Microfluidic devices

Abstract

To provide a micro passage device capable of suppressing the flow of a test liquid generated between micro passages.SOLUTION: A micro passage device 2 includes an opening 22 pressing a test liquid, a main passage 23, a plurality of micro passages 24, a storage part 25, an opening 26 and a gas permeable membrane 27. In the plurality of micro passages 24, the micro passages 24 included in each of a first and second groups are arranged in the X axial direction when viewing the micro passage device 2 in a plane view, and the first and second groups are arranged in the Y axial direction orthogonal to the X axial direction.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present disclosure relates to a plate-shaped microchannel device used in a test for causing a test liquid containing a sample to act on a drug.

Background Art

[0002] In order to test the susceptibility of bacteria to antibacterial drugs, etc., a method of testing using a microchannel device as in Patent Document 1 is known. For example, in Patent Document 1, air is press-fitted into a microchannel device including an inlet and an outlet communicating with the outside and a channel through which the test liquid supplied from the inlet flows toward the outlet side, and the previously introduced test liquid is pushed into the fine channel. A reaction part for storing the test liquid supplied from the inlet is provided in the channel, and the drug disposed in the reaction part acts on the bacteria.

Prior Art Documents

[0006] The microfluidic device of this disclosure is a plate-shaped microfluidic device used in tests in which a test solution containing a sample reacts with a drug. The microfluidic device comprises a main channel through which the injected test solution can flow, having a first opening into which the test solution is injected, an inlet end communicating with the first opening, and an outlet end located on the opposite side of the inlet end; a plurality of microchannels, each having a first end communicating with one of the main channels and a second end located on the opposite side of the first end; a second opening communicating with the second end of each microchannel; a storage section provided in each microchannel for storing the drug; a gas permeable membrane covering at least one of the plurality of second openings; and a third opening communicating with the outlet end. Multiple microchannels are divided into a first group and a second group, and the microchannels in each of the first and second groups are arranged in a first direction when the microchannel device is viewed from above, and the first and second groups are arranged in a second direction perpendicular to the first direction, and multiple microchannels have a flow resistance greater than that of the main channel. The opening and closing mechanism By closing the third opening, the main channel is completely filled with the test fluid, and then the test fluid is introduced into each of the multiple microchannels. [Effects of the Invention]

[0007] The above-described microfluidic device can suppress the flow of the test liquid between microfluidic channels. [Brief explanation of the drawing]

[0008] [Figure 1] This figure shows an example configuration of a microfluidic device according to the embodiment. [Figure 2] This figure shows an example of the overall configuration of a test apparatus according to the embodiment. [Figure 3]This figure shows an example of the peripheral configuration of a pipette nozzle in a test apparatus according to the embodiment. [Figure 4] This is a block diagram illustrating the control of a test apparatus according to an embodiment. [Figure 5] This figure shows an example configuration in which a test liquid is injected under pressure into the channel of a microfluidic device according to the embodiment. [Figure 6] This figure shows the state after the test liquid has been injected under pressure into the channel of the microfluidic device according to the embodiment. [Figure 7] This figure shows the state after the test liquid has been discharged from the main channel of the microfluidic device according to the embodiment. [Figure 8] This figure illustrates a method for discharging a test liquid from the main channel of a microfluidic device according to an embodiment. [Figure 9] This figure shows a modified configuration of a microfluidic device. [Figure 10] This figure shows another modified configuration of a microfluidic device. [Modes for carrying out the invention]

[0009] The embodiments will be described in detail below with reference to the drawings. Note that the same or corresponding parts in the drawings are denoted by the same reference numerals, and their descriptions will not be repeated.

[0010] [Configuration of Microfluidic Devices] Figure 1 shows an example configuration of a microfluidic device according to an embodiment. Figure 1 shows a plan view of the microfluidic device 2. The microfluidic device 2 is placed on the table of the test apparatus described later, and a test solution containing the sample is injected under pressure into each of the multiple microfluidic channels.

[0011] As shown in Figure 1, the microfluidic device 2 comprises a plate-shaped member 20 and a flow channel structure. The flow channel structure includes an opening 22 (first opening), a main flow channel 23, a microfluidic channel 24, a storage section 25, an opening 26 (second opening), a gas permeable membrane 27, a recovery section 28, and an opening 29 (third opening). Note that the microfluidic device 2 may also be configured without the opening 26 (second opening).

[0012] The opening 22 is connected to one end of the main channel 23 and communicates with the main channel 23. The test liquid is injected into the main channel 23 from the opening 22 using fluid pressure. The test liquid injected into the main channel 23 is then injected into the microchannel 24. In this embodiment, air pressure is used as the fluid pressure. The opening 22 is formed, for example, with a circular cross-section. The diameter of the opening 22 is, for example, 5 μm to 5 mm. In this embodiment, one main channel 23 is connected to the opening 22. The one main channel 23 is positioned to surround the outside of the multiple microchannels 24.

