Microfluidic device, test method using microfluidic device, and test apparatus using microfluidic device

Abstract

The present invention relates to a test method using a microfluidic device, which stabilizes the concentration of a drug after dissolving in a test liquid. The method brings a test liquid containing a test object into contact with a drug, and tests the effect of the drug on the test object. The method includes: a preparation step of preparing a microfluidic device (100), wherein the microfluidic device (100) has a plurality of microfluidic channels (22, 23, 25), a first opening (26) and a second opening (21) arranged at both ends of each of the plurality of microfluidic channels and communicating with the outside, a storage portion (24) respectively provided in the plurality of microfluidic channels (23) and storing the drug, and a gas permeable membrane (3) covering the first opening (26); a pressure-feeding step of applying a fluid pressure greater than the external pressure to the test liquid from a syringe pump (4) connected to the second opening (21) via the second opening (21), and feeding the test fluid to the storage portion (24); and an observation step of observing a target area set in the microfluidic channel (25).

Description

Technical Field

[0001] The present invention relates to a microfluidic device, a test method using the microfluidic device, and a test apparatus using the microfluidic device. Background Art

[0002] There is known a method for examining the sensitivity of bacteria to antibiotics using a microfluidic device (for example, see Patent Document 1).

[0003] The microfluidic device described in Patent Document 1 comprises an inlet and an outlet communicating with the outside, and a flow path through which a test solution supplied from the inlet flows toward the outlet. A reaction section is provided in the flow path, storing the test solution supplied from the inlet. The outlet is positioned downstream of the test solution flowing into the reaction section. Furthermore, a reagent is disposed in the reaction section, and the reagent acts on bacteria within the reaction section.

[0004] Prior art literature

[0005] Patent Literature

[0006] Patent Document 1: Japanese Patent Application Laid-Open No. 2017-67620 Summary of the Invention

[0007] Technical problem to be solved by the invention

[0008] The present inventors have discovered that in order to bring a test solution and a drug into contact and accurately test the effect of the drug on a subject (bacteria, etc.), it is crucial to stabilize the concentration of the drug after dissolving it in the test solution.

[0009] Conventional methods for testing the effects of drugs using microfluidic devices have not examined drug concentrations.

[0010] An object of the present invention is to stabilize the concentration of a drug dissolved in a test solution in a test method for testing the effect of the drug on the test subject by bringing a test solution containing a test subject into contact with the drug.

[0011] Solutions for solving the above technical problems

[0012] This specification incorporates all the contents of Japanese Patent Application No. 2019-103580 filed on June 3, 2019.

[0013] The first scheme of the present invention relates to a test method using a microfluidic device, wherein the microfluidic device brings a test fluid containing a test object into contact with a drug, and tests the effect of the drug on the test object, including: a preparation step, preparing a microfluidic device, the microfluidic device having a plurality of microfluidics, a first opening and a second opening arranged at both ends of each of the plurality of microfluidics and connected to the outside, a storage portion respectively provided in the plurality of microfluidics and storing the drug, and a gas permeable membrane covering the first opening; a pressure delivery step, applying a fluid pressure greater than the external pressure to the test fluid via the second opening from a pressure source connected to the second opening, and delivering the test fluid to the storage portion; an observation step, observing an object area set in the microfluidic device.

[0014] The second embodiment of the present invention relates to a microfluidic device that brings a test fluid containing a test object into contact with a drug and tests the effect of the drug on the test object, comprising: a first microfluidic channel having a first end and a second end through which the test fluid can flow; a storage portion that stores the drug and is connected to the second end in a manner that allows the test fluid to flow; a first opening that is connected to the storage portion; and a gas permeable membrane that covers the first opening.

[0015] A third embodiment of the present invention relates to a test apparatus using a microfluidic device, wherein the microfluidic device brings a test fluid containing a test subject into contact with a drug and tests the effect of the drug on the test subject, and comprises: a microfluidic device having a first microfluidic channel having a first end and a second end through which the test fluid can flow; a reservoir storing the drug and connected to the second end so that the test fluid can flow; a first opening communicating with the reservoir; a gas permeable membrane covering the first opening; a second microfluidic channel communicating between the reservoir and the first opening so that the test fluid can flow; and a second opening formed at the first end; a pump connected to the second opening for applying air pressure to the test fluid; a platform on which the microfluidic device is mounted; a drive mechanism for driving the platform in a horizontal direction; and a control unit for controlling the drive mechanism, wherein the control unit causes the drive mechanism to drive the platform so that the second microfluidic channel is located in an imaging area of ​​a microscope.

[0016] Effects of the Invention

[0017] According to the first aspect of the present invention, the first opening formed in communication with the reservoir in the microfluidic device is covered with a gas permeable membrane, and the method includes applying a fluid pressure greater than the external pressure to the test fluid to fluidically feed the test fluid to the reservoir.

[0018] Therefore, air contained in the test liquid stored in the reservoir is released through the gas-permeable membrane through the opening formed in communication with the reservoir, while the test liquid does not pass through the gas-permeable membrane. Consequently, the reservoir is filled with the test liquid, making it easy to store an appropriate amount of the test liquid in the reservoir. As a result, the concentration of the drug dissolved in the test liquid can be stabilized.

[0019] According to the second embodiment of the present invention, the microfluidic device comprises: a first microfluidic channel for allowing a test liquid to flow; a reservoir storing a reagent, and the test liquid flows into the first microfluidic channel; a first opening formed in communication with the reservoir; and a gas permeable membrane covering the first opening.

[0020] Therefore, the test liquid flows from the first microchannel into the reservoir. Once the reservoir is filled with the test liquid, the gas permeable membrane restricts the test liquid from flowing out of the first opening. This allows the reservoir to be filled with the test liquid, making it easy to store an appropriate amount of the test liquid in the reservoir. As a result, the concentration of the drug dissolved in the test liquid can be stabilized.

[0021] According to the third aspect of the present invention, by using the micro-channel device of the second aspect, an appropriate amount of test solution can be easily stored in the reservoir, thereby stabilizing the concentration of the drug dissolved in the test solution. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is a plan view showing an example of the micro-flow path device according to the first embodiment of the present invention.

[0023] Figure 2 This is a side cross-sectional view showing an example of the micro-flow path device according to the first embodiment.

[0024] Figure 3 It is a III-III cross-sectional view showing an example of the micro-flow path device according to the first embodiment.

[0025] Figure 4 It is a cross-sectional view taken along line IV-IV showing an example of the micro-flow path device according to the first embodiment.

[0026] Figure 5 This is a diagram showing an example of the configuration of a testing device.

[0027] Figure 6 This is a flowchart showing an example of processing by the control unit of the testing device.

[0028] Figure 7 This is a plan view showing an example of a micro-flow path device according to a second embodiment of the present invention.

[0029] Figure 8 This is a side cross-sectional view showing an example of the micro-flow path device according to the second embodiment.

[0030] Figure 9 This is a diagram showing an example of a captured image of the micro-flow channel device according to the second embodiment. DETAILED DESCRIPTION

[0031] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings.

[0032] In the following description, reference is made to mutually orthogonal X-axis, Y-axis, and Z-axis. The Z-axis is arranged along the vertical direction. The X-axis and Y-axis are arranged along the horizontal direction. The X-axis indicates the left-right direction, and the Y-axis indicates the front-back direction.

[0033] [1. Configuration of Microflow Channel Device According to First Embodiment]

[0034] Figure 1 1 is a top view showing an example of a micro-channel device 100 according to the first embodiment of the present invention. The micro-channel device 100 is placed on a platform of a test apparatus. Figure 4 The test apparatus is described.

[0035] like Figure 1 As shown, the micro-channel device 100 includes a plate-shaped member 1, a channel structure 2, and a gas permeable membrane 3. Figure 2 The plate-shaped member 1 will be described in detail.

[0036] The flow channel structure 2 includes an opening 21 , a microchannel 22 , a microchannel 23 , a reservoir 24 , a microchannel 25 , and an opening 26 .

[0037] Opening 21 corresponds to an example of a "second opening." Microchannels 22 and 23 correspond to an example of a "first microchannel." Opening 26 corresponds to an example of a "first opening." Microchannel 25 corresponds to an example of a "second microchannel." Microchannels 22, 23, and 25 correspond to an example of a "microchannel."

