JP2017090216A - Test device, test method, and test apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a test device capable enhancing test accuracy.SOLUTION: A test device comprises; a flow channel section 3 that includes a main flow channel 20 extending in one direction; a liquid injection section 5 for injecting a liquid from one end side of the flow channel section 3; a liquid collection section 6 for collecting the liquid flowing out from the other end side of the flow channel section 3; a channel trap section 4 provided between the main flow channel 20 and the liquid collection section 6 and having a portion of the flow channel section 3 folded back at least in a direction from the other end side to the one end side; and a liquid retaining section 19 into which at least a portion of the liquid in the main flow channel 20 flows when the main flow channel 20 is tilted. The liquid retaining section 19 is in communication with the main flow channel 20 via a relay channel 22 that allows the liquid to flow, and with the liquid collection section 6 via a connecting channel 23 that allows the liquid to flow.SELECTED DRAWING: Figure 1

Description

  The present invention relates to an inspection device, an inspection method, and an inspection apparatus.

  An antibody has a property of specifically binding to a substance such as a specific protein or pathogen that becomes an antigen (referred to as an antigen-antibody reaction). Immunoassay (immunoassay) uses such an antigen-antibody reaction and uses an antibody that specifically binds to the antigen to be measured, for example, a specific substance contained in a sample (specimen) such as blood or urine. It is a technique for detecting the antigen of. Immunoassays are used for various tests and diagnoses such as influenza, hepatitis, and pregnancy.

  As a typical immunoassay, there is an immunochromatography method. This method is a kind of chromatography, and is a technique in which a specimen containing an antigen is dropped onto a membrane on which a labeled antibody, a capture antibody, a metal colloid, and the like are fixed. In the case of this technique, a specific antigen is captured on the capture antibody, and the presence or absence of the specific antigen can be detected by observing the metal colloid attached to the labeled antibody. This method has a relatively short inspection time of several minutes to several tens of minutes, and the inspection method is relatively simple. This method is widely used, for example, for test kits used by individuals such as pregnancy test drugs, and for quick diagnosis of influenza in hospitals.

  As one of methods for quantitatively detecting not only the presence / absence of the antigen described above but also the amount and concentration of the antigen contained in the specimen, there is an enzyme immunoassay (ELISA) method. In this method, first, an antigen is immobilized on a well serving as a reaction field, a primary antibody that specifically adsorbs to the antigen is adsorbed, and then a secondary antibody labeled with an enzyme is adsorbed to the primary antibody. In this method, a reagent (substrate) that reacts with an enzyme to develop color or emit light is added. In the case of this method, the amount and concentration of the antigen contained in the specimen can be quantitatively detected by measuring the intensity of color development / luminescence. This method is used for testing allergens contained in foods, testing for trace amounts of viruses, and the like.

  Immunoassay methods such as ELISA and EIA (Enzyme Immunoassay) separate the antigen bound to the antibody and the antigen not bound to the antibody by washing with water (B / F separation). It is known that higher quantitativeness can be obtained in concentration measurement and the like than the immunochromatography method shown in 1.

  In addition, the ELISA method can test with fewer samples than the immunochromatography method. On the other hand, the examination takes a very long time and is difficult to use for quick diagnosis. Therefore, a chemiluminescence immunoassay device using magnetic fine particles having an antigen or antibody as a solid phase on the surface has been proposed as an ELISA method capable of shortening the examination time (see Patent Document 1).

  In this immunoassay apparatus, a cartridge (test device) that contains reagents necessary for immunoassay and performs a predetermined reaction process is used. Further, as a means for feeding a reagent or the like to the reaction field of the cartridge, for example, a flow pump by mechanical control is used. In addition, as an example of a flow pump, the flow type pump (Sep-Pak concentrator Uni) for pressurized solid phase extraction made from Waters is mentioned.

Japanese Patent No. 3839349

Conventional chemiluminescent immunoassay devices have been required to further improve the accuracy of the test.
One aspect of the present invention has been proposed in view of such conventional circumstances, an inspection device capable of increasing the accuracy of inspection, and an inspection method and inspection apparatus using such an inspection device. Is one of the purposes.

  In order to achieve the above object, an inspection device according to one aspect of the present invention includes a flow channel portion including a main flow channel extended in one direction, and a liquid for injecting liquid from one end side of the flow channel portion. At least a part of the flow path part is between the liquid injection part, a liquid recovery part for recovering the liquid flowing out from the other end side of the flow path part, and the main flow path and the liquid recovery part. A flow path trap part folded back in a direction from the end side toward the one end side and a liquid storage part into which at least a part of the liquid in the main flow path flows when the main flow path is inclined are provided. A cartridge main body, and the liquid storage section communicates with the main flow path via a relay flow path through which the liquid can flow, and communicates with the liquid recovery section via a communication flow path through which the liquid can flow. Has been.

  In the inspection device, the flow path trap portion has a folded flow path folded back to one side in the width direction of the main flow path, and the relay flow path is at a proximal end connected to the main flow path, It is good also as a structure opened to the inner surface of the other side of the width direction of a main flow path.

  In the inspection device, the main channel is formed so that the liquid is introduced from one end side in the one direction, and the relay channel has a portion including at least the base end in the width direction of the main channel. It is good also as a structure inclined so that it may approach the one end side of the said one direction as it goes to the other side.

  In the inspection device, the relay flow path may have a configuration in which an opening area at the base end is larger than a cross-sectional area of the main flow path at the base end.

  In the inspection device, the relay channel may have a configuration in which a cross-sectional area gradually decreases from the base end to a connection end with the liquid storage unit.

  In the inspection device, the communication channel may be configured such that at least a portion including one end connected to the liquid storage portion is inclined with respect to the one direction.

An inspection method according to one aspect of the present invention is an inspection method for inspecting for the presence or absence of a specific substance contained in a sample using any one of the above-described inspection devices. The flow path trap is obtained by injecting a liquid containing magnetic beads whose surface is modified with molecules from one end side of the flow path section into the flow path trap section and retaining the magnetic beads in the flow path trap section. Part as a reaction field for immunoassay,
By applying a magnetic force to the flow path trap section, the flow path trap section while retaining the magnetic beads in the flow path trap section in a state where the magnetic beads are attracted to the wall surface of the flow path trap section. The liquid feeding operation is performed.

  In the liquid feeding operation, in the liquid feeding operation, when liquid is allowed to flow from one end side of the flow path portion to the flow path trap portion, the extension direction of the main flow path is a direction along gravity. When the inspection device is held and the liquid flows out from the flow path trap part to the other end side of the flow path part, the liquid in the flow path trap part flows out from the other end side of the flow path part. The inspection device may be tilted in the direction.

  The test method may include a step of feeding a liquid containing a specimen to be tested when performing the immunoassay.

  An inspection apparatus according to one aspect of the present invention is an inspection apparatus for inspecting the presence or absence of a specific substance contained in a sample using any one of the inspection devices, and holding the device for holding the inspection device A device driving unit for rotating the inspection device, and a magnetic force applying unit for applying a magnetic force to the flow channel trap unit. A position for holding the inspection device such that the extending direction is a direction along gravity, and a position for tilting the inspection device in a direction in which the liquid in the flow path trap portion flows out from the other end side of the flow path portion. The inspection device is rotated, and the magnetic force application unit applies the magnetic force to the flow channel trap unit so that the magnetic beads are attracted to the wall surface of the flow channel trap unit. Characterized in that for retention of the magnetic beads in the flow path trap portion.

  The inspection apparatus may include a device inspection unit for inspecting the inspection device.

  The inspection apparatus may include an injection driving unit for operating the injection of liquid from the liquid injection unit.

According to one aspect of the present invention, by tilting the inspection device in a state in which a causative substance of noise is attracted by a magnet, a liquid with a small content of the causative substance can be caused to flow into the liquid reservoir. Therefore, a detection result with less noise can be obtained by detecting a detection target (antigen or the like) contained in the liquid in the liquid storage unit. Therefore, detection accuracy can be increased.
Since one aspect of the present invention has a communication channel, the liquid in the liquid reservoir can be introduced into the liquid recovery unit through the communication channel after the inspection is completed. Therefore, the liquid in the liquid storage unit can be recovered with an easy operation. Further, when the liquid is introduced into the liquid storage part, the air inside the liquid storage part can be discharged through the communication channel, so that the liquid can be smoothly introduced into the liquid storage part.

