlet) that is fluidly connected to the upstream of the first flow path 220 and through which the fluid 219 is introduced, and a sample inlet 233 (an example of a second fluid inlet) that is fluidly connected to the upstream of the second flow path 230 and through which the sample liquid 218 is introduced. As shown in Figure 15, the fluid inlet 223 and the sample inlet 233 are provided at separate locations on the substrate 210. In this embodiment, a connection portion X between the first flow path 220 and the second flow path 230 is located downstream of the first flow path 220 and the second flow path 230.

[0189] Next, each component of the fluid control unit 211 will be described in detail.

[0190] As shown in Figure 17, the first flow path 220 has a first flow path groove 221 formed to open on one surface (the lower surface in Figure 17) of the substrate 210, and a first coating material 222 covering the first flow path groove 221.

[0191] In this embodiment, as shown in FIG. 15 , the first flow channel 221 (221A, 221B) extends in a serpentine manner on the substrate 210 in the length direction (flow direction). Specifically, the first flow channel 221 (221A, 221B) has five parallel straight sections and four arc-shaped curved sections connecting the five straight sections. This configuration allows the fluid 219 introduced into the fluid inlet 223 to make four U-turns on the substrate 210 and reach the connection point X over a predetermined time, ranging from several minutes to several tens of minutes (e.g., 5 to 60 minutes). Thus, the first flow channel 220 of this embodiment is a timing flow channel capable of measuring a predetermined time. Details of the first flow channel 221 (221A, 221B) that constitutes this timing flow channel will be described later. The first flow channel 221 is set to have a width of 0.8 to 2.0 mm and a depth of 0.02 to 1 mm, for example.

[0192] In this embodiment, a substrate 210 made of a hydrophobic resin is used, and the surfaces (side surface 221D and top surface 221E) of the first flow channel 221 in the first flow channel 220 are hydrophobic (first property). Note that the bottom surface of the first flow channel 221 is positioned above and facing downward on the substrate 210 when the testing device 201 is in use, as shown in FIG. 17 , forming the top surface. Therefore, in the following description, this will be referred to as the top surface 221E. While the resin component constituting the substrate 210 is not particularly limited, in this embodiment, the resin 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 210 is preferably one that has either heat resistance or transparency, or both.

[0193] The surface of the first coating material 222 covering the first flow channel 221 is hydrophilic (second property). The first coating material 222 may be hydrophilic at least on the surface facing the first flow channel 221. In this embodiment, a hydrophilic resin film, such as a hydrophilic acrylic resin, is used. The resin constituting the first coating material 222 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 coating material made of a hydrophobic resin, or the surface may be made hydrophilic by subjecting the coating material made of a hydrophobic resin to a hydrophilic treatment, such as plasma treatment. In this embodiment, the first coating material 222 covers the entire back surface (lower surface in FIG. 3 ) of the substrate 210, including the first flow channel 221.

[0194] The thickness of the first covering material 222 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 221 can be easily sealed. Furthermore, when the thickness is 2 mm or less, good conformability to the irregularities of the substrate 210 can be easily obtained.

[0195] The first covering material 222 and the substrate 210 may be bonded by providing an adhesive layer on the first covering material 222 side to serve as a bonding layer with the substrate 210, or by bonding the substrate 210 and the covering material with an adhesive or the like, or by compressing the substrate 210 and the first covering material 222 together using thermocompression bonding.

[0196] The second flow path 230 in this embodiment has a second flow path groove 231 formed to open to the surface of the substrate 210 opposite the first flow path groove 221 (the upper surface in Figure 17), and a second coating material 232 covering the second flow path groove 231.

[0197] In this embodiment, second flow channel 231 is a linear groove that is shallower and shorter than first flow channel 221B. Specifically, the length of second flow channel 231 is set so that the length of first flow channel 220 from the outlet of fluid inlet 223 to connection portion X (referred to as flow channel length M221, not shown) is longer than the length of second flow channel 230 from the outlet of sample inlet 233 to connection portion X (referred to as flow channel length M22) ( FIGS. 15 and 16 ). In this embodiment, flow channel length M221 is set sufficiently long, for example, 10 times or more longer than flow channel length M22.

[0198] The width and depth of the second flow channel 231 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.

[0199] The second flow channel 231 is formed on the same substrate 210 as the first flow channel 221, and therefore the surfaces (side surface 231D and bottom surface 231E) of the second flow channel 231 are hydrophobic (first property). In this embodiment, the second coating material 232 uses the same hydrophilic resin film as the first coating material 222, and the surface 232A of the second coating material 232 is hydrophilic (second property).

[0200] The specimen liquid 218 used in the testing device 201 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 219 introduced into the fluid inlet 223. As described above, since the specimen liquid 218 and the fluid 219 are both hydrophilic liquids, the fluid 219 is repelled by the surface of the first flow channel 221 in the first flow channel 220 and exhibits the property of wetting and spreading on the surface of the first coating material 222. Similarly, the specimen liquid 218 is repelled by the surface of the first flow channel 221 and the surface of the second flow channel 231 in the second flow channel 230 and exhibits the property of wetting and spreading on the surfaces of the first coating material 222 and the second coating material 232.

[0201] Therefore, when fluid 219 is introduced into first flow path 220 from fluid inlet 223, fluid 219 flows along the hydrophilic surface of first coating material 222 and into first flow path 220. Similarly, when specimen liquid 218 is introduced into second flow path 230 from specimen inlet 233, specimen liquid 218 flows along surface 232A of second coating material 232, which is hydrophilic, and into second flow path 230.

[0202] The first covering material 222 and the second covering material 232 may be different in material, thickness, etc., as long as their surfaces are hydrophilic. Furthermore, the method for bonding the substrate 210 and the second covering material 232 may be different from the method for bonding the substrate 210 and the first covering material 222. In this embodiment, since the area of ​​the second covering material 232 is smaller than the area of ​​the first covering material 222, the first covering material 222 may be bonded by thermocompression bonding, and the second covering material 232 may be bonded by an adhesive layer or a bonding layer.

[0203] 17 , the first flow path 220 and the second flow path 230 are fluidly connected to each other by a portion of the flow path grooves 221, 231 intersecting with each other at the connection portion X. In this embodiment, the first flow path 220 intersects with the second flow path 230 at a substantially right angle on the downstream side of the fifth straight section of the first flow path 220.

[0204] In this embodiment, the thickness of the substrate 210 is approximately 0.7 mm. The depth D22 of the first flow path groove 221B is approximately 0.6 mm, and the depth D23 of the second flow path groove 231 is approximately 0.15 mm, so that the first flow path 220 and the second flow path 230 overlap by approximately 0.05 mm in the depth direction. With this configuration, a through hole is formed in the substrate 210 at the connection portion X, and the first covering material 222 and the second covering material 232 are located on both sides of the through hole.

[0205] Second coating material 232 is disposed at least at a location covering second flow channel 231 of second flow channel 230 on the surface of substrate 210 opposite to first coating material 222. In this embodiment, second coating material 232 is disposed so as to overlap connection portion X in a plan view of substrate 210. Second coating material 232 may extend so as to protrude from second flow channel 231 toward sample inlet 233.

[0206] Fluid inlet 223 is a through-hole formed in substrate 210, and although there are no limitations on its shape or size as long as it can introduce fluid 219 into first flow channel 220, in this embodiment it is a circular hole with a diameter of 2 to 5 mm (for example, a diameter of 4 mm). The top of fluid inlet 223 is open, and the bottom is covered with first covering material 222 extending from first flow channel 220.

[0207] Like the fluid inlet 223, the sample inlet 233 is a through-hole formed in the substrate 210. The shape and size of the sample inlet 233 are not limited as long as it allows the sample liquid 218 to be introduced into the second flow channel 230; however, in this embodiment, the sample inlet 233 is a circular hole with a diameter of 2 to 5 mm (e.g., 4 mm). The sample inlet 233 also has an open top and a covered bottom with the first coating material 222. In this embodiment, a reaction reagent is introduced into the sample inlet 233 along with the sample, and the sample inlet 233 is used as a reaction vessel for promoting a sample reaction (e.g., a nucleic acid amplification reaction). Therefore, the sample inlet 233 is maintained at a constant temperature (e.g., a predetermined temperature between 25 and 65°C) to allow the reaction to occur at a constant temperature. The sample inlet 233 can be maintained or heated by placing the entire testing device 201 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 233.

[0208] The outlet 240 indicates a region downstream from the connection portion X, and includes a downstream portion including the end of the first flow path 220, and a notch 240A that is in fluid communication with the end of the first flow path 220. The notch 240A opens on one side of the substrate 210, penetrates the substrate 210 in the thickness direction, and has a detection unit 250 attached thereto. The sidewall of the notch 240A is hydrophobic, similar to the substrate 210. The open lower surface of the notch 240A is covered with a hydrophilic first coating material 222 that extends from the first flow path 220.

[0209] The outer shape and size of the substrate 210 can be set appropriately taking into consideration ease of handling, etc. For example, if the substrate 210 is quadrilateral (square or rectangle), it is preferable that each side is 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 210 is not particularly limited, and may be other polygonal, circular, elliptical, or the like. The thickness of the substrate 210 is also not particularly limited, and can be, for example, 5 to 20 mm.

[0210] The resin substrate 210 can be produced by a resin molding processing technique, such as injection molding, transfer molding, or extrusion molding.

[0211] 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 is not particularly limited in degree and physical value. In this embodiment, the hydrophobic (first property) surface of the substrate 210 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 210 with water is preferably 70° or more, and more preferably 80° or more. The upper limit of the contact angle of the substrate 210 with water is preferably 95° or less, and more preferably 90° or less. Furthermore, the hydrophilic (second property) surfaces of the first coating material 222 and the second coating material 232 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 222 and the second coating material 232 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.

[0212] The fluid control unit 211 according to this embodiment has a fluid control function that automatically causes a reacted sample to flow out when an unreacted sample is introduced, and also has a timing function that measures a predetermined reaction time for the sample introduced into the sample inlet 233 to react with a reaction reagent. This is because the time (required time) for the fluid 219 to flow through the first flow channel 221 is regulated to a preset time (predetermined time). Next, the configuration of the first flow channel 221 related to the timing function of the first flow channel 220 will be described with reference to FIGS. 21 and 22 .

[0213] The fluid control unit 211 according to this embodiment has a characteristic configuration related to the timing function, in that the first flow path 220 includes a first section L21 (not shown). In this embodiment, the first section L21 starts from a starting point S and extends to a point P midway along the fifth straight section of the first flow path 220. In the first section L21, the width W21 of the first flow path groove 221A is 0.8 to 2.0 mm, and the depth D21 is 0.07 to 0.10 mm (70 to 100 μm). Setting the width W21 and depth D21 of the first flow path groove 221 within this range can suppress variation in the flow velocity of the fluid flowing through the flow path.

[0214] The width W21 of the first flow channel 221A is preferably 0.8 to 1.5 mm, and more preferably 0.9 to 1.2 mm. The depth D21 of the first flow channel 221A is preferably 0.09 to 0.10 mm, and more preferably 0.095 to 0.100 mm.

[0215] In this embodiment, the cross-sectional shape of the first flow channel 221A is quadrangular (particularly rectangular), but the shape is not limited thereto. The cross-sectional shape of the first flow channel 221 may be trapezoidal or semicircular, and in particular, if the cross-sectional shape of the first flow channel 221 is a trapezoid whose side on the opening side (the side of the first covering material 222) is larger than the side at the groove bottom of the first flow channel 221, the first flow channel 221 can be easily manufactured using a mold. In the case of such a shape, the width W21 and depth D21 of the first flow channel 221 refer to the maximum width and maximum depth of the first flow channel 221.

[0216] In this embodiment, a second section L22 is provided adjacent to the first section L21 and is deeper than the first flow channel 221A in the first section L21. In this embodiment, the depth D22 of the flow channel 221B in the second section L22 is set to 2 to 10 times the depth D21 of the first flow channel 221A in the first section (6 times in this embodiment). The width W2 of the first flow channel 221B in the second section is set to the same as the width W1 of the first flow channel 221A in the first section. By providing the second section L22, the flow rate can be reduced, allowing for longer measurement times without increasing the dimensions of the device. Therefore, a longer time (e.g., 10 to 30 minutes) can be set as the predetermined time.

[0217] Point P, which is the transition point from the first flow channel 221A in the first section L21 to the first flow channel 221B in the second section L22, has an inclined surface 221C as shown in FIG. 22 . In this embodiment, the angle θ between the top surface 221E of the first flow channel 221B and the inclined surface 221C is 100°. At point P, the first flow channel 221A in the first section L21 suddenly expands from a depth D21 to a depth D22 of the first flow channel 221B in the second section L22. This is a so-called sudden expansion pipe, and when the fluid 219 enters the first flow channel 221B, the flow of the fluid 219 cannot immediately follow the flow channel shape, and a vortex is formed at the sudden expansion portion, drawing in the surrounding fluid 219. 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 221E of the first flow channel 221B and the inclined surface 221C is not particularly limited, but is preferably 95° to 105°.

[0218] The ratio of the lengths of the first section L21 and the second section L22 (length of L21: length of L22) is not particularly limited, but is preferably 9: 1 to 5: 5. With such a ratio, the effect of suppressing time variation in the first section L21 can be easily obtained.

[0219] In this embodiment, the time required for fluid 219 to reach connection part X after being introduced into fluid inlet 223 is within an allowable error of, for example, ±5% of the predetermined time. In the above-described fluid control part 211, the time required for at least specimen liquid 218 to flow out of outlet 240 after fluid 219 is introduced into fluid inlet 223 and specimen liquid 218 is introduced into specimen inlet 233 is within an allowable error of, for example, ±5% of the predetermined time.

[0220] In this embodiment, the first flow path 220 is configured to have a higher conduit resistance than the second flow path 230. The conduit resistance of a flow path is determined by various conditions, and generally, the conduit resistance of the first flow path 220 is higher than that of the second flow path 230 when the first flow path 220 is longer, has a higher coefficient of friction, is narrower, or has a higher flow rate than the second flow path 230. In this embodiment, as described above, the flow path length M21 from the fluid inlet 223 to the connection portion X is sufficiently longer than the flow path length M22 from the sample inlet 233 to the connection portion X, and the conduit resistance of the first flow path 220 is higher than the conduit resistance of the second flow path 230.

[0221] [Detection Unit] In the testing device 201, the detection unit 250 is attached to a notch 240A of an outlet 240 provided on the substrate 210. In the testing device 201, the detection unit 250 is fluidically connected to the outlet 240 of the fluid control unit 211. A hydrophilic first coating material 222 provided on the underside of the outlet 240 guides the sample liquid 218 to the detection unit 250, enabling detection of the sample in the sample liquid flowing out of the outlet 240. While the fluid 219 passes through the first flow path 220 for a predetermined time, a reaction such as a nucleic acid amplification reaction of the sample progresses in the sample liquid 218 due to a reaction reagent, and the fluid control unit 211 causes the sample after the reaction for a predetermined time to flow into the detection unit 250. Therefore, the detection unit 250 can detect the sample (target substance) after the reaction. The detection unit of a commercially available test kit for immunochromatography or the like can be used as the detection unit 250. In this embodiment, a detection unit using chromatography paper with a conjugate pad (e.g., a nucleic acid chromatography strip) is used as the detection unit 250. Using chromatography paper with a conjugate pad as the detection unit 250 eliminates the need to add a developing solution.

[0222] <Inspection Method Using Inspection Device 201> Next, an inspection method using the inspection device 201 will be described in relation to the functions and actions of each part of the inspection device 201.

[0223] The specimen liquid 218 and the fluid 219 are prepared in advance. The specimen liquid 218 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 219 is a fluid control fluid for causing the specimen liquid 218 remaining in the second flow path 230 and the specimen inlet 233 to flow out the outlet 240, and also serves as a timing fluid for measuring a predetermined time by flowing through the first flow path 220. For this reason, the fluid 219 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 219 introduced into the fluid inlet 223 to reach the connection portion X is within a tolerance of ±5% of the predetermined time. Both the specimen liquid 218 and the fluid 219 are hydrophilic.

[0224] First, fluid 219 is introduced into fluid inlet 223, and sample liquid 218 is introduced into sample inlet 233. The introduction of fluid 219 into fluid inlet 223 and the introduction of sample liquid 218 into sample inlet 233 are preferably simultaneous, but may be slightly different, and the order of introduction is not particularly limited. As shown in FIGS. 18 and 19 , the surface 232A of second coating material 232 in second flow path 230 serves as a guide, causing a portion of sample liquid 218 to flow out of sample inlet 233, fill the second flow path 230, and be guided further to connection portion X. The sample liquid 218 then forms a droplet 218A at connection portion X. In this embodiment, droplet 218A wets and spreads on surface 232A of second coating material 232 above connection portion X and is held on surface 232A of second coating material 232 in a state in which it hangs downward due to surface tension and gravity. At this time, droplet 218A does not come into contact with first coating material 222. Even if droplet 218A comes into contact with side surface 221D and top surface 221E of first flow channel 221, or side surface 231D and bottom surface 231E of second flow channel 231, droplet 218A does not wet and spread because these surfaces are all hydrophobic, and instead becomes a rounded droplet due to surface tension. This configuration can prevent sample liquid 218 from flowing out of outlet 240 before droplet 218A comes into contact with fluid 219.

[0225] On the other hand, when fluid 219 is introduced into fluid inlet 223, it starts from starting point S and flows through first flow path 220 (220A, 220B) 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 220 according to this embodiment has a timing function, and can regulate the predetermined time by the time required for passing through first flow path 220, and the reaction between the specimen in specimen liquid 218 and the reaction reagent proceeds during this predetermined time.

[0226] Next, fluid 219, which has passed through first flow path 220 over a predetermined time, reaches connection portion X and comes into contact with droplet 218A. Then, as shown in FIG. 20 , at least sample liquid 218 flows out from outlet 240. In this manner, fluid 219 passing through first flow path 220 acts to cause sample liquid 218 remaining in second flow path 230 and sample inlet 233 to flow out to outlet 240. Fluid 219 passing through long first flow path 220 (220A, 220B) loses pressure (propulsive force) due to friction with the wall surfaces within the flow path before reaching connection portion X. Therefore, at connection portion X, the outflow of sample liquid 218 from second flow path 230 takes priority over the outflow of fluid 219 from first flow path 220. The fluid control unit 211 can also be called a "surface tension valve" that utilizes surface tension, because at the connection part X where two flow paths are connected, a 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.

[0227] According to the fluid control unit 211 of this embodiment, the sample liquid 218 in the second flow path 230 can be discharged to the outlet 240 by the action of the fluid 219 introduced into the first flow path 220 formed in the same substrate 210, without performing an operation to open the second flow path 230 from the outside. Furthermore, in the fluid control unit 211 of this embodiment, the second coating material 232 at least partially overlaps with the connection portion X in a plan view of the substrate 210, so that the surface 232A of the second coating material 232 can guide the sample liquid 218 to the connection portion X. That is, in the fluid control unit 211, the surface 232A of the second coating material 232 in the second flow path 230 serves as a guide that guides the sample liquid 218 to the connection portion X.