[0038] Opening 21 is located at one end of microchannel 22. Fluid pressure is used to press the test liquid into microchannel 22 from opening 21. In this embodiment, air pressure is used as the fluid pressure. Opening 21 is formed, for example, to have a circular cross-section. The diameter of opening 21 is, for example, 5 μm to 5 mm. In the first embodiment, four microchannels 22 are connected to opening 21. The four microchannels 22 are arranged radially with opening 21 as the center.

[0039] In the first embodiment, four microchannels 22 are connected to the opening 21, but the embodiments of the present invention are not limited thereto. It suffices that at least one microchannel 22 is connected to the opening 21. Furthermore, two microchannels 22 may be connected to the opening 21, or three microchannels 22 may be connected to the opening 21. Furthermore, five or more microchannels 22 may be connected to the opening 21.

[0040] The test liquid contains a test object. The test object can be bacteria (specifically, pathogenic bacteria). In a specific example, the test liquid can be a suspension of bacteria.

[0041] The microchannel 22 is configured to allow the test liquid to flow. One end of the microchannel 22 is connected to the opening 21 , and the other end of the microchannel 22 is connected to the microchannel 23 .

[0042] The microchannel 22 allows the test solution flowing in from the opening 21 to flow to the microchannel 23. The cross-section of the microchannel 22 is rectangular, and the width of the microchannel 22 is, for example, 1 μm to 1 mm. Multiple microchannels 23 are connected to the microchannel 22. In the first embodiment, 14 microchannels 23 are connected to one microchannel 22. In other words, one microchannel 22 branches into 14 microchannels 23.

[0043] The microchannel 22 includes a channel 221 and a channel 222 .

[0044] One end of the flow path 221 is connected to the opening 21, and the other end of the flow path 221 is connected to the flow path 222. The four flow paths 221 are arranged radially with the opening 21 as the center.

[0045] One end of the flow channel 222 is connected to the flow channel 221, and the other end of the flow channel 222 is connected to the micro flow channel 23. The flow channel 222 is arranged along the X-axis direction. Fourteen micro flow channels 23 are connected to one flow channel 222. In other words, one flow channel 222 branches into fourteen micro flow channels 23.

[0046] The microchannel 23 is configured to allow the test liquid to flow. The microchannel 23 is arranged along the Y-axis. One end of the microchannel 23 is connected to the microchannel 22, and the other end of the microchannel 23 is connected to the reservoir 24. Specifically, the end of the microchannel 23 in the negative direction (forward direction) of the Y-axis is connected to the microchannel 22, and the end of the microchannel 23 in the positive direction (rearward direction) of the Y-axis is connected to the reservoir 24.

[0047] The microchannel 23 allows the test solution flowing in from the microchannel 22 to flow to the reservoir 24. The cross section of the microchannel 23 is rectangular, and the width of the microchannel 23 is, for example, 1 μm to 1 mm.

[0048] Reservoir 24 is configured with a drug and connected to microchannel 23 to store the test solution flowing from microchannel 23. The test solution and the drug react in reservoir 24. The drug is, for example, an antibacterial drug. The drug can be solid or liquid. The drug is pre-placed in reservoir 24. That is, the drug is placed in reservoir 24 before the test solution flows into reservoir 24. In this embodiment, the drug is applied to the entire reservoir 24.

[0049] The reservoir 24 is formed in a rectangular parallelepiped shape, and the length of one side of the reservoir 24 is, for example, 10 μm to 10 mm.

[0050] exist Figure 1 In the embodiment, 56 (14 x 4) reservoirs 24 are formed on the plate-shaped member 1. The volume of the test solution stored in each of the 56 reservoirs 24 is the same. Meanwhile, the types and amounts of the drugs placed in the 56 reservoirs 24 may be the same or different.

[0051] The microfluidic channel 25 is configured to allow the test liquid to flow. The microfluidic channel 25 is arranged along the Y-axis. One end of the microfluidic channel 25 is connected to the reservoir 24, and the other end of the microfluidic channel 25 is connected to the opening 26. Specifically, the end of the microfluidic channel 25 in the negative direction (forward direction) of the Y-axis is connected to the reservoir 24, and the end of the microfluidic channel 25 in the positive direction (upward direction) of the Y-axis is connected to the opening 26.

[0052] The microchannel 25 allows the test solution flowing from the reservoir 24 to flow to the opening 26. The cross section of the microchannel 25 is rectangular, and the width of the microchannel 25 is, for example, 1 μm to 1 mm.

[0053] The opening 26 is connected to the other end of the microchannel 25. Specifically, the opening 26 is connected to the positive (rearward) end of the microchannel 25 in the Y-axis direction. The opening 26 is formed into a circular cross-section, for example. The diameter of the opening 26 is, for example, 5 μm to 5 mm.

[0054] The opening 26 is covered by the gas permeable membrane 3. Specifically, Figure 1 In the example, 56 openings 26 (= 14 openings × 4) are formed in the plate-like member 1. Of the 56 openings 26, 28 openings 26 formed at the positive end of the plate-like member 1 in the Y-axis direction are covered by one gas permeable membrane 3, and 28 openings 26 formed at the negative end of the plate-like member 1 in the Y-axis direction are covered by one gas permeable membrane 3. Two gas permeable membranes 3 are arranged along the X-axis direction.

[0055] The gas permeable membrane 3 has the function of allowing gas to permeate but preventing liquid from permeating. Examples of materials for the gas permeable membrane 3 include polytetrafluoroethylene (PTFE). The gas permeable membrane 3 is preferably water-repellent. The thickness of the gas permeable membrane 3 is 1 mm or less.

[0056] The gas permeable membrane 3 is fixed to the plate-like member 1 by bonding with an adhesive, ultrasonic welding, or the like. Examples of the adhesive include photocurable resins, thermosetting resins, and pressure-sensitive resins.

[0057] The microfluidic device 100 includes an imaging target area AR. The imaging target area AR is located within the microfluidic channel 25. The imaging target area AR represents the area imaged by the microscope. The imaging target area AR is located away from the reservoir 24. When a drug and a test solution are mixed within the reservoir 24, the imaging target area AR is located within the region where the mixture of the drug and the test solution within the reservoir 24 diffuses within a predetermined time. The predetermined time may be, for example, several hours.

[0058] like Figure 1 As shown, the microchannel 25 included in the imaging target area AR is recorded as a channel 251. That is, the microscope photographs the channel 251. In this embodiment, the microscope is a phase contrast microscope. In other embodiments, the microscope may also be an optical microscope. Figure 4 The following describes in detail the photography performed using a microscope.

[0059] Figure 2 1 is a side cross-sectional view showing an example of the micro-channel device 100 according to the first embodiment. Figure 2 1 is a side cross-sectional view along the microchannel 22 of the microchannel device 100 .

[0060] like Figure 2 As shown, the plate member 1 includes a first plate member 11 and a second plate member 12. The second plate member 12 is stacked on the first plate member 11. The second plate member 12 is arranged in the negative direction (downward direction) of the Z axis relative to the first plate member 11.

[0061] The first plate-shaped member 11 is formed of a transparent material in a rectangular plate shape. Examples of the material for the first plate-shaped member 11 include acrylic resins such as polymethyl methacrylate resin. A flow path structure 2 is formed in the first plate-shaped member 11. Specifically, the first plate-shaped member 11 includes an opening 21, a microchannel 22, a microchannel 23, a reservoir 24, a microchannel 25, and an opening 26. Figure 2 The opening 21 and the microchannel 22 are shown as examples.

[0062] The thickness of the first plate-shaped member 11 is not particularly limited, and is set to, for example, 0.5 mm to 3 mm.

[0063] The second plate-shaped member 12 is formed into a rectangular plate shape from a transparent material. Examples of the material for the second plate-shaped member 12 include acrylic resins such as polymethyl methacrylate. The second plate-shaped member 12 functions as part of the flow path structure 2. Specifically, the second plate-shaped member 12 serves as the lower surface of the microchannels 22, 23, reservoir 24, and 25.

[0064] The thickness of the second plate-shaped member 12 is not particularly limited, and is set to, for example, 0.5 mm to 3 mm.

