Micro flow passage device

Abstract

To prevent a sample solution from flowing back from a recovery unit to a main flow passage after the sample solution is discharged to the recovery unit for recovering the sample solution in the main flow passage.SOLUTION: A micro flow passage device 2 includes: an opening 22 for receiving a sample solution; a main flow passage 23 leading to the opening 22; and a recovery unit 40 provided in an exit-side end part 23b of the main flow passage 23. The recovery unit 40 includes: a pool 42 for storing a sample liquid; a connection flow passage 44 for connecting the pool 42 and the exit-side end part 23b to each other; and a protruding 46 arranged in the connection flow passage 44 to generate air bubbles which bock the connection flow passage between the protrusion and the inner wall of the connection flow passage.SELECTED DRAWING: Figure 6

Description

[Technical field]

[0001] The present disclosure relates to a plate-shaped microfluidic device used in a test in which a test liquid containing a specimen is reacted with a drug. [Background technology]

[0002] A method is known for testing the susceptibility of bacteria to antibacterial drugs using a microchannel device. For example, in JP 2017-67620 A (Patent Document 1), a microchannel device is provided with an inlet and an outlet communicating with the outside, and a channel through which a test liquid supplied from the inlet flows to the outlet side, and air is forced into the channel from the inlet to push the previously introduced test liquid into the fine channel. A reaction section is provided in the channel in which the test liquid supplied from the inlet is stored, and a drug placed in the reaction section acts on the bacteria.

[0003] JP 2022-044563 A (Patent Document 2) discloses a testing device that pressurizes a test liquid into multiple microchannels, and then applies air pressure to recover the test liquid in the main channel connected to the multiple microchannels in a recovery section. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2017-67620 A [Patent Document 2] JP 2022-044563 A Summary of the Invention [Problem to be solved by the invention]

[0005] According to the testing device disclosed in Patent Document 2, by discharging the test liquid remaining in the main flow path to a recovery section, each of the multiple micro flow paths can be isolated and the flow of the test liquid occurring in the flow paths can be suppressed. That is, in order to isolate each of the multiple micro flow paths, it is required to reliably discharge the test liquid from the main flow path to the recovery section and to keep the test liquid recovered in the recovery section within the recovery section.

[0006] The present disclosure has been made to solve such problems, and aims to cause the test liquid discharged into the collection section to remain within the collection section. [Means for solving the problem]

[0007] The microchannel device of the present disclosure is a plate-shaped microchannel device used for a test in which a test liquid containing a specimen is reacted with a drug. The microchannel device includes an opening for receiving the test liquid, a main channel communicating with the opening, a plurality of microchannels communicating with the main channel, and a recovery unit provided at an outlet end of the main channel opposite to an inlet end communicating with the opening, for recovering a portion of the test liquid. The recovery unit includes a pool for storing the test liquid discharged from the main channel, a connecting channel connecting the pool to the outlet end, and a protrusion disposed in the connecting channel so as to receive the test liquid discharged from the main channel and generate bubbles between the pool and an inner wall of the connecting channel to block the connecting channel. Effect of the Invention

[0008] According to the above-mentioned microchannel device, the provision of the protrusions creates air bubbles that prevent the test liquid from flowing back from the recovery section to the main channel, thereby allowing the test liquid to remain within the recovery section. [Brief description of the drawings]

[0009] [Figure 1] FIG. 1 is a diagram illustrating an example of the overall configuration of a test device. [Diagram 2] FIG. 2 is a block diagram for explaining control of a test device. [Diagram 3] FIG. 2 is a plan view of the microfluidic device. [Figure 4] 10 is a flowchart for explaining a press-fitting method for a testing device. [Diagram 5] FIG. 2 is a diagram for explaining the flow of a test liquid when the test liquid is injected by a test device. [Figure 6] FIG. [Figure 7] FIG. [Figure 8] FIG. [Figure 9] FIG. 13 is a diagram showing a schematic diagram of the state of the recovery section before and after the test liquid is discharged. [Figure 10] 13 is an image showing the state after the test liquid has been discharged into the recovery section. [Figure 11] 13 is an image showing the state after the test liquid has been discharged into a recovery section in a comparative example. [Figure 12] FIG. 11 is a cross-sectional view of a recovery section according to a modified example. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] Hereinafter, embodiments will be described in detail with reference to the drawings. In the drawings, the same or corresponding parts are designated by the same reference characters and their description will not be repeated.

[0011] [Test equipment configuration] A test apparatus 100 for injecting a test liquid into a microchannel device will be described with reference to Figs. 1 and 2. Fig. 1 is a diagram showing an example of the overall configuration of the test apparatus. Fig. 2 is a block diagram for explaining the control of the test apparatus. The test apparatus according to the present embodiment is an apparatus for measuring the test liquid by forcing a test liquid containing a specimen into a microchannel of a microchannel device, and an example of forcing a test liquid into a microchannel to measure the sensitivity of bacteria to an antibacterial drug (medicine) will be described below as an example. The test liquid includes a specimen. The specimen may be bacteria (in a specific example, a pathogenic bacterium). In a specific example, the test liquid may be a bacterial suspension. Of course, the test liquid is not limited to the above-mentioned test liquid as long as it is a test liquid that the test apparatus presses into the microchannel of the microchannel device.

[0012] With reference to Figures 1 and 2, the test apparatus 100 includes a test liquid placement unit 10, a pipette nozzle driving unit 12, a table driving unit 13, a pump 14, a pipette nozzle 15, a table 16, an opening / closing unit 30, an opening / closing driving unit 31, an application unit 32, a pump 33, an application driving unit 34 and a control unit 50.

[0013] The test liquid setting section 10 is a rack capable of arranging a plurality of test liquid containers 5 containing test liquids. The test liquid setting section 10 is capable of setting a plurality of test liquid containers 5 in the testing device 100 on a rack-by-rack basis.

[0014] The pipette nozzle 15 is fitted with a removable pipette tip 1 and aspirates or expels the test liquid from the test liquid container 5 through the tip of the pipette tip 1 .