It is a top view showing an example of 1 composition of an inspection device concerning a 1st embodiment of the present invention. It is sectional drawing of the test | inspection device by line segment A-A 'shown in FIG. It is a top view for demonstrating liquid feeding operation of the test | inspection device shown in FIG. It is a top view for demonstrating liquid feeding operation of the test | inspection device shown in FIG. It is a top view for demonstrating liquid feeding operation of the test | inspection device shown in FIG. It is a top view which shows the modification of the test | inspection device shown in FIG. It is a top view for demonstrating in order each process of the immunoassay using the test | inspection device shown in FIG. It is a top view for demonstrating in order each process of the immunoassay using the test | inspection device shown in FIG. It is a top view for demonstrating in order each process of the immunoassay using the test | inspection device shown in FIG. It is a top view for demonstrating in order each process of the immunoassay using the test | inspection device shown in FIG. It is a top view for demonstrating in order each process of the immunoassay using the test | inspection device shown in FIG. It is a top view for demonstrating in order each process of the immunoassay using the test | inspection device shown in FIG. It is a top view for demonstrating in order each process of the immunoassay using the test | inspection device shown in FIG. It is a top view for demonstrating in order each process of the immunoassay using the test | inspection device shown in FIG. It is a top view for demonstrating in order each process of the immunoassay using the test | inspection device shown in FIG. It is a top view which shows the example of 1 structure of the test | inspection device which concerns on 2nd Embodiment of this invention. It is a top view which shows the modification of the test | inspection device shown in FIG. It is a top view for demonstrating in order the process of the immunoassay using the test | inspection device shown in FIG. It is a top view for demonstrating in order the process of the immunoassay using the test | inspection device shown in FIG. It is a block diagram showing an example of 1 composition of an inspection device concerning one embodiment of the present invention. It is a block diagram which shows another structural example of the test | inspection apparatus which concerns on one Embodiment of this invention. It is sectional drawing which shows an example of the detection optical system which comprises a device test | inspection part.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.
In addition, in the drawings used in the following description, in order to make the features easy to understand, there are cases where the portions that become the features are enlarged for the sake of convenience, and the dimensional ratios of the respective components are not always the same as the actual ones. Absent. In addition, the materials, dimensions, and the like exemplified in the following description are merely examples, and the present invention is not necessarily limited thereto, and can be appropriately modified and implemented without departing from the scope of the invention. .

(Inspection device)
First, as a first embodiment of the present invention, for example, an inspection device 1 shown in FIGS. 1 and 2 will be described. FIG. 1 is a plan view showing the configuration of the inspection device 1. FIG. 2 is a cross-sectional view of the inspection device 1 taken along line AA ′ shown in FIG. In the following description, an XYZ orthogonal coordinate system is set, the X-axis direction is the length direction (vertical direction) of the inspection device 1, the Y-axis direction is the width direction (left-right direction) of the inspection device 1, and the Z-axis direction is As the thickness direction (front-rear direction) of the inspection device 1, the positional relationship between the respective parts will be described. One side in the width direction of the inspection device 1 (left side in FIG. 1, -Y direction) is referred to as a first direction, and the other side in the width direction (right side in FIG. 1, + Y direction, that is, opposite to the first direction). Direction) is referred to as a second direction. The first direction is one in the width direction of the main flow path 20, and the second direction is the other in the width direction of the main flow path 20.

  As shown in FIGS. 1 and 2, the inspection device 1 includes a cartridge body 2. The cartridge main body 2 includes a main body portion (first base material) 2a and a panel portion (second base material) 2b that covers the front surface of the main body portion 2a.

  The main body 2a is a transparent resin material having chemical resistance such as polyethylene terephthalate (PET) resin, polystyrene (PS) resin, polymethyl methacrylate (PMMA) resin, acrylonitrile styrene resin (AS) resin, or the like. It is formed in a substantially rectangular flat plate shape with a predetermined thickness using a glass material or the like. The panel portion 2b is formed to have an outer shape substantially coincident with the main body portion 2a using a substrate made of the same resin material or glass material as the main body portion 2a. The cartridge body 2 is joined and integrated in a state where the panel portion 2b is abutted against the front surface of the body portion 2a.

The cartridge main body 2 collects the liquid flowing out from the flow path part 3, the liquid injection part 5 for injecting liquid from the upper end (one end) side of the flow path part 3, and the lower end (other end) side of the flow path part 3. And a liquid recovery unit 6.
The flow path part 3 includes a main flow path 20, a flow path trap part 4, and a flow path expansion part 7.

  The flow path part 3 constitutes a circulation space for allowing the liquid to flow in or out inside the cartridge body 2. Specifically, the flow path portion 3 constitutes a circulation space having a rectangular cross section between the recess formed on the front surface of the main body portion 2a and the panel portion 2b. In addition, about the cross-sectional shape of the flow-path part 3, not only the rectangular shape mentioned above but circular shape, an ellipse shape, etc. are good.

  The main flow path 20 is provided so as to extend linearly in the length direction of the cartridge main body 2 in one direction. Further, the channel cross-sectional area of the main channel 20 (area of the cross section orthogonal to the length direction) is constant in the extending direction.

  The flow path trap part 4 is continuous with the lower end side of the main flow path 20, and a part of the flow path part 3 extends from the lower end side to the upper end side of the cartridge body 2 and from the upper end side to the lower end side of the cartridge body 2. It has a shape that is turned back and forth in the direction it heads. Specifically, the channel trap unit 4 includes a first bent channel 4a and an upward channel 4b (first) from one end (upper end) side to the other end (lower end) side of the channel unit 3. A folded channel), a second bent channel 4c, and a downward channel 4d (second folded channel).

The first bent flow path 4a is provided to bend obliquely upward from the lower end portion of the main flow path 20. The upward flow path 4b is provided to extend obliquely upward from the first bent flow path 4a. In FIG. 1, the upward flow path 4 b is formed to be inclined in a direction that rises from the first bending flow path 4 a toward the first direction side (left side in FIG. 1) in the width direction of the cartridge body 2. Yes. The upward flow path 4b is a flow path folded back in the first direction.
The second bent channel 4c is provided to bend from the upper end of the upward channel 4b toward the lower side of the cartridge body 2. The downward flow path 4d is provided extending downward from the second bending flow path 4c.

The cartridge body 2 is formed with a liquid storage portion 19 that is a space in which the liquid L can be stored. The liquid storage unit 19 is formed away from the main flow path 20 at a position on the second direction side (right side in FIG. 1) in the width direction of the cartridge body 2 with respect to the main flow path 20.
The liquid storage part 19 is a space formed between the recessed part formed in the main-body part 2a and the panel part 2b similarly to the flow-path part 3, for example (refer FIG. 2).

  Although the shape of the liquid storage part 19 is not specifically limited, For example, it can be set as the planar view rectangle which has the upper surface 19a, the side surface 19b, and the bottom face 19c. The upper surface 19 a is formed along the width direction of the cartridge body 2. The side surface 19b hangs along the length direction of the cartridge body 2 from both ends of the upper surface 19a. The bottom surface 19 c is formed along the width direction of the cartridge body 2.

The bottom surface 19c may be formed to be inclined so as to descend toward the first direction side (left side in FIG. 1). When the bottom surface 19c is inclined, the liquid does not easily remain in the liquid storage unit 19 when the liquid in the liquid storage unit 19 is collected.
The shape of the liquid storage unit 19 in plan view is not particularly limited, and may be a polygon such as a trapezoid or a triangle, or may be a circle.

The liquid storage unit 19 communicates with the main flow path 20 via the relay flow path 22.
The relay flow path 22 is open to the inner surface 20a on the second direction side (right side in FIG. 1, + Y direction side) of the main flow path 20 at the base end 22a (one end) connected to the main flow path 20. The relay flow path 22 opens to the side surface 19b on the first direction side (left side in FIG. 1, −Y direction side) of the liquid storage portion 19 at the tip 22b (the other end) connected to the liquid storage portion 19. Yes. The opening on the main flow path 20 side of the relay flow path 22 is preferably at a position higher than the first bent flow path 4a (position closer to one end in one direction; position closer to the + X direction in FIG. 1). The opening on the main flow path 20 side of the relay flow path 22 is at a position higher than the connection portion 4e of the downward flow path 4d (position closer to one end in one direction, that is, the + X direction side than the connection portion 4e). Is more preferable. The tip 22 b is a connection end with the liquid storage unit 19.

  The relay channel 22 is inclined so as to rise from the main channel 20 toward the liquid reservoir 29 toward the second direction side in the width direction of the cartridge body 2 (right side in FIG. 1). That is, the relay flow path 22 is inclined so as to approach one end in the length direction of the cartridge body 2 (the upper end in FIG. 1, the + X direction end) as it goes toward the second direction. Therefore, it is possible to prevent other liquid flowing in from the upper end side of the flow path part 3 from flowing into the liquid storage part 29 in a state where the main flow path 20 is directed in the direction of gravity, and to improve detection accuracy.

