Assay device and target molecule testing method

Abstract

Even when binding and washing of target molecules and their counterparts occur within a flow channel, it is possible to facilitate the binding of target molecules within the flow channel while reducing the inhibition of target molecule binding and washing due to the introduction of air bubbles into the flow channel. [Solution] The pretreatment unit 100 includes a pretreatment unit for detecting target molecules, in which the target molecules are bonded to a detection material for detecting the target molecules, and unreacted substances that were not bonded are separated by a washing solution. The pretreatment unit 100 is the place where the bonding and washing take place and includes a circulation channel 105, which is a tubular channel for circulating the liquid used for bonding and washing, and an air trap 112 that removes or captures bubbles mixed in the liquid introduced into the circulation channel 105 by utilizing the difference in properties between liquid and gas.

Description

Technical Field

[0001] The present disclosure relates to an assay device and a specimen inspection method.

Background Art

[0002] There is known a test called POCT (Point of Care Testing) that reduces the time from specimen collection to obtaining test results. Many assay devices used for POCT employ the principle of immunoassay methods. Some immunoassay methods require BF separation, which is the separation of unreacted substances. For example, Patent Document 1 discloses an assay cartridge that performs the binding of an analyte and a binder and subsequent washing within a channel. In the technique of Patent Document 1, a liquid sample containing the analyte is introduced into the cartridge through an inlet. In the technique of Patent Document 1, the channel is a sealed system.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] In the technique disclosed in Patent Document 1, problems occur when air bubbles are mixed into the sealed channel during the introduction of the liquid sample. Specifically, it is as follows. When the analyte is trapped in the air bubble, the binding of the analyte and subsequent washing are inhibited by this air bubble, and the detection accuracy of the analyte decreases. Further, the technique disclosed in Patent Document 1 does not consider stirring the fluid within the channel. Therefore, there is a possibility that the binding of the analyte within the channel becomes insufficient.

[0005] One objective of this disclosure is to provide an assay apparatus and a target molecule testing method that facilitates the binding of target molecules within the channel while reducing the inhibition of target molecule binding and washing due to the introduction of air bubbles into the channel, even when binding and washing of target molecules and binding targets are performed within the channel. [Means for solving the problem]

[0006] The above objectives are achieved by a combination of features described in the independent claims, and the subordinate claims provide further advantageous specific examples of the disclosure. The reference numerals in parentheses in the claims indicate correspondences with specific means described in the embodiments described later as one aspect, and do not limit the technical scope of this disclosure.

[0007] To achieve the above objective, the assay apparatus of the present disclosure is an assay apparatus used for detecting a target molecule, and includes a pre-treatment section (100) in which the target molecule is bonded to a detection material for detecting the target molecule, and washing is performed to separate unreacted substances that were not bonded by a washing solution, as a pre-treatment for detecting the target molecule, the pre-treatment section is a place in which the bonding and washing are performed, and includes a circulation channel (105) which is a tubular channel for circulating the liquid used for bonding and washing, and a bubble removal mechanism (112, 112a, 112b, 112c, 112d, 112e, 112f) which removes or captures bubbles mixed in the liquid introduced into the circulation channel by utilizing the difference in properties between liquid and gas.

[0008] To achieve the above objective, the target molecule testing method of this disclosure is a target molecule testing method used to detect a target molecule, and includes a pretreatment step for detecting the target molecule, in which the target molecule is bonded to a detection material for detecting the target molecule, and washing is performed to separate unreacted substances that were not bonded with a washing solution, the pretreatment step includes a circulation step in which a liquid is circulated in a circulation channel (105), which is a tubular channel for circulating the liquid used for bonding and washing, and a bubble removal step in which bubbles mixed in the liquid introduced into the circulation channel are removed or captured from the liquid by a bubble removal mechanism (112, 112a, 112b, 112c, 112d, 112e, 112f) that removes or captures bubbles from the liquid by utilizing the difference in properties between liquid and gas.