[0065] The second plate-shaped member 12 is directly fixed to the first plate-shaped member 11 by ultrasonic welding, or may be fixed via an adhesive. In the first embodiment, the second plate-shaped member 12 is described as being made of acrylic resin, but the second plate-shaped member 12 may also be made of glass.

[0066] The syringe pump 4 is connected to the opening 21. The syringe pump 4 presses the test liquid into the microchannel 22 from the opening 21. Specifically, the syringe pump 4 presses the test liquid into the microchannel 22 from the opening 21 by applying air pressure to the test liquid.

[0067] The syringe pump 4 corresponds to an example of a “pump.” Furthermore, the syringe pump 4 corresponds to an example of a “pressure source.”

[0068] The test solution flowing into the microchannel 22 passes through Figure 1 The microchannel 23 shown is stored in the reservoir 24 . Furthermore, the test liquid is applied with air pressure by the syringe pump 4 , so that the test liquid overflows from the reservoir 24 and flows into the microchannel 25 .

[0069] Then, when the microfluidic channel 25 is filled with the test liquid, air pressure is applied to the test liquid by the syringe pump 4, and the air contained in the test liquid is discharged to the outside of the microfluidic channel device 100 through the opening 26 and the gas permeable membrane 3. In this way, the air contained in the test liquid can be discharged to the outside of the microfluidic channel device 100. In the embodiment of the present invention, "outside" means the outside of the microfluidic channel device 100.

[0070] Figure 3 It is a III-III cross-sectional view showing an example of the micro-flow path device 100 according to the first embodiment. Figure 3 The upper middle figure is a top view corresponding to the III-III cross section of the micro-flow path device 100. Figure 3 The figure in the lower middle part is a III-III cross-sectional view of the micro-flow path device 100. Figure 1 The position of the III-III cross section is indicated by a single-dot chain line.

[0071] like Figure 3 As shown, the microchannel 23 extends along the Y-axis direction. The microchannel 23 is formed between the first plate-shaped member 11 and the second plate-shaped member 12. Specifically, the microchannel 23 is formed by forming a recess corresponding to the microchannel 23 in the first plate-shaped member 11 and covering the opening on the lower surface of the recess with the second plate-shaped member 12.

[0072] The reservoir 24 is formed in a cylindrical shape. It is formed between the first plate member 11 and the second plate member 12. Specifically, a cylindrical recess corresponding to the reservoir 24 is formed in the first plate member 11, and the opening of the lower surface of the recess is covered by the second plate member 12, thereby forming the reservoir 24.

[0073] The microchannel 25 extends along the Y-axis direction. The microchannel 25 is formed between the first plate-shaped member 11 and the second plate-shaped member 12. Specifically, a recess corresponding to the microchannel 25 is formed in the first plate-shaped member 11, and the opening on the lower surface of the recess is covered by the second plate-shaped member 12, thereby forming the microchannel 25.

[0074] The opening 26 is formed at the end of the microchannel 25 on the positive side in the Y-axis direction. The opening 26 is formed in a circular shape in the first plate-shaped member 11. The opening 26 is formed so as to communicate with the microchannel 25. In other words, a flow channel is formed in the first plate-shaped member 11, connecting the end of the microchannel 25 on the positive side in the Y-axis direction and the opening 26. This flow channel extends in the Z-axis direction and is formed in a cylindrical shape.

[0075] The gas permeable membrane 3 covers the opening 26. Specifically, the gas permeable membrane 3 is fixed to the surface (upper surface) on the Z-axis direction side of the first plate-shaped member 11 so as to cover the opening 26.

[0076] [2. Composition of the test apparatus]

[0077] Figure 4 2 is a diagram showing the structure of the test device 200. Figure 4 FIG is a cross-sectional view taken along line IV-IV showing an example of the micro-channel device 100 according to the first embodiment. Figure 1 The position of the IV-IV cross section is indicated by a single-dot chain line.

[0078] like Figure 4 As shown, the IV-IV section includes 28 flow paths 251. The flow paths 251 are shown as being included in Figure 1 The micro-channels 25 in the imaging target area AR are shown. Twenty-eight channels 251 are formed between the first plate-shaped member 11 and the second plate-shaped member 12 .

[0079] The test apparatus 200 includes a stage 5, a microscope 6, a motor 71, and a control unit 8. The motor 71 corresponds to a part of the "drive mechanism."

[0080] The microfluidic device 100 is placed on the platform 5. The platform 5 is formed in a flat plate shape. The microfluidic device 100 is fixed to the upper surface of the platform 5. The platform 5 is configured to be movable in the horizontal direction. Specifically, the platform 5 is configured to be movable along the X-axis direction and along the Y-axis direction.

[0081] A light source is disposed below the platform 5. The light source is disposed opposite the microscope 6. The platform 5 is configured to transmit light from the light source to the microscope 6. For example, an opening is formed in the platform 5 to transmit light from the light source to the microscope 6. Furthermore, the platform 5 is formed, for example, of a transparent material. Specifically, the platform 5 is formed of glass.

[0082] The motor 71 drives the stage 5 in response to instructions from the control unit 8. Specifically, the motor 71 drives the stage 5 so that the flow paths 251 are located within the imaging area of ​​the microscope 6. More specifically, the motor 71 drives the stage 5 so that each of the 28 flow paths 251 is located within the imaging area of ​​the microscope 6. Each of the 28 flow paths 251 is located at a position between P1 and P28. In other words, the motor 71 drives the stage 5 along the X-axis so that the imaging area of ​​the microscope 6 is located at a position between P1 and P28.

[0083] The control unit 8 controls the operation of the test apparatus 200. The control unit 8 includes a processor such as a CPU (Central Processing Unit) and memories such as ROM (Read Only Memory) and RAM (Random Access Memory). The memories store control programs. The processor controls the operation of the test apparatus 200 by executing the control programs. Alternatively, the memory of the control unit 8 may include an HDD (Hard Disk Drive).

[0084] The control unit 8 causes the motor 71 to drive the stage 5 so that the flow path 251 is located in the imaging area of ​​the microscope 6. Furthermore, when the flow path 251 is located in the imaging area of ​​the microscope 6, the control unit 8 causes the microscope 6 to image the flow path 251. Furthermore, the control unit 8 stores image data captured by the microscope 6 in a memory.

[0085] Specifically, the control unit 8 causes the motor 71 to drive the stage 5 so that position P1 is located within the imaging area of ​​the microscope 6. Then, with position P1 located within the imaging area of ​​the microscope 6, the control unit 8 causes the microscope 6 to image the flow path 251. Next, the control unit 8 causes the motor 71 to drive the stage 5 so that position P2 is located within the imaging area of ​​the microscope 6. That is, the control unit 8 causes the motor 71 to drive the stage 5 so that position P2 is located within the imaging area of ​​the microscope 6 by moving the stage 5 in the negative direction of the X-axis. Then, with position P2 located within the imaging area of ​​the microscope 6, the control unit 8 causes the microscope 6 to image the flow path 251.

[0086] By repeating the movement of the stage 5 in the negative direction of the X axis and the imaging of the flow channel 251 by the microscope 6 in this manner, the control unit 8 causes the microscope 6 to image the flow channel 251 at each of the positions P1 to P28 .

[0087] Figure 5 1 is a diagram showing an example of the overall configuration of the testing apparatus 200 .

[0088] like Figure 5 As shown in the right figure of FIG, the test apparatus 200 includes a dispensing station ST, a dispenser 9, a pump 4, and a moving mechanism ML.

[0089] The micro-channel device 100 is placed on the dispensing stage ST. The dispenser 9 injects the test solution into the micro-channel device 100. Specifically, the dispenser 9 stores the test solution and injects a predetermined amount of the test solution from the opening 21 of the micro-channel device 100.

[0090] Afterwards, the gas permeable membrane 3 is attached to the opening 26 of the microfluidic device 100. The pump 4 is then positioned above the microfluidic device 100 using the moving mechanism ML. The moving mechanism ML is configured to support the pump 4 and the dispenser 9 and to enable movement in the left-right direction DR1. The left-right direction DR1 represents the X-axis direction.

[0091] Then, the pump 4 applies air pressure to the test liquid through the opening 21 until the test liquid reaches the opening 26 .