[0228] The fluid control unit 211 according to this embodiment is configured such that the flow path length M21 of the first flow path 220 from the fluid inlet 223 to the connection portion X is greater than the flow path length M22 of the second flow path 230 from the analyte inlet 233 to the connection portion X. The first flow path 220 has a greater conduit resistance than the second flow path 230. Therefore, when the fluid 219 passing through the first flow path 220 comes into contact with the droplet 218A of the analyte liquid 218 formed at the connection portion X, the reacted analyte liquid 218 spontaneously flows out of the outlet 240 and into the detection unit 250. The lower opening of the notch 240A of the outlet 240 is covered with the first coating material 222 having a hydrophilic surface and extending from the first flow path 220. Therefore, the hydrophilic analyte liquid 218 can be rapidly introduced into the chromatography paper with a conjugate pad in the detection unit 250. Through the above-described steps, the analyte (target substance) can be detected in the detection unit 250.

[0229] 23, the test result in the test device 201 is confirmed by whether or not both the detection line C and the detection line T appear in the detection unit 250. If both the detection line C and the detection line T appear in the detection unit 250, it is positive, and if only the detection line C appears, it is negative.

[0230] In the fluid control unit 211 of the testing device 201, when the fluid 219 reaches the connection part X, the specimen liquid 218 flows out of the outlet automatically. In this way, the fluid control unit 211 opens the second flow path 230 in response to the action of the fluid 219 and discharges the specimen liquid 218, without requiring external control to open the second flow path 230.

[0231] Furthermore, in the fluid control unit 211 according to this embodiment, the fluid 219 introduced into the fluid inlet 223 passes through the first flow path 220 over a predetermined time, and the first flow path 220 functions as a timer that measures the reaction time of the specimen liquid 218, so that when the specimen liquid before reaction is introduced, the specimen liquid 218 that has reacted for a predetermined time can be introduced into the detection unit 250. This makes it possible to suppress variations in the test results due to variations in reaction time, and to improve the test accuracy while providing a test kit in the form of one that allows for simple and quick detection.

[0232] Furthermore, in this embodiment, the second flow channel 230 crosses the first flow channel 220 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 221 and the second flow channel groove 231. This makes it easy to manufacture the fluid control unit 211.

[0233] Next, inspection devices 202 to 205 according to fourth to seventh embodiments of the present invention will be described with reference to Figures 24 to 31. The inspection devices 202 to 205 each include fluid control units 212 to 215 that are different from the fluid control unit 211 according to the first embodiment. Specifically, the connection portion X is different because each of the inspection devices includes second flow paths 260, 270, 280, and 290 that are different from the second flow path 230 according to the first embodiment. Note that the same reference numerals are used for components that have the same functions as those of the previous embodiments and that are not significantly different in shape.

[0234] 4. Fourth Embodiment An inspection device 202 according to a fourth embodiment of the present invention will be described with reference to FIGS.

[0235] <Inspection Device 202> As shown in Fig. 24 , in the fluid control unit 212 of the inspection device 202, the downstream end of the second flow channel 261 of the second flow channel 260 is formed short so that it reaches a position midway through the first flow channel 220. In this configuration, the volume of the connection portion X between the first flow channel 220 and the second flow channel 260 is small, but as shown in Fig. 25 , the second coating material 232 at least partially overlaps the connection portion X in a plan view of the substrate 210. Therefore, the second coating material 232 can guide the specimen liquid 218 to the connection portion X, and a droplet 218B can be formed at the connection portion X. Therefore, when the fluid 219 passing through the first flow channel 220 comes into contact with the droplet 218B of the specimen liquid 218 at the connection portion X, the specimen liquid 218 flows out from the outlet 240. The fluid control section 212 has a fluid control function similar to that of the fluid control section 211, although the volume of the droplet 218B formed at the connection portion X is smaller than that of the fluid control section 211 of the third embodiment.

[0236] 5. Fifth Embodiment Next, a testing device 203 according to a fifth embodiment of the present invention will be described with reference to FIGS. 26 and 27 . <Testing Device 203> As shown in FIG. 26 , the fluid control unit 213 of the testing device 203 has a second flow channel 271 of a second flow channel 270 that is shorter than that of the second embodiment. The second flow channel 270 communicates with the first flow channel 220 while abutting against the side of the first flow channel 221. In this configuration, the connection portion X between the first flow channel 220 and the second flow channel 270 is a surface perpendicular to the substrate 210, and the volume of the connection portion X is even smaller than that of the second embodiment. However, as shown in FIG. 27 , the second coating material 232 at least partially overlaps the connection portion X in a plan view of the substrate 210. Even in this configuration, the second coating material 232 can guide the sample liquid 218 to the connection portion X, thereby forming a droplet 218C at the connection portion X. Therefore, when fluid 219 passing through first flow path 220 comes into contact with droplet 218C of specimen liquid 218 at connection portion X, specimen liquid 218 flows out from outlet 240. Although fluid control portion 213 can form droplet 218C at connection portion X even smaller than in the fourth embodiment, fluid control portion 213 has a fluid control function similar to that of fluid control portion 211 of the third embodiment.

[0237] 6. Sixth Embodiment Next, an inspection device 204 according to a sixth embodiment of the present invention will be described with reference to FIGS. 28 and 29 . <Inspection Device 204> In the fluid control unit 214 of the inspection device 204, the downstream end of the second flow channel 281 extends to a position that roughly overlaps with the innermost side surface 221D of the first flow channel 221 in a plan view. Furthermore, the depth D24 of the second flow channel 281 is changed to approximately 0.1 mm. With this configuration, a through-hole penetrating the substrate 210 is formed in the region where the first flow channel 220 and the second flow channel 280 overlap in a plan view. This allows the first flow channel 220 and the second flow channel 280 to communicate with each other. 29 , in this configuration, second coating material 232 at least partially overlaps connection portion X in a plan view of substrate 210, and surface 232A of second coating material 232 guides specimen liquid 218 to connection portion X, allowing droplet 218D to be formed over a wide area at connection portion X. Therefore, when fluid 219 passing through first flow path 220 comes into contact with droplet 218D of specimen liquid 218 at connection portion X, specimen liquid 218 flows out from outlet 240. Fluid control portion 214 has a smaller depth than second flow path groove 231 of fluid control portion 211 of the third embodiment, but has the same fluid control function as fluid control portion 211 of the third embodiment.

[0238] 7. Seventh Embodiment Next, a testing device 205 according to a seventh embodiment of the present invention will be described with reference to Figures 30 and 31. <Testing Device 205> In the fluid control unit 215 of the testing device 205, a second flow path 290 is formed inside the substrate 210, and the second flow path 290 fluidly connects the side of the sample inlet 233 to the front side 221D of the first flow path groove 221 of the first flow path 220. The cross-sectional shape of the second flow path 290 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 290 is hydrophilically coated, and this hydrophilic coating serves as a guide portion. According to this configuration, the inner surface of second flow path 290 is hydrophilic (second property), while side surface 221D of first flow path groove 221 of first flow path 220 is hydrophobic (first property). Therefore, sample liquid 218 introduced into sample inlet 233 is guided to connection portion X and forms droplet 218E that protrudes in a meniscus shape from connection portion X toward side surface 221D of first flow path groove 221. In this configuration, when fluid 219 passing through first flow path 220 comes into contact with droplet 218E of sample liquid 218 at connection portion X, sample liquid 218 flows out from outlet 240. Even if a guide portion is provided in second flow path 290 by other means instead of providing second coating material 232 as in fluid control portion 215, the fluid control function is maintained similar to that of fluid control portion 211 of the third embodiment.

[0239] Other embodiments of the first fluid control device and the second 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.

[0240] In the above embodiment, a configuration has been described in which hydrophilic liquids are used as sample liquid 218 and fluid 219, side surface 221D and top surface 221E of first flow channel 221 and side surface 231D and bottom surface 231E of second flow channel 231 are hydrophobic (first property), and surface 222A of first coating material 222 and surface 232A of second coating material 232 are hydrophilic (second property). However, in the present invention, the first property may be a property that prevents the fluid used from wetting and spreading, and the second property may be a property that allows the fluid used to wet and spread, and the relationship between hydrophobicity and hydrophilicity in the present invention may be reversed from that in the above embodiment. For example, when sample liquid 218 and fluid 219 are hydrophobic fluids such as organic solvents, the effects of the present invention can be achieved by making side surface 221D and top surface 221E of first flow channel 221 and side surface 231D and bottom surface 231E of second flow channel 231 hydrophilic (first property) and making surface 222A of first coating material 222 and surface 232A of second coating material 232 hydrophobic (second property). In this case, for example, substrate 210 may be formed from a hydrophilic resin, and first coating material 222 and second coating material 232 may be formed from a hydrophobic resin film.

[0241] 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 210 is made of a hydrophobic resin, but the substrate may be made of glass or resin, and the material is not particularly limited.

[0242] In the above embodiment, examples of connection portion X and droplets 218A to 218E have been described using inspection devices 201 to 205. 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 220 as long as the function of the present invention is not impaired.

[0243] In the above embodiment, an example has been described in which the outflow of specimen liquid 218 from the second flow path takes precedence over fluid 219 from first flow path 220. However, in the present invention, it is sufficient that at least the specimen flows out to outlet 240, and fluid 219 may flow out to outlet 240 together with specimen liquid 218.

[0244] In the above embodiment, the test devices 201 to 205 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.

[0245] In the above embodiment, an example was described in which the first fluid control device was applied as the fluid control units 211-215 having a timing function of the inspection devices 201-205. 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 221 (221A, 221B) are not limited to the above-mentioned ranges. In addition, it is not necessary to have both the first section L21 and the second section L22. For example, in the above embodiment, an example was shown in which the depth of the first flow channel 221 changes before and after point P, but an embodiment in which the depth does not change is also possible.

[0246] The first fluid control device of the present invention may be used as a fluid control device for a microchannel device for other applications that require discharging a fluid introduced into a channel, such as a chip for detecting water leaks and a device with a fixed-volume dispensing function.

[0247] The first fluid control device according to the present invention can be used, for example, as a valve structure for opening a flow channel in a microchannel device, and the second testing device according to the present invention can be used, for example, as various testing kits.

[0248] 8. Testing Apparatus According to an Eighth Embodiment Testing apparatus 301 as an eighth embodiment of the testing apparatus according to the present invention and a fluid control unit 311 in testing apparatus 301 as an eighth embodiment of the fluid control device according to the present invention will be described with reference to FIGS. 32 to 44. Fluid control unit 311 according to this embodiment includes three inlets (fluid inlet 323, diluent solvent reservoir 333, and specimen liquid reservoir 338) through which fluid 316, diluent solvent 317 (an example of a first fluid), and specimen liquid 318A (an example of a second fluid) are introduced, an outlet 340 through which both diluent solvent 317 and specimen liquid 318B flow out, and flow paths fluidically connected to these inlets, on a microchip substrate 310 (hereinafter referred to as substrate 310) (FIG. 32). A first coating material 322 laminated on one side of substrate 310 forms the bottom surfaces of the three inlets. The inspection device 301 according to this embodiment is used with the side where the three inlets open (the front side in FIG. 32 ) is located on the upper side and the side where the first covering material 322 is laminated (the rear side in FIG. 32 ) on the lower side. In the following description, when the orientation of the inspection device 301 is mentioned, it refers to the vertical direction based on the position where the inspection device 301 is placed so that the first covering material 322 is grounded (the position shown in FIGS. 33 , 34 , and 36 ). Furthermore, when the horizontal direction of the inspection device 301 is mentioned, it refers to the direction perpendicular to the above-mentioned vertical direction (i.e., the left-right direction in FIGS. 33 , 34 , and 36 or the direction perpendicular to the paper surface). The depth direction and height direction are also the same as the vertical direction. In the following description, the side of the substrate 310 where the three inlets open is defined as the front side, and the side where the first covering material 322 is laminated is defined as the back side.

[0249] [Overview of Testing Device 301] Testing device 301 according to this embodiment is used as a test kit for testing for infectious diseases caused by, for example, viruses, bacteria, etc., and, as shown in Fig. 32 , is provided with a fluid control unit 311 and a detection unit 350 on a microchip that can detect diluted specimen liquid that has flowed out from fluid control unit 311. As shown in Fig. 37 , testing device 301 is used by introducing dilution solvent 317 into dilution solvent reservoir 333 (an example of a first reservoir), introducing specimen liquid 318A, which will be a reaction liquid obtained by mixing a reaction reagent and a specimen, into specimen liquid reservoir 338 (an example of a second reservoir), and introducing fluid 316 into fluid inlet 323. When dilution solvent 317, specimen liquid 318A serving as a reaction liquid, and fluid 316 are introduced into dilution solvent reservoir 333, specimen liquid reservoir 338, and fluid inlet 323, respectively, after a predetermined time, for example, several minutes or more, dilution solvent 317 and specimen liquid 318B containing the gene amplification product after the reaction flow out together as mixture 319 from outlet 340, as shown in FIG. 42 . In this manner, mixture 319, which is a liquid in which specimen liquid 318B after the reaction is diluted with dilution solvent 317, flows out of outlet 340 on its own. Then, as shown in FIG. 43 , the gene amplification product (target substance) in mixture 319 is detected by detection unit 350. In the eighth to tenth embodiments, the terms "specimen" and "specimen liquid" are used regardless of whether they are before or after the reaction or the degree of progress of the reaction.

[0250] [Configuration of the Fluid Control Unit] Fluid control unit 311 (an example of a second fluid control device) has a function of, when dilution solvent 317 and specimen liquid 318A, which is a reaction liquid, are introduced into the microchip, causing dilution solvent 317 and specimen liquid 318B after the nucleic acid amplification reaction to flow out together. In other words, fluid control unit 311 has a function of diluting specimen liquid 318B with dilution solvent 317 on the microchip.

[0251] 42 , fluid control unit 311 includes main channel 320, outlet 340 fluidly connected downstream of main channel 320 and guiding both diluent solvent 317 and analyte liquid 318B, and diluent solvent reservoir 333 and analyte liquid reservoir 338 fluidly connected to main channel 320 and storing diluent solvent 317 and analyte liquid 318 (318A, 318B), respectively. In this embodiment, main channel 320 and diluent solvent reservoir 333 are fluidly connected via a first communication path 330, and main channel 320 and analyte liquid reservoir 338 are fluidly connected via a second communication path 335. For the sake of distinction, analyte liquid 318 immediately after storage, in which no reaction has progressed, will be referred to as analyte liquid 318A, and analyte liquid 318 after reaction will be referred to as analyte liquid 318B.

[0252] The fluid control unit 311 includes a first fluid control mechanism that controls the outflow of dilution solvent 317 from the dilution solvent reservoir 333, and a second fluid control mechanism that controls the outflow of specimen liquid 318 (318A, 318B) from the specimen liquid reservoir 338.

[0253] Next, the configuration of each part of the fluid control unit 311 will be described in detail.

[0254] As shown in the cross-sectional view of FIG. 33, the main channel 320 has a channel groove 321 formed on at least one surface of the substrate 310 and a first covering material 322 covering the channel groove 321 .

[0255] 35 and 36 , the main flow channel 320 is fluidly connected to the first communication passage 330 at a first connection portion X31 in a portion of the bottom surface of the flow channel groove 321 (321B) of the main flow channel 320. The main flow channel 320 is also fluidly connected to the second communication passage 335 at a second connection portion X32 in a portion of the bottom surface of the flow channel groove 321 (321B) of the main flow channel 320.

[0256] In this embodiment, as shown in FIG. 32 , the flow channel 321 (321A, 321B) of the main flow channel 320 extends in a serpentine manner on the substrate 310 in the length direction (flow direction of the fluid 316). Specifically, the flow channel 321 (321A, 321B) of the main flow channel 320 has five parallel straight sections and four arc-shaped curved sections connecting the five straight sections. With this configuration, the fluid 316 introduced into the fluid inlet 323 makes four U-turns on the substrate 310 and reaches the first connection portion X31 over a period of several minutes to several tens of minutes (e.g., 5 to 60 minutes). In this embodiment, the flow channel 321 of the main flow channel 320 is composed of a flow channel 321A and a flow channel 321B having different depths, as shown in FIGS. 32 and 34 . Specifically, the flow channel 321A connects to the flow channel 321B, which has a greater depth, at point P. The flow channel 321 (321A, 321B) has a restriction section 314 in which the time required for the fluid 316 to pass through is restricted. Details of the restriction section 314 will be described later, but the flow channel 321 (321A, 321B) of the main flow channel 320 is set to have a width in the range of 0.8 to 2.0 mm and a depth in the range of 0.02 to 1 mm, for example.

[0257] (First Fluid Control Mechanism and Second Fluid Control Mechanism) The first and second fluid control mechanisms according to this embodiment are both passive valves using surface tension and have the same configuration. In this embodiment, as shown in FIG. 37 , the first fluid control mechanism releases diluent 317, introduced into diluent reservoir 333 and remaining in diluent reservoir 333 and first connecting passage 330, by the action of fluid 316 introduced into main channel 320, and causes it to flow toward second connecting portion X32 ( FIGS. 39 and 40 ). The second fluid control mechanism, as shown in FIG. 39 , releases analyte liquid 318 (18B), introduced into analyte liquid reservoir 338 and remaining in analyte liquid reservoir 338 and second connecting passage 335, by the action of diluent 317, and causes it to flow toward outlet 340 ( FIGS. 40 and 42 ). At this time, analyte liquid 318B becomes a mixture 319 with diluent solvent 317. In other words, the first fluid control mechanism functions as a passive valve that opens the first communication passage 330 under the action of fluid 316, and the second fluid control mechanism functions as a passive valve that opens the second communication passage 335 under the action of dilution solvent 317.

[0258] As shown in Fig. 36 , the first communication passage 330 according to this embodiment has a first flow channel 331 formed to open on the surface of the substrate 310 opposite to the flow channel 321 (321B) of the main flow channel 320 (the upper surface in Fig. 35 ), and a second covering material 332 covering the first flow channel 331. Similarly to the first communication passage 330, the second communication passage 335 has a second flow channel 336 formed to open on the surface of the substrate 310 opposite to the flow channel 321 of the main flow channel 320 (the upper surface in Fig. 35 ), and a second covering material 332 covering the second flow channel 336. The second covering material 332 partially covers the surface of the substrate 310 (the upper surface in Fig. 36 ) so as to cover both the first flow channel 331 and the second flow channel 336. The shape, size, and the like of second coating material 332 are not limited as long as it covers first flow channel 331 and second flow channel 336. In this embodiment, as shown in Figure 35, second coating material 332 covers first flow channel 331 and second flow channel 336 and also partially covers diluent solvent reservoir 333 and specimen liquid reservoir 338. The portions of diluent solvent reservoir 333 and specimen liquid reservoir 338 that are not covered by second coating material 332 are openings. In this embodiment, first communicating channel 330 and first fluid control mechanism and second communicating channel 335 and second fluid control mechanism have the same configuration, so hereinafter, first communicating channel 330 and first fluid control mechanism will be described in detail, and detailed description of second communicating channel 335 and second fluid control mechanism will be omitted. 37, 39, 40, 42, and 43, a second coating material 332 is present on the surface of the substrate 310, as in FIG. 32, but is not shown for the sake of explanation.