[0013] The main channel 23 has an inlet end 23a that communicates with the opening 22 and an outlet end 23b located on the opposite side of 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 through them. 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 microchannels 24 are rectangular, and the widths of the main channel 23 and the microchannels 24 are, for example, 1 μm to 1 mm. However, the depth (height) of the main channel 23 and the microchannels 24 are different. For example, the depth of the main channel 23 is 0.5 mm, while the depth of the microchannels 24 is smaller at 0.025 mm. Therefore, the flow resistance of the microchannels 24 is greater than that of the main channel 23. By increasing the flow resistance of the microchannels 24 compared to the main channel 23, the test liquid flowing in from the opening 22 can, as described later, fill the main channel 23 once, and then flow into multiple microchannels 24 almost simultaneously.

[0014] When the microchannel device 2 is viewed in plan view as shown in FIG. 1, the horizontal direction of the drawing is the X-axis direction, the vertical direction of the drawing is the Y-axis direction, and the depth direction with respect to the drawing is the Z-axis direction. In the present embodiment, 32 microchannels 24 arranged side by side in the X-axis direction are grouped into one group, and two groups are arranged side by side in the Y-axis direction. That is, the microchannel device 2 has an upper group (first group) and a lower group (first group). Note that the direction of the arrow on the Y-axis is the upper side. Each of the plurality of microchannels 24 has a first side end portion 24a communicating with the main channel 23 and a second side end portion 24b located on the opposite side of the first side end portion 24a.

[0015] The plurality of microchannels 24 included in the upper group are each connected to the main channel 23 disposed above the microchannel device 2. Therefore, the plurality of microchannels 24 included in the upper group are arranged in the lower direction of the Y-axis, and the test liquid branched from the main channel 23 flows in the lower direction of the Y-axis. On the other hand, the plurality of microchannels 24 included in the lower group are each connected to the main channel 23 disposed below the microchannel device 2. Therefore, the plurality of microchannels 24 included in the lower group are arranged in the upper direction of the Y-axis, and the test liquid branched from the main channel 23 flows in the upper direction of the Y-axis.

[0016] After branching from the main channel 23 into the plurality of microchannels 24, a storage portion 25 is provided in the middle of each of the microchannels 24. Therefore, the test liquid flowing in from the opening 22 flows through the main channel 23 and the microchannels 24 and then flows into each storage portion 25.

[0017] The storage part 25 is where the agent is placed and is connected to the opening 22 via the main flow path 23 and the micro flow path 24, and stores the test liquid flowing in from the opening 22. In the storage part 25, the test liquid reacts with the agent. The agent is, for example, an antibacterial agent. The agent may be solid or liquid. The agent is placed in the storage part 25 in advance. That is, the agent is placed in the storage part 25 before the test liquid flows into the storage part 25. In the present embodiment, the agent is applied to the entire storage part 25.

[0018] The storage part 25 is formed in a rectangular parallelepiped shape. The length of one side of the storage part 25 is, for example, 10 μm to 10 mm.

[0019] In FIG. 1, 64 (= 32 × 2) storage parts 25 are formed in the plate-shaped member 20. The volumes of the test liquids stored in the 56 storage parts 25 are the same as each other. On the other hand, the types and amounts of the agents placed in the 64 storage parts 25 may be the same as each other or may be different from each other.

[0020] A micro flow path 24 is arranged between the storage part 25 and the opening 26. This micro flow path 24 is arranged along the Y-axis direction, with one end connected to the storage part 25 and the other end (the second side end 24b) connected to the opening 26. This micro flow path 24 causes the test liquid flowing into the storage part 25 to flow further to the opening 26.

[0021] The opening 26 is connected to the other end (the second side end 24b) of the micro flow path 24. The opening 26 is formed, for example, with a circular cross-section. The diameter of the opening 26 is, for example, 5 μm to 5 mm.

[0022] The openings 26 are covered by a gas permeable membrane 27. Specifically, in Figure 1, 32 openings 26 connected to multiple microchannels 24 included in the upper group and 32 openings 26 connected to multiple microchannels 24 included in the lower group are arranged facing each other. Therefore, 64 (=32 × 2) openings 26 are arranged along the X-axis in the central part of the microfluidic device 2. These 64 openings 26 are covered by a single gas permeable membrane 27. Note that the gas permeable membrane 27 may be divided into two sheets, covering 32 openings 26 in the upper group and 32 openings 26 in the lower group, rather than covering all 64 openings 26 with a single sheet. Alternatively, the gas permeable membrane 27 may cover at least one of the 64 openings 26.

[0023] The gas permeable membrane 27 has the function of allowing gases to pass through but preventing liquids from passing through. Examples of materials for the gas permeable membrane 27 include polytetrafluoroethylene (PTFE). Preferably, the gas permeable membrane 27 is water-repellent. The thickness of the gas permeable membrane 27 is 1 mm or less.

[0024] The gas permeable membrane 27 is fixed to the plate-shaped member 20 by adhesive bonding, ultrasonic fusion, or the like. Examples of adhesives include photocurable resins, thermosetting resins, and pressure-sensitive resins.