[0009] With the above configuration, the binding of the target molecule to the detection material and the washing of unreacted substances, which are pretreatments for detecting the target molecule, are performed in the circulation channel. Since the circulation channel is a channel through which liquid is circulated, the target molecule and the detection material are more easily agitated by this circulation. Therefore, the opportunity for binding between the target molecule and the detection material is increased, and it becomes possible to increase the proportion of binding between the target molecule and the detection material. In addition, since the circulation channel is tubular, there is a possibility that air bubbles mixed in the liquid in the circulation channel may circulate within the circulation channel together with the target molecule and the detection material. In contrast, with the above configuration, the air bubble removal mechanism removes or captures the air bubbles from the liquid. By utilizing the difference in properties between liquid and gas, it becomes possible to separate the liquid and the air bubbles. Therefore, the air bubble removal mechanism makes it possible to remove or capture the air bubbles from the liquid. Consequently, the air bubble removal mechanism reduces the amount of time that the target molecule and the detection material remain in contact with the air bubbles, making it less likely for binding and washing to be hindered. As a result, even when binding and washing of the target molecule to the target object occurs within the flow channel, it becomes possible to facilitate the binding of the target molecule within the flow channel while reducing the inhibition of target molecule binding and washing due to the introduction of air bubbles into the flow channel. [Brief explanation of the drawing]

[0010] [Figure 1] This figure shows an example of a general configuration of an inspection system. [Figure 2] This figure shows an example of the general configuration of a cartridge. [Figure 3] This is a schematic diagram illustrating example 1 of an air trap mechanism. [Figure 4] This is a schematic diagram illustrating example 2 of an air trap mechanism. [Figure 5] This is a schematic diagram illustrating example 3 of an air trap mechanism. [Figure 6] This is a schematic diagram illustrating example 4 of the air trap mechanism. [Figure 7] This is a schematic diagram illustrating example 5 of an air trap mechanism. [Figure 8] This is a schematic diagram illustrating example 6 of an air trap mechanism. [Figure 9] This figure shows an example of a schematic configuration of the sensor area in Embodiment 1. [Figure 10] This is a schematic diagram illustrating the function of a diaphragm. [Figure 11] This flowchart shows an example of the flow of detection-related processing in a cartridge. [Figure 12] This figure shows an example of the time variation of voltage measured by a sensor chip. [Figure 13] This figure shows an example of a schematic configuration of the sensor area in Embodiment 2. [Modes for carrying out the invention]

[0011] Multiple embodiments for disclosure will be described with reference to the drawings. For the sake of clarity, in some embodiments, parts having the same function as those shown in the drawings used in previous descriptions will be denoted by the same reference numerals, and their descriptions may be omitted. For parts denoted by the same reference numerals, refer to the descriptions in other embodiments.

[0012] (Embodiment 1) <Schematic Configuration of Inspection System 1> Hereinafter, Embodiment 1 of the present disclosure will be described with reference to the drawings. The inspection system 1 shown in FIG. 1 is used for inspecting a target molecule serving as a specimen. This inspection may be simply detecting the presence of the target molecule, or may even involve quantifying the target molecule.

[0013] In the present disclosure, the target molecule to be detected refers to a target molecule for which detection is desired in a sample. A sample refers to any solution, substance, mixture, etc. that contains a plurality of molecules and may contain at least one target molecule. Various substances can be the target molecule. Examples of the target molecule include viruses, cells, antigens, proteins, sugar chains, low-molecular-weight substances, bacteria, antibodies, lipids, peptides, nucleic acids, etc. The target molecule may be a pathogen itself such as a virus or bacteria, or may be a part of the pathogen such as a protein or nucleic acid.

[0014] In the inspection system 1 of the present disclosure, a complex in which a target molecule is bound to a solid phase and a labeling substance is formed, and the inspection of the target molecule is performed based on the detection signal generated by the labeling substance. The solid phase is a member for facilitating the separation between the target molecule and non-target substances other than the target molecule. The solid phase may be referred to as a fixing member. The solid phase only needs to be able to circulate in the circulation channel 105 described later together with the liquid and can be retained in a specific region in the circulation channel 105 by utilizing the properties of the solid phase. Preferably, magnetic beads are used as the solid phase. If magnetic beads are used, they can be retained in a specific region in the circulation channel 105 by magnetic force. Hereinafter, the case where magnetic beads are used as the solid phase will be taken as an example and the description will continue. A binding element (hereinafter, the first binding element) for capturing the target molecule is fixed to the magnetic beads serving as the solid phase. This fixing may be performed by a covalent bond between the amino group of the target molecule and the carboxyl group of the magnetic beads.

[0015] The first binding element shall have reaction specificity for the target molecule. The first binding element may be an antibody or an aptamer. The antibodies mentioned here include antibody fragments and modified antibodies that are substantially equivalent in reactivity to antibodies. The aptamer may be a nucleic acid aptamer or a peptide aptamer. The nucleic acid aptamer may be a DNA aptamer or an RNA aptamer. The nucleic acid aptamer may contain artificial nucleic acids. An aptamer is a nucleic acid molecule or peptide that specifically binds to a specific molecule. In the example of this embodiment, the case of using an antibody as the first binding element will be taken as an example to continue the explanation. Hereinafter, the complex of the solid phase and the first binding element will be continued to be explained as magnetic beads with antibodies.