[0015] The pipette nozzle driving unit 12 horizontally moves the pipette nozzle 15, the pump 14 connected to the pipette nozzle 15, the opening / closing unit 30, the application unit 32, and the pump 33 connected to the application unit 32. The pipette nozzle driving unit 12 also moves the pipette nozzle 15 and the pump 14 connected to the pipette nozzle 15 up and down. The pipette nozzle driving unit 12 can freely move the pipette nozzle 15 by, for example, a solenoid actuator or a stepping motor.

[0016] The table 16 is a support member for placing the micro-channel device 2 (see FIG. 3). The table 16 is formed in a flat plate shape, and the micro-channel device 2 is fixed to the upper surface. The table driving unit 13 can move the table 16 in the horizontal direction. The table driving unit 13 can freely move the table 16 by, for example, a solenoid actuator or a stepping motor. Of course, the table driving unit 13 may move the table 16 up and down, but not move the pipette nozzle 15 up and down. At least the pipette nozzle driving unit 12 and the table driving unit 13 are movement mechanisms for changing the relative positions of the pipette nozzle 15 and the micro-channel device 2.

[0017] Although not shown, pump 14 includes, for example, a syringe, a plunger capable of reciprocating movement within the syringe, and a drive motor for driving the plunger. Pump 14 is connected to pipette nozzle 15 via piping and reciprocates the plunger, thereby adjusting the air pressure within pipette tip 1 to suck the test liquid into pipette tip 1 or discharge the test liquid within pipette tip 1 to the outside. Pump 14 can also pump air out of pipette tip 1 by moving the plunger further in the direction of pushing it into the syringe while discharging the test liquid within pipette tip 1 to the outside.

[0018] The opening / closing unit 30 is a mechanism for opening and closing an opening 29 (see FIG. 3) formed in the microchannel device 2 described later. The opening / closing unit 30 includes an elastic member 30a provided at the tip of a rod-shaped support. The elastic member 30a is, for example, a silicone resin. The opening / closing drive unit 31 drives the opening / closing unit 30 to move the elastic member 30a up and down. The opening / closing drive unit 31 moves the elastic member 30a, which has moved directly above the opening 29, up and down, thereby pressing the elastic member 30a against or releasing it from the gas permeable membrane 27a covering the opening 29. In FIG. 1, the opening / closing unit 30 is illustrated as being provided in the same moving mechanism as the pipette nozzle 15, but the opening / closing unit 30 may be provided in a moving mechanism different from the pipette nozzle 15, and the application unit 32 may be moved by the opening / closing drive unit 31.

[0019] The applicator 32 applies a sealant to the openings and the like formed in the microchannel device 2. The applicator 32 is a nozzle that discharges a sealant such as silicone oil to the openings and the like, and applies the sealant to the openings and the like with the nozzle by the pump 33. The configuration of the applicator 32 is not limited to this, and may be a mechanism that applies the sealant to the openings and the like with a brush or the like.

[0020] The application drive unit 34 moves the application unit 32 to a position where the sealant is applied, and drives the pump 33. In Fig. 1, the application unit 32 is illustrated as being provided on the same movement mechanism as the pipette nozzle 15, but the application unit 32 may be provided on a movement mechanism different from that of the pipette nozzle 15, and the application drive unit 34 may move the application unit 32.

[0021] The control unit 50 controls the operation of the test apparatus 100. The control unit 50 includes a processor such as a CPU (Central Processing Unit) and a memory such as a ROM (Read Only Memory) and a RAM (Random access memory). The memory stores a control program. The processor executes the control program to control the operation of the test apparatus 100. The memory of the control unit 50 may include an HDD (Hard Disk Drive).

[0022] 2, the control unit 50 controls the test liquid setting unit 10, the pipette nozzle driving unit 12, the table driving unit 13, the pump 14, the opening / closing driving unit 31, the pump 33, and the application driving unit 34. By controlling these components, the control unit 50 injects the test liquid into the microchannel device 2 placed on the table 16, and applies a sealant to openings and the like formed in the microchannel device 2. The specific operation of the testing apparatus 100 will be described later with reference to FIG. 4.

[0023] The control unit 50 may be connected to an arithmetic processing device such as a computer that a user uses to manage the test apparatus 100. The arithmetic processing device receives inputs such as the amount of movement of the table 16 and the amount of test liquid to be injected into the microfluidic device 2.

[0024] [Microfluidic Device Configuration] 3 is a plan view of the microchannel device. The microchannel device 2 is placed on a table 16 of a test apparatus 100. In the following description, the surface of the microchannel device 2 on which the openings 22 are provided is defined as the XY plane, and the axis perpendicular to the XY plane is defined as the Z axis. In the following description, the surface on which the openings 22 are provided is defined as the top surface, the surface opposite to the top surface is defined as the bottom surface, and the positive direction of the Z axis may be referred to as the upside and the negative direction as the downside.

[0025] The microchannel device 2 is placed on the table 16 with the bottom surface, on which the openings 22 are not provided, serving as a mounting surface. As shown in Fig. 3, the microchannel device 2 includes a plate-like member 20 and a channel structure. The channel structure includes the openings 22, a main channel 23, a microchannel 24, a reservoir 25, an opening 26, and a recovery section 40 provided with an opening 29.

[0026] The opening 22 is connected to an inlet end 23a, which is one end of the main channel 23, and communicates with the main channel 23. The test liquid is forced into the main channel 23 from the opening 22 using fluid pressure. The test liquid forced into the main channel 23 is further forced into the microchannel 24. In this embodiment, air pressure is used as the fluid pressure. The opening 22 is formed, for example, to have a circular cross section. The opening 22 has a diameter of, for example, 5 μm to 5 mm. In this embodiment, one main channel 23 is connected to the opening 22. One main channel 23 is disposed at a position surrounding the outside of the multiple microchannels 24.