[0025] A single main channel 23 connected to the opening 22 is arranged to surround the outside of the microchannel 24 and is connected to a recovery section 28. The recovery section 28 is provided at the outlet end 23b of the main channel 23. The recovery section 28 recovers a portion of the test liquid that flows into the main channel 23 from the opening 22. The recovery section 28 is formed in the shape of a rectangular parallelepiped. The length of one side of the recovery section 28 is, for example, 10 μm to 10 mm. The recovery section 28 may be provided with a moisture-absorbing material (water-absorbing material) such as a sponge. This prevents backflow from the recovery section 28 to the main channel 23 and prevents the test liquid from volatilizing from the main channel 23.

[0026] The opening 29 is connected to the end of the recovery section 28 opposite to the end to which the main channel 23 is connected. The main channel 23 and the recovery section 28 are configured to allow the test liquid to flow from the opening 22 to the opening 29. The opening 29 can also be closed by the opening / closing section of the test apparatus, which will be described later. By closing the opening 29, the test liquid that has flowed into the main channel 23 is prevented from being discharged into the recovery section 28 and the opening 29. By opening the opening 29, the test liquid remaining in the main channel 23 can be discharged into the recovery section 28 and recovered.

[0027] [Device configuration] Next, a test apparatus that uses a microfluidic device 2 to perform a test in which a test solution containing a sample interacts with a drug will be described. Figure 2 is a diagram showing an example of the overall configuration of the test apparatus according to the embodiment. Figure 3 is a diagram showing an example of the peripheral configuration of the pipette nozzle in the test apparatus according to the embodiment. Figure 4 is a block diagram for explaining the control of the test apparatus according to the embodiment. The test apparatus of this disclosure is a device that measures the test solution by pressurizing the test solution containing the sample into the microfluidic device 2, and the following description will be given as an example in which the test solution is pressurized into the microfluidic device to measure the susceptibility of bacteria to an antibacterial agent (drug). The test solution contains a sample. The sample may be bacteria (pathogenic bacteria in a specific example). In a specific example, the test solution may be a bacterial suspension. Of course, the test apparatus of this disclosure is not limited to the above-mentioned test solution, as long as the test solution is pressurized into the microfluidic device 2.

[0028] Referring to Figures 2 to 4, the test apparatus 100 includes a test liquid setting unit 10, a pipette nozzle drive unit 12, a table drive unit 13, a pump 14, a pipette nozzle 15, a table 16, an opening / closing unit 30, an opening / closing drive unit 31, a dispensing unit 32, a pump 33, a dispensing drive unit 34, and a control unit 50.

[0029] The test solution storage section 10 is a rack on which multiple test solution containers 5 containing test solutions can be arranged. The test solution storage section 10 can set multiple test solution containers 5 in rack units relative to the test apparatus 100.

[0030] The pipette nozzle 15 has a detachable pipette tip 1 attached to it and draws or discharges the test solution from the test solution container 5 through the tip of the pipette tip 1. The pipette nozzle drive unit 12 moves the pipette nozzle 15 horizontally and vertically using a pump 14 connected to the pipette nozzle 15. The pipette nozzle drive unit 12 can move the pipette nozzle 15 freely, for example, by a solenoid actuator or a stepping motor.

[0031] The table 16 is a support member for mounting the microfluidic device 2. The table 16 is formed in a flat plate shape and fixes the microfluidic device 2 to its upper surface. The table drive unit 13 can move the table 16 horizontally. The table drive unit 13 can move the table 16 freely, for example, by a solenoid actuator or a stepping motor. Of course, the table drive unit 13 may be configured to move the table 16 up and down, while not moving the pipette nozzle 15 up and down. At least the pipette nozzle drive unit 12 and the table drive unit 13 are movement mechanisms for changing the relative position between the pipette nozzle 15 and the microfluidic device 2.

[0032] The pump 14, although not shown in the diagram, includes, for example, a syringe, a plunger capable of reciprocating within the syringe, and a drive motor for driving the plunger. The pump 14 is connected to the pipette nozzle 15 via piping, and by reciprocating the plunger, it can adjust the air pressure inside the pipette tip 1 to draw the test liquid into the pipette tip 1 or discharge the test liquid inside the pipette tip 1 to the outside. Furthermore, after the test liquid inside the pipette tip 1 has been discharged to the outside, the pump 14 can also expel air from the pipette tip 1 by moving the plunger in a direction that pushes it back into the syringe.

[0033] The opening / closing section 30 is a mechanism for opening and closing the opening 29 (third opening) of the microfluidic device 2. Specifically, the opening / closing section 30 is a mechanism that controls the opening to a closed state by blocking it with an elastic member, for example, a silicone resin 30a is provided at the end of a rod-shaped support. Since the opening / closing section 30 is attached to the pipette nozzle 15 at a predetermined position, it moves to the position of the opening 29 when the pipette nozzle 15 is moved to the opening 22 (first opening) of the microfluidic device 2. The opening / closing drive unit 31 drives the opening / closing section 30, which has moved to the position of the opening 29, to move the silicone resin 30a up and down, pressing the silicone resin 30a against the opening 29 to block it, and controlling the opening 29 to a closed state. In the test apparatus 100 shown in Figures 2 and 3, only one opening / closing section 30 is provided to match the configuration of the microfluidic device 2, but multiple opening / closing sections 30 may be provided according to the number of openings 29 that need to be opened and closed. Furthermore, the opening / closing drive unit 31 may not only move the silicone resin 30a up and down, but may also move the opening / closing unit 30 relative to the pipette nozzle 15.