[0016] The labeling substance is a substance for facilitating the detection of the target molecule. By generating a detection signal, the labeling substance facilitates the detection of the target molecule to which the binding element (hereinafter, the second binding element) to which the labeling substance 50 is bound is bound. The detection signal may be any signal that can be detected by an existing sensor. The detection signal can also be referred to as a signal. Examples of the detection signal include ions, electrical signals, heat, aggregation, fluorescence, dyes, and the like. The labeling substance may be a substance that generates a detection signal by itself, or may be an enzyme, a DNAzyme, or an RNAzyme that functions as a catalyst to generate a detection signal. In this embodiment, the case where the labeling substance is an enzyme will be taken as an example to continue the explanation. In the example of this embodiment, the case of using alkaline phosphatase (ALP) as the labeling substance will be taken as an example to continue the explanation. ALP catalyzes the chemical reaction of the substrate and generates hydrogen ions as the detection signal. As the substrate, p-nitrophenyl phosphate may be used. When p-nitrophenyl phosphate and water are subjected to a hydrolysis reaction using ALP as a catalyst, p-nitrophenol, phosphate ions, and hydrogen ions are generated.

[0017] As described above, the second binding element is bound to a labeling substance that generates a detection signal. The second binding element has reaction specificity for the target molecule. The binding of the second binding element and the labeling substance can be carried out, for example, by a covalent bond. The second binding element may be an antibody or an aptamer, as described for the first binding element. In this embodiment, we will continue the explanation using the case where an aptamer is used as the second binding element. Below, the complex of the labeling substance and the second binding element will be described as an aptamer-enzyme fusion. In other words, in this embodiment, the target molecule forms a complex with the antibody-coated magnetic bead and the aptamer-enzyme fusion. The antibody-coated magnetic bead and the aptamer-enzyme fusion correspond to the detection material.

[0018] The testing system 1 includes a cartridge 10 and an assay device 20, as shown in Figure 1. The cartridge 10 is a disposable component used in POCT to perform specific tests. The configuration of the cartridge 10 will be described later. The cartridge 10 is attached to and detached from the assay device 20. The assay device 20 performs diagnoses and other operations based on the information obtained from the cartridge 10. The assay device 20 is mainly composed of a computer equipped with, for example, a processor, volatile memory, non-volatile memory, I / O, and a bus connecting these. The assay device 20 performs the aforementioned diagnostic and other operations using this computer. The assay device 20 may be equipped with a user interface such as an operation input unit and a display device. The assay device 20 may be configured to include the cartridge 10.

[0019] <Overview of Cartridge 10> Next, the schematic configuration of cartridge 10 will be explained using Figure 2. As shown in Figure 2, cartridge 10 includes a labeling material holding area 101, a washing liquid holding area 102, a waste liquid area 103, a sensor area 104, a circulation channel 105, a labeling material introduction channel 106, a washing liquid introduction channel 107, a waste liquid channel 108, a sensor channel 109, a switching valve 110, a pump 111, an air trap 112, and a magnetic unit 113. Cartridge 10 corresponds to the assay device. Alternatively, the assay device 20 including cartridge 10 may correspond to the assay device.

[0020] The labeled substance holding area 101 holds an aptamer enzyme fusion, which is a complex of the labeled substance and the second binding element. The labeled substance holding area 101 holds a predetermined amount of buffer containing the aptamer enzyme fusion. The predetermined amount is an amount that fits within the volume of the circulation channel 105, which will be described later, and can be set to any arbitrary value. As the labeled substance holding area 101, a container made of resin, for example, that has a depression for holding liquid may be used.

[0021] The washing solution holding area 102 holds the washing solution. The washing solution is a liquid used to wash away unreacted substances from the binding of the target molecule to the antibody-coated magnetic beads and the aptamer enzyme fusion. The washing solution can be a washing buffer. The washing solution holding area 102 can be a container made of resin, for example, that has a depression for holding liquid. The amount of washing solution held in the washing solution holding area 102 should be an amount that allows for multiple washes with the aforementioned specified amount of washing solution.