In FIG. 1, the relay flow path 22 is inclined obliquely upward over the entire length, but the relay flow path 22 rises as a part of the length direction including at least the base end 22 a moves toward the second direction side. If it is inclined, the effect of increasing the detection accuracy by preventing the inflow of other liquids can be obtained.
The opening of the relay channel 22 on the liquid storage unit 19 side is preferably located at a position higher than the bottom surface 19c, for example, at the top of the side surface 19b.
The width of the relay channel 22 and the channel cross-sectional area can be constant in the length direction.

The liquid storage unit 19 is communicated with the liquid recovery unit 6 via the communication channel 23.
The communication channel 23 is open to the side surface 19b on the first direction side (left side in FIG. 1, -Y direction side) of the liquid storage unit 19 at the upper end 23b (one end) connected to the liquid storage unit 19. . The upper end 23b is preferably connected to a position including the lower end of the side surface 19b. The communication channel 23 opens on the upper surface of the liquid recovery unit 6 at the lower end 23 c (the other end) connected to the liquid recovery unit 6.

The communication channel 23 has first and second channels 23d and 23e in this order from the upper end 23b to the lower end 23c.
The first flow path 23d (downward inclined flow path) is inclined in a direction of descending from the upper end 23b toward the first direction side (left side in FIG. 1, -Y direction side). That is, the first flow path 23d is inclined in a direction away from one end (upper end, + X direction end) in the length direction of the cartridge body 2 as it goes toward the first direction.
The upper end 23b is at a position lower than the tip 22b of the relay flow path 22 (−X direction side from the tip 22b).
The second flow path 23e extends downward (−X direction) from the lower end of the first flow path 23d, and is connected to the liquid recovery unit 6 at the lower end 23c.

  Since the connecting flow path 23 has a bent shape having a first flow path 23d extending obliquely downward and a second flow path 23e extending downward, compared to a straight shape, The inclination angle (inclination angle with respect to the X direction) of the portion including the upper end 23b can be sufficiently increased. Therefore, it is difficult for the liquid flowing from the relay flow path 22 to the liquid storage portion 19 to flow into the communication flow path 23. Therefore, it becomes easier to store a necessary amount of liquid in the liquid storage unit 19, so that the measurement accuracy is further improved at the time of immunoassay described later.

  The communication channel is not limited to a bent shape, and may be a straight shape (straight shape). In the case of a straight shape, it is preferable that the connecting flow path is inclined so as to descend toward the first direction side (left side in FIG. 1).

The width of the communication channel 23 and the channel cross-sectional area can be constant in the length direction.
The relay flow path 22 and the communication flow path 23 are, for example, a space formed between a recess formed in the main body 2a and the panel 2b (see FIG. 2).

  The flow channel enlargement unit 7 is communicated with the liquid injection unit 5 and the main flow channel 20, respectively, and enlarges a partial flow channel cross-sectional area of the flow channel unit 3 between the liquid injection unit 5 and the main flow channel 20. Configures the buffer space. That is, the flow path expanding section 7 serves as a buffer space in the flow path section 3, for example, to prevent back flow of the liquid injected from the liquid injection section 5 into the flow path section 3, or in the flow path section 3. It has a function of preventing air (bubbles) from biting into the flowing liquid.

  Specifically, the flow path enlargement unit 7 includes a first buffer space 7a in which a cross-sectional area in the width direction increases continuously from the upper end of the main flow path 20 and the first buffer space 7a. The second buffer space 7b has a channel cross-sectional area in the width direction that is continuously constant toward the upper side.

  The liquid injection unit 5 includes an injection source 8 for injecting a liquid previously stored in the cartridge body 2 from the upper end side of the flow path expansion unit 7, and a liquid from the outside of the cartridge body 2 in the flow path expansion unit 7. Any one or more of the inlet 9 for injecting from the upper end side is included. In the present embodiment, the liquid injection unit 5 includes three injection sources 8 and one injection port 9, and these three injection sources 8 and one injection port 9 are located above the flow path expanding unit 7. The cartridge main body 2 is provided side by side in the width direction.

  The injection source 8 includes a liquid storage unit 10 that stores a liquid, and a liquid feeding unit 11 that pumps the liquid stored in the liquid storage unit 10 to the flow path expanding unit 7. An outlet channel 12 is provided on the lower end side of the liquid storage unit 10. The outlet channel 12 connects between the liquid storage unit 10 and the channel expansion unit 7. The liquid feeding part 11 is composed of a diaphragm valve, and is attached so as to close the hole 10a provided on the front surface (panel part 2b) of the liquid storage part 10.

  In the injection source 8, the liquid feeding part (diaphragm valve) 11 is pressed to inject the liquid from the outlet channel 12 to the channel expanding part 7 while pumping the liquid contained in the liquid container 10. can do.

  The injection source 8 is not necessarily limited to the above-described configuration. For example, the liquid storage unit 10 is packaged and an external force is applied to the liquid feeding unit 11 to open a part of the package seal, It is good also as a structure by which a liquid flows out out of the liquid storage part 10 to the exit flow path 12. FIG. In addition, as a method of opening a part of the package seal, a method of pressing the package or removing a package lid by pulling a film serving as a package lid can be used.

  The inlet 9 has a liquid storage part 13 in which liquid is temporarily stored. An outlet channel 14 is provided on the lower end side of the liquid storage unit 13. The outlet channel 14 connects between the liquid storage unit 13 and the channel expansion unit 7. On the other hand, an opening 15 is provided on the upper end side of the liquid storage unit 13.

  In the injection port 9, the liquid once stored in the liquid storage unit 13 is injected from the outside of the cartridge main body 2 into the liquid storage unit 13 through the opening 15, so that the liquid is once stored in the liquid storage unit 13 from the outlet channel 14. Can be injected.

  The liquid recovery unit 6 has a lower space 6 a that is enlarged in the length direction and the width direction inside the cartridge body 2. In addition, the liquid recovery unit 6 has upper spaces 6b located above the lower space 6a on both sides in the width direction of the lower space 6a. The downward flow path 4d communicates with one (left side in FIG. 1) of the upper space 6b.

  The liquid recovery part 6 has an air hole 16 and a protective wall 17 at a position that constitutes the other upper space 6b (right side in FIG. 1). The air hole 16 is provided through the cartridge body 2. In the inspection device 1, the air in the liquid recovery unit 6 can be degassed outside through the air holes 16.

  The protective wall 17 is provided below the air hole 16 so as to partition a part of the upper space 6b vertically. In the inspection device 1, it is difficult for the liquid to leak from the air holes 16 by the protective wall 17. The air hole 16 and the protective wall 17 may be configured to be provided on either the main body 2a or the panel 2b.

  An absorbent 18 that absorbs liquid may be provided inside the liquid recovery unit 6. For the absorbent material 18, for example, sponge, fiber, polymer, or the like can be used. In this embodiment, the absorber 18 is arrange | positioned over the substantially whole region of the lower space 6a.

  In the inspection device 1, the absorbent 18 absorbs the liquid, so that the liquid flowing out from the lower end of the flow path section 3 (downward flow path 4 d) can be stably held in the liquid recovery section 6. Therefore, even when the inspection device 1 is tilted, the liquid in the liquid recovery unit 6 can be prevented from flowing back through the flow path unit 3 or leaking out from the air holes 16.

  In the inspection device 1 having the above-described configuration, the flow path trap unit 4 can be used as a reaction field for immunoassay. Specifically, the liquid feeding operation of the test device 1 when the flow path trap unit 4 is used as a reaction field for immunoassay will be described with reference to FIGS. 3, 4, and 5.

  FIG. 3 is a plan view showing a state of the inspection device 1 when the liquid L containing the magnetic beads B is allowed to flow into the flow path trap unit 4. FIG. 4 is a plan view showing a state of the inspection device 1 when a magnetic force is applied to the flow path trap unit 4. FIG. 5 is a plan view showing a state of the inspection device 1 when the liquid L is caused to flow out from the flow path trap unit 4.

  When the flow path trap unit 4 is used as a reaction field for immunoassay, first, as shown in FIGS. 3 and 4, the magnetic beads B whose surface is modified with a polymer that specifically binds to a specific substance are flow paths. It stays in the trap part 4.

  About the magnetic bead B, a conventionally well-known thing can be selected suitably and can be used. For example, as the magnetic beads B, those made of a polymer material containing magnetic particles can be used. As the magnetic particles, for example, those made of a material that is relatively easily attracted by a magnetic force such as magnetite or permalloy can be used. Examples of the polymer material include biocompatible materials such as polystyrene, PMMA, polyvinyl chloride (PVC), silicone, water-soluble collagen, and thermoplastic elastomer. Examples of the polymer that modifies the surface of the magnetic bead B include antibodies, peptides, DNA aptamers, RNA aptamers, and sugar chains.