[0034] The coating unit 32 applies a sealing material to the openings 22, 29, etc., of the microfluidic device 2 in order to suppress the evaporation of the test liquid injected under pressure through these openings. Specifically, the coating unit 32 is a nozzle that discharges a sealing material, such as silicone oil, to the openings, etc., and the pump 33 applies the sealing material to the openings, etc., using this nozzle. The configuration of the coating unit 32 is not limited to this, and a mechanism that applies the sealing material to the openings, etc., using a brush or the like may also be used. The coating drive unit 34 moves the coating unit 32 to the position of the openings 22, 29, etc., of the microfluidic device 2 to which the sealing material is to be applied, and drives the pump 33. In Figures 2 and 3, the coating unit 32 is shown to be provided on the same moving mechanism as the pipette nozzle 15, but the coating unit 32 may be provided on a different moving mechanism from the pipette nozzle 15, and the coating drive unit 34 may move the coating unit 32. Note that if the evaporation of the test liquid is not a problem, the test apparatus 100 does not need to be provided with a coating unit 32.

[0035] 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 memory such as ROM (Read Only Memory) and RAM (Random Access Memory). The memory stores the control program. The processor controls the operation of the test apparatus 100 by executing the control program. The memory of the control unit 50 may also include an HDD (Hard Disk Drive).

[0036] The control unit 50 controls the motor of the table drive unit 13 to move the table 16 so that the microfluidic device 2 is in a predetermined position. After moving the microfluidic device 2 to the predetermined position, the control unit 50 controls the motor of the pipette nozzle drive unit 12 to move the pipette nozzle 15 in order to pressurize the test liquid into the opening 22 of the microfluidic channel 24 of the microfluidic device 2. Furthermore, the control unit 50 controls the opening / closing drive unit 31 to switch the open / closed state of the opening 29 of the microfluidic device 2. Finally, the control unit 50 controls the coating drive unit 34 to coat the opening 22, 29, etc. of the microfluidic device 2 with a sealing material.

[0037] Specifically, the control unit 50 controls the motor of the pipette nozzle drive unit 12 to move the pipette nozzle 15 to a predetermined position in the test liquid container 5, and controls the pump 14 to aspirate the test liquid from the test liquid container 5 through the tip of the pipette tip 1. Subsequently, the control unit 50 controls the motor of the pipette nozzle drive unit 12 to move the pipette nozzle 15 to the position of the opening 22 of the microfluidic device 2, and controls the pump 14 to pressurize the test liquid from the tip of the pipette tip 1 into the opening 22.

[0038] The control unit 50 can be connected to a processing unit 200, which is implemented by a personal computer (PC) or a dedicated computer. The user can manage the test apparatus 100 via the processing unit 200. For example, the processing unit 200 can set the amount of movement of the table 16 by the table drive unit 13, the amount of movement of the pipette nozzle 15 by the pipette nozzle drive unit 12, and the amount of test liquid to be aspirated or discharged from the tip of the pipette tip 1 by the pump 14. The processing unit 200 may also be electrically connected to other devices located adjacent to the test apparatus 100 to form a test system.

[0039] [Pressure injection of test fluid into microfluidic device] Next, a method for injecting the test liquid into the microfluidic device 2 using the test apparatus 100 will be described. Figure 5 is a diagram showing an example configuration in which the test liquid is injected into the channel of the microfluidic device 2 according to the embodiment. The plate-shaped member 20 of the microfluidic device 2 comprises an upper first plate-shaped member 20a and a lower second plate-shaped member 20b as shown in Figure 5. The second plate-shaped member 20b is laminated on the first plate-shaped member 20a. The second plate-shaped member 20b is positioned in the negative direction (downward direction) of the Z-axis shown in Figure 1 relative to the first plate-shaped member 20a.

[0040] The first plate-shaped member 20a and the second plate-shaped member 20b are formed in a rectangular plate shape from a transparent material. Examples of materials for the first plate-shaped member 20a and the second plate-shaped member 20b include acrylic resin such as polymethyl methacrylate resin and glass. A flow channel structure is formed in the first plate-shaped member 20a. Specifically, the first plate-shaped member 20a has an opening 22, a main flow channel 23, a microflow channel 24, a storage section 25, an opening 26, and a recovery section 28 (see Figure 1). The second plate-shaped member 20b 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 28. The thickness of the first plate-shaped member 20a and the second plate-shaped member 20b is not particularly limited, but can be set to, for example, 0.5 mm to 3 mm. The second plate-shaped member 20b is directly fixed to the first plate-shaped member 20a by ultrasonic melting, but it may also be fixed via an adhesive.

[0041] In this embodiment, the test liquid drawn in with the pipette tip 1 is pressurized with air pressure and injected into the microchannel 24 from the opening 22. As shown in Figure 5, the test liquid flowing in from the pipette tip 1 fills the microchannel 24, the reservoir 25, and the opening 26 via the opening 22 and the main channel 23. However, the microfluidic device 2 has multiple microchannels 24 that are connected via the main channel 23. Therefore, when the test liquid is injected into the microfluidic device 2, which branches from one opening 22 through the main channel 23 into multiple microchannels 24, a difference in liquid level (liquid head) occurs between each channel, and this difference causes flow in the test liquid between channels.