[0022] The waste liquid area 103 is for collecting waste liquid. The waste liquid includes liquids other than the target bead complex (hereinafter referred to as the target bead complex) after the binding of the target molecule to the antibody-attached magnetic bead. The waste liquid also includes liquids other than the sandwich complex (hereinafter referred to as the sandwich complex) after the binding of the target bead complex to the aptamer enzyme fusion. The waste liquid also includes the washing solution after washing. The waste liquid area 103 can be a container, for example, made of resin, that has a depression for collecting liquid.

[0023] The sensor area 104 performs sensing based on substances produced by the reaction between the aptamer enzyme fusion contained in the sandwich complex and the reaction solution. In this embodiment, the reaction solution contains a substrate such as p-nitrophenyl phosphate. The sensor area 104 corresponds to the sensor unit. Details of the sensor area 104 will be described later.

[0024] The circulation channel 105 is the site where the target molecule binds to the antibody-coated magnetic beads and aptamer enzyme fusion, and where unreacted substances that did not bind are washed away. The circulation channel 105 is a tubular channel through which the liquid used for binding and washing is circulated. For example, a tubular resin can be used as the circulation channel 105. In this embodiment, we will continue the explanation using the case where a silicone tube is used as the circulation channel 105.

[0025] The labeled substance introduction channel 106 is a channel for introducing a buffer containing the aptamer enzyme fusion from the labeled substance holding area 101 to the circulation channel 105. For the labeled substance introduction channel 106, for example, a tubular resin can be used. In this embodiment, the explanation will continue with an example where a silicone tube is used as the labeled substance introduction channel 106.

[0026] The cleaning fluid introduction channel 107 is a channel for introducing cleaning fluid from the cleaning fluid holding area 102 to the circulation channel 105. For the cleaning fluid introduction channel 107, for example, a tubular resin can be used. In this embodiment, the explanation will continue with an example where a silicone tube is used as the cleaning fluid introduction channel 107.

[0027] The wastewater channel 108 is a channel for discharging wastewater from the circulation channel 105 to the wastewater area 103. For the wastewater channel 108, for example, a tubular resin can be used. In this embodiment, we will continue the explanation using the case where a silicone tube is used as the wastewater channel 108.

[0028] The sensor channel 109 is a channel for exchanging liquid between the sensor area 104 and the circulation channel 105. In this embodiment, the reaction liquid is exchanged between the sensor area 104 and the circulation channel 105 through the sensor channel 109. For the sensor channel 109, for example, a tubular resin can be used. In this embodiment, the explanation will continue with an example where a silicone tube is used as the sensor channel 109.

[0029] The switching valve 110 is used to switch the opening and closing of the flow path. For example, the switching valve 110 can switch the opening and closing of the flow path by switching the compression and release of the silicone tube that serves as the flow path. The switching valve 110 may be configured to be driven according to the control of a microcontroller, IC, etc. The switching valve 110 may also be configured to be controlled from the assay device 20 via a communication path that is electrically connected when the cartridge 10 is installed in the assay device 20. The switching valve 110 includes switching valves 110a to 110h.

[0030] A switching valve 110a is provided in the cleaning fluid introduction channel 107. The switching valve 110a is provided in the region where the cleaning fluid introduction channel 107 and the circulation channel 105 are connected, for example as shown in Figure 2. The switching valve 110a is used to switch the opening and closing of the cleaning fluid introduction channel 107. A switching valve 110b is provided in the labeling substance introduction channel 106. The switching valve 110b is provided in the region where the labeling substance introduction channel 106 and the circulation channel 105 are connected, for example as shown in Figure 2. The switching valve 110b is used to switch the opening and closing of the labeling substance introduction channel 106. In this embodiment, as shown in Figure 2, the cleaning fluid introduction channel 107 and the labeling substance introduction channel 106 are connected to the circulation channel 105 through the same connection region (hereinafter referred to as the first connection region).

[0031] The switching valve 110g is provided in the sensor flow path 109. The switching valve 110g is provided in the region where the sensor flow path 109 and the circulation flow path 105 are connected, for example as shown in Figure 2. The switching valve 110g is used to switch the opening and closing of the sensor flow path 109. The switching valve 110h is provided in the waste liquid flow path 108. The switching valve 110h is provided in the region where the waste liquid flow path 108 and the circulation flow path 105 are connected, for example as shown in Figure 2. The switching valve 110h is used to switch the opening and closing of the waste liquid flow path 108. In this embodiment, as shown in Figure 2, the sensor flow path 109 and the waste liquid flow path 108 are connected to the circulation flow path 105 through the same connection region (hereinafter referred to as the second connection region).