[0027] The main channel 23 has an inlet end 23a communicating with the opening 22, and an outlet end 23b located on the opposite side to the inlet end 23a. The main channel 23 extending from the opening 22 further branches into a plurality of microchannels 24. The main channel 23 is connected to the plurality of microchannels 24 so that the test liquid can flow therethrough. The test liquid flowing in from the opening 22 flows through the main channel 23 into the plurality of branched microchannels 24. The cross sections of the main channel 23 and the microchannel 24 are rectangular, and the widths of the main channel 23 and the microchannel 24 are, for example, 1 μm to 1 mm. However, the main channel 23 and the microchannel 24 have different depths (heights). For example, the depth of the main channel 23 is 0.5 mm, while the depth of the microchannel 24 is as small as 0.025 mm. Therefore, the flow resistance of the microchannel 24 is greater than that of the main channel 23. By making the flow resistance of the micro-flow paths 24 larger than that of the main flow path 23, the test liquid flowing in from the opening 22 can fill the main flow path 23 once, and then flow into the multiple micro-flow paths 24 almost simultaneously, as described below.

[0028] In this embodiment, 32 microchannels 24 arranged in line in the X-axis direction are grouped together, and two groups are arranged in line in the Y-axis direction. That is, the microchannel device 2 has a first group on the positive side of the Y-axis and a second group on the negative side of the Y-axis. Each of the microchannels 24 has a first end portion 24a communicating with the main channel 23 and a second end portion 24b located on the opposite side to the first end portion 24a.

[0029] The microchannels 24 included in the first group are each connected to the main channel 23 arranged on the positive side of the Y axis of the microchannel device 2. The microchannels 24 included in the first group are each connected to the main channel 23 such that the first end 24a is located on the positive side of the Y axis and the second end 24b is located on the negative side of the Y axis. Therefore, the test liquid branched from the main channel 23 to the microchannels 24 included in the first group flows in the negative direction of the Y axis.

[0030] On the other hand, the multiple microchannels 24 included in the second group are each connected to the main channel 23 arranged on the negative side of the Y axis of the microchannel device 2. Also, the multiple microchannels 24 included in the second group are each connected to the main channel 23 such that the first side end 24a is located on the negative side of the Y axis and the second side end 24b is located on the positive side of the Y axis. Therefore, the test liquid branched from the main channel 23 to the multiple microchannels 24 included in the second group flows in the positive direction of the Y axis.

[0031] After the main flow channel 23 branches into a plurality of micro flow channels 24, a reservoir 25 is provided in each of the micro flow channels 24. Therefore, the test liquid flowing in from the opening 22 flows into each reservoir 25 via the main flow channel 23 and the micro flow channels 24.

[0032] The reservoir 25 has a drug disposed therein, is connected to the opening 22 via the main flow channel 23 and the micro flow channel 24, and stores the test liquid that flows in from the opening 22. In the reservoir 25, the test liquid reacts with the drug. The drug is, for example, an antibacterial drug. The drug may be a solid or a liquid. The drug is placed in the reservoir 25 in advance. That is, the drug is placed in the reservoir 25 before the test liquid flows into the reservoir 25. In this embodiment, the drug is applied to the entire reservoir 25.

[0033] The storage section 25 is formed in a rectangular parallelepiped shape. The length of one side of the storage section 25 is, for example, 10 μm to 10 mm.

[0034] 3, 64 (=32×2) storage sections 25 are formed on plate-like member 20. The volumes of test liquid stored in 56 storage sections 25 are the same. Meanwhile, the types and amounts of drug placed in 64 storage sections 25 may be the same or different.

[0035] A microchannel 24 is disposed between the storage section 25 and the opening 26. This microchannel 24 is disposed along the Y-axis direction, with one end connected to the storage section 25 and the other end (second side end 24b) connected to the opening 26. This microchannel 24 causes the test liquid that has flowed into the storage section 25 to flow further to the opening 26.

[0036] The opening 26 is connected to the other end (second side end 24b) of the microchannel 24. The opening 26 is formed, for example, to have a circular cross section. The diameter of the opening 26 is, for example, 5 μm to 5 mm.

[0037] The openings 26 are covered with a gas permeable film 27. Specifically, in FIG. 3, 32 openings 26 connected to a plurality of microchannels 24 included in a first group arranged on the positive side of the Y axis and 32 openings 26 connected to a plurality of microchannels 24 included in a second group arranged on the negative side of the Y axis are arranged to face each other. Therefore, 64 openings 26 (=32×2) are arranged along the X-axis direction in the central part of the microchannel device 2. These 64 openings 26 are covered with one gas permeable film 27. Note that the gas permeable film 27 may not cover the 64 openings 26 with one sheet, but may be divided into 32 openings 26 included in an upper group and 32 openings 26 included in a lower group and covered with two sheets. Also, the gas permeable film 27 may cover at least one of the 64 openings 26.

[0038] The gas permeable membrane 27 has a function of allowing gas to pass therethrough and preventing liquid from passing therethrough. Examples of materials for the gas permeable membrane 27 include polytetrafluoroethylene (PTFE). The gas permeable membrane 27 preferably has water repellency. The thickness of the gas permeable membrane 27 is 1 mm or less.

[0039] The gas permeable membrane 27 is fixed to the plate-like member 20 by bonding with an adhesive, ultrasonic fusion, etc. Examples of the adhesive include a photocurable resin, a thermosetting resin, and a pressure-sensitive resin.

[0040] The recovery section 40 is provided at the outlet end 23b of the main flow path 23. The recovery section 40 recovers a portion of the test liquid that has flowed into the main flow path 23 from the opening 22.

[0041] An opening 29 is provided at the top of the recovery section 40. The opening 29 is covered with a gas permeable membrane 27a. The main flow path 23 allows the test liquid to flow from the opening 22 to the recovery section 40. The opening 29 can be opened and closed by pressing and releasing the elastic member 30a of the opening / closing section 30 of the testing device 100 against and from above the gas permeable membrane 27a.

[0042] The cross-sectional area of ​​the connection flow path 44 (see FIG. 7) provided in the recovery unit 40 is larger than the cross-sectional area of ​​each of the microflow paths 24 and the main flow path 23. Therefore, the flow path resistance of the recovery unit 40 is smaller than that of the microflow path 24 and the main flow path 23. By making the flow path resistance of the recovery unit 40 smaller than that of the microflow path 24 and the main flow path 23, when air is sent from the opening 22 with the opening 29 open, the test liquid remaining in the main flow path 23 is discharged to the recovery unit 40.