[0042] Figure 6 shows the state after the test liquid has been injected under pressure into the flow channel of the microfluidic device 2 according to the embodiment. The upper path shown in Figure 6 is called path A, and the lower path is called path B. The test liquid flowing in from the opening 22 passes through the main flow channel 23 and splits into the microfluidic channel 24 of path A and the microfluidic channel 24 of path B, reaching their respective openings 26. As shown in Figure 6, since path B is further from the opening 22 than path A, the liquid head at the opening 26 of path A is higher than the liquid head at the opening 26 of path B. Because there is a difference in liquid head between path A and path B, flow occurs in the test liquid between path A and path B to eliminate this difference. If flow occurs in the test liquid within the storage sections 25 of path A and path B, it may become impossible to observe the correct results.

[0043] Therefore, in this embodiment, after injecting the test liquid into multiple microchannels 24, the test liquid remaining in the main channel 23 is discharged to the recovery section 28. By discharging the test liquid remaining in the main channel 23, each channel is made independent, preventing the multiple microchannels 24 from becoming a single channel via the main channel 23, thereby preventing flow due to differences in liquid head.

[0044] Figure 7 shows the state after the test liquid has been discharged from the main channel 23 of the microfluidic device 2 according to the embodiment. The upper path shown in Figure 7 is called path A, and the lower path is called path B. By discharging the test liquid from the main channel 23, the microfluidic channel 24 of path A and the microfluidic channel 24 of path B do not become a single channel via the main channel 23. Therefore, even if the liquid head at the opening 26 of path A is higher than the liquid head at the opening 26 of path B, no flow of the test liquid occurs between path A and path B in order to resolve this difference.

[0045] Figure 8 illustrates a method for discharging a test liquid from the main channel 23 of a microfluidic device 2 according to an embodiment. In Figure 8, multiple microfluidic channels 24 are connected to the main channel 23, and a recovery section 28 is provided at one end of the main channel 23 (the outlet end 23b). The recovery section 28 has an opening 29 at the end opposite to the end connected to the main channel 23. Although not shown, the main channel 23 is connected to an opening 22 at the end opposite to the end to which the recovery section 28 is connected.

[0046] When the test solution flows into the main channel 23, the flow resistance of each microchannel 24 is greater than that of the main channel 23. Therefore, the test solution will not flow into each microchannel 24 until the main channel 23 is completely filled with the test solution. To increase the flow resistance of each microchannel 24 compared to the main channel 23, the cross-sectional area of ​​the main channel 23 should be made larger than the cross-sectional area of ​​each microchannel 24. If the width of the main channel 23 and the width of each microchannel 24 are the same, the depth of the main channel 23 should be made deeper than the depth of each microchannel 24. For example, if the depth of the main channel 23 is 0.5 mm, and the depth of each microchannel 24 is 0.001 mm, the cross-sectional area of ​​the main channel 23 can be made 500 times the cross-sectional area of ​​each microchannel 24.

[0047] When the test liquid is introduced into the main channel 23, the opening 29 is sealed and closed by the silicone resin 30a of the opening / closing section 30. Therefore, the test liquid that has entered the main channel 23 is not discharged to the recovery section 28 at this stage. After the main channel 23 is completely filled with the test liquid, as shown in Figure 8, the test liquid flows into each of the microchannels 24 almost simultaneously. As a result, the test liquid flows into each of the microchannels 24 and each of the storage sections 25.

[0048] Subsequently, the silicone resin 30a of the opening / closing part 30 that is blocking the opening 29 is removed, and with the opening 29 open, air is blown in through the opening 22 to discharge the test liquid remaining in the main channel 23 to the recovery part 28, as shown in Figure 8. The air blown in through the opening 22 can be the air discharged from the pipette tip 1 to pressurize the test liquid. The recovery part 28 has a space (buffer space) that holds the test liquid in the main channel 23 that is discharged, and this space is larger than the volume of the main channel 23.

[0049] Whether or not the test liquid in the main channel 23 is discharged to the recovery unit 28 can be controlled by opening and closing the opening 29. Any test liquid remaining in the main channel 23 is discharged to the recovery unit 28 by air through the opening 22.

[0050] In this embodiment, the test liquid is injected under pressure into each microchannel 24, the test liquid remaining in the main channel 23 is discharged into the recovery section 28, and then a sealing material such as silicone oil is applied to the openings 22, 26, 29, etc. The sealing material applied to the openings 22, 26, 29, etc. is not limited to silicone oil 33a, but any material that remains in the openings 22, 26, 29, etc. and suppresses the evaporation of the test liquid may be used.

[0051] As shown in Figure 1, the microfluidic device 2 is configured such that all microfluidic channels 24 are connected to a single main channel 23. Therefore, the test liquid collected in the recovery section 28 is only the test liquid remaining in the single main channel 23. However, depending on the configuration of the microfluidic device, multiple main channels may be provided, and multiple microfluidic channels 24 may be connected to each main channel. For example, if four main channels are connected to an opening (first opening) into which the test liquid is injected, even if the main channels have the same shape, subtle differences in flow resistance will occur. When air is injected from the opening (first opening) to discharge the test liquid into the four main channels with different flow resistances, depending on the conditions of the injected air, there is a possibility that one main channel will remain unable to discharge the test liquid.