[0032] The switching valves 110c, 110d, 110e, and 110f are provided in the circulation passage 105. In this embodiment, the switching valve 110c is provided on the first connection area side between the aforementioned first connection area and the pump 111, as shown in Figure 2, for example. In this embodiment, the switching valve 110d is provided on the first connection area side between the aforementioned first connection area and the air trap 112, as shown in Figure 2, for example. In this embodiment, the switching valve 110e is provided on the second connection area side between the aforementioned second connection area and the pump 111, as shown in Figure 2, for example. In this embodiment, the switching valve 110f is provided on the second connection area side between the aforementioned second connection area and the air trap 112, as shown in Figure 2, for example. When all of the switching valves 110c, 110d, 110e, and 110f are open, circulation of liquid in the circulation passage 105 becomes possible.

[0033] Pump 111 is used to circulate the liquid in the circulation channel 105. A ring pump, syringe pump, or the like can be used as the pump 111. When using a ring pump, the liquid in the circulation channel 105 can be circulated by sequentially shifting the position where the ring pump compresses the silicone tube of the circulation channel 105. When using a syringe pump, the liquid in the circulation channel 105 can be circulated by the piston action of the syringe pump, which sucks in and discharges the liquid. Pump 111 may also be inserted in the middle of the circulation channel 105 and circulate the liquid by sucking in and discharging it. The direction in which the pump 111 circulates the liquid in the circulation channel 105 may be unidirectional or bidirectional (reciprocating). The process of circulating the liquid in the circulation channel 105 corresponds to the circulation process. Pump 111 may be driven according to the control of, for example, a microcontroller or IC. The pump 111 may be configured to be controlled from the assay device 20 via a communication path that is electrically connected when the cartridge 10 is installed in the assay device 20.

[0034] The air trap 112 is a bubble removal mechanism that removes or captures bubbles mixed in the liquid introduced into the circulation channel 105 by utilizing the difference in properties between liquid and gas. The process of removing or capturing bubbles from the liquid using the air trap 112 corresponds to the bubble removal process. The air trap 112 and the circulation channel 105 correspond to the pre-treatment section 100 where pre-treatment for detecting target molecules is performed. The pre-treatment involves binding the target molecule with the detection material, and washing to separate unreacted substances that did not bind using a washing solution. The process of performing this pre-treatment corresponds to the pre-treatment process. A method including this circulation process and the pre-treatment process, including the bubble removal process, corresponds to a target molecule inspection method. In this embodiment, the detection material is a target bead complex and an aptamer enzyme fusion.

[0035] Examples of the air trap 112 mechanism include the following mechanism examples 1 to 6. Below, mechanism examples 1 to 6 will be explained using Figures 3 to 8. In Figures 3 to 8, Li represents the liquid flowing through the circulation channel 105, and Bu represents the bubbles. Below, the air trap 112 in mechanism example 1 will be referred to as air trap 112a. Below, the air trap 112 in mechanism example 2 will be referred to as air trap 112b. Below, the air trap 112 in mechanism example 3 will be referred to as air trap 112c. Below, the air trap 112 in mechanism example 4 will be referred to as air trap 112d. Below, the air trap 112 in mechanism example 5 will be referred to as air trap 112e. Below, the air trap 112 in mechanism example 6 will be referred to as air trap 112f. Below, when air traps 112a to 112f in mechanism examples 1 to 6 are not distinguished, they will be referred to as air trap 112.

[0036] In mechanism example 1, the air trap 112a has an outlet 1121, a recess 1122, and an inlet 1123, as shown in Figure 3. The outlet 1121 is the point where the liquid circulating in the circulation channel 105 flows out. The outlet 1121 may be part of the circulation channel 105. The recess 1122 is a place to receive and collect the liquid that has flowed out from the outlet 1121. For the recess 1122, a container made of resin, for example, with a recess for collecting liquid may be used. The inlet 1123 is a place to allow the liquid collected in the recess 1122 to flow into the circulation channel 105. The inlet 1123 may be part of the circulation channel 105.

[0037] In the air trap 112a, as shown in Figure 3, the outlet 1121 is positioned higher in height than the inlet 1123. This allows the air trap 112a to remove bubbles mixed in the liquid introduced into the circulation channel 105 by utilizing the density difference between the liquid and the bubbles. In detail, bubbles are less dense than liquid and therefore move upward in height. Consequently, bubbles mixed in the liquid introduced into the circulation channel 105 are discharged from the outlet 1121 and do not head towards the inlet 1123, but instead move upward above the liquid. As a result, bubbles mixed in the liquid introduced into the circulation channel 105 are removed from the liquid by the air trap 112a.