[0043] In other words, the test device 100 prevents the test liquid that has flowed into the main flow path 23 from being discharged into the recovery section 40 by closing the opening 29, and discharges the test liquid remaining in the main flow path 23 into the recovery section 40 and recovers it by opening the opening 29.

[0044] The gas permeable membrane 27a may be made of the same material as the gas permeable membrane 27 covering the opening 26, or a different material, as long as it has a function of allowing gas to pass through and not allowing liquid to pass through. Examples of materials for the gas permeable membrane 27a include polytetrafluoroethylene (PTFE). The gas permeable membrane 27a is preferably water repellent. The thickness of the gas permeable membrane 27 is 1 mm or less. The gas permeable membrane 27a is fixed to the plate-like member 20 by bonding with an adhesive, ultrasonic fusion, or the like. Examples of adhesives include photocurable resin, thermosetting resin, and pressure-sensitive resin.

[0045] Providing gas permeable membrane 27a can reduce the risk of the test liquid overflowing from opening 29 when the test liquid is discharged into collection section 40. If collection section 40 is sufficiently large and the possibility of the test liquid overflowing from opening 29 is low, gas permeable membrane 27a does not need to be provided.

[0046] Further, the main flow channel 23 includes a sealing portion 28 between the connection portion 24c with the micro flow channel 24 located closest to the outlet end 23b among the multiple micro flow channels 24 and the outlet end 23b. The sealing portion 28 is sealed after the test liquid is discharged to the recovery portion 40. This physically blocks the main flow channel 23 and the recovery portion 40 and makes them independent from each other, thereby reliably preventing the test liquid discharged to the recovery portion 40 from flowing back into the main flow channel 23 (micro flow channel 24). The method of sealing the sealing portion 28 is not particularly limited. For example, the sealing may be performed by injecting silicone oil as a sealing material, or by fitting a sealing component into the sealing portion 28. In this embodiment, as an example, the sealing material applied by the application portion 32 is injected into the sealing portion 28. Note that when the method of sealing the opening 22 and the like is different from the method of sealing the sealing portion 28, the test device 100 has a function for realizing each sealing method.

[0047] Furthermore, the main channel 23 may further include a sealing portion between the inlet end 23a and a connection portion with the microchannel 24 that is located closest to the inlet end 23a among the multiple microchannels 24. The sealing portion provided in the vicinity of the inlet end 23a is sealed after the test liquid is discharged to the recovery portion 40, similar to the sealing portion 28. This physically blocks the opening 22 and the main channel 23 and makes them independent from each other, thereby reliably preventing the test liquid in the main channel 23 from flowing toward the opening 22. The sealing method is not particularly limited.

[0048] [Press-fitting method for test equipment] Fig. 4 is a flow chart for explaining a method for pressing the test device. The method for pressing the test device 100 according to this embodiment will be explained with reference to Fig. 4. First, the control unit 50 of the test device 100 controls the motor of the pipette nozzle driving unit 12 to move the pipette nozzle 15 to the position of a predetermined test liquid container 5, and controls the pump 14 to aspirate the test liquid in the test liquid container 5 from the tip of the pipette tip 1 (step S11). The control unit 50 controls the motor of the pipette nozzle driving unit 12 to move the pipette nozzle 15 to the position of the opening 22 of the microchannel device 2 (step S12).

[0049] Here, the position of the opening / closing unit 30 relative to the pipette nozzle 15 is determined in advance according to the position of the opening 29 of the recovery unit 40 relative to the opening 22 of the microchannel device 2. More specifically, the position of the opening / closing unit 30 is determined in advance so that the elastic member 30a of the opening / closing unit 30 is positioned above the opening 29 when the pipette nozzle 15 is moved to the position of the opening 22. Therefore, when the pipette nozzle 15 is aligned with the position of the opening 22 of the microchannel device 2 in step S12, the elastic member 30a of the opening / closing unit 30 moves to a position directly above the opening 29 of the recovery unit 40. Note that the opening / closing unit 30 may be moved by a moving mechanism different from the moving mechanism (pipette nozzle driving unit 12) that moves the pipette nozzle 15.

[0050] The control unit 50 controls the opening / closing drive unit 31 to move the elastic member 30a to a position where it closes the opening 29 of the collection unit 40 (step S13). More specifically, the control unit 50 presses the elastic member 30a against the gas permeable membrane 27a, thereby closing the entire opening 29 with the elastic member 30a.

[0051] After closing opening 29, control unit 50 controls pump 14 to discharge the test liquid from the tip of pipette tip 1 and pressurize the test liquid into the channels (main channel 23, microchannel 24) of microchannel device 2 (step S14).

[0052] The control unit 50 determines whether or not the test liquid has been pressed into the flow paths of all the micro-channel devices 2 (step S15). Note that the control unit 50 determines whether or not the test liquid has been pressed into the flow paths of all the micro-channel devices 2 based on, for example, the time for which the test liquid is pressed into the flow paths of the micro-channel devices 2 and the remaining amount of test liquid in the pipette tip 1. If the test liquid has not been pressed into the flow paths of all the micro-channel devices 2 (NO in step S15), the control unit 50 returns the process to step S14.

[0053] When the test liquid is forced into the flow channels of all the microchannel devices 2 (YES in step S15), the control unit 50 causes the opening / closing drive unit 31 to move the elastic member 30a from the position blocking the opening 29 to open the opening 29 (step S16). The control unit 50 controls the pump 14 to discharge air from the tip of the pipette tip 1, and discharges the test liquid remaining in the main flow channel 23 to the recovery unit 40 (step S17).

[0054] The control unit 50 controls the pipette nozzle driving unit 12 and the application driving unit 34 to inject the sealant into the sealing unit 28 (step S18). More specifically, the control unit 50 controls the pipette nozzle driving unit 12 to move the application unit 32 to directly above the sealing unit 28. Then, the control unit 50 controls the application driving unit 34 to move the application unit 32 to a position where the sealant can be injected into the sealing unit 28. Then, the control unit 50 drives the pump 33 to inject the sealant into the sealing unit 28.

[0055] The control unit 50 controls the pipette nozzle driving unit 12 to move the application unit 32 to the positions of the openings 22, 26, and 29, and controls the application driving unit 34 to apply the sealant to the openings 22, 26, and 29 (step S19).