[0052] If test liquid remains in one of the four main channels, even if air is subsequently injected through the opening (first opening), the air will escape from the channel from which the test liquid was successfully discharged, making it impossible to discharge the test liquid from the channel in which it remains. As described above, the multiple microchannels 24 connected to the main channel in which the test liquid remains generate a flow of test liquid between the paths to eliminate the difference in liquid head between the channels.

[0053] Therefore, in this embodiment, the number of openings 22 (first openings) into which the test liquid is injected is matched with the number of main channels 23, and the microchannels 24 included in each of the multiple groups are all connected to one main channel 23. In other words, instead of providing a single straight channel and connecting all the microchannels to that channel, the main channel 23 is arranged so that multiple microchannels 24, which are arranged in multiple groups on the plate-shaped member 20, are connected by a single channel. If all the microchannels were connected to a straight channel, the length of one side of the microchannel device would be approximately twice the length of one side of the microchannel device 2 shown in Figure 1, requiring the test equipment to be used and the refrigerator to be used for storage to be made larger. On the other hand, by arranging a single main channel 23 as in the microchannel device 2, the test liquid in the main channel 23 can be discharged to all the recovery sections 28 without changing the external dimensions.

[0054] Furthermore, in the microfluidic device 2 shown in Figure 1, the multiple openings 26 included in the upper group and the multiple openings 26 included in the lower group are arranged to face each other. Therefore, since all the openings 26 are arranged along the X-axis in the central part of the microfluidic device 2, all the openings 26 can be covered by a single gas permeable membrane 27, and it is also possible to reduce the number of gas permeable membranes 27.

[0055] [Changes in microfluidic devices] Note that the configuration of the microfluidic device is not limited to the configuration shown in Figure 1. Figure 9 shows a modified example of the configuration of the microfluidic device. The microfluidic device 2A shown in Figure 9 comprises a plate-shaped member 20 and a channel structure. The channel structure comprises an opening 22 (first opening), a main channel 23A, a microchannel 24, a storage section 25, an opening 26 (second opening), a gas permeable membrane 27, a recovery section 28, and an opening 29 (third opening). Note that parts of the microfluidic device 2A that are the same as or equivalent to those of the microfluidic device 2 shown in Figure 1 are denoted by the same reference numerals and their descriptions are not repeated.

[0056] In the microfluidic device 2A, one main channel 23A is positioned along the X-axis in the central part of the microfluidic device 2A. An opening 22 is connected to one end of the main channel 23A, and a recovery section 28 is connected to the other end of the main channel 23A. Multiple microfluidic channels 24 each communicate with the main channel 23A located in the central part. Specifically, the multiple microfluidic channels 24 included in the upper group are positioned in the upward direction of the Y-axis from the part communicating with the main channel 23A, and the test liquid branched from the main channel 23A flows in in the upward direction of the Y-axis. On the other hand, the multiple microfluidic channels 24 included in the lower group are positioned in the downward direction of the Y-axis from the part communicating with the main channel 23A, and the test liquid branched from the main channel 23A flows in in the downward direction of the Y-axis. Note that the length of the main channel 23A in the microfluidic device 2A can be shorter than the length of the main channel 23 in the microfluidic device 2.

[0057] In Figure 9, 32 openings 26 connected to multiple microchannels 24 in the upper group and 32 openings 26 connected to multiple microchannels 24 in the lower group are arranged on opposite sides of the microfluidic device 2A. Therefore, two gas permeable membranes 27 are required: one to cover the 32 openings 26 in the upper group and another to cover the 32 openings 26 in the lower group.

[0058] Next, Figure 10 shows another modified example of the configuration of the microfluidic device. The microfluidic device 2B shown in Figure 10 comprises a plate-shaped member 20 and a flow channel structure. The flow channel structure comprises an opening 22 (first opening), a main flow channel 23B, a microflow channel 24, a storage section 25, an opening 26 (second opening), a gas permeable membrane 27, a recovery section 28, and an opening 29 (third opening). Note that the same or equivalent parts of the microfluidic device 2B as those of the microfluidic device 2 shown in Figure 1 are denoted by the same reference numerals, and their descriptions will not be repeated.

[0059] In the microfluidic device 2B, one main channel 23B is positioned to pass outside the upper group and through the central part of the microfluidic device 2B. An opening 22 is connected to one end of the main channel 23B, and a recovery section 28 is connected to the other end of the main channel 23B. Multiple microfluidic channels 24 are connected as follows: the upper group is connected to the main channel 23B located on the outside, and the lower group is connected to the main channel 23B located in the central part. Specifically, the multiple microfluidic channels 24 included in the upper group are positioned downward along the Y-axis from the part that communicates with the outer main channel 23B, and the test liquid branched from the main channel 23B flows in downward along the Y-axis. On the other hand, the multiple microfluidic channels 24 included in the lower group are positioned downward along the Y-axis from the part that communicates with the central main channel 23B, and the test liquid branched from the main channel 23B flows in downward along the Y-axis. Furthermore, the length of the main channel 23B of the microfluidic device 2B can be made shorter than the length of the main channel 23 of the microfluidic device 2.