[0092] Afterwards, if Figure 5 As shown in the left figure of FIG, a micro-channel device 100 is placed on the platform 5. Figure 5 As shown in the left figure of FIG, the test apparatus 200 includes a drive mechanism 7 and a control unit 8. The drive mechanism 7 includes a motor 71. The motor 71 drives the drive mechanism 7 so that the platform 5 is driven along the left-right direction DR2. The left-right direction DR2 represents the X-axis direction. Figure 4 , the specific method of moving platform 5 is explained.

[0093] Furthermore, the test apparatus 200 may include a transport unit that moves the micro-fluidic device 100 placed on the dispensing stage ST to the stage 5 .

[0094] Furthermore, the test apparatus 200 may include an incubator. The incubator maintains the temperature of the microfluidic device 100. In this case, the bacteria and antimicrobial agent contained in the test solution can react at a desired temperature. Furthermore, the transport unit is preferably configured to transport the microfluidic device 100 between the incubator and the dispensing station ST and the platform 5.

[0095] [3. Processing by the control unit]

[0096] Figure 6 This is a flowchart showing an example of processing by the control unit 8 of the testing apparatus 200 .

[0097] Control unit 8 Figure 2 The operation of the syringe pump 4 is controlled as shown. A motor for driving the syringe pump 4 is connected to the syringe pump 4. The control unit 8 controls the operation of the syringe pump 4 via the motor. Figure 4 The following description will assume that the position P1 shown is located in the imaging area of ​​the microscope 6 .

[0098] First, in step S101, the microchannel device 100 is prepared, and the controller 8 controls the syringe pump 4 to pump the test solution into the reservoir 24. Specifically, the controller 8 controls the syringe pump 4 to fill the microchannel 23, the reservoir 24, and the microchannel 25 with the test solution.

[0099] Next, in step S103, the control unit 8 controls the syringe pump 4 to maintain the pressure applied to the test liquid for a predetermined period. Specifically, the control unit 8 controls the syringe pump 4 to apply air pressure to the test liquid for a predetermined period. The predetermined period is, for example, 1 minute.

[0100] Next, in step S105 , the test solution reacts with the drug placed in the reservoir 24 .

[0101] Next, in step S107, the control unit 8 causes the microscope 6 to image the flow channel 251. Furthermore, the control unit 8 stores the image data captured by the microscope 6 in the memory.

[0102] Next, in step S109 , the control unit 8 determines whether or not imaging of all the flow channels 251 has been completed.

[0103] If the control unit 8 determines that imaging of all the flow channels 251 is complete (step S109: Yes), the process ends. If the control unit 8 determines that imaging of all the flow channels 251 is not complete (step S109: No), the process proceeds to step S111.

[0104] Then, in step S111, the control unit 8 moves the stage 5 to image the next flow channel 251. Specifically, the control unit 8 causes the motor 71 to drive the stage 5 so that the next flow channel 251 enters the imaging area of ​​the microscope 6. Then, the process returns to step S107.

[0105] Step S101 corresponds to an example of a "preparation process" and a "pressure feeding process", and step S103 corresponds to an example of a "holding process". In addition, step S105 corresponds to an example of a "reaction process", and step S107 corresponds to an example of an "observation process".

[0106] [3. Effects of the Microflow Channel Device, Test Apparatus, and Test Method of the First Embodiment]

[0107] [3-1. Effects of the test method using a microfluidic device]

[0108] In step S101, the control unit 8 controls the syringe pump 4 to pressure-feed the test liquid to the storage unit 24. Furthermore, in step S103, the control unit 8 controls the syringe pump 4 to maintain the pressure applied to the test liquid for a predetermined period.

[0109] Air contained in the test liquid stored in the reservoir 24 is released through the gas-permeable membrane 3 from the opening 26 formed in communication with the reservoir 24, while the test liquid does not pass through the gas-permeable membrane 3. As a result, the test liquid fills the reservoir 24. As a result, an appropriate amount of the test liquid can be easily stored in the reservoir 24.

[0110] Furthermore, in step S103 , the control unit 8 controls the syringe pump 4 to apply air pressure to the test liquid for a predetermined period of time.

[0111] Therefore, air pressure is applied to the test liquid in the microchannel 22 or the microchannel 23 for a predetermined period of time. This makes it easy to apply pressure to the test liquid stored in the reservoir 24. As a result, the test liquid can be easily retained in the imaging target area AR.

[0112] Furthermore, the test liquid is a bacterial liquid, and the drug is an antibacterial drug.

[0113] Therefore, the effect of antimicrobial drugs on bacterial liquid can be verified efficiently.

[0114] [3-2. Effects of Microfluidic Device]

[0115] The microchannel device 100 includes a microchannel 23 for allowing a test solution to flow; a reservoir 24 containing a reagent and storing the test solution flowing from the microchannel 23; an opening 26 communicating with the reservoir 24; and a gas permeable membrane covering the opening 26.

[0116] Therefore, the test liquid flows from the microchannel 23 into the reservoir 24. When the test liquid fills the reservoir 24, the gas permeable membrane 3 restricts the test liquid from flowing out of the opening 26. As a result, the test liquid fills the reservoir 24. As a result, an appropriate amount of the test liquid can be easily stored in the reservoir 24.

[0117] The microchannel device 100 also includes a microchannel 25 that connects the reservoir 24 and the opening 26 and allows the test liquid to flow. An imaging target area AR to be imaged by the microscope 6 is arranged in the microchannel 25 .

[0118] Therefore, air contained in the test liquid flowing into the microchannel 25 is released from the opening 26 through the gas permeable membrane 3, while the test liquid does not pass through the gas permeable membrane 3. Thus, air contained in the test liquid in the microchannel 25 can be removed, and the test liquid can be clearly imaged in the imaging target area AR arranged in the microchannel 25.

[0119] In addition, the microfluidic device 100 includes a first plate-shaped member 11 and a second plate-shaped member 12 stacked on the first plate-shaped member 11, and the microfluidic channel 25 is formed at the boundary between the first plate-shaped member 11 and the second plate-shaped member 12. The first plate-shaped member 11 and the second plate-shaped member 12 forming the microfluidic channel 25 are transparent.

[0120] Therefore, the light emitted from the light source passes through the first plate-shaped member 11 and the second plate-shaped member 12 and reaches the microscope 6. Therefore, the test liquid can be clearly photographed.

[0121] The microchannel device 100 includes a plurality of microchannels 23 , a plurality of reservoirs 24 connected to the plurality of microchannels 23 , and a plurality of microchannels 25 connected to the plurality of reservoirs 24 . The plurality of microchannels 25 are formed adjacent to each other.

[0122] Therefore, since the plurality of microchannels 25 are formed adjacent to each other, the moving distance of the stage 5 on which the microchannel device 100 is mounted can be reduced when capturing images of the plurality of microchannels 25. This allows efficient imaging of the test solutions in the plurality of microchannels 25.

[0123] The micro-channel device 100 includes a second opening 21 formed in a micro-channel 22 . A syringe pump 4 for applying air pressure to a test solution is connected to the second opening 21 .

[0124] Therefore, the test liquid can be easily flowed in the microchannel 22. Furthermore, by fixing the gas permeable membrane 3 to the second plate-shaped member 12 so as to withstand the applied air pressure, the test liquid can be prevented from flowing out of the opening 26. Therefore, an appropriate amount of the test liquid can be easily stored in the reservoir 24.

[0125] [3-3. Effects of the test device equipped with a microfluidic device]

[0126] The test device 200 includes: a microfluidic device 100; a platform 5 on which the microfluidic device 100 is placed; a motor 71 that drives the platform 5 in a horizontal direction; and a control unit 8 that controls the motor 71. The control unit 8 causes the motor 71 to drive the platform 5 so that the microfluidic channel 25 is located in the imaging area of ​​the microscope.

[0127] Thus, since the test apparatus 200 includes the microfluidic device 100, an appropriate amount of test liquid can be stored in the reservoir 24. Furthermore, since the control unit 8 causes the motor 71 to drive the stage 5, positioning the microfluidic channel 25 within the imaging area of ​​the microscope, the test liquid in the microfluidic channel 25 can be efficiently imaged.