[0056] By performing control according to the above processing, the test apparatus 100 pressurizes the test liquid into the micro-channel device 2, discharges the test liquid into the recovery section 40, and applies a sealant to openings formed in the micro-channel device 2, etc.

[0057] FIG. 5 is a diagram for explaining the flow of the test liquid when the test liquid is pressed in by the test device. The test device 100 presses the test liquid from the opening 22 into the main channel 23 while closing the opening 29 and opening 26. When the test liquid flows into the main channel 23, the main channel 23 is first filled with the test liquid as shown in the upper part of FIG. 5 because the flow resistance of each microchannel 24 is larger than that of the main channel 23. After the main channel 23 is completely filled with the test liquid, the test liquid flows into each microchannel 24 as shown in the middle part of FIG. 5. At this time, since the opening 26 is open while the opening 29 is closed, the test liquid flows into each microchannel 24 and the storage section 25 without flowing into the recovery section 40.

[0058] After each microchannel 24 and reservoir 25 are filled with the test liquid, the testing device 100 removes the elastic member 30a of the opening / closing unit 30 that is blocking the opening 29, and while opening 29 is open, sends air through opening 22. As a result, as shown in the lower part of Fig. 5, the test liquid remaining in main channel 23 is discharged into recovery unit 40. Note that the air sent through opening 22 can be air discharged from pipette tip 1 to pressurize the test liquid.

[0059] Here, although opening 26 is open, the flow resistance of microchannel 24 is greater than the flow resistance of recovery section 40, so the test liquid in main flow channel 23 is not pushed out into microchannel 24 but is discharged into recovery section 40.

[0060] In the microchannel device 2, the test liquid flowing in from the pipette tip 1 passes through the opening 22 and the main channel 23 to fill the microchannel 24, the reservoir 25, and the opening 26. In the microchannel device 2, the multiple microchannels 24 communicate with each other via the main channel 23. Therefore, when the test liquid is injected, if a difference occurs in the height of the liquid surface (liquid head) between each channel or in the portion from the opening 22 to each channel, a flow of the test liquid occurs in each channel due to the difference. For example, if a difference occurs in the liquid head between the multiple microchannels 24, a flow of the test liquid occurs between each channel to eliminate the difference. As a result, a flow of the test liquid occurs in the reservoir 25 of the microchannel 24, and there is a possibility that a correct result cannot be observed.

[0061] The test apparatus 100 according to this embodiment pressurizes the test liquid into the channels (main channel 23, microchannel 24) of the microchannel device 2, and then discharges the test liquid remaining in the main channel 23 to the recovery section 40. This makes it possible to separate each of the multiple microchannels 24. As a result, even if a difference in the liquid level height occurs among the multiple microchannels 24, it is possible to prevent the flow of the test liquid that would occur due to the difference in height.

[0062] [Configuration of the collection section] FIG. 6 is a perspective view of the collection section. FIG. 7 is a cross-sectional view of the collection section. FIG. 8 is a plan view of the collection section. The configuration of the collection section 40 will be described with reference to FIGS. 6 to 8. In FIG. 6, the collection section 40 is viewed from the bottom side with the member (second plate-shaped member 20b in FIG. 7) constituting the bottom surface of the flow path, i.e., the surface opposite to the surface on which the opening is provided, removed. Also, in FIG. 8, the gas permeable membrane 27a is omitted for convenience.

[0063] The recovery section 40 includes a pool 42 for storing the test liquid, a connection flow path 44 connecting the pool 42 with the outlet end 23b, and a protrusion 46 provided on the connection flow path 44.

[0064] An opening 29 is provided at the top of the pool 42. The opening 29 is covered with a gas permeable membrane 27a. The pool 42 is a space for storing the test liquid discharged from the main flow path 23. The volume of the pool 42 is larger than the entire volume of the main flow path 23. Therefore, all of the test liquid remaining in the main flow path 23 can be collected in the pool 42. For example, when the depth of the main flow path 23 is 0.01 mm to 0.05 mm and the width is 0.1 mm to 1 mm, the diameter of the pool 42 is 10 mm to 15 mm and the depth is 1 mm to 5 mm. As an example, when the depth of the main flow path 23 is 0.03 mm and the width is 0.5 mm, the diameter of the pool 42 is 8 mm and the depth is 2.5 mm.

[0065] The connecting flow path 44 includes a straight flow path 450 extending from the outlet end 23b and an inclined flow path 440 communicating with the straight flow path 450. The inclined flow path 440 is configured such that the flow path cross-sectional area increases from the straight flow path 450 toward the pool 42, i.e., from the outlet end 23b toward the pool 42.

[0066] At least one inclined surface 442 inclined toward the outside of the inclined flow path 440 is formed in the inclined flow path 440. In the present embodiment, three inclined surfaces 442 are formed in the inclined flow path 440. More specifically, the inclined surface 442 is formed on two surfaces constituting the side surfaces of the inclined flow path 440 and on the surface on which the openings 29 and 22 are formed.

[0067] Specifically, inclined flow channel 440, a first inclined surface 444 is formed on the surface on the side where openings 29 and 22 are formed, and a second inclined surface 446 and a third inclined surface 448 are formed which constitute a tapered section in which the flow channel width becomes wider from outlet end 23b toward pool 42. For example, inclined flow channel 440, the end on the straight flow channel 450 side has a width of 0.1 mm to 1 mm and a depth of 0.01 mm to 0.05 mm, the end on the pool 42 side has a width of 5 to 6 mm and a depth of 1 mm to 5 mm, and the length from the end on the main flow channel 23 side to the end on the pool 42 side is 2 to 6 mm.

[0068] The inclination angle θa with respect to the flow path surface extending from the inclined surface 442 is less than 90 degrees. More specifically, the inclination angle θ1 of the first inclined surface 444 with respect to the horizontal plane 452 is less than 90 degrees. The inclination angle θ2 of the second inclined surface 446 with respect to the first side surface 454 is less than 90 degrees. Furthermore, the inclination angle θ3 of the third inclined surface 448 with respect to the second side surface 456 is less than 90 degrees. In addition, the taper angle θb of the tapered portion formed by the second inclined surface 446 and the third inclined surface 448 is less than 180 degrees. The inclination angle θa is, for example, 15 degrees to 45 degrees. Note that the inclination angles θ1, θ2, and θ3 may be the same angle or different angles.