[0259] In this embodiment, the first flow channel groove 331 in the first communication passage 330 is a linear groove that is shallower and shorter than the flow channel groove 321B of the main flow channel 320. Specifically, as shown in Figure 35, the length of the first flow channel groove 331 is set so that the length of the main flow channel 320 from the outlet of the fluid inlet 323 to the first connecting portion X31 (referred to as flow channel length M31, not shown) is longer than the length of the first communication passage 330 from the outlet of the dilution solvent reservoir 333 to the first connecting portion X31 (referred to as flow channel length M32). In this embodiment, the flow channel length M31 is set sufficiently long, for example, to be 10 times or more longer than the flow channel length M32.

[0260] The width and depth of the first flow channel groove 331 in the first communication passage 330 are not particularly limited, but in this embodiment, for example, 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.

[0261] As shown in FIGS. 35 and 36 , the main flow path 320 and the first communication path 330 are fluidly connected to each other by partially intersecting the flow path grooves 321 (321B) and 331 at the first connection portion X31. The main flow path 320 and the second communication path 335 are fluidly connected to each other by partially intersecting the flow path grooves 321 (321B) and 336 at the second connection portion X32. In this embodiment, as shown in the plan view of FIG. 35 , the first communication path 330 and the second communication path 335 are connected in a manner that protrudes into the main flow path 320. In this embodiment, the first connection portion X31 is located downstream of the fifth straight section of the main flow path 320, and the second connection portion X32 is located downstream of the first connection portion X31. In this embodiment, the length of the flow path groove 321B between the first connection portion X31 and the second connection portion X32 is preferably short, e.g., shorter than the lengths of the first communication path 330 and the second communication path 335.

[0262] In this embodiment, the thickness of the substrate 310 is approximately 0.75 mm. The depth D32 of the flow channel groove 321B of the main flow channel 320 is approximately 0.6 mm, and the depth D33 of the first flow channel groove 331 of the first communicating channel 330 is approximately 0.15 mm. Therefore, the groove bottoms (321Bb and 331b) of the main flow channel 320 and the first communicating channel 330 are on approximately the same plane, and the flow channel groove 321B of the main flow channel 320 and the second flow channel groove 336 overlap at their groove bottoms, thereby providing fluid communication with each other. With this configuration, a through hole is formed in the substrate 310 at the first connecting portion X31, and the first coating material 322 and the second coating material 332 are located on both sides of the through hole, respectively.

[0263] As described above, the second coating material 332 is disposed on the surface of the substrate 310 opposite to the first coating material 322 at least in a position covering the first flow channel 331 of the first communicating channel 330 and the second flow channel 336 of the second communicating channel 335. In the present embodiment, the second coating material 332 is disposed so as to overlap the first connecting portion X31 and the second connecting portion X32, respectively, in a plan view of the substrate 310. In the present embodiment, the second coating material 332 is not disposed on the upper surfaces of the diluent reservoir 333 and the sample liquid reservoir 338, but may extend from the first flow channel 331 toward the diluent reservoir 333 and the sample liquid reservoir 338. Furthermore, in the present embodiment, the first flow channel 331 and the second flow channel 336 are covered with the same second coating material 332, but the first flow channel 331 and the second flow channel 336 may each be covered with a different coating material.

[0264] In this embodiment, a substrate 310 made of a hydrophobic resin is used, and the surfaces (side surface 321Ba and top surface 321Bb) of the flow channel 321B in the main flow channel 320 are hydrophobic (first property). Note that the bottom surface of the flow channel 321B in the main flow channel 320 is positioned on the upper side and forms the top surface as shown in FIG. 36 when the testing device 301 is in use, and is therefore referred to as top surface 321Bb in the following description. While the resin component constituting the substrate 310 is not particularly limited, in this embodiment, the resin 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 310 is preferably one that has either heat resistance or transparency, or both.

[0265] The surface of the first covering material 322 covering the flow channel 321 of the main flow channel 320 is hydrophilic (second property). The first covering material 322 may be hydrophilic at least on the surface facing the flow channel 321 (321A, 321B) of the main flow channel 320. In this embodiment, a hydrophilic resin film, such as a hydrophilic acrylic resin, is used. The resin constituting the first covering material 322 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 322 covers the entire back surface (lower surface in FIG. 36 ) of the substrate 310, including the flow channel 321 (321A, 321B) of the main flow channel 320.

[0266] The first flow channel 331 is formed on the same substrate 310 as the flow channel 321 of the main flow channel 320, and therefore the surfaces (side surface 331a and bottom surface 331b) of the first flow channel 331 are hydrophobic (first property). In this embodiment, the second coating material 332 uses the same hydrophilic resin film as the first coating material 322, and a surface 332A of the second coating material 332 is hydrophilic (second property).

[0267] The specimen liquid 318 (318A, 318B) used in the testing device 301 of this embodiment is an aqueous solution containing a reaction reagent and a specimen. Furthermore, an aqueous solution such as water or a buffer solution is used as the dilution solvent 317 and the fluid 316 introduced into the fluid inlet 323. Since the specimen liquid 318, dilution solvent 317, and fluid 316 are all hydrophilic liquids, in the main flow channel 320, the fluid 316 is repelled by the surfaces of the flow channel grooves 321 (321A, 321B) of the main flow channel 320 and exhibits the property of wetting and spreading on the surface of the first coating material 322. Similarly, the dilution solvent 317 is repelled by the surface of the flow channel 321 of the main flow channel 320 and the surface of the first flow channel 331 in the first connecting passage 330, but exhibits the property of wetting and spreading on the surfaces of the first coating material 322 and the second coating material 332, and the specimen liquid 318 is repelled by the surface of the flow channel 321 (321A, 321B) of the main flow channel 320 and the surface of the second flow channel 336 in the second connecting passage 335, but exhibits the property of wetting and spreading on the surfaces of the first coating material 322 and the second coating material 332.

[0268] Therefore, when fluid 316 is introduced into main channel 320 from fluid inlet 323, fluid 316 flows along the hydrophilic surface of first coating material 322 and into main channel 320. Similarly, when diluent solvent 317 is introduced into diluent solvent reservoir 333, diluent solvent 317 flows along hydrophilic surface 332A of second coating material 332 and into first communicating channel 330, forming droplet 317a at first connecting portion X31. When analyte liquid 318A is introduced into analyte liquid reservoir 338, analyte liquid 318A flows along hydrophilic surface 332A of second coating material 332 and into second communicating channel 335, forming droplet 317a at second connecting portion X32.

[0269] 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 spreads, and the degree and physical value of the property are not particularly limited. In this embodiment, the hydrophobic (first property) surface of the substrate 310 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 310 with water is preferably 70° or more, and more preferably 80° or more. The upper limit of the contact angle of the substrate 310 with water is preferably 95° or less, and more preferably 90° or less. Furthermore, the hydrophilic (second property) surfaces of the first coating material 322 and the second coating material 332 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 322 and the second coating material 332 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.

[0270] Fluid inlet 323 is composed of a through-hole formed in substrate 310 and first covering material 322. That is, fluid inlet 323 is configured so as to store fluid 316, with the through-hole formed in substrate 310 as its inner wall and first covering material 322 extending from main channel 320 as its bottom. The shape and size of fluid inlet 323 are not limited as long as it can introduce fluid 316 into main channel 320, but in this embodiment, it is a circular hole with a diameter of 2 to 5 mm (for example, a diameter of 4 mm). The top of the through-hole of fluid inlet 323 is open.

[0271] In this embodiment, the outlet 340 indicates a region downstream from the second connection portion X32, and includes a downstream portion including the end of the main channel 320, and a notch 340A that is in fluid communication with the end of the main channel 320. The notch 340A opens on one side of the substrate 310, penetrates the substrate 310 in the thickness direction, and is the location where the detection unit 350 is attached. The sidewall of the notch 340A is hydrophobic, similar to the substrate 310. The open lower surface of the notch 340A is covered with a hydrophilic first coating material 322 that extends from the main channel 320.

[0272] The outer shape and size of the substrate 310 can be set appropriately taking into consideration ease of handling, etc. For example, if the substrate 310 is quadrilateral (square or rectangle), it is preferable that each side be 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 310 is not particularly limited, and may be other polygonal, circular, elliptical, or the like. The thickness of the substrate 310 is also not particularly limited, and can be, for example, 5 to 20 mm. The resin substrate 310 can be produced by resin molding processing techniques, such as injection molding, transfer molding, or extrusion molding.

[0273] Similar to the fluid inlet 323, the diluent solvent reservoir 333 is configured by a through-hole formed in the substrate 310 and a first coating material 322. That is, the diluent solvent reservoir 333 has the through-hole formed in the substrate 310 as its inner wall portion, and the first coating material 322 extending from the main channel 320 as its bottom portion, and is configured to be able to store the diluent solvent 317. The top of the through-hole of the diluent solvent reservoir 333 is open.

[0274] Similar to fluid inlet 323 and diluent solvent reservoir 333, analyte liquid reservoir 338 is also composed of a through-hole formed in substrate 310 and first coating material 322. That is, analyte liquid reservoir 338 has the through-hole formed in substrate 310 as its inner wall portion, and first coating material 322 extending from main channel 320 as its bottom portion, and is configured to be able to store analyte liquid 318 (318A, 318B). The top of the through-hole of analyte liquid reservoir 338 is open.

[0275] In the fluid control unit 311 according to this embodiment, the fluid inlet 323, dilution solvent reservoir 333, and specimen liquid reservoir 338 have bottom surfaces formed from a single sheet of first covering material 322, and are located on the same plane.

[0276] The internal volumes and internal volume ratios of the diluent solvent reservoir 333 and the specimen liquid reservoir 338 are set so that, when the diluent solvent 317 and the specimen liquid 318A are fully filled, the specimen liquid 318B after the nucleic acid amplification reaction will have a predetermined dilution factor. In this embodiment, the heights of the diluent solvent reservoir 333 and the specimen liquid reservoir 338 are the same as the thickness of the substrate 310, and therefore the volume ratio is set by setting the cross-sectional area ratio of the diluent solvent reservoir 333 and the specimen liquid reservoir 338 to the desired dilution factor. In this embodiment, the ratio of the cross-sectional area of ​​the specimen liquid reservoir 338 to the cross-sectional area of ​​the diluent solvent reservoir 333 (cross-sectional area of ​​the diluent solvent reservoir 333:cross-sectional area of ​​the specimen liquid reservoir 338) is set to a ratio of 10:1 to 2:1, preferably 6:1 to 2:1 (e.g., approximately 5:1), and the volume of the diluent solvent reservoir 333 is set to be larger than the volume of the specimen liquid reservoir 338.

[0277] In this embodiment, the diluent solvent reservoir 333 is a circular hole having a diameter of 3 to 6 mm (for example, a diameter of 4 mm). The shape of the diluent solvent reservoir 333 is not limited as long as it can introduce the diluent solvent 317 into the first communication passage 330.

[0278] In this embodiment, the specimen liquid reservoir 338 is a circular hole with a diameter of 1 to 3 mm (e.g., 1.5 mm). The shape of the specimen liquid reservoir 338 is not limited as long as it can introduce the specimen liquid 318 (318A, 318B) into the second communication path 335. In this embodiment, a reaction liquid containing a mixture of a specimen and a reaction reagent is introduced into the specimen liquid reservoir 338, and the specimen liquid reservoir 338 is used as a reaction vessel for carrying out a nucleic acid amplification reaction that amplifies genes in the specimen. Therefore, the specimen liquid reservoir 338 is kept 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 specimen liquid reservoir 338 can be kept warm or heated by placing the entire testing device 301 in a thermostatic bath or room, or by placing a heating device such as a heater in contact with the underside of the diluent solvent reservoir 333.

[0279] By using the above-described configuration, the dilution solvent 317 in the dilution solvent reservoir 333 and the specimen liquid 318B in the specimen liquid reservoir 338 can flow out toward the outlet 340 at a volume ratio corresponding to the cross-sectional area ratio of the through holes while maintaining the same liquid level height.

[0280] In this embodiment, the diluent reservoir 333 and the specimen liquid reservoir 338 are positioned such that the diluent reservoir is located upstream of the main channel 320 and the specimen liquid reservoir 338 is located downstream of the main channel 320 .

[0281] The thickness of the first covering material 322 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 flow channel 321 of the main flow channel 320 can be easily sealed. Furthermore, when the thickness is 2 mm or less, good conformability to the irregularities of the substrate 310 can be easily obtained.

[0282] The first covering material 322 and the substrate 310 may be bonded by providing an adhesive layer on the first covering material 322 side to serve as a bonding layer with the substrate 310, or by bonding the substrate 310 and the covering material with an adhesive or the like, or by compressing the substrate 310 and the first covering material 322 together using thermocompression bonding.

[0283] The first covering material 322 and the second covering material 332 described above may be different in material, thickness, etc., as long as their surfaces are hydrophilic. Furthermore, the method for bonding the substrate 310 and the second covering material 332 may be different from the method for bonding the substrate 310 and the first covering material 322. In this embodiment, since the area of ​​the second covering material 332 is smaller than the area of ​​the first covering material 322, the first covering material 322 may be bonded by thermocompression bonding, and the second covering material 332 may be bonded by an adhesive layer or a bonding layer.

[0284] 32 , in the fluid control unit 311 according to this embodiment, the flow channel 321 (321A, 321B) of the main flow channel 320 has a flow channel 314 in which the time required for the fluid 316 to pass is restricted. That is, the fluid 316 passes through the flow channel 314 of the flow channel 321 of the main flow channel 320 for a required time corresponding to a preset predetermined time, and therefore the outflow time from the introduction of the sample liquid 318A to the outflow of both the sample liquid 318B and the diluent solvent 317 can be restricted.

[0285] In the restricted section 314, the fluid 316 passes through the flow channel 321 of the restricted section 314 for a predetermined time, which may be within a range of 5 to 30 minutes, such as 5, 10, or 20 minutes. In this embodiment, the time required for the restricted section 314 is appropriately set according to the reaction time required for the specimen in the specimen liquid 318A to react with the reaction reagent, and it is desirable that the difference between the predetermined time and the time required for the fluid 316 to pass through is within a tolerance of ±10%, preferably ±5%. With this configuration, the diluent solvent 317 can flow out from the first connection part X31 after the predetermined time.

[0286] In the regulated section 314, it is only necessary that the time required for the fluid 316 to pass through is regulated. The regulated section may be set afterwards by measuring the time required for the flow groove 321 of the main flow path 320 that has already been created, or the time required for the fluid 316 to pass through may be set by adjusting the length, width, depth, etc. of the flow groove 321 of the main flow path 320 to predetermined dimensions.

[0287] The restriction section 314 according to this embodiment includes a first section L31 (not shown). In this embodiment, the first section L31 starts from a starting point S and extends to a point P midway along the fifth straight section of the main channel 320. The first section L31 is a section in which the flow channel groove 321A of the main channel 320 has a width W31 of 0.8 to 2.0 mm and a depth D31 of 0.07 to 0.10 mm (70 to 100 μm). Setting the width W31 and depth D31 of the flow channel groove 321A of the main channel 320 within this range can suppress variation in the flow velocity of the fluid flowing through the flow channel.

[0288] The width W31 of the flow channel groove 321A of the main flow channel 320 is preferably 0.8 to 1.5 mm, and more preferably 0.9 to 1.2 mm. The depth D31 of the flow channel groove 321A of the main flow channel 320 is preferably 0.09 to 0.10 mm, and more preferably 0.095 to 0.100 mm.

[0289] In this embodiment, as shown in FIG. 34 , the main flow path 320 includes a second section L32, which is continuous with the first section L31 (not shown) and is deeper than the flow groove 321A of the main flow path 320 in the first section L31. In this embodiment, the depth D32 of the flow groove 321B of the main flow path 320 in the second section L32 is set to 2 to 10 times the depth D31 of the flow groove 321A in the first section (6 times in this embodiment). In the main flow path 320, the width W32 of the flow groove 321B in the second section is set to the same as the width W31 of the flow groove 321A in the first section. By including the second section L32 in the main flow path 320, the flow rate can be reduced, allowing for longer measurement times without increasing the dimensions of the device. Therefore, a longer time (e.g., 10 to 30 minutes) can be set as the predetermined time.

[0290] Point P, which is the transition point from flow groove 321A of main flow path 320 in first section L31 to flow groove 321B in second section L32, has an inclined surface 321C as shown in FIG. 34 . In this embodiment, the angle θ between the top surface 321E of flow groove 321B of main flow path 320 and inclined surface 321C in FIG. 34 is 100°. At point P, flow groove 321A of main flow path 320 in first section L31 suddenly expands from depth D31 to depth D32 of flow groove 321B in second section L32. This is a so-called sudden expansion pipe, and when fluid 316 enters flow groove 321B from flow groove 321A, the flow of fluid 316 cannot immediately follow the flow path shape and draws in surrounding fluid 316, 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 321E of the flow channel 321B of the main flow channel 320 and the inclined surface 321C is not particularly limited, but is preferably 95° to 105°.

[0291] The ratio of the lengths of the first section L31 and the second section L32 (length of L1: length of L2) is not particularly limited, but is preferably 9:1 to 5:5. With such a ratio, it is easy to obtain the effect of suppressing time variation in the first section L31.

[0292] In this embodiment, the cross-sectional shape of the flow channel grooves 321 (321A, 321B) of the main flow channel 320 is quadrangular (particularly rectangular), but the shape is not limited thereto. The cross-sectional shape of the flow channel grooves 321 (321A, 321B) of the main flow channel 320 may be trapezoidal or semicircular. In particular, if the cross-sectional shape of the flow channel grooves 321 (321A, 321B) of the main flow channel 320 is a trapezoid whose opening side (first covering material 322 side) is larger than the bottom side of the flow channel grooves 321 (321A, 321B), the flow channel grooves 321 of the main flow channel 320 can be easily manufactured using a mold. In the case of such a shape, the widths W31 and W32 and the depths D31 and D32 of the flow channel grooves 321 (321A, 321B) refer to the maximum width and maximum depth of the flow channel grooves 321 (321A, 321B).

[0293] In the present embodiment, the main flow path 320 is configured to have a greater conduit resistance than the first communicating path 330. The conduit resistance of a flow path is determined by various conditions, and generally, the main flow path 320 will have a greater conduit resistance than the first communicating path 330 when the main flow path 320 is longer, has a greater conduit friction coefficient, is narrower, or has a higher flow rate than the first communicating path 330. In the present embodiment, as described above, the flow path length M31 from the fluid inlet 323 to the first connecting portion X31 is sufficiently longer than the flow path length M32 from the dilution solvent reservoir 333 to the first connecting portion X31, and the conduit resistance of the main flow path 320 is greater than the conduit resistance of the first communicating path 330.