[0060] In Figure 10, 32 openings 26 connected to multiple microchannels 24 in the upper group are located in the central part of the microfluidic device 2B, while 32 openings 26 connected to multiple microchannels 24 in the lower group are located on one side of the microfluidic device 2B. Therefore, two gas permeable membranes 27 are required: one to cover the 32 openings 26 in the upper group and another to cover the 32 openings 26 in the lower group.

[0061] [Other variations] (1) In the test apparatus 100 according to the embodiment, the opening 29 is closed by sealing it with the silicone resin 30a of the opening / closing part 30, but the apparatus is not limited to this, and any configuration that switches the open / closed state of the opening 29 is acceptable. For example, if an opening / closing mechanism (such as a shutter) is provided in advance for the opening 29 of the microfluidic device 2, the opening / closing part 30 may be configured to switch the state of the opening / closing mechanism.

[0062] (2) In the test apparatus 100 according to the embodiment, a sealing material is applied to the openings 22, 26, and 29, but the invention is not limited to this, and any configuration is acceptable as long as the evaporation of the test liquid is suppressed. For example, the evaporation of the test liquid may be suppressed by attaching pre-prepared covers to the openings 22, 26, and 29.

[0063] (3) The cross-section of the opening 29 is formed in a circular shape and is in communication with the recovery section 28. Therefore, when air is introduced from the opening 22 with the opening 29 open to discharge the test liquid remaining in the main channel 23 to the recovery section 28, depending on the pressure of the introduced air, the test liquid may not only be discharged into the recovery section 28 but may also overflow from the opening 29. For this reason, the opening 29 may be covered with a gas permeable membrane.

[0064] In Figure 1, an opening 29 is provided at the end of the recovery section 28 opposite to the end to which the main channel 23 is connected. However, the recovery section 28 itself may have an opening, thus eliminating the need for an opening 29. Furthermore, the opening provided in the recovery section 28 may be covered with a gas permeable membrane. Also, the recovery section 28 itself may not be provided at the outlet end 23b of the main channel 23.

[0065] [Pattern] Those skilled in the art will understand that the embodiments described above are specific examples of the following embodiments.

[0066] (Section 1) A microfluidic device according to one embodiment is a plate-shaped microfluidic device used in a test in which a test solution containing a sample reacts with a drug, and comprises a main channel through which the injected test solution can flow, having a first opening into which the test solution is injected, an inlet end communicating with the first opening, and an outlet end located on the opposite side of the inlet end, each having a plurality of microchannels, each having a first end communicating with the main channel and a second end located on the opposite side of the first end, a second opening communicating with the second end of each microchannel, a storage section provided in each microchannel for storing the drug, and a gas permeable membrane covering at least one of the plurality of second openings, wherein the plurality of microchannels include a first group and a second group, the microchannels included in each of the first group and the second group are arranged side by side in a first direction when the microfluidic device is viewed from above, and the first group and the second group are arranged side by side in a second direction perpendicular to the first direction.

[0067] According to the microfluidic device described in paragraph 1, all of the test liquid in the channel can be discharged, thus suppressing the flow of the test liquid between the microfluidic channels.

[0068] (Section 2) The microfluidic device described in paragraph 1 further comprises a recovery section provided at the outlet end for recovering a portion of the test liquid, and a third opening provided in the recovery section.

[0069] According to the microfluidic device described in paragraph 2, all of the test liquid discharged from the main channel can be collected in the recovery section.

[0070] (Section 3) A microfluidic device according to paragraph 1 or 2, wherein, when the microfluidic device is viewed from above, the second openings included in the first group and the second openings included in the second group are arranged to face each other, and one main channel is positioned to surround the outside of the multiple microfluidic channels.

[0071] According to the microfluidic device described in Section 3, the second openings included in the first group and the second openings included in the second group are arranged to face each other, thereby reducing the number of gas permeable membranes 27.

[0072] (Section 4) The microfluidic device described in paragraph 3, wherein the gas permeable membrane covers the second opening included in the first group and the second opening included in the second group with a single membrane.

[0073] According to the microfluidic device described in Section 4, the number of gas permeable membranes covering the second opening can be reduced to one.

[0074] (Section 5) The microfluidic device described in paragraph 1, wherein, when the microfluidic device is viewed from above, the second openings included in the first group and the second openings included in the second group are arranged on opposite sides of the microfluidic device, and one main channel is arranged in the central part of the microfluidic device.

[0075] According to the microfluidic device described in Section 5, the length of a single main channel can be shortened.

[0076] (Section 6) The microfluidic device described in paragraph 1, wherein, when the microfluidic device is viewed from above, the second opening included in the first group is located in the central part of the microfluidic device, the second opening included in the second group is located on one side of the microfluidic device, and one main channel is located outside the first group and in a position that passes through the central part of the microfluidic device.

[0077] According to the microfluidic device described in Section 6, the length of a single main channel can be shortened.