[0038] The air trap 112a is not limited to being provided as a single unit for each circulation channel 105. For example, multiple air traps 112a may be provided for each circulation channel 105. In other words, the air trap 112a may have one or more sets of outlet 1121, recess 1122, and inlet 1123.

[0039] In mechanism example 2, the air trap 112b is a chamber structure provided on the upper side in the height direction, where a portion of the circulation channel 105 bulges out. The air trap 112b can capture bubbles mixed in the liquid introduced into the circulation channel 105 by utilizing the density difference between the liquid and the bubbles. Further details are as follows.

[0040] Since bubbles have a lower density than liquid, they move upward in the vertical direction compared to liquid. Therefore, bubbles mixed in the liquid introduced into the circulation channel 105 move towards the air trap 112b, which has a chamber structure. As a result, bubbles mixed in the liquid introduced into the circulation channel 105 are captured in the air trap 112b and stop circulating in the circulation channel 105. The configuration of the air trap 112b is not limited to having only one air trap 112b for the circulation channel 105. For example, the configuration may include multiple air traps 112b for the circulation channel 105.

[0041] In mechanism example 3, the air trap 112c has a chamber structure in which a part of the circulation channel 105 bulges out on the upper side in the height direction, as shown in Figure 5. Furthermore, the air trap 112c has a bubble outlet 1124 on the upper side in the height direction of its chamber structure. The air trap 112c can remove bubbles mixed in the liquid introduced into the circulation channel 105 by utilizing the density difference between the liquid and the bubbles. Details are as follows.

[0042] Since bubbles have a lower density than liquid, they move upward in the vertical direction compared to liquid. Therefore, bubbles mixed in the liquid introduced into the circulation channel 105 move towards the air trap 112c, which has a chamber structure. Bubbles that move towards the air trap 112c are released out of the circulation channel 105 through the outlet 1124. In this way, bubbles mixed in the liquid introduced into the circulation channel 105 are removed by the air trap 112c. Furthermore, according to mechanism example 3, since bubbles are released from the outlet 1124 of the chamber structure, it is not necessary to continuously capture bubbles in the chamber structure. Therefore, it becomes possible to miniaturize the chamber structure. The air trap 112c is not limited to a configuration where only one is provided for the circulation channel 105. For example, the air trap 112c may also be configured to have multiple air traps 112c for the circulation channel 105.

[0043] In mechanism example 4, the air trap 112d has a chamber structure in which a part of the circulation channel 105 bulges out on the upper side in the height direction, as shown in Figure 6. In the air trap 112d, a permeable membrane 1125 is provided in the chamber structure to divide the space in the height direction. The permeable membrane 1125 has selective permeability, which prevents the liquid flowing through the circulation channel 105 from passing through but allows air bubbles to pass through. The permeable membrane 1125 may be in the form of a gel. In addition, the space in the chamber structure above the permeable membrane 1125 in the height direction is a layer of gas. The air trap 112d can capture air bubbles mixed in the liquid introduced into the circulation channel 105 by utilizing the density difference between the liquid and the air bubbles. Further details are as follows.

[0044] Since bubbles have a lower density than liquid, they move upward in the vertical direction compared to liquid. Therefore, bubbles mixed in the liquid introduced into the circulation channel 105 move towards the air trap 112d, which has a chamber structure. Bubbles that move towards the air trap 112c pass through the permeable membrane 1125 and are captured in the gas layer of the chamber structure. As a result, bubbles mixed in the liquid introduced into the circulation channel 105 are captured in the air trap 112d and stop circulating in the circulation channel 105. The configuration of the air trap 112d is not limited to having only one air trap 112d for the circulation channel 105. For example, multiple air traps 112d may be provided for the circulation channel 105. Furthermore, the mechanism example 4 and mechanism example 3 may be combined. In other words, an outlet for bubbles may be provided on the upper side in the vertical direction of the chamber structure of the air trap 112d.

[0045] In mechanism example 5, the air trap 112e is a plurality of columnar structures with uneven surfaces, installed inside the circulation channel 105, as shown in Figure 7. The columnar structures can be installed so as to protrude from the inner wall of the circulation channel 105. The air trap 112e can capture bubbles mixed in the liquid introduced into the circulation channel 105 by utilizing the difference in properties between the liquid and the bubbles. Further details are as follows.