[0294] [Configuration of the Detection Unit] In the testing device 301, the detection unit 350 is attached to a notch 340A in the outlet 340 provided in the substrate 310. With this configuration, the detection unit 350 in the testing device 301 is fluidically connected to the outlet 340 of the fluid control unit 311, and a mixed solution 319 of a dilution solvent 317 and a specimen liquid 318B is guided to the detection unit 350 by a hydrophilic first coating material 322 provided on the underside of the outlet 340. The detection unit 350 can then detect the target substance (gene amplification product) contained in the mixed solution 319 flowing out of the outlet 340. The fluid control unit 311 allows the post-reaction specimen liquid 318B, which has undergone a nucleic acid amplification reaction for a predetermined period of time, to flow into the detection unit 350 together with the dilution solvent 317. The mixed solution 319 flowing into the detection unit 350 is specimen liquid 318B diluted to properties (viscosity, concentration, etc.) suitable for detection, making it easy to detect the target substance (gene amplification product). The detection unit of a commercially available test kit for immunochromatography or the like can be used as the detection unit 350. In this embodiment, a detection unit using chromatography paper with a conjugate pad (e.g., a nucleic acid chromatography strip) is used as the detection unit 350. Using chromatography paper with a conjugate pad as the detection unit 350 eliminates the need to add a developing solution.

[0295] [Inspection Method Using Inspection Device 301] Next, an inspection method using inspection device 301 will be described in relation to the functions and actions of each part of inspection device 301.

[0296] The specimen liquid 318A, dilution solvent 317, and fluid 316 are prepared in advance. The specimen liquid 318A is a reaction liquid before the nucleic acid amplification reaction has progressed, which is prepared by mixing a specimen, such as saliva or a nasopharyngeal swab collected from a human or animal, with a reaction reagent, such as a nucleic acid amplification reagent. The dilution solvent 317 is a solvent for diluting the specimen liquid 318B after the nucleic acid amplification reaction, and is a liquid such as water or a buffer solution. The fluid 316 is a fluid control fluid for causing the specimen liquid 318A remaining in the first communication passage 330 and the dilution solvent reservoir 333 to flow toward the second connection portion X32, and also serves as a timing fluid for measuring a predetermined time based on the time required for the specimen liquid 318A to pass through the restricted section 314 of the main flow path 320. For this reason, a liquid with small viscosity variations, such as water or a buffer solution, is used as the fluid 316, and it has been confirmed in advance that the time required for the fluid 316 introduced into the fluid inlet 323 to reach the first connection part X31 is within a tolerance of ±5% of a predetermined time. The specimen liquid 318, the diluent solvent 317, and the fluid 316 are all hydrophilic.

[0297] 37 , fluid 316 is introduced into fluid inlet 323, diluent 317 is introduced into diluent solvent reservoir 333, and specimen liquid 318A is introduced into specimen liquid reservoir 338. The introduction of fluid 316 into fluid inlet 323 and the introduction of specimen liquid 318A into specimen liquid reservoir 338 are preferably simultaneous, but may be slightly different, and the order of introduction is not particularly limited. Diluent 317 only needs to be introduced into diluent solvent reservoir 333 by the time fluid 316 reaches first connection portion X31. Diluent 317 may be introduced before fluid 316 and specimen liquid 318A, may be introduced simultaneously with fluid 316 and specimen liquid 318A, or may be introduced after the introduction of fluid 316 and specimen liquid 318A and before fluid 316 reaches first connection portion X31.

[0298] As shown in Figures 37 and 38, the diluent solvent 317 introduced into the diluent solvent reservoir 333 is guided by the surface 332A of the second coating material 332 in the first connecting passage 330, causing a portion of the diluent solvent to flow out of the diluent solvent reservoir 333, fill the first connecting passage 330, and be guided further to the first connecting portion X31. The diluent solvent 317 then forms a droplet 317a at the first connecting portion X31. In this embodiment, as shown in Figure 38, the droplet 317a wets and spreads on the surface 332A of the second coating material 332 above the first connecting portion X31 and is held on the surface 332A of the second coating material 332 in a state where it hangs down due to surface tension and gravity. At this time, the droplet 317a does not come into contact with the first coating material 322. Even if the droplet 317a comes into contact with the side surface 321Ba and the top surface 321Bb of the flow channel 321 of the main flow channel 320, or the side surface 331a and the bottom surface 331b of the first flow channel 331, the droplet 317a does not wet and spread because these surfaces are all hydrophobic, and the droplet 317a becomes a rounded droplet due to surface tension. With this configuration, the droplet 317a is held at the first connection part X31, and the dilution solvent 317 does not flow out from the first connection part X31 before coming into contact with the fluid 316.

[0299] Similarly, as shown in FIG. 37 , the sample liquid 318A introduced into the sample liquid reservoir 338 is guided by the surface 332A of the second coating material 332 in the second connecting passage 335, causing a portion of the sample liquid to flow out of the sample liquid reservoir 338, fill the second connecting passage 335, and be guided to the second connecting portion X32. The sample liquid 318A then forms a droplet 318a at the second connecting portion X32. The droplet 318a of the sample liquid 318A assumes a state similar to that of the droplet 317a of the dilution solvent 317 shown in FIG. 38 and is held on the surface 332A of the second coating material 332. With this configuration, the droplet 318a of the sample liquid 318 (318A, 318B) is held at the second connecting portion X32, and the sample liquid 318 (318A, 318B) does not flow out of the second connecting portion X32 before coming into contact with the dilution solvent 317.

[0300] On the other hand, when fluid 316 is introduced into fluid inlet 323, it departs from starting point S, passes through restricted section 314 of main channel 320 for a predetermined time (e.g., a preset time such as 20 minutes), and arrives just before first connection portion X31 ( FIG. 39 ). Main channel 320 according to this embodiment can regulate the predetermined time by the time required to pass through main channel 320, and during this predetermined time, a nucleic acid amplification reaction between the sample and reaction reagent in sample liquid 318A progresses, resulting in sample liquid 318B containing a nucleic acid amplification product.

[0301] When the fluid 316 that has passed through the main channel 320 over a predetermined time reaches the first connection portion X31, it comes into contact with the droplets 317a of the diluent solvent 317. Then, as shown in FIGS. 40 and 41 , at least the diluent solvent 317 flows out from the first connection portion X31. In this manner, the fluid 316 that has passed through the main channel 320 acts to cause the diluent solvent 317 that has remained in the first communication passage 330 and the diluent solvent reservoir 333 to flow out. The fluid 316 that has passed through the main channel 320, which has a long channel length, loses pressure (propulsion force) due to friction with the wall surfaces within the channel before reaching the first connection portion X31. Therefore, at the first connection portion X31, the outflow of the diluent solvent 317 from the first communication passage 330 takes priority over the outflow of the fluid 316 from the main channel 320. The fluid control unit 311 can also be called a "surface tension valve" that utilizes surface tension, since at the first connection part X31 where two flow paths are connected, a 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.

[0302] According to the fluid control unit 311 of this embodiment, the diluent solvent 317 in the first communicating path 330 can be released by the action of the fluid 316 introduced into the same substrate 310, without requiring an operation to open the first communicating path 330 from outside the microchip. Furthermore, in the fluid control unit 311 of this embodiment, the second coating material 332 at least partially overlaps with the first connecting portion X31 in a plan view of the substrate 310, so that the surface 332A of the second coating material 332 can guide the diluent solvent 317 to the first connecting portion X31. That is, in the fluid control unit 311, the surface 332A of the second coating material 332 in the first communicating path 330 serves as a guide that guides the diluent solvent 317 to the first connecting portion X31.

[0303] The fluid control unit 311 according to this embodiment is configured so that the flow path length M31 of the main flow path 320 from the fluid inlet 323 to the first connecting portion X31 is greater than the flow path length M32 of the first communicating passage 330 from the diluent solvent reservoir 333 to the first connecting portion X31, and the main flow path 320 has a greater conduit resistance than the first communicating passage 330. Therefore, when the fluid 316 passing through the main flow path 320 comes into contact with the droplet 317a of the diluent solvent 317 formed at the first connecting portion X31, the diluent solvent 317 naturally flows out of the first connecting portion X31 and into the second connecting portion X32.

[0304] Similarly, the diluent solvent 317 flowing out from the first connection portion X31 reaches just before the second connection portion X32 ( FIG. 40 ) and comes into contact with the droplet 318a of the sample liquid 318B. Then, the sample liquid 318B flows out together with the diluent solvent 317 from the second connection portion X32. That is, the diluent solvent 317 flowing out from the first connection portion X31 acts to cause the sample liquid 318B that had remained in the second communication path 335 and the sample liquid reservoir 338 to flow out. This acts as a "surface tension valve" similar to the first connection portion X31.

[0305] Here, the second communication passage 335 and the flow channel 321B of the main flow channel 320 between the first connection portion X31 and the second connection portion X32 are both short, and the cross-sectional area of ​​the flow channel 321B is large, so pressure loss due to friction is sufficiently small, and there is no significant difference in the conduit resistance between the two. Therefore, there is essentially no difference in the outflow of the diluent solvent 317 and the analyte liquid 318B from the second connection portion X32 due to conduit resistance. The outflow of the diluent solvent 317 and the analyte liquid 318B from the second connection portion X32 is performed so that the liquid level H31 of the diluent solvent 317 in the diluent solvent reservoir 333 and the liquid level H32 of the analyte liquid 318B in the analyte liquid reservoir 338 are equalized so that their potential energies (potential heads) are the same.

[0306] The outflow of diluent solvent 317 from diluent solvent reservoir 333 and the outflow of specimen liquid 318B from specimen liquid reservoir 338 will be described with reference to the cross-sectional views of each reservoir in Figure 44. In Figure 44, S1 indicates the cross section taken along line E-E in Figure 39, S2 indicates the cross section taken along line G-G in Figure 42, and S3 indicates the cross section taken along line H-H in Figure 43. As shown in Figure 44, diluent solvent 317 and specimen liquid 318B are substantially fully introduced into diluent solvent reservoir 333 and specimen liquid reservoir 338, respectively, before outflow. Because the height of each reservoir is equal to the thickness of substrate 310, the liquid level H31 in diluent solvent reservoir 333 and the liquid level H32 of specimen liquid 318B in specimen liquid reservoir 338 are the same (S1). Next, the action of fluid 316 causes diluent solvent 317 to flow out from first connection portion X31, and then, as shown in Figure 42, when diluent solvent 317 and specimen liquid 318B flow out from second connection portion X32, diluent solvent 317 and specimen liquid 318B flow out together while maintaining the same liquid level heights H31 and H32 (S2). The flow rate ratio of diluent solvent 317 and specimen liquid 318B at this time is the cross-sectional area ratio of diluent solvent reservoir 333 and specimen liquid reservoir 338. Finally, diluent solvent 317 and specimen liquid 318B flow out while maintaining the same liquid level heights H31 and H32 until they reach a level at which they can flow out (S3). In this embodiment, the dilution solvent 317 in the dilution solvent reservoir 333 and the specimen liquid 318B in the specimen liquid reservoir 338 flow out together toward the outlet 340 at a volume ratio corresponding to the cross-sectional area ratio of each reservoir, so that the specimen liquid 318B is diluted by the dilution solvent 317 at a constant dilution ratio.

[0307] The lower opening of notch 340A of outlet 340 is covered with first coating material 322 with a hydrophilic surface that extends from main channel 320, so that mixed solution 319 of hydrophilic dilution solvent 317 and sample liquid 318B can be quickly introduced onto the chromatography paper with a conjugate pad in detection unit 350. Through the above-mentioned steps, gene amplification products (target substances) can be detected in detection unit 350.

[0308] The test result in the test device 301 is confirmed by whether or not both the detection line C and the detection line T appear in the detection unit 350, as shown in an example in Fig. 43. If both the detection line C and the detection line T appear in the detection unit 350, it is positive, and if only the detection line C appears, it is negative.

[0309] In the fluid control unit 311 of the testing device 301, when the fluid 316 reaches the first connection part X31, the mixed liquid 319 of the dilution solvent 317 and the specimen liquid 318B eventually flows out of itself to the outlet 340. In this way, even without external control to open the first communicating path 330, the fluid control unit 311 opens the first communicating path 330 in response to the action of the fluid 316, and opens the second communicating path 335 in response to the action of the dilution solvent 317, allowing the dilution solvent 317 and the specimen liquid 318B to flow out.

[0310] Furthermore, in the fluid control unit 311 according to this embodiment, the fluid 316 introduced into the fluid inlet 323 passes through the restricted section 314 of the main channel 320 over a predetermined time, and then both the dilution solvent 317 and the specimen liquid 318B flow out, so that when the specimen liquid 318A, which is the reaction liquid before the reaction, is introduced, the specimen liquid 318B after the nucleic acid amplification reaction for a predetermined time can be diluted and introduced into the detection unit 350. The presence of the restricted section 314 suppresses variations in the test results due to variations in reaction time, and the specimen liquid 318B is diluted to properties (viscosity, concentration, etc.) suitable for detection before detecting the nucleic acid amplification product, so that the test accuracy can be improved while still providing a test kit in the form of one that allows for simple and rapid detection.

[0311] As described above, the fluid control unit 311 of the testing device 301 of this embodiment allows small volumes of diluent solvent 317 and specimen liquid 318B to flow out together on the microchip. At this time, it is possible to allow diluent solvent 317 and specimen liquid 318B to flow out together at a volume ratio corresponding to the ratio of the internal volumes of diluent solvent reservoir 333 and specimen liquid reservoir 338. In particular, in this embodiment, diluent solvent 317 in diluent solvent reservoir 333 and specimen liquid 318B in specimen liquid reservoir 338 can simultaneously flow out toward outlet 340 at a volume ratio corresponding to the cross-sectional area ratio of the through-holes while maintaining liquid level heights H31 and H32.

[0312] Furthermore, since the first fluid control mechanism and the second fluid control mechanism of this embodiment are surface tension valves, it is possible to realize a fluid control mechanism in which the dilution solvent 317 and the specimen liquid 318B mix autonomously without any external action.

[0313] Furthermore, in the fluid control unit 311 of this embodiment, the flow channel 321 of the main flow channel 320 has a regulated section 314, so that when a fluid 316 is introduced into the main flow channel 320 and the fluid 316 comes into contact with a droplet 317a of diluent solvent 317 at the first connection portion X31, the diluent solvent 317 flows out from the first connection portion X31, and then, when the diluent solvent 317 comes into contact with a droplet of sample liquid 318B at the second connection portion X32, the sample liquid 318B can flow out from the second connection portion X32 together with the diluent solvent 317.

[0314] 9. Testing Apparatus According to the Ninth Embodiment A testing apparatus 302 according to a ninth embodiment of the present invention will be described using FIGS. 45 to 47. The testing apparatus 302 according to the ninth embodiment differs from the eighth embodiment in the configuration of the fluid control unit. Specifically, the testing apparatus 302 includes a fluid control unit 312 that includes a sample liquid reservoir 360 that has a different shape from the sample liquid reservoir 338 according to the eighth embodiment. The testing apparatus 302 is used in the same manner as the testing apparatus 301. The following description will focus on the differences from the eighth embodiment. Note that points that are not specifically described are the same as those in the eighth embodiment.

[0315] The specimen liquid reservoir 360 in the testing device 302 is formed by joining a cylindrical member 361 to the upper part of a through-hole 339 in the substrate 310, so that the specimen liquid reservoir 360 protrudes above the substrate 310. In particular, the inner wall of the specimen liquid reservoir 360 is formed by connecting an inner wall 361A of the cylindrical member 361 to a side wall 339A of the through-hole 339 in the substrate 310. The height of the inner wall of the specimen liquid reservoir 360 is 5 to 15 times (e.g., 8 to 9 times) that of the specimen liquid reservoir 338 of the eighth embodiment. Here, the height of the diluent solvent reservoir 333 is the shortest distance from the rear surface to the front surface of the substrate 310 (i.e., the thickness of the substrate 310), and the height of the sample liquid reservoir 360 is the shortest distance from the rear surface of the substrate 310 to the open top surface of the sample liquid reservoir 360 (the top surface 361B of the cylindrical member 361) when the testing device 302 is installed ( FIG. 46 ). The cross-sectional area of ​​the through-hole 339 of the substrate 310 and the cross-sectional area of ​​the inner diameter of the cylindrical member 361 are smaller than those of the sample liquid reservoir 338 according to the eighth embodiment. Although not limited thereto, the cross-sectional area of ​​the sample liquid reservoir 360 according to this embodiment is set to 1 / 16 to 1 / 4 (e.g., 1 / 8) of the cross-sectional area of ​​the sample liquid reservoir 338. In this way, the sample liquid reservoir 360 according to this embodiment has the same internal volume as the sample liquid reservoir 338 according to the eighth embodiment by changing the cross-sectional area and height.

[0316] Although not limited to this, an example is possible in which the diluent solvent reservoir 333 has a height of 0.75 mm and an inner diameter of 4.0 mm, and the sample liquid reservoir 360 has a height of 6.45 mm (the height of the cylindrical member is 5.7 mm) and an inner diameter of 1.5 mm. In this case, the internal volume of the diluent solvent reservoir 333 is 9.4 mm, and the internal volume of the sample liquid reservoir 360 is 11.4 mm.

[0317] The diluent solvent reservoir 333 is unchanged from the eighth embodiment, and the height of the sample liquid reservoir 360 is relatively greater than the height of the diluent solvent reservoir 333. With this configuration, the communication portion where the taller sample liquid reservoir 338 communicates with the main channel 320 (i.e., second connection portion X32) is located closer to the outlet 340 than the communication portion between the diluent solvent reservoir 333 and the main channel 320 (i.e., first connection portion X31).

[0318] The outflow of diluent solvent 317 from diluent solvent reservoir 333 and the outflow of specimen liquid 318B from specimen liquid reservoir 360 will be described with reference to the cross-sectional views of each reservoir in Figure 47. S1 shows the state of fluid 316, diluent solvent 317, and specimen liquid 318B corresponding to the cross section taken along line E-E (Figure 39) in the eighth embodiment. Similarly, S2 shows the state of fluid 316, diluent solvent 317, and specimen liquid 318B corresponding to the cross section taken along line G-G (Figure 42), and S3 shows the state of fluid 316, diluent solvent 317, and specimen liquid 318B corresponding to the cross section taken along line H-H (Figure 43).

[0319] 39 in the eighth embodiment, the cross sections of the diluent solvent reservoir 333 and the specimen liquid reservoir 338 are in the state of S1 in FIG. 47, and when the diluent solvent reservoir 333 and the specimen liquid reservoir 338 are fully filled with the diluent solvent 317 and the specimen liquid 318A, respectively, the liquid level H33 of the specimen liquid 318B in the specimen liquid reservoir 360 is greater than the liquid level H31 of the diluent solvent 317. In this embodiment, the liquid level H33 is set to about eight times the liquid level H31.