[0078] (Section 7) The microfluidic device described in paragraph 2, wherein the recovery section is a buffer space larger than the volume of the main channel.

[0079] According to the microfluidic device described in Section 7, since the recovery section is a buffer space larger than the volume of the main channel, all of the test liquid remaining in the main channel can be recovered.

[0080] (Section 8) The microfluidic device described in paragraph 7, wherein a water-absorbing member is provided in the buffer space.

[0081] The microfluidic device described in Section 8 can prevent backflow from the recovery section to the main channel and prevent the volatilization of the test liquid from the main channel.

[0082] (Section 9) A microfluidic device as described in any one of paragraphs 1 to 8, wherein the flow resistance of the microfluidic channel is greater than the flow resistance of the main channel.

[0083] According to the microfluidic device described in Section 9, since the flow resistance of the microfluidic channels is greater than the flow resistance of the main channel, the test fluid from the main channel can be introduced into each microfluidic channel almost simultaneously.

[0084] (Section 10) A microfluidic device according to any one of paragraphs 2, 7, and 8, wherein the gas permeable membrane further covers the third opening.

[0085] According to the microfluidic device described in Section 10, when the test liquid remaining in the main channel is discharged to the recovery section, the risk of the test liquid not remaining in the recovery section but being discharged from the third opening can be reduced.

[0086] (Section 11) A microfluidic device according to any one of paragraphs 1 to 10, wherein the plurality of microfluidic channels further include a third group.

[0087] According to the microfluidic device described in paragraph 11, even more microfluidic channels can be provided.

[0088] The embodiments disclosed herein should be considered in all respects to be illustrative and not restrictive. The scope of the present invention is indicated by the claims rather than by the description of the embodiments above, and all modifications within the meaning and scope equivalent to the claims are intended to be included. [Explanation of symbols]

[0089] 1 Pipette tip, 2, 2A, 2B Microfluidic device, 5 Test solution container, 10 Test solution placement section, 12 Pipette nozzle drive unit, 13 Table drive unit, 14, 33 Pump, 15 Pipette nozzle, 16 Table, 22, 26, 29 Opening, 23 Main channel, 24 Microfluidic channel, 25 Storage section, 27 Gas permeable membrane, 28 Recovery section, 30 Opening / closing section, 31 Opening / closing drive unit, 32 Dispensing section, 34 Dispensing drive unit, 50 Control unit, 100 Test apparatus, 200 Processing unit.

Claims

1. A plate-shaped microfluidic device used in tests in which a test solution containing a sample reacts with a drug, The first opening into which the test liquid is injected under pressure, The main channel has an inlet end that communicates with the first opening and an outlet end located on the opposite side of the inlet end, and the injected test liquid can flow through it. Each of the multiple microchannels has a first side end that communicates with one of the main channels, and a second side end that is located on the opposite side of the first side end, A second opening that communicates with the second end of each microchannel, Each microchannel is provided with a storage section in which the drug is stored, A gas permeable membrane covering at least one of the plurality of second openings, It comprises a third opening that communicates with the aforementioned outlet end, The aforementioned multiple microchannels are divided into a first group and a second group, The microchannels included in the first group and the second group are arranged in a first direction when the microchannel device is viewed in plan, The first group and the second group are arranged side by side in a second direction perpendicular to the first direction, The aforementioned plurality of microchannels have a greater flow resistance than the main channel. A microfluidic device that, by closing the third opening with an opening and closing mechanism, fills the main channel entirely with the test liquid and then allows the test liquid to flow into each of the plurality of microfluidic channels.

2. The outlet end further comprises a recovery section for recovering a portion of the test liquid, The third opening is provided in the recovery section, as described in claim 1, for the microfluidic device.

3. When the microfluidic device is viewed from above, the second openings included in the first group and the second openings included in the second group are arranged to face each other. The microfluidic device according to claim 1 or claim 2, wherein one of the main channels is positioned to surround the outside of the plurality of microfluidic channels.

4. The microfluidic device according to claim 3, wherein the gas permeable membrane covers the second openings included in the first group and the second openings included in the second group with a single membrane.

5. When the microfluidic device is viewed in plan, the second opening included in the first group and the second opening included in the second group are arranged on opposite sides of the microfluidic device, The microfluidic device according to claim 1, wherein one of the main channels is located in the central part of the microfluidic device.

6. When the microfluidic device is viewed from above, the second opening included in the first group is located in the central part of the microfluidic device, and the second opening included in the second group is located on one side of the microfluidic device. The microfluidic device according to claim 1, wherein one of the main channels passes outside the first group and is positioned to pass through the central portion of the microfluidic device.

7. The microfluidic device according to claim 2, wherein the recovery section is a buffer space larger than the volume of the main channel.

8. The microfluidic device according to claim 7, wherein a water-absorbing member is provided in the buffer space.

9. The microfluidic device according to any one of claims 1 to 8, wherein the flow resistance of the microfluidic channel is greater than the flow resistance of the main channel.

10. The microfluidic device according to any one of claims 1, 2, 7, and 8, wherein the gas permeable membrane further covers the third opening.

11. The microfluidic device according to any one of claims 1 to 10, further comprising a third group of the plurality of microfluidic channels.

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