  The particle size of the magnetic beads B is preferably in the range of 10 nm to 500 μm. If the particle size of the magnetic beads B is too large, the surface area involved in the reaction will be small, so that measurement will take time. On the other hand, when the particle size of the magnetic beads B is too small, the magnetic force becomes weak, so that it is difficult to attract the magnetic beads B with a magnet M described later.

  In the inspection device 1 of the present embodiment, in order to retain the magnetic beads B in the flow path trap unit 4, first, as shown in FIG. 3, the liquid L containing the magnetic beads B is injected from the upper end side of the main flow path 20. . At this time, the inspection device 1 is held so that the extending direction of the main flow path 20 (the length direction of the cartridge main body 2) is the direction along the gravity. Thereby, the liquid L can be made to flow into the flow path trap part 4 from the upper end side of the main flow path 20 using gravity.

  Here, holding the inspection device 1 in the direction along the gravity means holding the inspection device 1 in a direction in which the liquid L naturally flows from the upper end side to the lower end side of the main flow path 20 due to gravity. Therefore, in the present embodiment, the main flow path 20 is not limited to the case where the inspection device 1 is held so that the extension direction of the main flow path 20 (the length direction of the cartridge body 2) and the gravity direction coincide with each other. If the liquid L can flow from the upper end side to the lower end side, the inspection device 1 can be held so that the main flow path 20 is inclined with respect to the direction of gravity.

  When the inspection device 1 is held in a direction along the gravity, the liquid L in the flow path trap unit 4 has the same horizontal height on the inflow side and the outflow side according to the siphon principle. . In this state, the magnetic beads B can be retained in the flow path trap unit 4. Strictly speaking, the liquid level on the inflow side is slightly higher than the liquid level on the outflow side due to the tension of the liquid L applied when the liquid L flows out to the liquid recovery unit 6 side.

  Next, in the inspection device 1 of the present embodiment, as shown in FIG. 4, the magnetic force is applied to the flow path trap unit 4 by bringing a magnet M serving as a magnetic force application unit closer to the flow path trap unit 4. As a result, the magnetic beads B are attracted to the wall surface of the flow path trap unit 4.

  For the magnet M, a permanent magnet or an electromagnet can be used. Moreover, as a permanent magnet, ferromagnetic materials, such as a ferrite magnet, a neodymium magnet, a samarium cobalt magnet, can be mentioned, for example. Further, the magnetic force applying means is not limited to the above-described method of bringing the magnet M close to the flow path trap unit 4, for example, by passing a current through an electromagnet (magnetic coil) that is close to the flow path trap unit 4. A magnetic force may be applied to the trap unit 4.

  Next, in the inspection device 1 of the present embodiment, as illustrated in FIG. 5, the liquid L in the flow path trap unit 4 remains in the flow path unit 3 (downward) while the magnetic force is applied to the flow path trap unit 4. The inspection device 1 is tilted in the direction of flowing out from the lower end side of the flow path 4d). In the present embodiment, the inspection device 1 is tilted to one side (left side in the drawing) with respect to the direction along gravity. As a result, while the magnetic beads B are retained in the flow path trap section 4, the liquid L in the flow path trap section 4 is transferred from the lower end side of the flow path section 3 (downward flow path 4d) to the liquid recovery section 6. And can be drained.

  Thereafter, the inspection device 1 is held in a direction along the gravity. Thereby, in the state which made the magnetic bead B stay in the flow path trap part 4, the liquid feeding operation with respect to the flow path trap part 4 mentioned above can be performed repeatedly.

  As described above, in the inspection device 1 of the present embodiment, the liquid feeding operation using the gravity described above can be performed with respect to the flow path trap unit 4 without using a pump. Thereby, it is possible to perform the immunoassay described later more easily.

  Further, in the inspection device 1 of the present embodiment, the downward flow path 4d of the above-described flow path trap section 4 is connected downward with respect to the upper space 6b of the liquid recovery section 6, so that liquid feeding using gravity is performed. During operation, the liquid L flowing out from the downward flow path 4d to the upper space 6b is relatively difficult to be transmitted to the side surface of the liquid recovery unit 6 constituting the upper space 6b. Thereby, it is possible to prevent contamination by the liquid L in the upper space 6b.

  In addition, this invention is not necessarily limited to the structure of the said test | inspection device 1, A various change can be added in the range which does not deviate from the meaning of this invention.

[Modification]
As a modification of the inspection device 1, a configuration of the inspection device 1A shown in FIG. 6 will be described. FIG. 6 is a plan view showing the configuration of the inspection device 1A. In the following description, the same parts as those of the inspection device 1 are not described and are denoted by the same reference numerals in the drawings.

  An inspection device 1 </ b> A illustrated in FIG. 6 includes a channel trap unit 4 </ b> A instead of the channel trap unit 4. The flow path trap part 4A has a shape in which a part of the flow path part 3 is folded back in the direction from the lower end side to the upper end side of the cartridge body 2.

  Specifically, the channel trap part 4A is configured by sequentially passing the first bent channel 4a and the upward channel 4b from one end (upper end) side to the other end (lower end) side of the channel unit 3. Have. And the upward flow path 4b is connected with one (left side in FIG. 6) upper space 6b. For this reason, one upper space 6b has a shape extended upward from the upper space 6b shown in FIG. The rest of the configuration is basically the same as that of the inspection device 1 described above.

  In the test device 1A shown in FIG. 6, the channel trap part 4A can be used as a reaction field for immunoassay, as in the test device 1. Further, when the flow path trap part 4A is used as a reaction field for immunoassay, the flow path trap part 4A is retained in the state where the magnetic beads B are retained in the flow path trap part 4A, as in the case of the test device 1. It is possible to carry out a liquid feeding operation.

  As described above, in the inspection device 1A shown in FIG. 6, similarly to the inspection device 1, the liquid supply operation using the gravity described above performs the liquid supply operation on the flow path trap unit 4A without using a pump. It is possible. Thereby, it is possible to perform the immunoassay described later more easily.

(Inspection method)
Next, an inspection method according to an embodiment of the present invention will be described. In the inspection method of the present embodiment, an inspection method using the inspection device 1 is exemplified, but the inspection device to which the present invention is applied, for example, the inspection device 1A and inspection devices 21 and 21A described later are similarly applied. It is possible to use.

  In the test method using the test device 1, the magnetic bead B described above is retained in the flow channel trap unit 4, thereby using the flow channel trap unit 4 as a reaction field for immunoassay. When the flow path trap unit 4 is used as a reaction field for immunoassay, the above-described liquid feeding operation is performed on the flow path trap unit 4 while the magnetic beads B are retained in the flow path trap unit 4.

  Thereby, in the test | inspection method of this embodiment, it is possible to perform liquid feeding operation with respect to the flow path trap part 4 using gravity, without using a pump. Moreover, it is possible to perform the immunoassay described later more easily.

[Immunoassay]
Next, an example of immunoassay using the test device 1 will be described with reference to FIGS. 7 to 15 are plan views for sequentially explaining each step of the immunoassay using the test device 1 described above.

  In the immunoassay using the test device 1, first, the liquid L1 containing the magnetic beads B is injected from the upper end side of the main flow path 20 as shown in FIG. At this time, the inspection device 1 is held in a direction along the gravity. Thereby, the liquid L can be made to flow into the flow path trap part 4 from the upper end side of the main flow path 20 using gravity. Further, the surface of the magnetic bead B is modified in advance with the capture antibody Ab1, as shown in the enlarged view of the encircled portion in FIG.

  Next, as shown in FIG. 8, a magnetic force is applied to the channel trap unit 4 by bringing the magnet M close to the channel trap unit 4. As a result, the magnetic beads B are attracted to the wall surface of the flow path trap unit 4. In this state, the inspection device 1 is tilted in the direction in which the liquid L1 in the channel trap unit 4 flows out from the lower end side of the channel unit 3 (downward channel 4d). By inclining the inspection device 1, the flow path portion 3 is also inclined. The inclination direction of the inspection device 1 is the first direction side (left side in FIG. 8) in the width direction of the cartridge body 2. In this state, the inclination angle of the upward flow path 4b with respect to the horizontal plane becomes small. Therefore, it is preferable to incline the inspection device 1 until the upward flow path 4b is horizontal or diagonally downward to the left. Thereby, the liquid L1 in the flow path trap unit 4 can be allowed to flow out from the lower end side of the flow path unit 3 (downward flow path 4d) while the magnetic beads B are retained in the flow path trap unit 4. .