[0128] The micro-channel device 100 includes a plurality of micro-channels 25 . The control unit 8 causes the motor 71 to drive the stage 5 so that each of the plurality of micro-channels 25 is positioned within the imaging region of the microscope 6 .

[0129] This allows efficient imaging of each test liquid within the plurality of microchannels 25 .

[0130] [4. Other Embodiments of Microfluidic Device]

[0131] In the microchannel device 100 of the first embodiment, the imaging target area AR to be imaged by the microscope 6 is arranged in the microchannel 25 , but the present invention is not limited thereto.

[0132] Furthermore, the first plate-shaped member 11 and the second plate-shaped member 12 are transparent, but the embodiments of the present invention are not limited to this. It suffices that the portion of the first plate-shaped member 11 and the portion of the second plate-shaped member 12 that form the microchannel 25 be transparent. In other words, it suffices that the portion of the first plate-shaped member 11 and the portion of the second plate-shaped member 12 that corresponds to the imaging target area AR be transparent.

[0133] Although 28 openings 26 are covered by one gas permeable membrane 3 , the present invention is not limited thereto. One gas permeable membrane 3 may cover one opening 26 or multiple (for example, two) openings 26 .

[0134] The syringe pump 4 applies air pressure to the test liquid, but the present invention is not limited thereto. Any pump can be used as long as it applies air pressure to the test liquid. The pump can be a plunger pump or a diaphragm pump.

[0135] Furthermore, although 56 reservoirs 24 are formed in the micro-flow channel device 100 , the number may be one or two or more.

[0136] Furthermore, the microchannel 22 of the channel structure 2 branches into 14 microchannels 23, but the microchannel 22 only needs to be connected to at least one microchannel 23. That is, the microchannel 22 may be connected to one microchannel 23, or the microchannel 22 may branch into two or more microchannels 23.

[0137] Furthermore, the microchannels 22 , 23 , reservoirs 24 , and 25 are formed in the first plate-shaped member 11 , but the microchannels 22 , 23 , reservoirs 24 , and 25 may be formed in the second plate-shaped member 12 .

[0138] The micro-flow path device 100 of the first embodiment is merely an example of an aspect of the micro-flow path device 100 of the present invention, and any modifications and applications are possible without departing from the spirit of the present invention.

[0139] [5. Configuration of Microflow Channel Device of Second Embodiment]

[0140] Figure 7 1 is a top view showing an example of a micro-channel device 100 according to a second embodiment of the present invention. The micro-channel device 100 is placed on Figure 4 On the platform 5 of the test apparatus 200 shown.

[0141] like Figure 7 As shown, the micro-channel device 100 includes a plate-shaped member 1, a channel structure 2, and a gas permeable membrane 3. Two channel structures 2 are formed on the plate-shaped member 11 of the micro-channel device 100.

[0142] The flow channel structure 2 includes an opening 21 , a microchannel 22 , a microchannel 23 , a microchannel 25A, a reservoir 24 , and an opening 26 .

[0143] Opening 21 corresponds to an example of a "second opening." Microchannel 22, microchannel 23, and microchannel 25A correspond to an example of a "first microchannel." Opening 26 corresponds to an example of a "first opening." Microchannel 23 corresponds to an example of a "second channel." Microchannel 25A corresponds to an example of a "first channel."

[0144] The opening 21 is disposed at one end of the microchannel 22. The test solution is pressed into the microchannel 22 through the opening 21. The opening 21 is formed, for example, in a circular cross-section. The diameter of the opening 21 is, for example, 5 μm to 5 mm. The microchannel 22 is connected to the opening 21.

[0145] The test liquid is, for example, a bacterial liquid. Specifically, the test liquid is a suspension of bacteria. The microchannel 22 is configured to allow the test liquid to flow. One end of the microchannel 22 is connected to the opening 21 , and the other end of the microchannel 22 is connected to the microchannel 23 .

[0146] One end of the microchannel 23 is connected to the microchannel 22 , and the other end of the microchannel 23 is connected to the microchannel 25A. The microchannel 23 corresponds to an example of a “second channel.” The microchannel 23 is composed of a microchannel 231 , a microchannel 232 , a microchannel 233 , and a microchannel 234 .

[0147] Microchannels 231 through 234 are formed along the Y-axis. The positive (upward) ends of each microchannel 231 through 234 along the Y-axis are connected to microchannel 22, while the negative (downward) ends of each microchannel 231 through 234 along the Y-axis are connected to microchannel 25A. Each microchannel 231 through 234 has a rectangular cross-section. The width W1 of each microchannel 231 through 22 is, for example, 1 μm to 1 mm.

[0148] One end of microchannel 25A is connected to microchannel 23, and the other end of microchannel 25A is connected to reservoir 24. Microchannel 25A was photographed using a microscope. In other words, microchannel 25A corresponds to an example of a "first channel." Microchannel 25A is composed of microchannel 251, microchannel 252, microchannel 253, and microchannel 254.

[0149] Microchannels 251 through 254 are formed along the Y-axis. The positive (upward) ends of each of microchannels 251 through 254 along the Y-axis are connected to microchannels 231 through 234. Specifically, microchannel 251 is connected to microchannel 231, and microchannel 252 is connected to microchannel 232. Furthermore, microchannel 253 is connected to microchannel 233, and microchannel 254 is connected to microchannel 234.

[0150] Each of the microchannels 251 to 254 has a rectangular cross-section, and each of the microchannels 251 to 254 has a width W2 of, for example, 0.1 μm to 0.1 mm.

[0151] The ends of the microchannels 251 to 254 on the negative side (lower side) of the Y axis are connected to the reservoir 24. The microchannels 251 to 254 are arranged adjacent to each other.

[0152] Reservoir 24 is equipped with a drug and connected to microchannel 25A. It stores the test solution flowing from microchannel 25A. The test solution and the drug react in reservoir 24. The drug is, for example, an antibacterial drug. The drug can be either solid or liquid. The drug is pre-placed in reservoir 24. That is, it is already there before the test solution flows into reservoir 24.

[0153] The reservoir 24 is composed of a reservoir 241, a reservoir 242, a reservoir 243, and a reservoir 244. The test liquid flows from the microchannel 251 into the reservoir 241. The test liquid flows from the microchannel 252 into the reservoir 242. The test liquid flows from the microchannel 253 into the reservoir 243. The test liquid flows from the microchannel 254 into the reservoir 244.

[0154] Opening 26 is formed at the positive Z-axis (upward) end of reservoir 24. Opening 26 consists of opening 261, opening 262, opening 263, and opening 264. Opening 261 is formed at the upward end of reservoir 241, opening 262 is formed at the upward end of reservoir 242, opening 263 is formed at the upward end of reservoir 243, and opening 264 is formed at the upward end of reservoir 244.

[0155] Each of the openings 261 to 264 is formed in a circular cross-section, for example. The diameter of each of the openings 261 to 264 is, for example, 5 μm to 5 mm.

[0156] The opening 26 is covered by the gas permeable membrane 3. Specifically, Figure 7 In the example, eight (=4×2) openings (openings 261 to 264) are formed in the plate-like member 1. The eight openings are covered by one gas permeable membrane 3. The one gas permeable membrane 3 is arranged along the X-axis direction.

[0157] The gas-permeable membrane 3 is made of a material having high gas permeability and low liquid permeability. A person skilled in the art would be able to conceive of a number of candidate materials having these properties. In an embodiment of the present invention, the gas-permeable membrane 3 is made of polytetrafluoroethylene (PTFE). The gas-permeable membrane 3 is preferably water-repellent. The thickness of the gas-permeable membrane 3 is 1 mm or less.

[0158] The gas permeable membrane 3 is fixed to the plate-like member 1 by bonding with an adhesive, ultrasonic welding, or the like. Examples of the adhesive include photocurable resins, thermosetting resins, and pressure-sensitive resins.

[0159] Figure 8 This is a side cross-sectional view showing an example of the micro-flow path device 100 according to the second embodiment.

[0160] like Figure 8 As shown in FIG, the plate-shaped member 1 includes a first plate-shaped member 11 and a second plate-shaped member 12. The second plate-shaped member 12 is stacked on the first plate-shaped member 11.