[0069] The protrusion 46 is disposed in the connecting flow path 44 so as to receive the test liquid discharged from the main flow path 23 and generate air bubbles between the protrusion 46 and the inner wall of the connecting flow path 44 to block the connecting flow path 44. When air is sent from the opening 22 and the test liquid remaining in the main flow path 23 is discharged to the recovery section 40, the test liquid and the air collide with the protrusion 46, and air bubbles are generated at the boundary between the test liquid and the air in the connecting flow path 44, between the inner wall of the connecting flow path 44 and the protrusion 46. Since the flow path cross-sectional area of ​​the flow path between the protrusion 46 and the inner wall of the connecting flow path 44 is small, the connection flow path 44 is blocked by the air bubbles. In addition, the air bubbles remain in the connecting flow path 44 due to surface tension. As a result, the discharged test liquid can be prevented from flowing back into the main flow path 23 due to the air bubbles.

[0070] In this embodiment, the protrusion 46 is provided in the inclined flow channel 440 with the inclined surface 442 as the installation surface. More specifically, the installation surface of the protrusion 46 is the first inclined surface 444. When the microchannel device 2 is viewed in plan, the protrusion 46 has a shape that tapers toward the outlet end 23b. The protrusion 46 has a size that does not completely block the flow channel of the inclined flow channel 440.

[0071] For example, the protrusion 46 has a size such that, when the microchannel device 2 is viewed in a plane, a flow channel having a width approximately equal to that of the straight flow channel 450 or the main flow channel 23 is formed on both sides of the protrusion 46. For example, when the microchannel device 2 is viewed in a plane, the protrusion 46 has a size such that the distance between the protrusion 46 and the inner wall of the inclined flow channel 440 is 0.1 mm to 1 mm. More specifically, when the inclined flow channel 440 has a width of 0.5 mm and a depth of 0.03 mm at the end on the main flow channel 23 side, a width of 5.5 mm and a depth of 2.5 mm at the end on the pool 42 side, and a length from the end on the main flow channel 23 side to the end on the pool 42 side of 4 mm, the size of the protrusion 46 is as follows, for example. The protrusion 46 is a quadrangular pyramid that is an equilateral triangle with one side of 1 mm when the microchannel device 2 is viewed in a plane. In this case, when the microchannel device 2 is viewed in a plane, a flow channel having a width of 0.5 mm is formed on both sides of the protrusion 46.

[0072] The provision of the protrusions 46 allows bubbles of sufficient size to be generated, and in addition, the flow path cross-sectional area around the protrusions 46 and the flow path cross-sectional area of ​​the straight flow path 450 are sufficiently small, so that the bubbles generated by the protrusions 46 can block the connecting flow path 44 and remain in the connecting flow path 44 due to surface tension.

[0073] The plate-like member 20 includes a first plate-like member 20a having a plurality of openings and a flow path structure, and a second plate-like member 20b laminated on the first plate-like member 20a. The thicknesses of the first plate-like member 20a and the second plate-like member 20b are not particularly limited, but are set to, for example, 0.5 mm to 3 mm. The second plate-like member 20b is directly fixed to the first plate-like member 20a by ultrasonic melting, but may be fixed via an adhesive.

[0074] The first plate-shaped member 20a and the second plate-shaped member 20b are formed of a transparent material and are formed into a rectangular plate shape when viewed from above the microchannel device 2. Examples of materials for the first plate-shaped member 20a and the second plate-shaped member 20b include an acrylic resin such as polymethylmethacrylate resin, glass, and the like.

[0075] The first plate-shaped member 20a has an opening and a flow path structure formed therein. More specifically, the first plate-shaped member 20a has an opening 22, a main flow path 23, a micro flow path 24, a reservoir 25, an opening 26, and a recovery section 40 provided with an opening 29 formed therein.

[0076] The second plate-like member 20b is a flat member and functions as the bottom surface of each flow channel. More specifically, it functions as the lower surface of the opening 22, the main flow channel 23, the microflow channel 24, the storage section 25, the opening 26, and the recovery section 40. Specifically, of the wall surfaces constituting each flow channel of the microflow channel device 2, the surface facing the surface on which the opening 22 is formed (the surface constituting the second plate-like member 20b) is flat.

[0077] Fig. 9 is a schematic diagram showing the state of the recovery section before and after the test liquid is discharged. Fig. 10 is an image showing the state after the test liquid is discharged into the recovery section. Fig. 11 is an image showing the state after the test liquid is discharged into the recovery section in a comparative example. No protrusions are provided on the connection flow path 90 in the comparative example.

[0078] The testing device 100 discharges air from the tip of the pipette tip 1 and discharges the test liquid remaining in the main flow path 23 to the recovery section 40. When the air pressure applied when discharging the test liquid is released, the test liquid in the connection flow path 44 may flow back into the main flow path 23 due to capillary action, and therefore it is necessary to keep the test liquid in the recovery section 40.

[0079] When air is sent from the opening 22 and the test liquid remaining in the main flow path 23 is discharged into the pool 42, the air sent from the opening 22 and the test liquid collide with the protrusion 46, and air bubbles A are generated at the boundary between the test liquid and the air. As shown in the lower part of FIG. 9, the generated air bubbles A are large enough to block the connecting flow path 44. More specifically, as shown in FIG. 10, air bubbles A large enough to block the connecting flow path 44 are generated in the connecting flow path 44 provided with the protrusion 46. On the other hand, as shown in FIG. 11, small air bubbles are generated in the connecting flow path 90 not provided with the protrusion, but air bubbles A large enough to block the connecting flow path 44 as shown in FIG. 10 are not generated. Also, as shown in FIG. 10, the protrusion 46 is disposed in the connecting flow path 44, so that the cross-sectional area of ​​the flow path is small, and the generated air bubbles block the flow path between the protrusion 46 and the inner wall of the connecting flow path 44.