[0320] Thereafter, the action of fluid 316 causes diluent solvent 317 to flow out from first connection portion X31. When diluent solvent 317 reaches second connection portion X32, diluent solvent 317 comes into contact with droplet 318a of sample liquid 318B, opening second communication path 335. In this embodiment, based on the difference in potential energy (difference in potential head) between diluent solvent 317 and sample liquid 318, sample liquid 318B, which has a larger liquid level height H33, flows preferentially from second connection portion X32 toward outlet 340. Sample liquid 318B continues to flow preferentially out from second connection portion X32 until it matches the liquid level height H31 of diluent solvent 317. Thereafter, when the liquid level height H33 of sample liquid 318B matches the liquid level height H31 of diluent solvent 317, as shown in S2 of FIG. 47 , diluent solvent 317 and sample liquid 318B both flow out so that their liquid levels match, as shown in S3. As in the eighth embodiment, the flow rate ratio of diluent solvent 317 to specimen liquid 318B at this time is the cross-sectional area ratio of diluent solvent reservoir 333 to specimen liquid reservoir 360. Because the cross-sectional area of ​​diluent solvent reservoir 333 is larger than the cross-sectional area of ​​specimen liquid reservoir 360, a mixed liquid with a higher ratio of diluent solvent 317 than specimen liquid 318B flows out from stages S2 to S3.

[0321] According to the testing device 302 of this embodiment, the sample liquid 318B is preferentially flowed toward the outlet 340 first, followed by the diluent solvent 317, allowing the sample liquid 318B and the diluent solvent 317 to flow out sequentially. This configuration allows a high-concentration or high-viscosity solution such as the sample liquid 318B to be washed away with a diluent or the like in the main channel 320 and the outlet 340. Even with this configuration, the diluent solvent 317 in the diluent solvent reservoir 333 and the sample liquid 318B in the sample liquid reservoir 360 both flow out toward the outlet 340 at a volume ratio corresponding to the ratio of the internal volumes of the respective reservoirs, so that the sample liquid 318B is diluted by the diluent solvent 317 at a constant dilution ratio. Even when the diluent solvent 317 flows out sequentially after the sample liquid 318B, the sample liquid 318B can easily reach the detection unit 350, facilitating rapid detection of the nucleic acid amplification product (target substance) in the detection unit 350.

[0322] 10. Testing Apparatus According to the Tenth Embodiment Next, a testing apparatus 303 according to a tenth embodiment of the present invention will be described using FIGS. 48 to 52. A fluid control unit 313 according to the tenth embodiment differs from the fluid control unit 311 according to the eighth embodiment in the shape of the main channel 320 and the arrangement of the diluent solvent reservoir 333 and the specimen liquid reservoir 338 relative to the main channel 320. The following description will focus on the differences from the eighth embodiment. Note that points not specifically described are the same as those in the eighth embodiment. Note that the diluent solvent reservoir 333 and the specimen liquid reservoir 338 according to this embodiment are arranged differently from those in the eighth embodiment, but have the same shape and size.

[0323] The main channel 320 in the testing device 303 has, downstream of the restriction section 314, a branch point Q, a first branch path 371 fluidly connected to the diluent reservoir 333 between the branch point Q and the outlet 340, and a second branch path 372 fluidly connected to the sample liquid reservoir 338 between the branch point Q and the outlet 340. A channel length L33 from the branch point Q to the first connection point X31 (i.e., the communication portion between the diluent reservoir 333 and the first branch path 371) is different from a channel length L34 from the branch point Q to the second connection point X32 (i.e., the communication portion between the sample liquid reservoir 338 and the second branch path 372). In this embodiment, the channel length L33 is longer than the channel length L34. The first branch path 371 and the second branch path 372 are each directly fluidly connected to the outlet 340. Therefore, in this embodiment, the outlet 340 is only the notch 340A in the base plate 310.

[0324] 49, in the testing device 303, fluid 316, diluent solvent 317, and specimen liquid 318A are first introduced into fluid inlet 323, diluent solvent reservoir 333, and specimen liquid reservoir 338, respectively. As shown in the cross-sectional view of FIG. 52 (S1), the liquid level H31 of diluent solvent and the liquid level H32 of specimen liquid 318B before they flow out are substantially the same.

[0325] Fluid 316 passes through restriction section 314, branches into first branch path 371 and second branch path 372 at branch point Q, and reaches second connection portion X32 before first connection portion X31, as shown in Figure 50. Fluid 316 then contacts droplet 318a of sample liquid 318B at second connection portion X32 first, and sample liquid 318B flows out of second connection portion X32 first. With regard to the liquid level heights of diluent solvent 317 and sample liquid 318B in Figure 50, only liquid level height H32 in sample liquid reservoir 338 is reduced, as shown in the cross-sectional view of Figure 52 (S2).

[0326] Thereafter, when the fluid 316 reaches the first connection portion X31 and comes into contact with the droplet 317a at the first connection portion X31, the diluent solvent 317 flows out from the second connection portion X32 toward the outlet 340, as shown in FIG. 51 . Then, as shown in the cross-sectional view of FIG. 52 (S3), the liquid level of the diluent solvent 317 decreases with a time lag. As in the eighth embodiment, the flow rate ratio of the diluent solvent 317 and the sample liquid 318B flowing out with a time lag is the cross-sectional area ratio of the diluent solvent reservoir 333 and the sample liquid reservoir 360. In this way, the diluent solvent 317 and the sample liquid 318B pass through the first branch path 371 and the second branch path 372, respectively, and flow out to the outlet 340, where the nucleic acid amplification product is detected in the detection unit 350.

[0327] Even with this configuration, diluent solvent 317 in diluent solvent reservoir 333 and specimen liquid 318B in specimen liquid reservoir 338 flow out together toward outlet 340 at a volume ratio that corresponds to the ratio of the internal volumes of the reservoirs (in this embodiment, the ratio of the cross-sectional areas of the through-holes of the reservoirs), so specimen liquid 318B is diluted at a constant dilution ratio. Furthermore, by branching main channel 320 and varying the flow path lengths L33, L34 from branch point Q to each communicating portion, diluent solvent 317 and specimen liquid 318B can be caused to flow out at different times. Even if diluent solvent 317 flows out after specimen liquid 318B at different times, specimen liquid 318B can easily reach detection unit 350, facilitating rapid detection of nucleic acid amplification products (target substances) in detection unit 350.

[0328] Other embodiments of the second fluid control device and the third 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.

[0329] In the eighth and ninth embodiments described above, the diluent solvent reservoir 333 and the specimen liquid reservoir 338 are configured such that the diluent solvent reservoir 333 is located upstream and the specimen liquid reservoir 338 is located downstream in the main flow path 320. However, the present invention is not limited to this configuration, and the diluent solvent reservoir 333 may be located downstream and the specimen liquid reservoir 338 may be located upstream.

[0330] In the above ninth embodiment, the diluent solvent reservoir 333 and the sample liquid reservoir 338 are described as being configured such that the height of the sample liquid reservoir 338 is greater than the height of the diluent solvent reservoir 333. However, the present invention is not limited to this configuration, and the height of the diluent solvent reservoir 333 may be greater than the height of the sample liquid reservoir 338.

[0331] In the above tenth embodiment, a configuration in which the flow path length L33 is longer than the flow path length L34 has been described as an example. However, the present invention is not limited to this configuration, and the flow path length L34 may be longer than the flow path length L33.

[0332] In the above embodiment, a fluid control mechanism using a surface tension valve has been described as an example. However, the fluid control mechanism is not limited to such a configuration, and for example, other fluid control devices using other fluid control mechanisms may also be used.

[0333] In the above embodiment, an example was described in which, in the fluid control mechanism for the inspection devices 301 to 303, the main flow path 320 and the first communication path 330 overlap at the bottom portions of the respective flow path grooves, and the first connection portion X31 is formed so that the first communication path 330 protrudes into the main flow path 320 in a front view, as shown in FIG. However, the first connection portion X31 and the second connection portion X32 are not limited to such a configuration as long as they fluidly connect the main flow path 320 and the first communication path 330, and the main flow path 320 and the second communication path 335. For example, as shown in FIGS. 53 and 54, the first connection portion X31 and the second connection portion X32 may be formed by providing the first communication path 330 and the second communication path 335, respectively, so as to cross the main flow path 320 in a plan view. In this case, in a microchannel device having fine channels, it is not necessary to precisely control the processing dimensions of the connection portion between channel groove 321 of main channel 320 and first channel groove 331, and the connection portion between channel groove 321 of main channel 320 and second channel groove 336, making it easier to manufacture the fluid control mechanism. Also, for example, as shown in Figures 55 and 56, first communication passage 330 and second communication passage 335 may be provided so as to abut against the side wall of main channel 320, and the main channel 320 and first communication passage 330, and the main channel 320 and second communication passage 335 may be fluidly connected at the side wall portions of each channel groove to form the connection portion. In this case, the depth D34 of the second channel groove is set to be deeper than D33 in the above embodiment.

[0334] In the above embodiment, the test devices 301 to 303 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.

[0335] In the above embodiment, an example has been described in which the main flow path 320 and the flow path grooves 321 (321A, 321B) that configure the main flow path 320 have the restriction section 314. However, the present invention is not limited to such a configuration, and the restriction section 314 may not be provided.

[0336] In the above embodiment, an example was described in which the restricted section 314 includes a first section L31 and a second section L32 in this order from the starting point S. However, this configuration is not limited to this. The second section L32 may be located before the first section L31, or the second section L32 may be sandwiched between first sections L31, or the first section L31 may be sandwiched between second sections L32. Furthermore, while an example was described in which the first section L31 is longer than the second section L32, this configuration is not limited to this. The second section L31 may be longer than the first section L31. Furthermore, while an example was described in which the second section L32 has the same width as the first section L31, this configuration is not limited to this. The width of the second section L32 may be larger than the width of the first section L31. For example, the width of the second section L32 may be two to four times the width of the first section L31.

[0337] The second fluid control device and the third testing device according to the present invention can be used, for example, as a dilution device in a microchip and a testing device using the same.

[0338] 11. Eleventh Embodiment An inspection device 401 according to an eleventh embodiment of the present invention will be described with reference to Figures 57 to 71. When terms indicating directions are used in the following description of this specification, unless otherwise specified, the vertical direction refers to the up-down direction on the plane of the drawing, and the horizontal direction refers to the left-right direction on the plane of the drawing that is perpendicular to the plane of the drawing. Furthermore, the up-down direction, depth direction, and height direction also refer to the up-down direction on the plane of the drawing.

[0339] [Overview of Testing Device 401] Testing device 401 according to the present invention is used as a test kit for testing for infectious diseases caused by, for example, viruses, bacteria, etc., and includes a specimen preparation unit 410 (an example of a dilution device according to the present invention) and a detection unit 420. Specimen preparation unit 410 reacts a specimen such as saliva or a nasopharyngeal swab with a nucleic acid amplification reagent (an example of a reaction reagent), and has the function of diluting specimen liquid 418B after the reaction before introducing it into detection unit 420. In the eleventh to thirteenth embodiments, the terms "specimen" and "specimen liquid" are used regardless of whether they are before or after the reaction or the degree of progress of the reaction.

[0340] [Configuration of the specimen preparation section] As shown in Figures 57 to 61, the specimen preparation section 410 is composed of a diluent outlet section 430 that discharges diluent 417 into a specimen dilution tank 440 (an example of a specimen dilution section), and the specimen dilution tank 440 that reacts with the introduced specimen and dilutes the specimen after the reaction.

[0341] (Configuration of Diluent Outlet Portion) The diluent outlet port 430 according to this embodiment is formed on a microchannel chip substrate (substrate 411). As shown in cross-sectional views such as Figures 57 and 64, the diluent outlet port 430 according to this embodiment includes a first flow channel 412 formed on at least one surface of the substrate 411, a first coating material 413 covering the first flow channel 412, a fluid inlet 431 (an example of a fluid receiving portion) that communicates with the first flow channel 412 and through which a fluid 416 is introduced, and a diluent reservoir 435 (an example of a diluent receiving portion) that communicates with the first flow channel 412 and through which a diluent 417 is introduced. The fluid inlet 431 is located upstream of the first flow channel 412, and the diluent reservoir 435 is located downstream of the fluid inlet 431 and downstream of the first flow channel 412.

[0342] In this embodiment, the substrate 411 is erected approximately vertically so that the outflow direction downstream of the first flow channel 412 is vertically downward (the direction of the arrow in Figure 57) and the longitudinal direction of the substrate 411 is positioned in the up-down direction.

[0343] As shown in the side view of Fig. 58, the diluent reservoir 435 is formed in a pocket shape on one surface of the substrate 411. In detail, a fixing portion 436A of a pocket-shaped member 436 having the shape shown in Fig. 63 is fixed to an attachment portion 411A on one surface of the substrate 411 shown in Fig. 62, thereby forming a diluent storage portion for the diluent 417 in the diluent reservoir 435. The diluent reservoir 435 is in fluid communication with the second flow channel 434 via a diluent inlet 433 formed as a through-hole in the substrate 411.

[0344] As shown in FIG. 67 , in a front view (partially enlarged view) of the upright substrate 411, the second flow channel 434, which connects the diluent inlet 433 and the first flow channel 412, intersects with the first flow channel 412 at a right angle. The first flow channel 510, which is formed by the first flow channel 412 and the first covering material 413, and the second flow channel 520, which is formed by the second flow channel 434 and the second covering material 432, have a connection portion X. In this embodiment, as shown in FIG. 57 , the first flow channel 412 constituting the first flow channel 510 has five parallel straight sections and four arc-shaped curved sections connecting the five straight sections, and the fluid 416 introduced into the fluid inlet 431 makes four U-turns on the substrate 411 to reach the connection portion X. That is, the second flow channel 520 intersects the fifth straight section of the first flow channel 510 at a substantially right angle. An outlet 415 for discharging at least a diluent 417 is provided downstream of the first flow channel 412 .

[0345] As will be described in detail later, the diluent outlet 430 according to this embodiment includes a fluid control mechanism that controls the outflow of the diluent 417 from the diluent reservoir 435. As shown in FIG. 69 , the diluent 417 introduced into the diluent reservoir 435 fills the second flow channel 434 and is configured to remain at the connection portion X. When the fluid 416 introduced into the fluid inlet 431 reaches the connection portion X, the second flow channel 520 is opened, and as shown in FIG. 71 , the diluent 417 flows out of the diluent reservoir 435 via the diluent inlet 433 and reaches the outlet 415. Because the diluent outlet 430 includes the fluid control mechanism, when the fluid 416 is introduced into the fluid inlet 431 and the diluent 417 is introduced into the diluent reservoir 435, at least the diluent 417 autonomously flows out from the outlet 415.

[0346] Furthermore, as shown in FIG. 57 , the diluent outflow section 430 according to this embodiment has a restriction section 414 in which the time required for the fluid 416 to pass through the first flow channel 412 is restricted. That is, the fluid 416 passes through the restriction section 414 of the first flow channel 412 for a time corresponding to a preset time. Specifically, the time required for the fluid 416 to pass through is adjusted by the length, width, depth, etc. of the first flow channel 412. As shown in FIG. 66 , the first flow channel 412 is composed of a first flow channel 412A and a first flow channel 412B, which have different depths with point P as the boundary. Details of the restriction section 414 will be described later.

[0347] In this way, the diluent outflow section 430 of this embodiment has a time control function that controls the outflow time of the diluent 417 and a fluid control function that controls the outflow of the diluent 417 and causes the diluent 417 to flow out autonomously, and is therefore configured to autonomously cause the diluent 417 to flow out from the outlet 415 a predetermined time after the fluid 416 is introduced.

[0348] (Overview of Specimen Dilution Tank) When specimen liquid 418A, which is a reaction liquid obtained by mixing a nucleic acid amplification reagent and a specimen, is introduced into specimen dilution tank 440 according to this embodiment as shown in Fig. 59, a nucleic acid amplification reaction of the virus in the specimen proceeds, and specimen liquid 418B containing a gene amplification product is obtained as shown in Fig. 60. In this way, specimen dilution tank 440 functions as a specimen reaction tank.

[0349] In this embodiment, as described above, restriction section 414 is set so that the time it takes for diluent 417 to flow from diluent outlet 430 into specimen dilution tank 440 is a predetermined time. Therefore, as shown in Fig. 59, when specimen liquid 418A, which serves as a reaction liquid, is introduced into specimen dilution tank 440 to initiate a reaction between the specimen and the nucleic acid amplification reagent, fluid 416 is introduced into fluid inlet 431, and as shown in Fig. 60, fluid 416 reaches connection portion X, and after a predetermined time, diluent 417 autonomously flows into specimen dilution tank 440. When specimen liquid 418B containing the gene amplification product in specimen dilution tank 440 is diluted to a predetermined dilution ratio to become mixture 419, mixture 419 is introduced into detection unit 420 as shown in Fig. 61.

[0350] That is, as diluent 417 flows out of outlet 415 of diluent outlet 430 after a predetermined time and gradually flows into specimen dilution tank 440, the liquid level rises, and diluent 417 and specimen liquid 418B after the nucleic acid amplification reaction are mixed at a predetermined ratio to form mixture 419. In this embodiment, the amount of specimen liquid 418A introduced into specimen dilution tank 440 is set to a predetermined amount, and detection unit 420 is installed so that its lower end is positioned at liquid level H41 at which specimen liquid 418B after the nucleic acid amplification reaction has a predetermined dilution ratio (preferably between 10 and 50 times, e.g., 20 times). Therefore, when mixture 419 reaches the predetermined liquid level H41, specimen liquid 418B is diluted to the predetermined ratio. In the testing device 401, when the mixed liquid 419 of the dilution liquid 417 and the specimen liquid 418B reaches a predetermined liquid level height H41 or higher, the mixed liquid 419 reaches the lower end of the detection section 420 and is quickly introduced into the detection section 420.

[0351] [Configuration of the Detection Unit] The detection unit 420 detects the sample introduced from the sample dilution tank 440. In this embodiment, a thin, elongated piece of chromatography paper (e.g., a nucleic acid chromatography strip) with a conjugate pad is used as the detection unit 420, and the vicinity of the upper end of the detection unit 420 is fixed to the substrate 411 so that the lower end of the detection unit 420 is located at the liquid level height H41. Such a detection unit 420 absorbs the mixed liquid 419 containing the sample, making it easy for the detection unit 420 to quickly detect the sample (target substance). The detection unit 420 is not limited to the above-described one, and a detection unit of a commercially available test kit for immunochromatography or the like can be suitably used.

[0352] With the above configuration, the testing device 401 is configured such that by introducing the fluid 416 at approximately the same time as the start of the nucleic acid amplification reaction in the sample dilution tank 440, the sample liquid 418B that has been reacted for a predetermined time is diluted to a state (viscosity, concentration, etc.) suitable for detection, and the target substance (gene amplification product) in the sample liquid 418B is autonomously detected. The test result is confirmed, for example, by whether or not both a detection line C and a detection line T appear in the detection unit 420, as shown in Figure 61. The appearance of both the detection line C and the detection line T in the detection unit 420 indicates a positive result, and the appearance of only the detection line C indicates a negative result.