[0046] Surface tension is generated on the columnar structures provided inside the circulation channel 105 by the liquid flowing through the circulation channel 105. Since the surface of the liquid has the property of trapping gas molecules, it becomes possible to trap bubbles due to the surface tension generated on the columnar structures. Furthermore, in mechanism example 5, the surface of the columnar structures has irregularities, which makes it easier to generate surface tension. In addition, in mechanism example 5, multiple columnar structures are provided, making it easier to trap more bubbles. It is preferable that the surface irregularities of the columnar structures consist of multiple fine irregularities to facilitate the generation of surface tension. It is also preferable that multiple columnar structures are provided within a predetermined range so that they are not too far apart from each other. This makes it easier for bubbles to remain trapped by the columnar structures as they are sandwiched and trapped between multiple columnar structures. The predetermined range can be set arbitrarily.

[0047] In mechanism example 6, as shown in Figure 8, the circulation channel 105 is assumed to be at least partially arc-shaped. In mechanism example 6, as shown in Figure 8, the air trap 112f is a chamber structure provided on the outer circumference of the arc-shaped portion of the circulation channel 105, with a part of the circulation channel 105 bulging outwards. The air trap 112f can remove bubbles mixed in the liquid introduced into the circulation channel 105 by utilizing the density difference between the liquid and the bubbles. Further details are as follows.

[0048] In the arc-shaped portion of the circulation channel 105, a centrifugal force is generated in the flowing fluid, directed toward the outer periphery. Furthermore, bubbles, which have a lower density than the liquid, are pressed toward this outer periphery by the centrifugal force generated in the liquid and are captured by the chamber structure of mechanism example 6. As a result, bubbles mixed in the liquid introduced into the circulation channel 105 are captured by the air trap 112f and cease to circulate in the circulation channel 105. The configuration of the air trap 112f is not limited to having only one air trap 112f for the circulation channel 105. For example, multiple air traps 112f may be provided for the circulation channel 105.

[0049] Returning to Figure 2, the magnetic force unit 113 holds the antibody-coated magnetic beads in the liquid flowing through the circulation channel 105 in a specific region of the circulation channel 105 by magnetic force. The magnetic force unit 113 can be installed outside the circulation channel 105, near a specific region of the circulation channel 105. The specific region can be arbitrarily set. For example, the specific region could be between the second connection region and the pump 111. In the following explanation, we will continue using the example where the specific region is between the second connection region and the pump 111. The magnetic force unit 113 can hold or release the antibody-coated magnetic beads in a specific region of the circulation channel 105 by, for example, moving a magnet closer to or further away from the circulation channel 105. In this case, the drive device can be configured to switch the distance between the circulation channel 105 and the magnet. Alternatively, the magnetic force unit 113 can hold or release the antibody-coated magnetic beads in a specific region of the circulation channel 105 by, for example, generating or dissipating magnetic force in an electromagnet. In this case, the magnetism in the electromagnet can be generated or dissipated by turning the electric current through it. The magnetic force unit 113 may be configured to be driven according to the control of, for example, a microcontroller or IC. The magnetic force unit 113 may also be configured to be controlled from the assay device 20 via a communication path that is electrically connected when the cartridge 10 is mounted on the assay device 20.

[0050] Next, the schematic configuration of the sensor area 104 in this embodiment will be described using Figure 9. As shown in Figure 3, the sensor area 104 in this embodiment includes a sensor chip 141, a sensor container 142, and a diaphragm 143.

[0051] The sensor chip 141 performs sensing based on the substance produced by the reaction between the aptamer enzyme fusion contained in the sandwich complex and the reaction solution. Specifically, it performs sensing based on the substance produced by the reaction between the enzyme in this aptamer enzyme fusion and the reaction solution. The sensor chip 141 corresponds to the sensor. In this embodiment, sensing is performed based on hydrogen ions as a detection signal produced by the reaction between ALP and p-nitrophenyl phosphate. As the sensor chip 141, a hydrogen ion sensor for measuring the concentration of these hydrogen ions may be used. As the hydrogen ion sensor, a semiconductor sensor that detects hydrogen ions using a metal oxide semiconductor may be used. The sensing result from the sensor chip 141 can be transmitted to the assay device 20 via a communication path that is electrically connected when the cartridge 10 is attached to the assay device 20. The hydrogen ion sensor obtains a voltage corresponding to the hydrogen ion concentration as the sensing result. The assay device 20 may detect the presence of the target molecule from the sensing result from the sensor chip 141, or it may even perform quantitative analysis of the target molecule.