[0080] In this way, when the test liquid is discharged from the main flow path 23, the protrusions 46 generate air bubbles A that can block the connecting flow path 44. The generated air bubbles A remain in the connecting flow path 44 due to surface tension. The air bubbles A that remain in the connecting flow path 44 can prevent the test liquid from flowing back from the recovery unit 40 to the main flow path 23, and as a result, the test liquid can be retained in the recovery unit 40.

[0081] As long as the air bubble A remains in the connecting flow path 44, the backflow of the test liquid can be prevented. However, if the air bubble A moves from inside the connecting flow path 44 to the pool 42 or the main flow path 23, this effect cannot be obtained. In this embodiment, after the test liquid is discharged into the recovery section 40, the testing device 100 injects the sealant into the sealing section 28 before applying the sealant to each of the openings 26, 29, that is, as early as possible. This makes it possible to reliably prevent the test liquid from flowing back into the main flow path 23.

[0082] Furthermore, the recovery unit 40 includes a pool 42 that is larger in volume than the main channel 23 in order to recover the test liquid in the main channel 23. When attempting to form a pool 42 with a larger volume than the main channel 23 in the plate-like member 20, it is necessary to increase the cross-sectional area of ​​the pool 42 in order to reduce the size of the microchannel device 2 and the flow channel resistance. Therefore, the connection channel 44 has a shape in which the channel is widened in the depth direction or width direction. In this embodiment, the recovery unit 40 includes an inclined channel 440 in which an inclined surface 442 with an inclination angle θa of less than 90 degrees is formed, thereby widening the channel cross-sectional area from the outlet end 23b toward the pool 42.

[0083] Here, when the inclination angle θ1 of the first inclined surface 444 with respect to the horizontal plane 452 is 90 degrees or more, the angle formed by the first inclined surface 444 and the upper surface of the flow path is less than 90 degrees. Therefore, the distance between the first inclined surface 444 and the upper surface of the flow path becomes closer. As a result, the test liquid may accumulate at the boundary portion between the first inclined surface 444 and the upper surface of the flow path. In this embodiment, the inclination angle θa is less than 90 degrees. Therefore, it is possible to prevent the test liquid from accumulating at the boundary portion between the inclined surface 442 and the flow path surface extending from the inclined surface 442. In other words, it is possible to prevent the test liquid from remaining in the connection flow path 44, and as a result, it is possible to prevent the test liquid from flowing back from the recovery unit 40 to the main flow path 23.

[0084] Furthermore, in this embodiment, the projection 46 has a shape that tapers toward the outlet end 23b. As a result, it is possible to prevent the test liquid from accumulating at the boundary between the projection 46 and the installation surface of the projection 46. In other words, it is possible to prevent the test liquid from remaining in the connection flow path 44, and as a result, it is possible to prevent the test liquid from flowing back from the recovery unit 40 to the main flow path 23.

[0085] In the present embodiment, the protrusion 46 is provided in the inclined flow path 440 of the connecting flow path 44, in which the inclined surface 442 is formed. The inclined flow path 440 is a flow path with a wide flow path cross-sectional area. Therefore, the protrusion 46 can be easily provided.

[0086] The second plate-like member 20b is a flat member and functions as the bottom surface of each flow channel. That is, among the wall surfaces constituting each flow channel of the microchannel device 2, the surface facing the surface on which the opening 22 is formed, i.e., the surface constituted by the second plate-like member 20b, is flat. This allows the flow channel structure to be simplified, and the microchannel device 2 to be easily manufactured.

[0087] Moreover, the connection flow path 44 according to this embodiment includes a tapered portion composed of a second inclined surface 446 and a third inclined surface 448. Since the taper angle θb of the tapered portion is less than 180 degrees, it is possible to prevent the test liquid from accumulating at the boundary portion between the tapered portion and the flow path surface extending from the tapered portion, i.e., the boundary portion between the second inclined surface 446 and the flow path surface extending from the second inclined surface 446, and the boundary portion between the third inclined surface 448 and the flow path surface extending from the third inclined surface 448. In other words, it is possible to prevent the test liquid from remaining in the connection flow path 44, and as a result, it is possible to prevent the test liquid from flowing back from the recovery section 40 to the main flow path 23.

[0088] In this embodiment, the cross-sectional area of ​​the channel can be abruptly enlarged by further providing a tapered portion in the inclined channel 440 in which the first inclined surface 444 is formed. This allows the length of the connection channel 44 to be shortened, which contributes to realizing a miniaturization of the microchannel device 2.

[0089] [Variations] In the above embodiment, the connection flow path 44 is formed with an inclined surface 442 having an inclination angle θa of less than 90 degrees. The connection flow path 44 may also have an inclined surface with an inclination angle θa of 90 degrees. FIG. 12 is a cross-sectional view of a recovery section according to a modified example. The recovery section 40a may have an inclined surface 442a with an inclination angle θa of 90 degrees. Even if the inclination angle θa is 90 degrees, by providing the protrusion 46, bubbles are formed, and the generated bubbles block the flow path between the main flow path 23 and the pool 42, preventing the test liquid from flowing back from the recovery section 40 to the main flow path 23.

[0090] In the above embodiment, the protrusion 46 is formed on the inclined surface 442. Note that the protrusion 46 may be provided in the connecting flow path 44 between the pool 42 and the outlet end 23b, and may be provided in the straight flow path 450, for example.

[0091] In the above embodiment, the inclined flow passage 440 includes a tapered portion configured by the second inclined surface 446 and the third inclined surface 448. It is to be noted that the inclined flow passage 440 does not necessarily have to include a tapered portion.

[0092] In the above embodiment, opening 29 is provided in the upper part of pool 42. Note that opening 29 may be provided in another flow path that is further connected to pool 42. Also in this case, opening 29 is preferably covered with gas permeable membrane 27a.

[0093] [Aspects] It will be understood by those skilled in the art that the above-described embodiments are illustrative of the following aspects.