[0353] The configuration of each of the fluid control mechanism, the restriction section 414, the diluent outlet section 430, and the specimen dilution tank 440 will be described in detail below.

[0354] (Fluid Control Mechanism) First, the fluid control mechanism will be described. As shown in FIGS. 67 to 71 , the fluid control mechanism includes a first flow path 510, a second flow path 520, and an outlet 415 fluidly connected to a connection portion X between the first flow path 510 and the second flow path 520. A pocket-shaped member 436 constituting a diluent reservoir 435 is located in front of (on the front side of the page) the diluent inlet 433 in FIGS. 67 , 69 , and 71 , and above the diluent inlet 433 in FIGS. 68 and 70 , and stores the diluent 417 therein; however, this is not shown for ease of explanation. As shown in FIGS. 67 and 68 , the first flow path 510 and the second flow path 520 are fluidly connected to each other at the connection portion X by a portion of the first flow path groove 412 and the second flow path groove 434 intersecting with each other.

[0355] The fluid control mechanism in the diluent outlet 430 has a function of releasing the diluent 417, which has been introduced into the diluent reservoir 435 and remains in the diluent reservoir 435 and the second flow path 520, by the action of the fluid 416 that has flowed through the first flow path 510, and causing it to flow out through the outlet 415. In other words, the fluid control mechanism in the diluent outlet 430 has a function of a passive valve that opens the second flow path 520 in response to the action of the fluid 416.

[0356] In this embodiment, a passive valve is configured by utilizing surface tension due to the hydrophobic and water-repellent properties of the flow path surface. Specifically, in the fluid control mechanism according to this embodiment, the surface of the first flow path 510 has a first property, which is either hydrophobic or hydrophilic, the surface of the first coating material 413 of the first flow path 510 facing the first flow path groove 412 has a second property, which is the other of hydrophobic and hydrophilic, and the second flow path 520 has the second property, and includes a guide portion that guides the diluent 417 introduced into the diluent reservoir 435 to a connection portion X between the first flow path 510 and the second flow path 520. When the diluent 417 is introduced into the diluent reservoir 435 and the diluent inlet 433, the diluent 417 guided by the guide portion forms a droplet 417A at the connection portion X.

[0357] In this embodiment, a substrate 411 made of a hydrophobic resin is used, and in the arrangement shown in Figure 68, the surfaces (side surface 412D and top surface 412E) of the first flow channel 412 in the first flow channel 510 are hydrophobic (first property). The resin component constituting the substrate 411 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 411 is preferably one that has either heat resistance or transparency, or both.

[0358] The surface of the first coating material 413 covering the first flow channel 412 is hydrophilic (second property). The first coating material 413 may be hydrophilic at least on the surface facing the first flow channel 412. In this embodiment, a hydrophilic resin film, such as a hydrophilic acrylic resin, is used. The resin constituting the first coating material 413 is preferably one that has either heat resistance or transparency, or both. A hydrophilic portion may be formed by applying a hydrophilic coating to a coating material made of a hydrophobic resin, or the surface may be made hydrophilic by subjecting the coating material made of a hydrophobic resin to a hydrophilic treatment such as plasma treatment. In this embodiment, the first coating material 413 covers the entire back surface (lower surface in FIG. 68 ) of the erected substrate 411, including the first flow channel 412.

[0359] The thickness of the first covering material 413 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 412 can be easily sealed. Furthermore, when the thickness is 2 mm or less, good conformability to the irregularities of the substrate 411 can be easily obtained.

[0360] The first covering material 413 and the substrate 411 may be bonded by providing an adhesive layer on the first covering material 413 side to serve as a bonding layer with the substrate 411, or by bonding the substrate 411 and the first covering material 413 together using an adhesive or the like, or by compressing the substrate 411 and the first covering material 413 together using thermocompression bonding.

[0361] The second flow channel 434 according to this embodiment is formed so as to open to the surface of the substrate 411 opposite to the first flow channel 412 (the upper surface in FIG. 68 ). The second flow channel 434 is covered with a second coating material 432 to form a second flow channel 520. The first flow channel 412 is covered with a coating material 413 (referred to as the first coating material 413) as described above to form the first flow channel 510.

[0362] The second covering material 432 is disposed at least in a portion covering the second flow channel 434 on the surface of the substrate 411 opposite to the first covering material 413. In this embodiment, the second covering material 432 is disposed so as to overlap the connection portion X in a front view of the substrate 411. The second covering material 432 may extend so as to protrude from the second flow channel 434 toward the diluent inlet 433.

[0363] In this embodiment, the second flow channel 434 is a linear groove that is shallower and shorter than the first flow channel 412B. Specifically, the length of the second flow channel 434 is set so that the length of the first flow channel 510 from the outlet of the fluid inlet 431 to the connection portion X (referred to as flow channel length M41, not shown) is longer than the length of the second flow channel 520 from the outlet of the diluent inlet 433 to the connection portion X (referred to as flow channel length M42) ( FIG. 67 ). In this embodiment, the flow channel length M41 is set sufficiently long, for example, 10 times or more longer than the flow channel length M42.

[0364] The width and depth of the second flow channel 434 are not particularly limited, but in this embodiment, for example, 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 0.5 mm.

[0365] The second flow channel 434 is formed on the same substrate 411 as the first flow channel 412, and therefore the surfaces (side surface 434D and bottom surface 434E) of the second flow channel 434 are hydrophobic (first property). In this embodiment, the second coating material 432 uses the same hydrophilic resin film as the first coating material 413, and the surface 432A of the second coating material 432 is hydrophilic (second property).

[0366] Diluent 417 introduced into diluent reservoir 435 is an aqueous solution such as water or a buffer solution, and fluid 416 introduced into fluid inlet 431 is an aqueous solution such as water or a buffer solution. Since both fluid 416 and diluent 417 are hydrophilic liquids, in first flow path 510, fluid 416 is repelled by the surface of first flow path groove 412 and exhibits the property of wetting and spreading on the surface of first coating material 413. Similarly, diluent 417 is repelled by the surface of first flow path groove 412 and the surface of second flow path groove 434 in second flow path 520 and exhibits the property of wetting and spreading on the surfaces of first coating material 413 and second coating material 432.

[0367] Therefore, when a fluid 416 is introduced into the first flow path 510 from the fluid inlet 431, the fluid 416 flows along the hydrophilic surface of the first coating material 413 and into the first flow path 510. Similarly, when a diluent 417 is introduced into the second flow path 520 from the diluent reservoir 435, the diluent 417 flows along the hydrophilic surface 432A of the second coating material 432 and into the second flow path 520.

[0368] The first covering material 413 and the second covering material 432 may be different in material, thickness, etc., as long as their surfaces are hydrophilic. Furthermore, the method for bonding the substrate 411 and the second covering material 432 may be different from the method for bonding the substrate 411 and the first covering material 413. In this embodiment, since the area of ​​the second covering material 432 is smaller than the area of ​​the first covering material 413, the first covering material 413 may be bonded by thermocompression bonding, and the second covering material 432 may be bonded by an adhesive layer or a bonding layer.

[0369] Although this is an example of one embodiment and is not limited thereto, the thickness of the substrate 411 in this embodiment is approximately 0.75 mm. The depth D41 of the first flow channel 412A is 0.1 mm, the depth D42 of the first flow channel 412B is approximately 0.4 mm, and the depth D43 of the second flow channel 434 is approximately 0.35 mm. Therefore, the groove bottom portions (412E and 434E) of the first flow channel 510 and the second flow channel 520 are on approximately the same plane, and the groove bottom portions of the first flow channel 412B and the second flow channel 434 overlap, thereby fluidly communicating with each other. With this configuration, a through hole is formed in the substrate 411 at the connection portion X, and the first coating material 413 and the second coating material 432 are located on both sides of the through hole.

[0370] Fluid inlet 431 is a through-hole formed in substrate 411, and although there are no limitations on its shape or size as long as it can introduce fluid 416 into first flow channel 510, in this embodiment it is a circular hole with a diameter of 2 to 5 mm (for example, a diameter of 4 mm). One side of the through-hole of fluid inlet 431 is open, and the other side is covered with first covering material 413 extending from first flow channel 510.

[0371] Like fluid inlet 431, diluent inlet 433 is a through-hole formed in substrate 411, and although there are no limitations on its shape or size as long as it can introduce diluent 417 into second flow channel 520, in this embodiment it is a circular hole with a diameter of 2 to 5 mm (for example, a diameter of 4 mm). One side of the through-hole of diluent inlet 433 opens to pocket-shaped member 436 (diluent reservoir side), and the other side is covered with first covering material 413.

[0372] The outlet 415 represents a region downstream from the connection portion X and includes a downstream end portion of the first flow path 510 (having a first flow path groove 412B with a depth D42) and a notch 415A that is fluidically connected to the downstream end portion of the first flow path 510. The notch 415A opens on one side of the substrate 411 and penetrates the substrate 411 in the thickness direction. In this embodiment, a specimen dilution tank 440 is attached to the lower end portion of the notch 415A. The sidewall of the notch 415A is hydrophobic, similar to the substrate 411. The open side of the notch 415A is covered with a hydrophilic first coating material 413 that extends from the first flow path 510.

[0373] The outer shape and size of the substrate 411 can be set appropriately taking into consideration ease of handling, etc. For example, if the substrate 411 is quadrilateral (square or rectangle), it is preferable that each side is 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 411 is not particularly limited, and may be other polygonal, circular, elliptical, or the like. The thickness of the substrate 411 is also not particularly limited, and can be, for example, 5 to 20 mm.

[0374] The resin substrate 411 can be produced by a resin molding process technique, such as injection molding, transfer molding, or extrusion molding.

[0375] 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 spreads, and the degree and physical value of the property are not particularly limited. In this embodiment, the surface of the substrate 411, 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 411 with water is preferably 70° or more, and more preferably 80° or more. The upper limit of the contact angle of the substrate 411 with water is preferably 95° or less, and more preferably 90° or less. Furthermore, the surfaces of the first coating material 413 and the second coating material 432, 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 413 and the second coating material 432 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.

[0376] Specimen dilution tank 440 is not particularly limited as long as it has a capacity large enough to accommodate diluent 417 and specimen liquid 418 (418A, 418B). In this embodiment, specimen dilution tank 440 is formed from a resin microtube, which is fixed to the lower end of notch 415A of substrate 411. Specifically, two vertically extending notches are made in opposing positions at the upper opening of the microtube, and substrate 411 is inserted and fixed into the notches so as to receive the lower end of notch 415A of substrate 411, allowing diluent 417 flowing out of outlet 415 to be stored.

[0377] Specimen dilution tank 440 is preferably configured to be kept at a constant temperature (for example, a predetermined temperature between 25 and 65°C) while functioning as a specimen reaction tank for nucleic acid amplification reaction, so that the reaction can be carried out at a constant temperature. Specimen dilution tank 440 can be kept warm or heated by placing the entire testing device 401 in a thermostatic bath or room, or by placing a heating device such as a heater only around specimen dilution tank 440.

[0378] (Restricted Section) As described above, the first flow channel 412 associated with the diluent outlet 430 has a restricted section 414 in which the time required for the fluid 416 to pass through is restricted. In the restricted section 414, the fluid 416 passes through the first flow channel 412 of the restricted section 414 for a predetermined time, for example, within a range of 5 to 30 minutes, such as 5, 10, or 20 minutes. In this embodiment, the time required for the restricted section 414 is appropriately set according to the reaction time for the specimen in the specimen liquid 418A to react with the reaction reagent, and is desirably set within a tolerance of ±10%, preferably ±5%. With this configuration, the diluent 417 can be discharged from the diluent outlet 430 after the predetermined time.

[0379] The restriction section 414 only needs to restrict the time required for the fluid 416 to pass through, and the restriction section may be set afterwards by measuring the time required for the first flow channel 412 that has already been created, or the time required for the fluid 416 to pass through may be set by adjusting the length, width, depth, etc. of the first flow channel 412 to predetermined dimensions.

[0380] In the restriction section 414 according to this embodiment, the first flow path 510 includes a first section L41 (not shown). In this embodiment, the first section L41 starts from a starting point S and extends to a point P midway along the fifth straight section of the first flow path 510. The first section L41 is a section in which the width W41 of the first flow path groove 412A is 0.8 to 2.0 mm and the depth D41 is 0.07 to 0.10 mm (70 to 100 μm). Setting the width W41 and depth D41 of the first flow path groove 412A within this range can suppress variation in the flow velocity of the fluid flowing through the flow path.

[0381] The width W41 of the first flow channel 412A is preferably 0.8 to 1.5 mm, and more preferably 0.9 to 1.2 mm. The depth D41 of the first flow channel 412A is preferably 0.09 to 0.10 mm, and more preferably 0.095 to 0.100 mm.

[0382] In this embodiment, as shown in FIG. 62 , a second section L42, which is deeper than the first flow channel 412A in the first section L41, is provided adjacent to the first section L41 (not shown). In this embodiment, the depth D42 of the first flow channel 412B in the second section L42 is set to 2 to 10 times the depth D41 of the first flow channel 412A in the first section L41 (particularly 4 times in this embodiment). The width W42 of the first flow channel 412B in the second section is set to the same as the width W41 of the first flow channel 412A in the first section. By including the second section L42, the flow rate can be reduced, allowing for longer measurement times without increasing the dimensions of the device. Therefore, the predetermined time can be set to a long time, such as 10 to 30 minutes.

[0383] Point P, which is the transition point from the first flow channel 412A of the first section L41 to the first flow channel 412B of the second section L42, has an inclined surface 412C as shown in FIG. 66 . In this embodiment, the angle θ between the top surface 412E of the first flow channel 412B and the inclined surface 412C in FIG. 66 is 124°. At point P, the first flow channel 412A of the first section L41 suddenly expands from a depth D41 to a depth D42 of the first flow channel 412B of the second section L42. This is a so-called sudden expansion pipe, and when the fluid 416 enters the first flow channel 412B, the flow of the fluid 416 cannot immediately follow the flow channel shape, drawing in the surrounding fluid 416 and 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 412E of the first flow channel 412B and the inclined surface 412C is not particularly limited, but is preferably 110° to 135°.

[0384] The ratio of the lengths of the first section L41 and the second section L42 (length of L41: length of L42) is not particularly limited, but is preferably 9: 1 to 5: 5. With such a ratio, the effect of suppressing time variation in the first section L41 is easily obtained.

[0385] In this embodiment, the cross-sectional shape of the first flow channel 412 (412A, 412B) is quadrangular (particularly rectangular), but the shape is not limited thereto. The cross-sectional shape of the first flow channel 412 (412A, 412B) may be trapezoidal or semicircular. In particular, if the cross-sectional shape of the first flow channel 412 (412A, 412B) is a trapezoid in which the side on the opening side (the side of the first covering material 413) is larger than the side on the groove bottom of the first flow channel 412 (412A, 412B), the first flow channel 412 can be easily manufactured using a mold. In the case of such a shape, the widths W41 and W42 and the depths D41 and D42 of the first flow channel 412 (412A, 412B) refer to the maximum width and maximum depth of the first flow channel 412 (412A, 412B).

[0386] In this embodiment, the first flow path 510 is configured to have a higher conduit resistance than the second flow path 520. The conduit resistance of a flow path is determined by various conditions, and generally, the first flow path 510 has a higher conduit resistance than the second flow path 520 when the first flow path 510 is longer, has a higher conduit friction coefficient, is narrower, or has a higher flow rate than the second flow path 520. In this embodiment, as described above, the flow path length M41 from the fluid inlet 431 to the connection portion X is sufficiently longer than the flow path length M42 from the diluent inlet 433 to the connection portion X, and the conduit resistance of the first flow path 510 is greater than the conduit resistance of the second flow path 520.

[0387] [Inspection Method Using Inspection Device 401] Next, an inspection method using the inspection device 401 will be described in relation to the functions and actions of each part of the inspection device 401.

[0388] The specimen liquid 418A, the fluid 416, and the diluent 417 are prepared in advance. The specimen liquid 418A 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 (pre-reaction liquid). The fluid 416 is a fluid control fluid for causing the diluent 417 remaining in the second flow path 520 and the diluent inlet 433 to flow out the outlet 415, and regulates the predetermined time based on the time required for the fluid to flow through the regulated section 414 of the first flow path 510. For this reason, the fluid 416 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 416 introduced into the fluid inlet 431 to reach the connection portion X is within a tolerance of ±5% of the predetermined time. The diluent 417 is a fluid for diluting the specimen liquid 418B after the nucleic acid amplification reaction, and is a liquid such as water or a buffer solution. The sample liquid 418 (418A, 418B), the fluid 416 and the diluent 417 are all hydrophilic.

[0389] The order in which the specimen liquid 418A, fluid 416, and diluent 417 are introduced into the testing device 401 is not limited. For example, the diluent 417 may be introduced into the diluent reservoir 435 first, the specimen liquid 418A (specimen and reaction reagent) may then be introduced into the specimen dilution tank 440, and the fluid 416 may then be introduced into the fluid inlet 431. The specimen liquid 418A and the fluid 416 are preferably introduced simultaneously, but may be introduced in a slightly different order, and the order of introduction is not particularly limited. The diluent 417 may be introduced as shown in FIG. 59 by the time the fluid 416 reaches the connection portion X. As shown in FIGS. 69 and 70 , the surface 432A of the second coating material 432 in the second flow path 520 serves as a guide, causing a portion of the diluent 417 to flow out of the diluent inlet 433, fill the second flow path 520, and be further guided to the connection portion X. The diluent 417 then forms a droplet 417A at the connection portion X. In this embodiment, the droplet 417A spreads over the surface 432A of the second coating material 432 above the connection portion X in FIG. 70 and is held on the surface 432A of the second coating material 432 in a drooping state due to surface tension and gravity. At this time, the droplet 417A does not contact the first coating material 413. Even if the droplet 417A contacts the side surface 412D and top surface 412E of the first flow channel 412 or the side surface 434D and bottom surface 434E of the second flow channel 434, the droplet 417A does not spread because these surfaces are all hydrophobic, and instead becomes a rounded droplet due to surface tension. This configuration can prevent the diluent 417 from flowing out of the outlet 415 before the droplet 417A contacts the fluid 416.

[0390] 60, when fluid 416 is introduced into fluid inlet 431, it starts from starting point S and flows through first flow path 510 (first flow path grooves 412A, 412B) over a predetermined time (e.g., a preset time such as 20 minutes) until it reaches connecting portion X. First flow path 510 according to this embodiment can regulate the predetermined time by the time required for the fluid to pass through first flow path 510, and the reaction between the specimen in specimen liquid 418A and the reaction reagent proceeds during this predetermined time.