[0161] The first plate-shaped member 11 is formed of a transparent material in a rectangular plate shape. Examples of the material for the first plate-shaped member 11 include acrylic resins such as polymethyl methacrylate. The flow path structure 2 is formed in the first plate-shaped member 11. Specifically, the first plate-shaped member 11 includes an opening 21, a microchannel 22, a microchannel 25A, a reservoir 25, and an opening 26.

[0162] The opening 21 is formed in a circular shape in the first plate-shaped member 11. The opening 21 is formed to communicate with the microchannel 22. Specifically, a channel is formed in the first plate-shaped member 11, connecting the end of the microchannel 22 on the positive side in the Y-axis direction with the opening 21. This channel extends in the Z-axis direction and is formed in a cylindrical shape.

[0163] The thickness of the first plate-shaped member 11 is not particularly limited, and is set to, for example, 0.5 mm to 3 mm.

[0164] The second plate-shaped member 12 is formed into a rectangular plate shape from a transparent material. Examples of the material for the second plate-shaped member 12 include acrylic resins such as polymethyl methacrylate. The second plate-shaped member 12 functions as part of the flow path structure 2. Specifically, the second plate-shaped member 12 serves as the lower surface of the microchannel 22, microchannel 25A, and reservoir 24.

[0165] The thickness of the second plate-shaped member 12 is not particularly limited, and is set to, for example, 0.5 mm to 3 mm.

[0166] The second plate-shaped member 12 is directly fixed to the first plate-shaped member 11 by ultrasonic welding, or may be fixed via an adhesive. In the second embodiment, the second plate-shaped member 12 is described as being made of acrylic resin, but the second plate-shaped member 12 may also be made of glass.

[0167] The opening 21 is connected to a syringe pump 4 (not shown). The syringe pump 4 presses the test liquid into the microchannel 22 from the opening 21. Specifically, the syringe pump 4 presses the test liquid into the microchannel 22 from the opening 21 by applying air pressure to the test liquid.

[0168] The syringe pump 4 corresponds to an example of a “pump”.

[0169] The test liquid that has flowed into the microchannel 22 is stored in the reservoir 24 via the microchannel 23 and the microchannel 25A. Furthermore, by applying air pressure to the test liquid via the syringe pump 4, the air contained in the test liquid is discharged to the outside of the microchannel device 100 via the opening 26 and the gas permeable membrane 3. In this way, the reservoir 24 is filled with the test liquid.

[0170] [6. Photographed Image of Micro-Flow Channel Device According to Second Embodiment]

[0171] Photographs of the test apparatus 200 of the micro-channel device 100 according to the second embodiment and the reference Figure 4 The test apparatus 200 has the same configuration as described above.

[0172] That is, the test apparatus 200 includes a stage 5, a microscope 6, a motor 71, and a control unit 8. Figure 4 The test apparatus 200 described here is different from the reference test apparatus 200. Figure 4 The description of the same configuration as the test apparatus 200 described above will be omitted.

[0173] The testing apparatus 200 captures and generates images of the microchannel 25A according to the instruction of the control unit 8. Specifically, the testing apparatus 200 captures and generates images of the two microchannels 25A formed in the microchannel device 100 according to the instruction of the control unit 8 and stores the image data in a memory.

[0174] For example, the microscope 6 first observes the negative direction ( X-axis) of the two microchannels 25A formed in the microchannel device 100. Figure 7 The microchannel 25A (left direction in FIG) is photographed to generate an image.

[0175] Next, according to the instruction from the control unit 8, the motor 71 moves the platform 5 in the negative direction of the X axis ( Figure 7 ) so that the positive direction of the X axis ( Figure 7 The microchannel 25A (in the right direction) enters the imaging area of ​​the microscope 6.

[0176] Then, the microscope 6 captures an image of the microchannel 25A in the positive direction of the X-axis according to the instruction of the control unit 8 and generates an image.

[0177] Figure 9 This is a diagram showing an example of a captured image FV of the micro-flow channel device 100 according to the second embodiment.

[0178] like Figure 9 As shown, the captured image FV includes images of each of the microchannels 251 to 254 .

[0179] Since the width W2 of each of the microchannels 251 to 254 is narrow and the microchannels 251 to 254 are arranged adjacent to each other, the microchannels 251 to 254 can be included in one captured image FV.

[0180] [7. Effects of the Microflow Channel Device of the Second Embodiment]

[0181] In the micro-channel device 100 of the second embodiment, the opening 26 is formed in the reservoir 24 . In addition, the opening 26 is covered with the gas permeable membrane 3 .

[0182] Therefore, the test liquid flows from the microchannel 23 into the reservoir 24. When the test liquid fills the reservoir 24, the gas permeable membrane 3 restricts the test liquid from flowing out of the opening 26. As a result, the test liquid fills the reservoir 24. As a result, an appropriate amount of the test liquid can be easily stored in the reservoir 24.

[0183] Furthermore, air contained in the test solution stored in the microchannel 25A and the reservoir 24 is exhausted to the outside of the microchannel device 100 via the opening 26 and the gas permeable membrane 3. Therefore, since the air contained in the test solution in the microchannel 25A can be removed, the test solution in the microchannel 25A can be clearly imaged.

[0184] Furthermore, the micro-channel device 100 includes an opening 21 formed in the micro-channel 22 and a syringe pump 4 for applying air pressure to the test solution through the opening 21 .

[0185] Therefore, the test liquid can be easily flowed within the microchannel 23. Furthermore, by fixing the gas permeable membrane 3 to the second plate-shaped member 12 so as to withstand the applied air pressure, the test liquid can be prevented from flowing out of the opening 26. Consequently, an appropriate amount of the test liquid can be easily stored in the reservoir 24.

[0186] The microchannel device 100 includes a microchannel 25A to be photographed by a microscope and a microchannel 23 connected to the microchannel 25A. The microchannel 25A is formed so that its horizontal width W2 is narrower than that of the microchannel 23 .

[0187] Therefore, the microchannel 25A can be included in the captured image FV at a high magnification (for example, 100 times).

[0188] The microchannel device 100 includes a plurality of microchannels 25A (microchannels 251 to 254 ) and a plurality of microchannels 23 . The plurality of microchannels 25A are formed adjacent to each other.

[0189] Thereby, the microchannels 251 to 254 can be included in one captured image FV.

[0190] The microchannel device 100 includes a first plate member 11 and a second plate member 12 stacked on the first plate member 11 . A microchannel 25 is formed at the boundary between the first plate member 11 and the second plate member 12 . The first plate member 11 and the second plate member 12 forming the microchannel 25 are transparent.

[0191] Therefore, the light emitted from the light source passes through the first plate-shaped member 11 and the second plate-shaped member 12 and reaches the microscope 6. This allows the test liquid in the microchannel 25A to be clearly imaged.

[0192] [8. Other Embodiments of Microfluidic Device]

[0193] In the micro-flow channel device 100 of the second embodiment, the opening 26 is formed in the reservoir 24 , but the present invention is not limited thereto.

[0194] Furthermore, the first plate member 11 and the second plate member 12 are transparent, but the present invention is not limited thereto. It suffices that a portion of the first plate member 11 and a portion of the second plate member 12 forming the microchannel 25A are transparent.

[0195] In addition, a bacterial liquid is used as the test liquid. However, a chemical liquid such as paint can also be used as the test liquid. In this case, it is preferable to change the type of the drug arranged in the storage part 24 according to the type of the test liquid.

[0196] Furthermore, four openings 26 are covered by one gas permeable membrane 3 , but the present invention is not limited thereto. One gas permeable membrane 3 may cover one opening 26 or multiple openings 26 (for example, two) may be covered by one gas permeable membrane 3 .

[0197] In addition, the syringe pump 4 applies air pressure to the test liquid, but the content of the embodiment of the present invention is not limited to this. Any pump can apply air pressure to the test liquid. The pump can be a plunger pump or a diaphragm pump.

[0198] Two flow channel structures 2 are formed in the micro-flow channel device 100 , but the number may be one or three or more.

[0199] Furthermore, while the microchannel 25A of the channel structure 2 is composed of four microchannels 251 to 254, the microchannel 25A only needs to be composed of at least one microchannel. That is, the microchannel 25A may be composed of one microchannel, two microchannels, or three microchannels. Furthermore, the microchannel 25A may be composed of five or more microchannels.