  Before sending the liquid L1, a liquid containing a blocking agent such as skim milk or albumin is sent by the same liquid feeding operation as the liquid L1, and the blocking agent is applied to the wall surface of the flow path trap unit 4. You may provide the blocking process etc. which fix | fix. In addition, after the liquid L1 is fed, a cleaning step of feeding a cleaning liquid such as water and cleaning the inside of the flow path unit 3 by a liquid feeding operation similar to the liquid L1 may be provided.

  As for the operation of feeding the cleaning liquid, after the magnetic liquid is applied to the flow path trap section 4 by the magnet M, the cleaning liquid is poured from the upper end side to the lower end side of the flow path section 3 and then inside the flow path trap section 4. A method in which the cleaning liquid is circulated from the upper end side to the lower end side of the flow path portion 3 by tilting the inspection device 1 in a direction in which the liquid flows out from the lower end side of the flow path portion 3 (downward flow path 4d). May be. Further, for example, a magnetic force is applied to the flow path trap unit 4 by the magnet M, and the inspection device 1 in a direction in which the liquid in the flow path trap unit 4 flows out from the lower end side of the flow path unit 3 (downward flow path 4d). A method may be used in which the cleaning liquid is continuously circulated from the upper end side to the lower end side of the flow path portion 3 in a state where the channel portion 3 is inclined.

  Further, the cleaning process is not limited to the case where the above-described process of circulating the cleaning liquid is provided between the liquid that has flowed into the flow path trap section 4 and the liquid that has flowed into the flow path trap section 4 later. The cleaning may be performed with a liquid that is introduced later. Note that the same liquid feeding operation can also be performed in the cleaning step performed in the following steps.

  Next, as shown in FIG. 9, in a state where a magnetic force is applied to the flow path trap unit 4 by the magnet M, a liquid L2 containing a specimen to be examined is injected from the upper end side of the main flow path 20. At this time, the inspection device 1 is held in a direction along the gravity. Thereby, the liquid L2 can be caused to flow from the upper end side of the main flow path 20 to the flow path trap section 4 using gravity while the magnetic beads B are retained in the flow path trap section 4. After the liquid L <b> 2 is introduced, the magnet M is separated from the channel trap unit 4 to release the state in which the magnetic force is applied to the channel trap unit 4. As a result, the magnetic beads B are more evenly distributed throughout at least the liquid L2 in the flow path trap part 4 without being locally biased in the liquid L2.

  Further, in the flow path trap section 4, as shown in an enlarged view in the encircled portion in FIG. 9, when the specimen contains an antigen Ag that specifically binds to the capture antibody Ab1, the antigen Ag is obtained from the antigen-antibody reaction. By binding to the capture antibody Ab1, it is captured by the magnetic beads B.

Next, as shown in FIG. 10, a magnetic force is applied to the channel trap unit 4 by bringing the magnet M closer to the channel trap unit 4. As a result, the magnetic beads B are attracted to the wall surface of the flow path trap unit 4. In this state, the inspection device 1 is tilted in a direction in which the liquid L2 in the channel trap unit 4 flows out from the lower end side of the channel unit 3 (downward channel 4d). The inclination direction of the inspection device 1 is the first direction side (left side in FIG. 10) in the width direction of the cartridge body 2.
Thereby, the liquid L2 in the channel trap unit 4 can flow out from the lower end side of the channel unit 3 (downward channel 4d) while the magnetic beads B remain in the channel trap unit 4. . Thereafter, as a cleaning process, a cleaning liquid such as water is sent in a state where the magnet M is brought close to the flow path trap unit 4. Thus, excess antigen Ag that has not reacted with the capture antibody Ab1 is washed away (referred to as B / F separation).

  Next, as shown in FIG. 11, a liquid L3 containing a labeled antibody Ab2 labeled with the enzyme En is injected from the upper end side of the main channel 20 in a state where a magnetic force is applied to the channel trap unit 4 by the magnet M. At this time, the inspection device 1 is held in a direction along the gravity. Thereby, the liquid L3 can be caused to flow from the upper end side of the main flow path 20 to the flow path trap section 4 using gravity while the magnetic beads B are retained in the flow path trap section 4. After injecting the liquid L3, the magnet M is separated from the flow path trap part 4 to release the state in which the magnetic force is applied to the flow path trap part 4. As a result, the magnetic beads B are more evenly distributed over at least the entire liquid L3 in the flow path trap unit 4 without being locally biased in the liquid L3.

  Further, in the flow path trap section 4, as shown in an enlarged view in the encircled portion in FIG. 11, the labeled antibody Ab2 contained in the liquid L3 is captured by the magnetic beads B by binding to the antigen Ag by the antigen-antibody reaction. The

Next, as shown in FIG. 12, a magnetic force is applied to the channel trap unit 4 by bringing the magnet M closer to the channel trap unit 4. As a result, the magnetic beads B are attracted to the wall surface of the flow path trap unit 4. In this state, the inspection device 1 is tilted in a direction in which the liquid L3 in the flow path trap section 4 flows out from the lower end side of the flow path section 3 (downward flow path 4d). The inclination direction of the inspection device 1 is the first direction side (left side in FIG. 12) in the width direction of the cartridge body 2.
Accordingly, the liquid L3 in the flow path trap unit 4 can be allowed to flow out from the lower end side of the flow path unit 3 (downward flow path 4d) while the magnetic beads B are retained in the flow path trap unit 4. . Thereafter, as a cleaning process, a cleaning liquid such as water is sent in a state where the magnet M is brought close to the flow path trap unit 4. Thereby, excess labeled antibody Ab2 that has not reacted with the antigen Ag is washed away (referred to as B / F separation).

  Next, as shown in FIG. 13, a liquid L4 containing a substrate (labeled substrate) S that reacts with the enzyme En of the labeled antibody Ab2 and emits light or emits light in a state where a magnetic force is applied to the flow path trap unit 4 by the magnet M. Is injected from the upper end side of the main flow path 20. At this time, the inspection device 1 is held in a direction along the gravity. Thereby, the liquid L4 can be caused to flow from the upper end side of the main flow path 20 to the flow path trap section 4 using gravity while the magnetic beads B are retained in the flow path trap section 4. After the liquid L4 is introduced, the magnet M is separated from the flow path trap part 4 to release the state in which the magnetic force is applied to the flow path trap part 4. Thereby, the magnetic beads B are more evenly distributed over at least the whole of the liquid L4 in the flow path trap part 4 without being locally biased in the liquid L4.

  Further, in the flow path trap section 4, as shown in an enlarged view in the encircled portion in FIG. 13, the labeled substrate S contained in the liquid L4 generates a labeled product Sn as a reaction with the enzyme En. In this embodiment, the case where a fluorescent product capable of emitting light by irradiation with excitation light is generated as the labeled product Sn by using a fluorescent substrate as the labeled substrate S is illustrated.

  In this state, for example, when the excitation light is irradiated to the liquid L4 in the flow path section 3, the label product (fluorescence product) Sn emits fluorescence. Therefore, in the immunoassay using the test device 1, the amount or concentration of the antigen Ag contained in the specimen is quantitatively measured by measuring the emission intensity of the labeled product Sn when the liquid L4 is irradiated with the excitation light. Can be detected.

  Here, when measuring the emission intensity of the labeled product Sn, as shown in FIG. 14, a magnetic force is applied to the channel trap part 4 by the magnet M, and the magnetic beads B are retained in the channel trap part 4. In the state where the luminescent substrate S is dispersed in the liquid L4, the direction in which the liquid L4 in the channel trap part 4 flows out from the other end side of the channel part 3 (downward channel 4d) is opposite. Tilt the inspection device 1 to the side.

  The inclination direction of the inspection device 1 is the second direction side (the right side in FIG. 14) in the width direction of the cartridge body 2. At this time, the inspection device 1 is tilted until at least a part of the liquid L4 in the flow path section 3 (main flow path 20) flows into the liquid storage section 19 through the relay flow path 22. Since the inclination direction of the inspection device 1 is the second direction side (the right side in FIG. 14) opposite to the upward flow path 4b, the liquid L4 passes from the flow path section 3 through the flow path trap section 4. There is no spillage.

Since the relay flow path 22 opens to the inner surface 20a on the second direction side (the right side in FIG. 14), at least a part of the liquid L4 flows smoothly into the liquid reservoir 19 through the relay flow path 22. .
Since the communication channel 23 is formed in the liquid storage unit 19, when the liquid L 4 is introduced into the liquid storage unit 19, the air inside the liquid storage unit 19 can be discharged through the communication channel 23. it can. Therefore, the liquid L4 can be smoothly introduced into the liquid storage unit 19.