[0094] (Item 1) A microchannel device according to one embodiment is a plate-shaped microchannel device used in a test in which a test liquid containing a specimen is reacted with a drug. The microchannel device includes an opening for receiving the test liquid, a main channel communicating with the opening, a plurality of microchannels communicating with the main channel, and a recovery unit provided at an outlet end of the main channel opposite to an inlet end communicating with the opening, for recovering a portion of the test liquid. The recovery unit includes a pool for storing the test liquid discharged from the main channel, a connecting channel connecting the pool to the outlet end, and a protrusion disposed in the connecting channel so as to receive the test liquid discharged from the main channel and generate air bubbles between the pool and an inner wall of the connecting channel to block the connecting channel.

[0095] According to the microchannel device described in paragraph 1, the provision of the protrusions generates air bubbles, which can prevent the test liquid from flowing back from the recovery section to the main channel, thereby allowing the test liquid to remain in the recovery section.

[0096] (Item 2) In the microchannel device according to item 1, the connecting channel includes an inclined channel having an inclined surface that is inclined toward the outside of the connecting channel, and the inclination angle of the inclined surface with respect to the channel surface extending from the inclined surface is less than 90 degrees.

[0097] According to the microchannel device described in the second aspect, since the inclination angle is less than 90 degrees, it is possible to prevent the test liquid from accumulating at the boundary between the inclined surface and the channel surface extending from the inclined surface. In other words, it is possible to prevent the test liquid from remaining in the connecting channel, and as a result, it is possible to prevent the test liquid from flowing back from the recovery section to the main channel.

[0098] (Item 3) In the microchannel device according to item 2, among the wall surfaces constituting each channel, the surface opposite to the surface provided with the opening is flat.

[0099] According to the microchannel device described in item 3, the channel structure can be simplified, and the microchannel device can be easily manufactured.

[0100] (Item 4) According to the microchannel device described in item 2 or 3, the inclined surface is formed on one of the wall surfaces constituting the connecting channel, the wall surface on the side where the opening is provided.

[0101] According to the microchannel device described in item 4, it is possible to prevent the test liquid from accumulating at the boundary between the inclined surface and the channel surface extending from the inclined surface. In other words, it is possible to prevent the test liquid from remaining in the connecting channel, and as a result, it is possible to prevent the test liquid from flowing back from the recovery section to the main channel.

[0102] (Item 5) In the microchannel device according to any one of items 2 to 4, the protrusion is provided on the inclined channel.

[0103] According to the microchannel device described in the fifth aspect, the inclined channel is a channel with an increased cross-sectional area, so that protrusions can be easily provided.

[0104] (Item 6) In the microchannel device according to any one of items 1 to 5, the protrusion has a shape tapered toward the outlet end.

[0105] According to the microchannel device described in item 6, it is possible to prevent the test liquid from accumulating at the boundary between the protrusions and the surface on which the protrusions are placed, that is, it is possible to prevent the test liquid from remaining in the connecting channel, and as a result, it is possible to prevent the test liquid from flowing back from the recovery section to the main channel.

[0106] (Item 7) In the microchannel device according to any one of items 1 to 6, the connection channel includes a tapered section in which the channel width increases from the outlet end toward the pool, and the taper angle of the tapered section is less than 180 degrees.

[0107] According to the microchannel device described in item 7, it is possible to prevent the test liquid from accumulating at the boundary between the tapered portion and the channel surface extending from the tapered portion. In other words, it is possible to prevent the test liquid from remaining in the connecting channel, and as a result, it is possible to prevent the test liquid from flowing back from the recovery portion to the main channel.

[0108] The embodiments disclosed herein should be considered to be illustrative and not restrictive in all respects. The scope of the present invention is defined by the claims, not by the description of the embodiments described above, and is intended to include all modifications within the meaning and scope of the claims. [Explanation of symbols]

[0109] 1 pipette tip, 2 microfluidic device, 5 test liquid container, 10 test liquid placement section, 12 pipette nozzle drive section, 13 table drive section, 14, 33 pump, 15 pipette nozzle, 16 table, 20 plate-shaped member, 20a first plate-shaped member, 20b second plate-shaped member, 22, 26, 29 opening, 23 main flow channel, 23a inlet end, 23b outlet end, 24 microfluidic channel, 24a first side end, 24b second side end, 24c connection section, 25 storage section, 27, 27a gas permeable membrane, 28 sealing section, 30 opening / closing section, 30a elastic member, 31 opening / closing drive section, 32 coating section, 34 coating drive section, 40, 40a recovery section, 42 pool, 44, 90 connection flow channel, 46 protrusion, 50 control section, 100 Test apparatus, 440 inclined flow path, 442, 442a inclined surfaces, 444 first inclined surface, 446 second inclined surface, 448 third inclined surface, 450 straight flow path, 452 horizontal surface, 454 first side, 456 second side.

Claims

1. A plate-shaped microfluidic device used in a test in which a test liquid containing a specimen and a drug are reacted with each other, an opening for receiving the test liquid; A main flow path communicating with the opening; A plurality of microchannels communicating with the main channel; a recovery section provided at an outlet end of the main flow path opposite an inlet end communicating with the opening, the recovery section recovering a portion of the test liquid; The recovery section includes: A pool for storing the test liquid discharged from the main flow path; A connecting flow path connecting the pool and the outlet end; a protrusion disposed in the connecting flow path so as to receive the test liquid discharged from the main flow path and generate air bubbles between the protrusion and an inner wall of the connecting flow path, the air bubbles blocking the connecting flow path.

2. The connection flow path has an inclined flow path having an inclined surface that is inclined toward an outside of the connection flow path, The microfluidic device according to claim 1 , wherein an inclination angle of the inclined surface with respect to a channel surface extending from the inclined surface is less than 90 degrees.

3. The microchannel device according to claim 2 , wherein, of the walls constituting each of the channels, a surface facing the surface on which the opening is provided is flat.

4. 4. The microchannel device according to claim 2, wherein the inclined surface is formed on one of the wall surfaces constituting the connecting channel, the wall surface being on a side where the opening is provided.

5. The microchannel device according to claim 2 , wherein the protrusion is provided on the inclined channel.

6. The microchannel device according to claim 1 , wherein the protrusion has a shape tapered toward the outlet end.

7. the connecting flow passage has a tapered portion in which the flow passage width increases from the outlet end toward the pool, 4. The microchannel device according to claim 1, wherein the taper angle of the tapered portion is less than 180 degrees.

Images