[0200] Furthermore, the microchannel 22 , the microchannel 23 , the microchannel 25A, and the reservoir 24 are formed in the first plate-shaped member 11 , but may be formed in the second plate-shaped member 12 .

[0201] The second embodiment is merely an example of the aspect of the micro-flow path device 100 of the present invention, and any modifications and applications are possible without departing from the spirit of the present invention.

[0202] [9. Plan]

[0203] Those skilled in the art will understand that the above-mentioned embodiment examples are specific examples of the following schemes.

[0204] (Item 1)

[0205] One scheme of a test method using a microfluidic device brings a test fluid containing a test object into contact with a drug, and tests the effect of the drug on the test object, comprising: a preparation step of preparing a microfluidic device, the microfluidic device having a plurality of microfluidics, a first opening and a second opening arranged at both ends of each of the plurality of microfluidics and connected to the outside, a storage portion respectively provided in the plurality of microfluidics and storing the drug, and a gas permeable membrane covering the first opening; a pressure delivery step of applying a fluid pressure greater than the external pressure to the test fluid from a pressure source connected to the second opening via the second opening, and delivering the test fluid to the storage portion; and an observation step of observing a target area set in the microfluidic device.

[0206] According to the test method using a microfluidic device described in item 1, the first opening formed in the microfluidic device and connected to the storage part is covered with a gas permeable membrane, and the method includes a pressure-feeding process of applying a fluid pressure greater than the external pressure to the test liquid to feed the test liquid to the storage part.

[0207] Therefore, air contained in the test liquid stored in the reservoir is released through the gas-permeable membrane through the opening formed in communication with the reservoir, while the test liquid does not pass through the gas-permeable membrane. This allows the reservoir to be filled with the test liquid, making it easy to store an appropriate amount of test liquid in the reservoir. As a result, the concentration of the drug dissolved in the test liquid can be stabilized.

[0208] (Item 2)

[0209] The test method according to item 1 further includes a maintaining step of maintaining the fluid pressure applied to the test fluid for a predetermined period of time.

[0210] According to the test method using a microfluidic device described in item 2, during the holding step, the fluid pressure applied to the test fluid is maintained for a predetermined period. This allows the test fluid to fill the reservoir, further allowing an appropriate amount of test fluid to be stored in the reservoir. Consequently, the concentration of the drug dissolved in the test fluid can be further stabilized.

[0211] (Item 3)

[0212] In the test method using a micro-channel device according to Item 1 or Item 2, air pressure is applied to the test liquid in the holding step.

[0213] According to the test method using a microfluidic device described in item 3, air pressure is applied to the test liquid during the holding step. This allows for appropriate pressure to be applied to the test liquid. This allows the test liquid to fill the reservoir, further allowing for an appropriate amount of test liquid to be stored in the reservoir. Consequently, the concentration of the drug dissolved in the test liquid can be further stabilized.

[0214] (Item 4)

[0215] In the test method using a microfluidic device according to any one of items 1 to 3, the test solution is a bacterial solution, and the drug is an antibacterial drug.

[0216] According to the test method using the microfluidic device described in item 4, the test liquid is a bacterial solution and the drug is an antibiotic. This stabilizes the concentration of the antibiotic dissolved in the bacterial solution, allowing accurate evaluation of the effect of the antibiotic on the bacterial solution.

[0217] (Item 5)

[0218] A microfluidic device of one embodiment is used to bring a test fluid containing a test object into contact with a drug and to test the effect of the drug on the test object, and comprises: a first microfluidic channel having a first end and a second end through which the test fluid can flow; a storage portion storing the drug and connected to the second end in a manner that allows the test fluid to flow; a first opening connected to the storage portion; and a gas permeable membrane covering the first opening.

[0219] According to the microfluidic device described in item 5, the test liquid flows from the first microfluidic channel into the reservoir. Once the reservoir is filled with the test liquid, the gas permeable membrane restricts the test liquid from flowing out of the first opening. This allows the reservoir to be filled with the test liquid, making it easy to store an appropriate amount of the test liquid in the reservoir. As a result, the concentration of the drug dissolved in the test liquid can be stabilized.

[0220] (Item 6)

[0221] The micro-channel device according to item 5 includes a second micro-channel that connects the reservoir and the first opening and allows the test liquid to flow, and the second micro-channel is photographed under a microscope.

[0222] The microfluidic device according to item 6 includes a second microfluidic channel that connects the reservoir and the first opening, allowing the test fluid to flow, and the second microfluidic channel is imaged by a microscope. Therefore, the drug diffuses from the reservoir into the second microfluidic channel. Consequently, the concentration of the drug dissolved in the test fluid in the second microfluidic channel can be stabilized. As a result, imaging with a microscope can be performed while the concentration of the drug dissolved in the test fluid is stabilized.

[0223] (Item 7)

[0224] In the microfluidic device described in item 6, it has a first plate-shaped part and a second plate-shaped part 12 stacked on the first plate-shaped part, the second microfluidic path is formed at the boundary between the first plate-shaped part and the second plate-shaped part, and a part of the first plate-shaped part and a part of the second plate-shaped part forming the second microfluidic path are transparent.

[0225] According to the microfluidic device described in item 7, a portion of the first plate-shaped member and a portion of the second plate-shaped member forming the second microfluidic channel are transparent. Therefore, light incident on the second microfluidic channel can be prevented from being blocked. This facilitates imaging of the second microfluidic channel using a microscope.

[0226] (Item 8)

[0227] In the microfluidic device described in item 6 or 7, it comprises: a plurality of the first microfluidic paths; a plurality of storage portions, each connected to the plurality of the first microfluidic paths; a plurality of the second microfluidic paths, each connected to the plurality of the storage portions, and the plurality of the second microfluidic paths are formed adjacent to each other.

[0228] According to the microchannel device of claim 8, the plurality of second microchannels are formed adjacent to each other. Therefore, the plurality of second microchannels can be photographed in a single shot. Therefore, the second microchannels can be photographed efficiently.

[0229] (Item 9)

[0230] The micro-channel device according to any one of items 6 to 8 includes a second opening formed in the first micro-channel, and a pump for applying air pressure to the test liquid is connected to the second opening.

[0231] According to the microfluidic device described in item 9, a pump for applying air pressure to the test liquid is connected to the second opening. Thus, the pump applies air pressure to the test liquid, filling the reservoir with the test liquid, making it easy to store an appropriate amount of test liquid in the reservoir. As a result, the concentration of the drug dissolved in the test liquid can be stabilized.

[0232] (Item 10)

[0233] In the micro-flow channel device according to Item 5, the first opening is formed in the reservoir.

[0234] According to the micro-channel device described in item 10, since the first opening is formed in the reservoir, an appropriate amount of the test solution can be easily stored in the reservoir, thereby stabilizing the concentration of the drug dissolved in the test solution.

[0235] (Item 11)

[0236] The micro-channel device according to item 10 includes a second opening formed in the first micro-channel, and a pump for applying air pressure to the test liquid is connected to the second opening.

[0237] According to the microfluidic device described in item 11, a pump for applying air pressure to the test liquid is connected to the second opening. Thus, the pump applies air pressure to the test liquid, filling the reservoir with the test liquid, making it easy to store an appropriate amount of test liquid in the reservoir. As a result, the concentration of the drug dissolved in the test liquid can be stabilized.

[0238] (Item 12)

[0239] In the microchannel device described in item 10 or 11, the first microchannel includes a first channel to be photographed using a microscope and a second channel other than the first channel, and the horizontal width of the first channel is formed to be narrower than that of the second channel.

[0240] According to the micro-channel device described in Item 12, the horizontal width of the first channel is formed to be narrower than that of the second channel. This makes it easier to image the first channel using a microscope.

[0241] (Item 13)

[0242] The micro-channel device according to item 12 includes a plurality of the first micro-channels, each of the plurality of first micro-channels includes the first channel and the second channel, and the plurality of first channels are formed adjacent to each other.

[0243] According to the microfluidic device described in item 13, the plurality of first flow paths are formed adjacent to each other. Therefore, the plurality of first flow paths can be photographed with a single microscope image. As a result, the first flow paths can be photographed efficiently.