In this state, it is preferable to irradiate the liquid L4 in the liquid reservoir 19 with excitation light. The excitation light is preferably applied to the liquid L4 in a region outside the magnet M region. In this case, by allowing the magnetic beads B to remain in the flow path trap unit 4, the light emission of the labeled product Sn in the liquid storage unit 19 is not easily inhibited by the presence of the magnetic beads B.
Note that the measurement of the emission intensity of the labeled product Sn is not limited to the above-described method, and for example, the measurement may be performed without tilting the inspection device 1 without applying a magnetic force.

  Thereby, inhibition of the detection light by each labeled product Sn can be reduced, and detection sensitivity and quantitativeness can be improved. Moreover, since the liquid L4 staying in the flow path trap part 4 is almost fixed, it is possible to easily perform measurement with high quantitativeness.

  The labeled antibody Ab2 is not limited to the one labeled with the enzyme En described above. In addition to the enzyme En, the labeled antibody Ab2 is labeled with a substance that develops color or emits light by reacting with the labeled substrate S contained in the liquid L4. Labeled antibody Ab2 may be used. When the labeled antibody Ab2 labeled with such a substance is used, a labeled product Sn is generated from the substance by reacting the labeled substrate S contained in the liquid L4 with the substance of the labeled antibody Ab2. At the same time, the labeled product Sn is desorbed from the labeled antibody Ab2. Therefore, by detecting this labeled product Sn, it is possible to quantitatively detect the amount or concentration of the antigen Ag contained in the specimen.

  As labeled antibody Ab2, labeled antibody Ab2 previously labeled with a substance that develops color or emits light (labeled substance) may be used. In this case, the substrate (labeled substrate) S can be omitted in the step shown in FIG. 13 after the step shown in FIG. Further, by detecting the labeling substance of the labeled antibody Ab2 bound to the antigen Ag, it is possible to quantitatively detect the amount or concentration of the antigen Ag contained in the specimen.

  Furthermore, instead of the liquid L3 containing the labeled antibody Ab2 labeled with the enzyme En or the labeling substance described above, the liquid containing the primary antibody that specifically binds to the antigen Ag is flowed from the upper end side of the main flow path 20 to the flow path trap section. 4, after the primary antibody is bound to the antigen Ag, the liquid containing the secondary antibody that specifically binds to the primary antibody and is labeled with the enzyme En is placed on the upper end side of the main channel 20. The secondary antibody may be bound to the primary antibody by allowing the secondary antibody to flow into the flow path trap section 4.

  In this case, the liquid L4 containing the labeled substrate S is caused to flow from the upper end side of the main flow path 20 into the flow path trap section 4 so that the labeled substrate S generates a labeled product Sn as a reaction with the enzyme En of the secondary antibody. .

  A plurality of secondary antibodies can be bound to one primary antibody. In this case, amplification of a signal when detecting the labeled product Sn is possible by a plurality of secondary antibodies (labeled antibodies) labeled with the enzyme En. In addition, when a secondary antibody is used, it is not necessary to label the primary antibody with the enzyme En, and it is possible to expand the range of selection of a secondary antibody (labeled antibody) suitable for the primary antibody to be used.

  Examples of the labeling substrate S include chemiluminescent substrates such as luciferin, luminol, acridinium, and oxalate, and fluorescent materials such as fluorescein isothiocyanate (FITC) and green fluorescent protein (GFP). On the other hand, examples of the enzyme include peroxidase, luciferase, aequorin and the like. Examples of the enzyme substrate include 3- (p-hydroxyphenol) propionic acid and analogs thereof, luciferin and luciferin analogs, coelenterazine and coelenterazine analogs, and the like. Further, at least one or more of these labeling substrates S can be used.

  In addition, examples of the non-luminescent labeling substance include radioactive labeling substances used in known radioimmunoassay methods. The method for binding the labeling substance to the labeled antibody Ab2 is not particularly limited, and known methods can be applied.

  The type of antigen Ag is not particularly limited and is appropriately selected according to the purpose of biochemical examination. Specific examples of the antigen Ag include proteins derived from pathogens such as myocardial markers, colds, hepatitis, acquired immune deficiency, and pathogens such as bacteria, peptides, nucleic acids, lipids, sugar chains, and the like.

  For the capture antibody Ab1 and the labeled antibody Ab2, it is necessary to prepare in advance a specimen that specifically binds to a specific antigen Ag. Such an antibody should be appropriately selected from conventionally known ones. Is possible.

  In addition, if there is a location in the channel where you do not want to adsorb antigen Ag, capture antibody Ab1, labeled antibody Ab2, etc., it is not necessary to perform surface treatment such as coating to improve the water repellency of the location in advance. Can be prevented.

  As described above, in the immunoassay using the test device 1, the presence or absence of the antigen Ag in the sample to be tested is qualitatively detected, and the amount or concentration of the antigen Ag contained in the sample is quantified. Can be detected automatically. Further, by using the test device 1, the above-described immunoassay can be performed more easily.

  In the inspection device 1, by tilting the inspection device 1 in a state where the magnetic beads B are attracted by the magnet M, the liquid L 4 with a small content of the magnetic beads B can be caused to flow into the liquid storage unit 19. Therefore, a detection result with less noise caused by the magnetic beads B can be obtained by detecting the detection target (antigen Ag or the like) contained in the liquid L4 in the liquid reservoir 19. Therefore, detection accuracy can be increased.

  The inspection device 1 may detect the liquid L4 in the liquid storage unit 19 without using the magnet M. In this case, the content of the magnetic beads B of the liquid L4 in the liquid storage unit 19 increases, but since the magnet M is not used, there are fewer restrictions on the arrangement of detection devices (for example, optical systems), and The degree of design freedom can be increased.

  In the inspection device 1, since the liquid storage unit 19 is separated from the main flow path 20, it is between the portion that exerts magnetism on the liquid L by the magnet M and the portion that provides the liquid L for optical measurement (liquid storage unit 19). A sufficient distance can be secured. Therefore, the freedom degree of design of the apparatus attached to the test | inspection device 1 can be raised.

As shown in FIG. 15, after the measurement is completed, the posture of the inspection device 1 is returned so that the length direction of the cartridge body 2 is in the direction along the gravity.
Thereby, the liquid L4 in the liquid storage part 19 can be made to flow into the liquid collection | recovery part 6 through the connection flow path 23 using gravity. Therefore, the liquid L4 in the liquid storage unit 19 can be collected by an easy operation.

  Since the first flow path 23d of the communication flow path 23 is inclined with respect to the main flow path 20, when the main flow path 20 is directed in the direction of gravity, the liquid L4 is in the second direction side of the first flow path 23d ( It becomes easy to flow along the inner surface 23a on the right side). Therefore, the liquid L4 can be reliably and efficiently introduced into the liquid recovery unit 6 as compared with the case where the communication channel 23 is not inclined.

  In addition, as an immunoassay using the said test | inspection device 1, well-known immunoassay methods, such as a sandwich immunoassay method, an indirect antibody immunoassay method, a bridging immunoassay method, are employable, for example, in particular to the method mentioned above. It is not limited.

(Inspection device)
As a second embodiment of the present invention, an inspection device 21 shown in FIG. 16 will be described. In addition, about the site | part equivalent to the test | inspection device of above-mentioned embodiment, while abbreviate | omitting description, the same code | symbol is attached | subjected in drawing.
The inspection device 21 can have the same configuration as the inspection device 1 shown in FIG.
The relay channel 32 is a channel that connects the main channel 20 and the liquid storage unit 19, and the main channel 20 and the liquid storage unit 19 are communicated with each other via the relay channel 32.

  The relay flow path 32 is open to the inner surface 20 a on the second direction side (right side in FIG. 16, + Y direction side) of the main flow path 20 at the base end 32 c (one end) connected to the main flow path 20. The relay flow path 32 opens to the side surface 19b on the first direction side (left side in FIG. 16, −Y direction side) of the liquid storage unit 19 at the tip 32d (the other end) connected to the liquid storage unit 19. Yes. The tip 32 d is a connection end with the liquid storage unit 19.

  The relay channel 32 preferably has an opening area at the base end 32c larger than a channel cross-sectional area of the main channel 20 at the base end 32c (area of a cross section perpendicular to the main channel 20). As a result, the liquid in the main channel 20 flows smoothly into the relay channel 32.

  The relay flow path 32 is preferably formed in a shape (tapered shape) in which the width of the flow path is gradually narrowed from the base end 32c to the front end 32d. The relay channel 32 has a channel cross-sectional area that gradually decreases from the base end 32c to the tip 32d. For this reason, the opening area of the relay flow path 32 at the base end 32c is larger than the opening area of the relay flow path 32 at the distal end 32d. The cross-sectional area of the relay flow path 32 is an area of a cross section perpendicular to the center line in the width direction of the relay flow path 32.