[0391] Next, the fluid 416 that has passed through the first flow path 510 over a predetermined time period reaches the connection portion X and comes into contact with the droplet 417A. Then, as shown in FIGS. 61 and 71 , at least the diluent 417 flows out from the outlet 415. In this manner, the fluid 416 that has passed through the first flow path 510 acts to cause the diluent 417 that has remained in the second flow path 520 and the diluent inlet 433 to flow out to the outlet 415. The fluid 416 that has passed through the long first flow path 510 (first flow grooves 412A, 412B) loses pressure (propulsion force) due to friction with the wall surfaces within the flow path before reaching the connection portion X. Therefore, at the connection portion X, the outflow of the diluent 417 from the second flow path 520 takes priority over the outflow of the fluid 416 from the first flow path 510. The diluent outlet 430 can also be called a "surface tension valve" that utilizes surface tension, since 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.

[0392] According to the diluent outlet 430 of this embodiment, the diluent 417 in the second flow path 520 can be discharged to the outlet 415 by the action of the fluid 416 introduced into the first flow path 510 formed in the same substrate 411, without requiring an external operation to open the second flow path 520. Furthermore, in the diluent outlet 430 of this embodiment, as shown in FIG. 67 , the second coating material 432 at least partially overlaps the connection portion X in the front view of the substrate 411, so that the surface 432A of the second coating material 432 can guide the analyte liquid 418 to the connection portion X. That is, in the diluent outlet 430, the surface 432A of the second coating material 432 in the second flow path 520 serves as a guide that guides the diluent 417 to the connection portion X.

[0393] Diluent outlet section 430 according to this embodiment is configured such that flow path length M41 of first flow path 510 from fluid inlet 431 to connection portion X is greater than flow path length M42 of second flow path 520 from diluent inlet 433 to connection portion X, and first flow path 510 has a greater conduit resistance than second flow path 520. Therefore, when fluid 416 passing through first flow path 510 comes into contact with droplet 417A of diluent 417 formed at connection portion X, diluent 417 naturally flows out from outlet 415 and into specimen dilution tank 440. One side of the through-hole in substrate 411 of notch 415A of outlet 415 is covered with first coating material 413 having a hydrophilic surface that extends from first flow channel 510, and substrate 411 is erected so that the outflow direction downstream of first flow channel 412 faces downward, so that hydrophilic diluent 417 travels through first coating material 413 and is quickly introduced into specimen dilution tank 440. Through the above-described steps, diluent 417 can be introduced into specimen dilution tank 440 after a predetermined time.

[0394] In the specimen dilution tank 440, the reaction between the specimen in the specimen liquid 418A and the reaction reagent (nucleic acid amplification reagent) progresses until the diluent 417 is introduced after a predetermined time, to form a specimen liquid 418B containing a gene amplification product after the nucleic acid amplification reaction, into which the diluent 417 is introduced. When the diluent 417 flows in and a mixed liquid 419 of the diluent 417 and the specimen liquid 418B reaches a liquid level height H41 as shown in Figure 61, the mixed liquid 419 comes into contact with the lower end of the detection unit 420, and the chromatography paper of the detection unit 420 quickly absorbs the mixed liquid 419.

[0395] 61, the test result in the test device 401 is confirmed by whether or not both the detection line C and the detection line T appear in the detection unit 420. If both the detection line C and the detection line T appear in the detection unit 420, it is positive, and if only the detection line C appears, it is negative.

[0396] When the fluid 416 reaches the connection part X, the diluent outlet part 430 of the testing device 401 causes the diluent 417 to naturally flow out to the outlet 415. In this way, the diluent outlet part 430 opens the second flow path 520 in response to the action of the fluid 416 and discharges the diluent 417, even without external control to open the second flow path 520.

[0397] In the diluent outlet 430 according to this embodiment, the fluid 416 introduced into the fluid inlet 431 passes through the restricted section 414 of the first flow path 510 over a predetermined time, causing the diluent 417 to flow out after the predetermined time. Therefore, according to the testing device 401 according to this embodiment, the diluent 417 is introduced into the sample liquid 418B that has been reacted for a predetermined time, and the sample can be detected after diluting it to a predetermined dilution ratio. Consequently, the diluent outlet 430 functions as a timer that measures the reaction time of the sample liquid 418A. That is, according to the testing device 401, the sample liquid 418A containing the sample before reaction introduced into the sample dilution tank 440 becomes the sample liquid 418B after the nucleic acid amplification reaction after a predetermined time. The sample liquid 418B is then autonomously diluted with the diluent 417, and the mixture 419 at the predetermined dilution ratio is autonomously introduced into the detection unit 420. Therefore, it is possible to suppress variations in test results due to variations in reaction time while providing a dilution mechanism that can dilute the specimen liquid 418B after the nucleic acid amplification reaction to a concentration suitable for detection by the detection unit 420. Therefore, it is possible to improve the test accuracy while providing a test kit that allows for simple and short-time detection.

[0398] 62 and 67 , in the front view, the second flow path 520 is provided so as to protrude into the first flow path 510. That is, in the front view, the second flow path 520 is in a state of protruding into the first flow path 510. Therefore, it is possible to easily provide the connection portion X while suppressing the outflow of the diluent 417 from the second flow path 520 to the first flow path 510.

[0399] According to the testing device 401 of this embodiment, the post-reaction sample liquid 418B diluted to a predetermined dilution ratio or greater can be introduced into the detection unit 420, facilitating detection of the target substance (gene amplification product) in the detection unit 420. The testing device 401 includes at least a diluent outlet 430 on the microchip. The diluent 417 flowing from the diluent outlet 430 dilutes the sample liquid 418B in the sample dilution tank 440. This allows a grace period before the sample liquid 418A and the diluent 417 mix, allowing the sample to react with the reaction reagent in advance in the sample dilution tank 440. Furthermore, according to the testing device 401 of this configuration, the outflow of the diluent 417, not the sample liquid 418, is controlled by the fluid control mechanism. Since the sample liquid 418 (418A, 418B) does not pass through the fluid control mechanism, the properties of the sample that can be used are not limited by the fluid control mechanism. For example, a sample containing a surfactant can be diluted in the sample liquid 418. That is, since the sample liquid 418 can contain a surfactant, it becomes possible to extract genes from bacteria or viruses that have thick cell walls and carry out an amplification reaction.

[0400] In the testing device 401 according to this embodiment, the substrate 411 is arranged upright, so that the diluent 417 is quickly discharged from the outlet 415 and easily introduced into the specimen dilution tank 440. This makes it difficult for an error to occur in the measurement of the required time. In addition, the specimen liquid 418 introduced into the specimen dilution tank 440 and the diluent 417 are easily mixed.

[0401] In the inspection device 401 according to this embodiment, the diluent reservoir 435 is formed in a pocket shape, so that it is easy to hold a large volume of diluent while the substrate 411 is in an upright position. In addition, by forming the diluent reservoir 435 with a specified cross-sectional area, etc., it is easy to measure the diluent 417.

[0402] Next, an inspection device 401B which is a modified example of the eleventh embodiment of the present invention will be described with reference to FIGS. 72 and 73. FIG.

[0403] As shown in Figure 72, the testing device 401B differs significantly from the testing device 401 in that the substrate 411 is not erected but is arranged substantially horizontally. In the testing device 401B, the second flow path 520 and the diluent inlet 433 are provided closer to the notch 415A of the outlet 415 than in the testing device 401 of the eleventh embodiment, thereby shortening the length of the outlet 415. Furthermore, in the testing device 401B, as shown in the cross-sectional view of Figure 73, the first coating material 413 arranged on the underside of the outlet 415 of the substrate 411 is peeled off, and the peeled first coating material 413 is arranged to hang down in the specimen dilution tank 440 arranged below the substrate 411.

[0404] In the testing device 401B, the base plate 411 is not erected, and therefore the pocket-shaped diluent reservoir 435 as in the testing device 401 is not provided. In addition, the detection unit 420 is fixed to the edge of the specimen dilution tank 440 at a position where the lower end thereof is at the liquid level height H42.

[0405] 72 shows the state immediately after fluid 416 has been introduced into fluid inlet 431, diluent 417 has been introduced into diluent inlet 433, and a pre-measured amount of specimen liquid 418A has been introduced into specimen dilution tank 440. Even with this configuration, diluent 417 can be discharged from outlet 415 along first coating material 413, and can be introduced into specimen dilution tank 440. Testing device 401B introduces diluent 417 into specimen dilution tank 440 more slowly than testing device 401, but otherwise achieves substantially the same effects as testing device 401. Note that testing device 401B may have a larger capacity diluent inlet 433 instead of diluent reservoir 435 of testing device 401, or a separate diluent reservoir fluidically connected to diluent inlet 433 may be provided.

[0406] 12. Twelfth Embodiment Next, an inspection apparatus 402 according to a twelfth embodiment of the present invention will be described with reference to FIGS.

[0407] The testing device 402 according to the twelfth embodiment differs from the testing device 401B according to the modified example of the eleventh embodiment in the configuration of the sample preparation unit 410. Therefore, only the sample preparation unit 410 will be described. In the testing device 402, the sample dilution tank 460 is fixed to the downstream end of the first flow channel 412 and to the underside of the substrate 411. That is, the diluent 417 flows directly into the sample dilution tank 460 from the first flow channel 412B. Figures 74 and 75 show the state immediately after fluid 416 is introduced into the fluid inlet 431, diluent 417 is introduced into the diluent inlet 433, and a pre-measured sample liquid 418A is introduced into the sample dilution tank 460.

[0408] Specimen dilution tank 460 has diluent outlet 439 formed as a through-hole in substrate 411 at its upper portion, and cylindrical container 461 having a bottom 461A and the same inner diameter as diluent outlet 439 is connected below diluent outlet 439. With this configuration, the inner surface of diluent outlet 439 is continuous with inner wall 461B of cylindrical container 461, forming the inner wall of specimen dilution tank 460. Specimen dilution tank 460 has bottom 461A that is continuous with the lower end of inner wall 461B of cylindrical container 461 and is horizontal with substrate 411. Inner wall 461B of specimen dilution tank 460 has outlet 461C and is fluidly connected to first flow channel 412B on substrate 411. The outlet 461C is provided at a height H43 where the internal volume of the diluent inlet 433 (which functions as a diluent reservoir in the testing device 402) and the sample liquid 418A introduced into the sample dilution tank 460 have a predetermined volume ratio.

[0409] In the testing device 402, the bottom surface (bottom 461A) of the specimen dilution tank 460 is located below the substrate 411. Therefore, in the specimen dilution tank 460, the diluent 417 stored in the diluent inlet 433 autonomously flows into the specimen liquid 418B after the nucleic acid amplification reaction. This facilitates a simple structure. Furthermore, in the specimen dilution tank 460, the diluent 417 and the specimen liquid 418B are mixed due to the difference in height to form the mixed liquid 419 as shown in FIG. 76 , which facilitates mixing of the diluent 417 and the specimen liquid 418B. The mixed liquid 419 reaches a predetermined height H43 and is discharged from the outlet 461C, and is introduced into the detection unit 420 via the pipe 462 connected to the outlet 461C. The detection unit and other components may be configured similarly to those of the eleventh embodiment, and the detection unit may be disposed horizontally (not shown).

[0410] 13. Thirteenth Embodiment Next, an inspection device 403 according to a thirteenth embodiment of the present invention will be described with reference to FIGS.

[0411] [Configuration of Testing Device 403] The testing device 403 according to the thirteenth embodiment is a device obtained by modifying the configuration of the testing device 401, and integrating the diluent outlet unit 430, specimen dilution tank 488, and detection unit 420 into a single cassette. As shown in Fig. 77, the testing device 403 is used by being set upright in a warming device 470 (S01). The warming device 470 has a window 470a through which the test results can be visually observed.

[0412] 78 , the testing device 403 includes a main body circuit board 481 on which a diluent outlet 430, a specimen dilution tank 488, and a detection unit 420 are mounted, a front cover 482 that covers the front of the main body circuit board 481, and a diluent introduction button 483 for starting the introduction of fluid and diluent. The front cover 482 is provided with a window 482a for viewing the test results at a position overlapping with a window 470a of the warming device 470.

[0413] The inspection device 403 according to this embodiment differs significantly from the inspection device 401 according to the eleventh embodiment in the following respects.

[0414] In the testing device 403, the diluent 417, which serves as both a fluid and a diluent, is supplied from a single diluent reservoir 484. That is, in the testing device 403, the fluid 416 and the diluent 417 are the same liquid (water or buffer solution), the fluid 416 is the diluent 417, and the main body substrate 481 is provided with the diluent reservoir 484, which serves as both the fluid inlet and the diluent inlet in the testing device 401.

[0415] In the testing device 403, the diluent reservoir 484 is configured to be fluidly connected to the first flow path 510 and the second flow path 520 when the diluent introduction button 483 is pressed, causing the diluent 417 to flow into the first flow path 510 and the second flow path 520. For example, when the diluent introduction button 483 shown in Fig. 77 is pressed (S03), the bottom surface 484A of the diluent reservoir 484 is opened, causing the diluent 417 to flow out, as shown in Figs. 79 and 80.

[0416] The testing device 403 includes a first communication path 485 and a second flow path 520 branching from a diluent reservoir 484. The first communication path 485 connects the diluent reservoir 484 and the first flow path 510. When the diluent 417 is introduced from the diluent reservoir 484 through the first communication path 485 into the first flow path 510, the diluent 417 passes through the second flow path 520 and forms a droplet 417A at the connection portion X while the diluent 417 passes through the restricted section 414 of the first flow path 510. The testing device 403, like the testing device 401, is configured such that the fluid control mechanism causes the diluent 417 flowing out from the diluent reservoir 484 through the second flow path 520 to flow out from the outlet 487. At least a portion of the cross section of the outlet 487 in the outflow direction of the diluent 417 is hydrophilic. The restriction section 414 and the fluid control mechanism have the same configuration as those of the inspection device 401 according to the eleventh embodiment.

[0417] In the testing device 403, the specimen dilution tank 488 is configured to include at least a portion of the main body substrate 481. In this embodiment, as shown in S02 in Fig. 77 , when a container 490 containing specimen liquid 418A, which is a mixture of a specimen and a reaction reagent, is set in a specimen container receptacle 491 configured to include the main body substrate 481, the bottom of the container 490 is opened and the specimen liquid 418A flows into the specimen dilution tank 488 (Fig. 79). This configuration is merely an example, and specimen liquid 418A may be introduced directly into the specimen dilution tank 488, or a freeze-dried reaction reagent may be sealed in the specimen dilution tank 488 in advance, and the specimen or a nucleic acid extract extracted from the specimen may be introduced directly into the specimen dilution tank 488.

[0418] In testing device 403, detection unit 420 is housed in through-hole 481B formed in main body substrate 481. At least one surface of main body substrate 481 is provided with detection flow channel 489 that connects specimen dilution reservoir 488 and detection unit 420. Mixed solution 419 in specimen dilution reservoir 488 flows out to detection unit 420 via detection flow channel 489.

[0419] According to the testing device 403, since the diluent 417 is used as the fluid, one reservoir can serve as both the fluid receiving section and the diluent receiving section, making it easy to make the device simple and compact.

[0420] [Inspection Method Using Inspection Device 403] Next, a series of inspection methods using the inspection device 403 will be described.

[0421] First, as shown in S01 of FIG. 77 , the testing device 403 is inserted into a recess in the warming device 470. As shown in FIG. 78 , the diluent 417 is pre-filled in the diluent reservoir 484 in the testing device 403. The interior of the warming device 470 is set to a predetermined temperature of, for example, 60 to 68°C in the case of the LAMP method. Next, as shown in S02 of FIG. 77 , a container 490 containing a specimen liquid 418A (a mixture of a specimen and a reaction reagent) is set in the testing device 403. Then, as shown in FIG. 79 , the bottom of the container 490 breaks, and the specimen liquid 418A is introduced into the specimen dilution tank 488. Next, as shown in S03 of FIG. 77 , the diluent introduction button 483 is pressed, and the diluent 417 is introduced from the diluent reservoir 484 into the first communication path 485 and the second flow path 520. Diluent 417 introduced into second flow path 520 forms droplet 417A at connection portion X. Diluent 417 introduced into first communication path 485 passes through restricted section 414 for a predetermined time, as shown in Figure 80. Restricted section 414 is set so that this predetermined time corresponds to the reaction time of the nucleic acid amplification reaction of specimen liquid 418A in specimen dilution tank 488. While diluent 417 passes through restricted section 414, the nucleic acid amplification reaction progresses in specimen liquid 418A, and specimen liquid 418A becomes specimen liquid 418B containing a nucleic acid amplification product after the reaction.

[0422] Next, when the diluent 417 that has passed through the regulated section 414 in the first flow path 510 comes into contact with the droplet 417A at the connection portion X, the diluent 417 flows out of the diluent reservoir 484, and as shown in Figure 81, the diluent 417 flows into the specimen dilution tank 488 through the outlet 487.

[0423] As diluent 417 is introduced into specimen dilution tank 488 containing specimen liquid 418B, diluent 417 and specimen liquid 418 form mixture 419, and the liquid level rises. As shown in Figure 82, when mixture 419 reaches a predetermined liquid level H44, mixture 419 containing the post-reaction gene amplification product reaches detection unit 420 via detection flow channel 489. The gene amplification product is then detected in detection unit 420, and a test result, positive or negative, is displayed (Figure 82). As shown in S04 of Figure 77, the test result can be visually confirmed through viewing window 482a in front cover 482 of testing device 403 and window 470a in warming device 470.

[0424] Other embodiments of the dilution device and the fourth 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.

[0425] In the above embodiment, an example has been described in which the dilution device according to the present invention is applied as a specimen preparation unit of the testing devices 401 to 403. However, the present invention is not limited to such a configuration, and may be used for other purposes requiring a dilution device.

[0426] In the above embodiment, an example has been described in which the first flow path and the first flow channel 412 (412A, 412B) constituting the first flow path have the restriction section 414. However, this configuration is not limited to this, and the restriction section 414 may not be included. Furthermore, the restriction section 414 is not limited to the form of the flow channel described in the above embodiment. For example, an example has been described in which the restriction section 414 includes a first section L41 and a second section L42 in this order from the starting point S. However, this configuration is not limited to this, and the second section L42 may be located before the first section L41, or the second section L42 may be sandwiched between the first sections L41, or the first section L41 may be sandwiched between the second sections L42. Furthermore, although an example has been described in which the first section L41 is longer than the second section L42, this configuration is not limited to this, and the second section may be longer than the first section L41. Furthermore, although an example in which the second section L42 has the same width as the first section L41 has been described, the present invention is not limited to such a configuration, and the width of the second section L42 may be larger than the width of the first section L41. For example, the width of the second section L42 may be two to four times the width of the first section L41.

[0427] In the above embodiment, the test devices 401 to 403 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.

[0428] In the above embodiment, an example has been described in which a surface tension valve is used as a configuration for realizing the fluid control mechanism of the inspection devices 401 to 403. However, the present invention is not limited to such a configuration, and other fluid control devices may also be used.