[0244] (Item 14)

[0245] In the microfluidic device described in item 12 or 13, it comprises a first plate-shaped part and a second plate-shaped part stacked on the first plate-shaped part, the first microfluidic path is formed at the boundary between the first plate-shaped part and the second plate-shaped part, and a portion of the first plate-shaped part and a portion of the second plate-shaped part forming the first flow path are transparent.

[0246] According to the microfluidic device described in item 14, a portion of the first plate-shaped member and a portion of the second plate-shaped member forming the first flow channel are transparent. Therefore, light incident on the first flow channel can be prevented from being blocked. This facilitates imaging of the first flow channel using a microscope.

[0247] (Item 15)

[0248] One embodiment of a test apparatus using a microfluidic device brings a test fluid containing a test subject into contact with a drug and tests the effect of the drug on the test subject. The apparatus comprises: a microfluidic device having a first microfluidic channel having a first end and a second end through which the test fluid can flow; a reservoir storing the drug and connected to the second end so that the test fluid can flow; a first opening communicating with the reservoir; a gas permeable membrane covering the first opening; a second microfluidic channel communicating between the reservoir and the first opening so that the test fluid can flow; and a second opening formed at the first end; a pump connected to the second opening for applying air pressure to the test fluid; a platform on which the microfluidic device is mounted; a drive mechanism for driving the platform in a horizontal direction; and a control unit for controlling the drive mechanism, wherein the control unit causes the drive mechanism to drive the platform so that the second microfluidic channel is located in an imaging area of ​​a microscope.

[0249] According to the test apparatus using the microfluidic device described in Item 15, a test liquid flows from the first microfluidic channel into the reservoir. Once the reservoir is filled with the test liquid, the gas permeable membrane restricts the test liquid from flowing out of the first opening. This allows the reservoir to be filled with the test liquid, making it easy to store an appropriate amount of the test liquid in the reservoir. As a result, the concentration of the drug dissolved in the test liquid can be stabilized.

[0250] (Item 16)

[0251] In the test apparatus using the microchannel device according to Item 15, the microchannel device includes a plurality of the second microchannels, and the control unit causes the drive mechanism to drive the stage so that each of the plurality of second microchannels is located in the imaging area of ​​the microscope.

[0252] According to the test apparatus using the microfluidic device described in Item 16, the driving mechanism drives the stage so that each of the plurality of second microfluidic channels is located in the imaging area of ​​the microscope.

[0253] Description of Reference Numerals

[0254] 200 test equipment

[0255] 100 Microfluidic Devices

[0256] 1 Plate-shaped component

[0257] 11 First plate-shaped member

[0258] 12 Second plate-shaped member

[0259] 2 Flow path structure

[0260] 21 openings (1st opening)

[0261] 22 microchannels (1st microchannel, microchannel)

[0262] 23 Microfluidic channel (1st microfluidic channel, 2nd microfluidic channel, microfluidic channel)

[0263] 24 Storage Department

[0264] 25 Microchannel (Second Microchannel, Microchannel)

[0265] 25A microfluidic channel (1st microfluidic channel, 1st microfluidic channel, microfluidic channel)

[0266] 251~254 Microchannel

[0267] 26 openings (2nd opening)

[0268] 3 Gas permeation membrane

[0269] 4 Syringe pump (pump, pressure source)

[0270] 5 Platform

[0271] 6 Microscope

[0272] 7 Drive mechanism

[0273] 71 Motor

[0274] 8. Control Unit

[0275] 9 Distributor

[0276] AR subject area

[0277] DR1, DR2 left and right directions

[0278] ML mobile mechanism

[0279] FV capture image

[0280] P1~P28 position

[0281] ST dispensing station

[0282] W1, W2 width.

Claims

1. A test method using a microfluidic device, wherein the microfluidic device brings a test solution containing a test object into contact with a drug, and tests the effect of the drug on the test object, characterized in that: include: a preparation step of preparing a microfluidic device comprising a plurality of microfluidic channels, a first opening and a second opening disposed at both ends of each of the plurality of microfluidic channels and communicating with the outside, a storage portion disposed in the microfluidic channels and storing the drug, and a gas permeable membrane covering the first opening; a pressure-feeding step of applying a fluid pressure greater than an external pressure to the test fluid from a pressure source connected to the second opening through the second opening, thereby feeding the test fluid to the storage portion; an observation step of observing a target area set in the microchannel, The reservoir is provided on the second opening side relative to the target region in the longitudinal direction of the microchannel.

2. The test method using a microfluidic device according to claim 1, wherein: The method includes a maintaining step of maintaining the fluid pressure applied to the test fluid for a predetermined period of time.

3. The test method using a microfluidic device according to claim 2, wherein: In the holding step, air pressure is applied to the test liquid.

4. The test method using a microfluidic device according to claim 1, wherein: The test liquid is a bacterial liquid, and the drug is an antibacterial drug.

5. A microfluidic device that brings a test solution containing a test object into contact with a drug and tests the effect of the drug on the test object, characterized in that: have: a first microchannel having a first end and a second end, and capable of allowing the test liquid to flow; a storage portion storing the drug and connected to the second end in a manner allowing the test liquid to flow; a first opening communicating with the storage portion; a gas permeable membrane covering the first opening, The reservoir is provided between the first opening and the second end in the longitudinal direction of the first microchannel.

6. The microfluidic device according to claim 5, wherein: A second microchannel is provided, connecting the storage portion and the first opening, allowing the test liquid to flow. The second microchannel was photographed under a microscope.

7. The microfluidic device according to claim 6, wherein: have: a first plate-shaped member; a second plate-shaped member stacked on the first plate-shaped member, The second microchannel is formed at a boundary between the first plate-shaped member and the second plate-shaped member. A portion of the first plate-shaped member and a portion of the second plate-shaped member forming the second microchannel are transparent.

8. The microfluidic device according to claim 6, wherein: have: a plurality of said first microchannels; a plurality of said storage portions, connected to the plurality of said first microchannels respectively; a plurality of said second microchannels, connected to the plurality of said storage portions respectively, A plurality of the second microchannels are formed adjacent to each other.

9. The microfluidic device according to claim 5, wherein: comprising a second opening formed in the first microchannel, A pump for applying air pressure to the test liquid is connected to the second opening.

10. The microfluidic device according to claim 5, wherein: The first opening is formed in the storage portion.

11. The microfluidic device according to claim 10, wherein: comprising a second opening formed in the first microchannel, A pump for applying air pressure to the test liquid is connected to the second opening.

12. The microfluidic device according to claim 10, wherein: The first microchannel includes a first channel to be imaged using a microscope and a second channel other than the first channel. The first flow path is formed to have a width in the horizontal direction narrower than that of the second flow path.

13. The microfluidic device according to claim 12, wherein: having a plurality of the first microchannels, The plurality of first microchannels respectively include the first channel and the second channel, A plurality of the first flow paths are formed adjacent to each other.

14. The microfluidic device according to claim 12, wherein: have: a first plate-shaped member; a second plate-shaped member stacked on the first plate-shaped member, The first microchannel is formed at a boundary between the first plate-shaped member and the second plate-shaped member. A portion of the first plate-shaped member and a portion of the second plate-shaped member forming the first flow path are transparent.

15. A test device using a microfluidic device, wherein the microfluidic device brings a test solution containing a test object into contact with a drug, and tests the effect of the drug on the test object, characterized in that: have: A microfluidic device comprising a first microfluidic channel having a first end and a second end through which the test liquid can flow, a reservoir storing the reagent and connected to the second end so that the test liquid can flow, a first opening communicating with the reservoir, a gas permeable membrane covering the first opening, a second microfluidic channel communicating between the reservoir and the first opening so that the test liquid can flow, and a second opening formed at the first end; a pump connected to the second opening and applying air pressure to the test liquid; a platform, carrying the microfluidic device; A driving mechanism drives the platform in a horizontal direction; a control unit, which controls the driving mechanism; The control unit causes the driving mechanism to drive the platform so that the second microchannel is located in an imaging area of ​​a microscope. The reservoir is provided between the first opening and the second end in the longitudinal direction of the first microchannel.

16. The test device using the microfluidic device according to claim 15, wherein: The microchannel device comprises a plurality of second microchannels. The control unit causes the driving mechanism to drive the stage so that each of the plurality of second microchannels is located in an imaging region of the microscope.

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