The upper surface 32a and the lower surface 32b of the relay flow path 32 are inclined so as to rise toward the second direction side in the width direction of the cartridge body 2 (right side in FIG. 16). That is, the upper surface 32a and the lower surface 32b are inclined so as to approach one end in the length direction of the cartridge body 2 (upper end in FIG. 16, end in the + X direction) toward the second direction side. Therefore, the direction of the relay flow path 32 (the direction of the center line in the width direction) approaches the one end in the length direction of the cartridge body 2 (the upper end in FIG. 16, the + X direction end) as it goes toward the second direction. It is the direction which inclines to.
The inclination angle of the upper surface 32a with respect to the width direction of the cartridge body 2 is smaller than the inclination angle of the lower surface 32b.

  In the inspection device 21, since the opening area of the relay flow path 32 at the tip 32 d is small, the liquid in the liquid storage unit 19 hardly flows back to the relay flow path 32. Therefore, a sufficient amount of liquid can be ensured in the liquid storage part 19, and detection of antigen Ag etc. can be made easy.

[Modification]
An inspection device 21 </ b> A illustrated in FIG. 17 is a modification of the inspection device 21. The inspection device 21 </ b> A is different from the inspection device 21 in that the flow path trap unit 4 </ b> A is provided instead of the flow path trap unit 4.

(Inspection method)
As shown in FIG. 18, for example, in the above-described immunoassay, the test device 21 is in the second direction side (the right side in FIG. 18) in the width direction of the cartridge body 2 in a state where the magnetic beads B are attracted by the magnet M. When tilted in the direction, at least a part of the liquid L4 flows into the liquid reservoir 19 through the relay flow path 32.

  When the inspection device 21 is tilted in the direction of the second direction (the right side in FIG. 18), the larger the tilt, the easier the liquid L4 flows toward the upper end side of the main flow path 20, but at the base end 32c. Since the opening area of the relay flow path 32 is sufficiently large, the liquid L4 can be reliably guided to the relay flow path 32 and efficiently introduced into the liquid storage unit 19.

In the inspection device 21, by tilting the inspection device 21 in a state where the magnetic beads B are attracted by the magnet M, the liquid L 4 having a small content of the magnetic beads B can be caused to flow into the liquid storage unit 19.
Therefore, by detecting the detection target (antigen Ag or the like) contained in the liquid L4 in the liquid storage unit 19, a detection result with less noise caused by the magnetic beads B can be obtained, and the detection accuracy can be improved. it can.

  In the inspection device 21, as in the inspection device 1, the liquid storage unit 19 is separated from the main flow path 20, and therefore, a part that magnetizes the liquid L by the magnet M and a part that provides the liquid L for optical measurement (liquid storage It is possible to ensure a sufficient distance from the portion 19). Therefore, the freedom degree of design of the apparatus attached to the test | inspection device 1 can be raised.

As shown in FIG. 19, after completion of the measurement, the posture of the inspection device 21 is returned so that the length direction of the cartridge body 2 is in the direction along the gravity.
Thereby, since the liquid L4 in the liquid storage part 19 can be made to flow into the liquid collection | recovery part 6 through the connection flow path 23, the liquid L4 in the liquid storage part 19 can be collect | recovered by easy operation. Further, by inclining the inspection device 1 in the direction in which the liquid L4 in the flow path trap part 4 flows out from the lower end side of the flow path part 3 (downward flow path 4d), the liquid L4 in the flow path trap part 4 is allowed to flow. It can be made to flow out from the lower end side of the flow path part 3 (downward flow path 4d).

(Inspection equipment)
Next, as one embodiment of the present invention, for example, inspection apparatuses 100A and 100B using the inspection device 1 shown in FIGS. 20 and 21 will be described. FIG. 20 is a block diagram showing the configuration of the inspection apparatus 100A. FIG. 21 is a block diagram illustrating a configuration of the inspection apparatus 100B.

  In the present embodiment, the inspection apparatuses 100A and 100B using the inspection device 1 are exemplified. However, the inspection devices 1A, 21, and the inspection devices 1A, 21, 21A can be used similarly.

  The inspection apparatuses 100A and 100B of this embodiment include a device holding unit 101 that holds the inspection device 1 as shown in FIGS. 20 and 21 and a device inspection unit 102 that inspects the inspection device 1. In addition, the inspection apparatus 100A includes a light emitting unit 103 and a light receiving unit 104 as the device inspection unit 102 as shown in FIG. On the other hand, the inspection apparatus 100B includes a light receiving unit 104 as the device inspection unit 102 as shown in FIG.

  The device holding unit 101 holds the inspection device 1 in a direction along gravity. The mechanism for holding the inspection device 1 is not particularly limited, and a conventionally known mechanism can be used.

  In this state, the inspection apparatuses 100A and 100B of the present embodiment can perform the liquid feeding operation on the flow path trap unit 4 using the above-described gravity without using a pump. In this state, it is possible to perform immunoassay using the above-described test device 1. Therefore, in the inspection apparatuses 100A and 100B of the present embodiment, the apparatus configuration can be simplified, and the entire apparatus can be reduced in size and cost, and the maintainability can be improved by simplifying the apparatus configuration.

  In the device inspection unit 102 illustrated in FIG. 20, the inspection device 1 is irradiated with excitation light emitted from the light emitting unit 103. On the other hand, the light receiving unit 104 receives light from a light emitting substrate that emits light when excited by excitation light (hereinafter referred to as detection light). Thus, it is possible to qualitatively detect the presence or absence of an antigen contained in the specimen from the emission intensity of the detection light, and to quantitatively detect the amount or concentration of the antigen.

  On the other hand, in the device inspection unit 102 shown in FIG. 21, the light receiving unit 104 receives light from the luminescent substrate that emits light (hereinafter referred to as detection light). Thus, it is possible to qualitatively detect the presence or absence of an antigen contained in the specimen from the emission intensity of the detection light, and to quantitatively detect the amount or concentration of the antigen.

  The inspection apparatuses 100 </ b> A and 100 </ b> B of this embodiment include an injection driving unit 105 that automatically performs an injection operation on the liquid injection unit 5 of the inspection device 1. The injection drive unit 105 plays a role of pressure-feeding the liquid stored in the liquid storage unit 10 to the outlet channel 12 by pressing the liquid transfer unit 11 of the injection source 8 described above.

  The mechanism for pressing the liquid feeding unit 11 is not particularly limited, and a conventionally known mechanism can be used. Moreover, in the structure which packaged the liquid storage part 10, it is good also as a structure which performs operation which opens a part of seal | sticker of a package.

  The injection driving unit 105 is not limited to a configuration in which a plurality of operation mechanisms are provided in accordance with the number of injection sources 8, and selectively operates the plurality of injection sources 8 while changing the position with one operation mechanism. It is good also as a structure. In addition, about the timing which operates each injection source 8, it is necessary to provide a time difference.

  Furthermore, when the liquid injection operation is manually performed on the liquid injection unit 5 of the inspection device 1, the injection driving unit 105 can be omitted.

  The inspection apparatuses 100 </ b> A and 100 </ b> B of this embodiment include a device driving unit 106 for rotating the inspection device 1 and a magnetic force application unit 107 for applying a magnetic force to the flow path trap unit 4. .

  The device driving unit 106 rotates the device holding unit 101 that holds the inspection device 1. Thereby, the inspection device 1 can be tilted to one side (counterclockwise) with respect to the direction along the gravity, or the inspection device 1 can be tilted toward the other side (clockwise) with respect to the direction along the gravity. it can.

  The magnetic force application unit 107 is located between the position where the magnet M overlaps the flow path trap part 4 and the position where the magnet M does not overlap the flow path trap part 4 along the surface of the inspection device 1 on the panel part 2b side. Slide the magnet M. Thereby, the magnet M can be brought close to the flow path trap part 4, or the magnet M can be moved away. Further, the magnetic force application unit 107 is not limited to the above-described sliding operation, and may be directly operated in a direction in which the magnet M is brought closer to or away from the flow path trap unit 4. Further, in the magnetic force application unit 107, as the above-described magnetic force application unit, a magnetic force is applied to the flow path trap unit 4 by flowing a current through an electromagnet (magnetic coil) that is brought close to the flow path trap unit 4. Good.

  The mechanism for rotating the device holding unit 101 and the mechanism for sliding the magnet M are not particularly limited, and conventionally known mechanisms can be used.

  In the inspection apparatuses 100A and 100B according to the present embodiment, in addition to the above-described configuration, for example, calculation is performed based on the results detected by the control unit that controls driving of each unit, the power supply unit that supplies power, and the device inspection unit 102 And an output unit that outputs the result of the operation performed by the operation unit as a signal.