[0429] In the above embodiment, in the fluid control mechanism of the inspection devices 401 to 403, as shown in FIGS. 67 and 68 , the first flow path 510 and the second flow path 520 overlap at the bottom of their respective flow path grooves, and the second flow path 520 protrudes into the first flow path 510 in the front view, forming a connection portion X. However, the connection portion X is not limited to such a configuration as long as the first flow path 510 and the second flow path 520 are fluidically connected. For example, as shown in FIGS. 83 and 84 , the second flow path 520 may be provided so as to abut against the side wall of the first flow path 510, and the first flow path 510 and the second flow path 520 may be fluidically connected at the side wall portions of the respective flow path grooves, thereby forming the connection portion X. In this case, the depth of the second flow path groove is D44, which is deeper than D43 in the above embodiment. Alternatively, as shown in FIGS. 85 and 86 , the connection portion X may be formed by providing the second flow path 520 so as to cross the first flow path 510 in the front view. In this case, it is not necessary to precisely control the processing dimensions of the connection portion X between the first flow channel 412 and the second flow channel 434 in a microchannel device having a fine flow channel, and the diluent outlet portion 430 is easy to manufacture.

[0430] In the thirteenth embodiment described above, an example was described in which the detection unit 420 is accommodated in a through-hole 481B formed in the main body substrate 481. However, the present invention is not limited to such a configuration, and the detection unit 420 may be accommodated in a recess formed on at least one surface of the main body substrate 451. Furthermore, in the thirteenth embodiment described above, as shown in FIGS. 78 to 82 , an example was described in which the diluent 417 flows from the diluent reservoir 484 through a single flow path, and the first communicating path 485 and the second flow path 520 partially overlap. However, the first communicating path 485 and the second flow path 520 may not overlap, and the diluent 417 may flow from the diluent reservoir 484 through two flow paths, the first communicating path 485 and the second flow path 520, respectively.

[0431] The dilution device and the fourth testing device according to the present invention can be used, for example, as a dilution device on a microchannel chip and a testing kit using the same.

[0432] 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.

[0433] [First and second embodiments] 1: Inspection device 2: Inspection device 10, 30: Timekeeping unit (timekeeping device) 11: Substrate 12: Flow channel 13: Covering material 14: Sample liquid inlet 15, 35: Outlet 20: Detection unit 31: Fluid inlet 32: Sample inlet S: Start point G: End point W: Width of flow channel D: Depth of flow channel L1: First section L2: Second section [Third to seventh embodiments] 201-205: Inspection device 210: Substrate 211-215: Fluid control unit (fluid control device) 218: Sample liquid (sample) 218A-218E: Droplet 219: Fluid 220: First flow channel 221: First flow channel 222: First covering material 223: Fluid inlet (first fluid inlet) 230: Second flow path 231: Second flow path groove 232: Second covering material 232A: Surface of second covering material (guide portion) 233: Specimen inlet (second fluid inlet) 240: Outlet 250: Detection portion X: Connection portion W: Width of flow path groove D: Depth of flow path groove [Eighth to Tenth Embodiments] 301-303: Inspection device 310: Substrate 311-313: Fluid control unit (fluid control device) 316: Fluid 317: Dilution solvent 317a: Droplet 318 (318A, 318B): Specimen liquid (specimen) 318a: Droplet 319: Diluted specimen liquid 320: Main flow path 321: Flow path groove of main flow path 322 : First covering material 323 : Fluid inlet 330 : First communication passage331: Flow channel of first communication path (first flow channel) 332: Second covering material 332A: Surface of second covering material 333: Dilution solvent reservoir (first reservoir) 335: Second communication path 336: Flow channel of second communication path (second flow channel) 338, 360: Sample liquid reservoir (second reservoir) 340: Outlet 350: Detection unit 371: First branch path 372: Second branch path X31: First connection portion X32: Second connection portion Q: Branch point W: Width of flow channel D: Depth of flow channel [Eleventh to thirteenth embodiments] 401, 401B, 402, 403: Inspection device 410: Sample preparation unit (dilution device) 411, 481: Substrate (main substrate) 412: Flow channel (first flow channel) 413: Coating material (first coating material) 414: Restriction section 415: Outlet 416: Fluid 417: Diluent 417A: Droplet 418, 418A, 418B: Specimen liquid 420: Detection section 430: Diluent outlet 431: Fluid inlet (fluid receiving section) 432: Second coating material 433: Diluent inlet 434: Second flow channel 435: Diluent reservoir (diluent receiving section) 436: Pocket-shaped member 440, 460: Specimen dilution tank (specimen dilution section) 470: Heating device 483: Diluent introduction button 484: Diluent reservoir 487: Outlet 488: Specimen dilution tank (specimen dilution section) 489: Detection flow channel 510: First flow channel 520: Second flow channel H41 to H44: Liquid level X: Connection portion

Claims

1. A timing device comprising: a flow channel formed on at least one surface of a substrate; a coating material covering said flow channel; and a fluid inlet port communicating with said flow channel, said flow channel having a section having a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm, and capable of measuring a predetermined time based on the time required for the fluid introduced at the inlet to reach a predetermined destination located downstream of said flow channel.

2. The timing device of claim 1, wherein the required time is configured to be within a tolerance of ±5% of the predetermined time.

3. A timepiece according to claim 1, wherein at least one of said flow channel and said covering material has a hydrophilic portion that comes into contact with said fluid passing through said flow channel.

4. A timing device according to any one of claims 1 to 3, wherein the flow channel further has another section that is deeper than the section.

5. A timing method using a timing device comprising: a flow channel formed on at least one surface of a substrate; a coating material covering said flow channel; and a fluid inlet port communicating with said flow channel, said flow channel having a section with a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm, said timing method starting measurement of a predetermined time when the fluid is introduced into said inlet, and determining that the predetermined time has elapsed when the fluid reaches a predetermined end point located downstream of said flow channel.

6. An inspection device comprising a timing unit which, when a fluid and a specimen are introduced, causes at least the specimen to flow out after a predetermined time, and a detection unit which can detect the specimen that has flowed out from the timing unit, wherein the timing unit comprises: a flow groove formed on at least one surface of a substrate; a coating material which covers the flow groove; a fluid receiving portion which communicates with the flow groove and into which the fluid is introduced; a specimen receiving portion which communicates with the flow groove and into which the specimen is introduced; and an outlet located downstream of the flow groove and through which at least the specimen flows out, wherein the flow groove has a section which is 0.8 to 2.0 mm wide and 70 to 100 μm deep, wherein when the fluid is introduced into the fluid receiving portion and the specimen is introduced into the specimen receiving portion, at least the specimen flows out of the outlet after the predetermined time, and the detection unit is in fluid communication with the outlet, and the predetermined time is regulated by the time required for the fluid introduced into the fluid receiving portion to reach a predetermined destination which is located downstream of the flow groove.

7. The testing device as described in claim 6, wherein the timing unit is provided with a specimen liquid inlet which serves as the fluid receiving unit and specimen receiving unit, into which specimen liquid containing the fluid and the specimen is introduced, and the predetermined destination point is the outlet.

8. The testing device described in claim 6, wherein the timing unit comprises: a fluid inlet located upstream of the flow outlet and serving as the fluid receiving unit; and a sample inlet located downstream of the fluid inlet and serving as the sample receiving unit in fluid communication with the flow outlet, and the predetermined destination point is the sample inlet.

9. The testing device according to any one of claims 6 to 8, wherein at least a portion of a cross section of the outlet in the outflow direction of the sample is hydrophilic.

10. A fluid control device comprising: a first flow path having a flow groove formed on one surface of a substrate and a coating material covering the flow 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 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 groove having a first property which is either hydrophobic or hydrophilic, and a surface of the coating material facing the flow groove has a second property which is 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.

11. A fluid control device as described in claim 10, wherein the second flow path has a second flow path groove formed on a surface of the substrate opposite the flow path groove of the first flow path, and a second coating material covering the second flow path groove, and the second coating material at least partially overlaps with the connection portion in a plan view of the substrate.

12. The fluid control device according to claim 11, wherein the surface of the second covering material on the side of the second flow channel is the guide portion.

13. The fluid control device according to any one of claims 10 to 12, wherein the first flow path has a larger pipeline resistance than the second flow path.

14. A fluid control device as described in any one of claims 10 to 12, further comprising: a first fluid inlet port fluidly connected to the first flow path and through which a first fluid is introduced; and a second fluid inlet port fluidly connected to the second flow path and through which a second fluid is introduced, wherein the length of the first flow path from the first fluid inlet port to the connecting portion is greater than the length of the second flow path from the second fluid inlet port to the connecting portion.

15. An inspection device comprising a fluid control section which causes at least a specimen to flow out when a fluid and a specimen are introduced therein, and a detection section capable of detecting the specimen flowing out from the fluid control section, wherein the fluid control section comprises: a first flow path having a flow groove formed on at least one surface of a substrate and a coating material covering the flow groove; a second flow path fluidically connected to the first flow path at least one of a side surface and a bottom surface of the flow groove; a fluid inlet port fluidically connected to the first flow path and through which the fluid is introduced; a specimen inlet port fluidically connected to the second flow path and through which the specimen is introduced; and an outlet port fluidically connected from a connection portion between the first flow path and the second flow path and for guiding the specimen, wherein the first flow path has a surface of the flow groove having a first property which is either hydrophobic or hydrophilic, and a surface of the coating material facing the flow groove having a second property which is the other of hydrophobic and hydrophilic, and the second flow path has the second property and comprises a guide section which guides the specimen introduced into the second flow path to the connection portion, An inspection device configured so that when the sample is introduced into the sample inlet, the sample guided by the guide section forms a droplet at the connection portion, and when the fluid is introduced into the fluid inlet and the fluid comes into contact with the droplet at the connection portion, at least the sample flows out from the outlet, and the detection section is in fluid communication with the outlet.

16. The testing device according to claim 15, wherein 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 when the fluid and the specimen are introduced, at least the specimen flows out after a predetermined time.

17. A fluid control device on a microchip, which flows out both a first fluid and a second fluid introduced therein, comprising: a main flow path having a flow groove formed on at least one surface of a substrate and a coating material covering the flow groove; an outlet fluidically connected to the downstream of the main flow path and for guiding both the first fluid and the second fluid; a first reservoir and a second reservoir fluidically connected to the main flow path and in which the first fluid and the second fluid are stored, respectively; a first fluid control mechanism for controlling the outflow of the first fluid from the first reservoir; and a second fluid control mechanism for controlling the outflow of the second fluid from the second reservoir.

18. A fluid control device as described in claim 17, wherein the first reservoir and the second reservoir have a predetermined volume ratio, one is located upstream and the other is located downstream in the main flow path, the outlet, the first reservoir and the second reservoir each have a through hole formed in the substrate and have a bottom formed of a coating material covering the lower opening of the through hole, and the first fluid and the second fluid both flow out at the predetermined volume ratio.

19. The fluid control device of claim 18, wherein the first reservoir and the second reservoir are configured so that one protrudes above the substrate, the one having a greater height than the other.

20. A fluid control device as described in claim 19, wherein the height of the second reservoir is greater than the height of the first reservoir, and the communicating portion between the second reservoir and the main flow path is located closer to the outlet than the communicating portion between the first reservoir and the main flow path.

21. A fluid control device as described in claim 17, wherein the first reservoir and the second reservoir have a predetermined volume ratio, the main flow path has a branch point, a first branch path fluidly connected to the first reservoir between the branch point and the outlet, and a second branch path fluidly connected to the second reservoir between the branch point and the outlet, a flow path length from the branch point to a portion where the first reservoir and the first branch path communicate with each other is different from a flow path length from the branch point to a portion where the second reservoir and the second branch path communicate with each other, and the first fluid and the second fluid flow out together at the predetermined volume ratio.

22. A fluid control device comprising: a first communication passage fluidically connecting the main flow path and the first reservoir; and a second communication passage fluidically connecting the main flow path and the second reservoir; the main flow path is fluidically connected to the first communication passage and the second communication passage at at least one of a side surface and a bottom surface of the flow groove of the main flow path; the first fluid control mechanism comprises: the main flow path; a surface of the flow groove has a first property which is either hydrophobic or hydrophilic; the surface of the coating material facing the flow groove has a second property which is the other of hydrophobic and hydrophilic; the first communication passage has the second property and has a first guide portion which guides the first fluid introduced into the first reservoir to a first connection portion between the main flow path and the first communication passage; when the first fluid is introduced into the first reservoir, the first fluid guided to the first guide portion forms first droplets at the first connection portion, thereby controlling the outflow of the first fluid from the first reservoir; and the second fluid control mechanism comprises:

22. The fluid control device according to any one of claims 18 to 21, wherein the main flow path has: a surface of the flow groove having a first property which is either hydrophobic or hydrophilic; a surface of the coating material facing the flow groove having a second property which is the other of hydrophobic and hydrophilic; the second communicating passage having the second property and including a second guide portion which guides the second fluid introduced into the second reservoir to a second connecting portion between the main flow path and the second communicating passage; and when the second fluid is introduced into the second reservoir, the second fluid guided to the second guide portion forms second droplets at the second connecting portion, thereby controlling the outflow of the second fluid from the second reservoir.

23. A testing device comprising, on a microchip, a fluid control section which allows both introduced specimen and diluent solvent to flow out, and a detection section which can detect the specimen flowing out from the fluid control section, wherein the fluid control section comprises: a main flow path having a flow groove formed on at least one surface of a substrate and a coating material which covers the flow groove; an outlet which is fluidly connected downstream of the main flow path and which guides both the specimen and the diluent solvent; a first reservoir and a second reservoir which are fluidly connected to the main flow path and in which the diluent solvent and the specimen are respectively stored; a first fluid control mechanism which controls the outflow of the diluent solvent from the first reservoir; and a second fluid control mechanism which controls the outflow of the specimen from the second reservoir, wherein the detection section is fluidly connected to the outlet.

24. The inspection device described in claim 23, further comprising a communication passage that fluidly connects the main flow path and the first reservoir, the main flow path being fluidly connected to the communication passage at least on one of a side surface and a bottom surface of the flow groove, and the first fluid control mechanism, wherein the main flow path has a surface of the flow groove having a first property that is either hydrophobic or hydrophilic, and a surface of the coating material facing the flow groove having a second property that is the other of hydrophobic and hydrophilic, and the communication passage has the second property and has a guide section that guides either the analyte or the diluent solvent introduced into the first reservoir to a connection portion between the main flow path and the communication passage, and when either the analyte or the diluent solvent is introduced into the first reservoir, the either the analyte or the diluent solvent guided to the guide section forms droplets at the connection portion, thereby controlling the outflow of either the analyte or the diluent solvent from the first reservoir.

25. The inspection device described in claim 24, wherein the flow groove of the main flow path has a regulated section in which the time required for the fluid to pass through is regulated, and the device is provided with a fluid inlet port fluidly connected to the flow groove of the main flow path and for introducing the fluid, and when the fluid, the dilution solvent and the specimen are introduced into the fluid inlet port, the first reservoir and the second reservoir, respectively, the fluid comes into contact with the droplet at the connection portion, and after a predetermined time, the specimen and the dilution solvent flow out together.

26. The inspection device according to claim 25, wherein the restriction section includes a section in which the flow channel has a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm.

27. A dilution device comprising: a diluent outlet section which flows out at least a diluent when a fluid is introduced; and a specimen dilution section which, as a specimen is introduced, dilutes the specimen with the diluent flowing out from the diluent outlet section, wherein the diluent outlet section comprises: a flow groove formed on at least one surface of a substrate; a covering material covering the flow groove; a fluid receiving section communicating with the flow groove and into which the fluid is introduced; a diluent receiving section communicating with the flow groove and into which the diluent is introduced; a fluid control mechanism which controls the outflow of the diluent from the diluent receiving section; and an outlet located downstream of the flow groove and through which at least the diluent flows out, wherein when the fluid is introduced into the fluid receiving section and the diluent is introduced into the diluent receiving section, at least the diluent flows out from the outlet, and the specimen dilution section is configured so that when a mixture of the diluent and the specimen reaches a predetermined liquid level, the specimen dilution section dilutes the specimen to a predetermined ratio.

28. A dilution device as described in claim 27, wherein the flow channel has a regulated section in which the time required for the fluid to pass through is regulated, and when the fluid and the diluent are introduced, at least the diluent flows out after a predetermined time.

29. The dilution device according to claim 28, wherein the regulated section includes a section in which the flow channel has a width of 0.8 to 2.0 mm and a depth of 70 to 100 μm.

30. The dilution device according to claim 27, wherein the substrate is erected so that the outflow direction downstream of the flow channel faces downward.

31. The dilution device according to claim 30, wherein the diluent receiving portion is formed in the shape of a pocket on at least one surface of the base plate.

32. The dilution device according to any one of claims 27 to 31, wherein the diluent outlet portion comprises: a first flow path formed by the flow groove and the covering material; and a second flow path fluidly connected to the diluent receiving portion and to at least one of a side surface and a bottom surface of the first flow path, and the fluid control mechanism comprises: a surface of the first flow path having a first property which is either hydrophobic or hydrophilic, a surface of the covering material of the first flow path facing the flow groove having a second property which is the other of hydrophobic and hydrophilic, the second flow path having the second property and comprising a guide portion which guides the diluent introduced into the diluent receiving portion to a connection portion between the first flow path and the second flow path, and when the diluent is introduced into the diluent receiving portion, the diluent guided by the guide portion forms droplets at the connection portion.

33. The dilution device of claim 32, wherein the fluid in the diluent outlet section is the diluent, and the diluent reservoir serves as both the fluid receiving section and the diluent receiving section, the diluent reservoir being fluidly connected to each of the first flow path and the second flow path, and when the diluent is introduced from the diluent reservoir into the first flow path, the diluent flowing out from the diluent reservoir through the second flow path flows out from the outlet.

34. An inspection device comprising: a diluent outlet section which flows out at least a diluent when a fluid is introduced into it; a specimen dilution section which receives a specimen and dilutes the specimen with the diluent flowing out from the diluent outlet section; and a detection section capable of detecting the specimen flowing out from the specimen dilution section, wherein the diluent outlet section comprises: a flow groove formed on at least one surface of a substrate; a covering material covering the flow groove; a fluid receiving section which communicates with the flow groove and into which the fluid is introduced; a diluent receiving section which communicates with the flow groove and into which the diluent is introduced; a fluid control mechanism which controls the outflow of the diluent from the diluent receiving section; and an outlet located downstream of the flow groove and through which at least the diluent flows out, wherein when the fluid is introduced into the fluid receiving section and the diluent is introduced into the diluent receiving section, at least the diluent flows out from the outlet, and the specimen dilution section is configured so that when a mixture of the diluent and the specimen reaches or exceeds a predetermined liquid level, the mixture reaches the detection section.

35. The testing device of claim 34, wherein the specimen dilution section is configured to include at least a part of the substrate, the detection section is housed in a through hole formed in the substrate or a recess formed in at least one surface of the substrate, and at least one surface of the substrate further comprises a detection flow groove communicating the specimen dilution section and the detection section, and the mixed liquid in the specimen dilution section flows out to the detection section via the detection flow groove.

Images