[Detection optics]
Next, an example of the detection optical system constituting the device inspection unit 102 shown in FIGS. 20 and 21 will be described with reference to FIG. FIG. 22 is a cross-sectional view showing the configuration of the detection optical system.

  In the detection optical system shown in FIG. 22, the light emitting unit 103 and the light receiving unit 104 are arranged with the inspection device 1 held by the device holding unit 101 interposed therebetween. In the light emitting unit 103, a light emitting element 108 and a collimating lens 109 are arranged in order on the optical axis AX1 in a direction approaching the inspection device 1. In the light receiving unit 104, a collimating lens 110, an optical filter 111, a condensing lens 112, and a light receiving element 113 are sequentially arranged on the optical axis AX2 in a direction away from the inspection device 1. Yes.

  The optical axis AX1 on the light emitting unit 103 side has an angle inclined with respect to the main surface of the inspection device 1. On the other hand, the optical axis AX2 on the light receiving unit 104 side has an angle perpendicular to the main surface of the inspection device 1. That is, the optical axis AX1 and the optical axis AX2 intersect each other at the detection position D of the inspection device 1 so that the optical path of the excitation light emitted by the light emitting unit 103 and the optical path of the detection light received by the light receiving unit 104 do not coincide. doing.

  The light emitting element 108 is made of, for example, a semiconductor laser and irradiates excitation light toward the detection position D of the inspection device 1. The collimating lens 109 collimates the excitation light toward the detection position D of the inspection device 1. The collimating lens 110 collimates detection light toward the light receiving element 113. Further, instead of the collimating lens 110, a lens that condenses the detection light toward the light receiving element 113 may be used. The optical filter 111 cuts light other than the detection light (excitation light or light from the outside) and improves the S / N ratio of the detection light incident on the light receiving element 113. The condensing lens 112 condenses the detection light toward the light receiving element 113. The light receiving element 113 includes, for example, a photomultiplier tube, a solid-state imaging device (CCD), an avalanche photodiode, a photodiode, or the like, and receives detection light.

  A light shielding path 115 that shields the optical path between the light emitting element 108 and the inspection device 1 is provided on the light emitting unit 103 side across the inspection device 1. Thereby, it is possible to shield the excitation light from leaking to the outside and the external light from entering the inspection device 1.

  In addition, a light shielding path 116 that shields the optical path on the extension of the optical axis AX1 is provided on the opposite side of the light emitting unit 103 with the inspection device 1 interposed therebetween. Thereby, it is possible to shield the excitation light from entering the light receiving unit 104 side.

  A light shielding path 117 that shields the optical path between the inspection device 1 and the light receiving element 113 is provided on the light receiving unit 104 side with the inspection device 1 interposed therebetween. Accordingly, it is possible to shield the detection light from leaking outside and the external light from entering the light receiving element 113.

  The device holding unit 101 is provided with an opening 101a on the light emitting unit 103 side through which excitation light passes and an opening 101b on the light receiving unit 104 side through which detection light passes. The opening 101b on the light receiving unit 104 side functions as a stop. Thereby, the spot size of the detection light received by the light receiving element 113 can be made constant, and the detection light received by the light receiving unit 104 can be quantified.

  The device inspection unit 102 is not necessarily limited to the configuration of the detection optical system described above, and can be implemented with appropriate modifications. For example, the device holding unit 101 may be provided with a heater (not shown) for heating the inspection device 1. Thereby, the inspection device 1 can be held at a specific temperature.

  DESCRIPTION OF SYMBOLS 1,1A, 21,21A ... Inspection device 2 ... Cartridge main body 2a ... Main-body part (1st base material) 2b ... Panel part (2nd base material) 3 ... Flow path part 4a ... 1st bending flow path 4b ... Upward flow path (folded flow path) 4c ... Second bent flow path 4d ... Downward flow path 4, 4A ... Flow path trap section 5 ... Liquid injection section 6 ... Liquid recovery section 6a ... Lower space 6b ... Upper space DESCRIPTION OF SYMBOLS 7 ... Channel expansion part 8 ... Injection source 9 ... Injection port 10 ... Liquid storage part 11 ... Liquid feeding part 12 ... Outlet channel 13 ... Liquid storage part 14 ... Outlet channel 15 ... Opening part 16 ... Air hole 17 ... Protection Wall 18 ... Absorbent material 19 ... Liquid reservoir 20 ... Main flow path 20a ... Inner surface 22, 2 ... Relay flow path 22a, 32c ... Base end 22b, 32c ... Tip (connection with liquid reservoir) End) 23 ... Communication channel 23d ... First channel 23b ... Upper end (one end) DESCRIPTION OF SYMBOLS 100A, 100B ... Inspection apparatus 101 ... Device holding part 102 ... Device inspection part 103 ... Light emission part 104 ... Light receiving part 105 ... Injection drive part 106 ... Device drive part 107 ... Magnetic force application part 108 ... Light emitting element 109 ... Collimating lens 110 ... Collimator Lens 111 ... Optical filter 112 ... Condensing lens 113 ... Light receiving element 115, 116, 117 ... Light blocking path B ... Magnetic bead M ... Magnet L, L1-L4 ... Liquid Ab1 ... Capture antibody Ab2 ... Labeled antibody Ag ... Antigen En ... Enzyme S: Labeled substrate Sn: Labeled product

Claims (12)

A flow path portion including a main flow path extended in one direction;
A liquid injection part for injecting liquid from one end side of the flow path part;
A liquid recovery part for recovering the liquid flowing out from the other end side of the flow path part;
A flow path trap part in which a part of the flow path part is folded at least from the other end side toward the one end side between the main flow path and the liquid recovery part;
A liquid storage part into which at least a part of the liquid in the main flow channel flows when the main flow channel is inclined,
The liquid storage unit is in communication with the main channel via a relay channel through which the liquid can flow, and an inspection device in communication with the liquid recovery unit through a communication channel through which the liquid can flow . The flow path trap portion has a folded flow path folded on one side in the width direction of the main flow path,
The inspection device according to claim 1, wherein the relay channel is opened at an inner surface on the other side in the width direction of the main channel at a base end connected to the main channel. The main flow path is formed so that the liquid is introduced from one end side in the one direction,
The relay channel is inclined so that at least a portion including the base end approaches one end side in the one direction as it goes to the other side in the width direction of the main channel. Or the inspection device of 2.   The inspection device according to claim 2, wherein the relay channel has an opening area at the base end larger than a cross-sectional area of the main channel at the base end.   The inspection device according to claim 2, wherein the relay flow path gradually decreases in cross-sectional area from the base end to a connection end with the liquid storage unit.   6. The communication channel according to claim 1, wherein at least a portion including one end connected to the liquid storage portion is inclined with respect to the one direction. Inspection device. An inspection method for inspecting for the presence or absence of a specific substance contained in a sample using the inspection device according to any one of claims 1 to 6,
Injecting a liquid containing magnetic beads whose surface is modified with a polymer that specifically binds to the specific substance from one end side of the flow path part to the flow path trap part,
By retaining the magnetic beads in the channel trap part, the channel trap part is used as a reaction field for immunoassay,
By applying a magnetic force to the flow path trap section, the flow path trap section while retaining the magnetic beads in the flow path trap section in a state where the magnetic beads are attracted to the wall surface of the flow path trap section. An inspection method characterized in that a liquid feeding operation is performed. In the liquid feeding operation, when the liquid is allowed to flow from the one end side of the flow channel portion to the flow channel trap portion, the inspection device is held so that the extension direction of the main flow channel is a direction along gravity. And
When the liquid flows out from the flow path trap part to the other end side of the flow path part, the inspection device is tilted in a direction in which the liquid in the flow path trap part flows out from the other end side of the flow path part. The inspection method according to claim 7.   The method according to claim 7, further comprising a step of feeding a liquid containing a specimen to be examined when performing the immunoassay. An inspection apparatus for inspecting the presence or absence of a specific substance contained in a sample using the inspection device according to any one of claims 1 to 6,
A device holding unit for holding the inspection device;
A device driver for rotating the inspection device;
A magnetic force application part for applying a magnetic force to the flow path trap part,
The device driving unit is configured to hold a position of the inspection device so that an extension direction of the main channel is in a direction along gravity, and a liquid in the channel trap unit flows out from the other end side of the channel unit. Rotating the inspection device between a position where the inspection device is tilted in a direction to be
The magnetic force application unit retains the magnetic beads in the flow path trap part in a state where the magnetic beads are attracted to the wall surface of the flow path trap part by applying a magnetic force to the flow path trap part. Inspection equipment.   The inspection apparatus according to claim 10, further comprising a device inspection unit for inspecting the inspection device.   The inspection apparatus according to claim 10 or 11, further comprising an injection driving unit for operating the injection of the liquid from the liquid injection unit.

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