[0052] By testing a sample in which the presence or absence of a target molecule is uncertain using the testing system 1, it becomes possible to determine whether or not the target molecule is present in the sample. For example, if the target molecule is a pathogen or a part thereof, it becomes possible to determine whether or not the pathogen is present in the sample. This makes it suitable for use in testing whether or not a pathogen has infected the human body.

[0053] The sensor container 142 is a container in which the sensor chip 141 is provided. The sensor container 142 can be any container, for example, made of resin, that has a recess for holding liquid. As shown in Figure 3, the sensor container 142 holds the reaction liquid RL. The sensor chip 141 is provided in the sensor container 142 so as to be immersed in the reaction liquid RL. Specifically, as shown in Figure 3, it is provided on the lower side of the sensor container 142 in the height direction. As shown in Figure 3, the sensor container 142 is connected to the sensor channel 109, allowing the reaction liquid RL to be added to and removed from the circulation channel 105 via the sensor channel 109. As shown in Figure 3, the sensor container 142 has an opening on the upper side in the height direction.

[0054] The diaphragm 143 is provided to close the upper opening of the sensor container 142 as described above. The diaphragm 143 is an insertion and removal mechanism that moves the reaction liquid RL sealed in the sensor container 142 into and out of the circulation channel 105. The diaphragm 143 moves the reaction liquid RL sealed in the sensor container 142 into and out of the circulation channel 105 via the sensor channel 109. This draws the sandwich composite obtained by the aforementioned bonding and washing from inside the circulation channel 105 into the sensor container 142. The process of inserting and removing the reaction liquid RL by the insertion and removal mechanism and the accompanying drawing in of the sandwich composite corresponds to the insertion and removal process. The diaphragm 143 is an elastic membrane and may be made of metal or non-metal. With the above configuration, by moving the reaction liquid RL into and out of the circulation channel 105, the object to be detected can be brought from the circulation channel 105 into the sensor container 142. Therefore, there is no need to use a separate transport liquid to bring the object to be detected into the sensor container 142. As a result, the reaction solution RL is not diluted by the transport liquid, and a decrease in the detection sensitivity of the target can be prevented. The diaphragm 143 may be driven by hydraulics or by electric power. The diaphragm 143 may be configured to be driven according to the control of a microcontroller, IC, etc. The diaphragm 143 may also be configured to be controlled from the assay device 20 via a communication path that is electrically connected when the cartridge 10 is installed in the assay device 20.

[0055] Here, the function of the diaphragm 143 will be explained using Figure 10. In Figure 10, the switching valves 110e and 110g are omitted for simplification. In Figure 10, Co represents the sandwich composite. Figure 10 shows the flow of the reaction liquid RL in response to the change in the diaphragm 143. In the state before the change in the diaphragm 143, the sandwich composite Co is held in a specific region within the circulation channel 105 by the magnetic force of the magnetic force unit 113. This sandwich composite Co is assumed to be in the state after the aforementioned bonding and cleaning have been completed. Hereafter, the process in which the diaphragm 143 is pushed downward in the height direction will be called the discharge process. Also below, the process in which the diaphragm 143 is pulled upward in the height direction will be called the suction process.

[0056] First, as shown in Figure 10, during the discharge process, the diaphragm 143 bends downward, causing the pressure inside the sensor container 142 to rise. This causes the reaction liquid RL sealed inside the sensor container 142 to flow out into the sensor channel 109. This flow of reaction liquid RL reaches the region in the circulation channel 105 where the sandwich composite Co is held, via the sensor channel 109. During the discharge process, the switching valves 110e and 110g are assumed to be open. The magnetic force holding the sandwich composite Co by the magnetic force unit 113 can be released when moving to the next suction process.

[0057] Next, as shown in Figure 10, during the suction process, the diaphragm 143 flexes upward, causing the pressure inside the sensor container 142 to decrease. As a result, the reaction liquid RL that had been flowing out of the sensor container 142 to the circulation channel 105 is drawn back into the sensor container 142. At this time, the sandwich complex Co is also drawn into the sensor container 142 from the circulation channel 105, along with the reaction liquid RL. Then, inside the sensor container 142, the sensor chip 141 performs sensing based on the substances produced by the reaction between the enzyme in the sandwich complex Co and the reaction liquid RL.

[0058] Preferably, the volume of the sensor container 142 changes in accordance with the change in the amount of reaction liquid remaining in the sensor container 142 when the reaction liquid sealed inside the sensor container 142 is moved in and out of the circulation channel 105. This makes it possible to quickly suppress pressure fluctuations inside the sensor container 142 and reduce noise such as the intrusion of external air due to negative pressure. Such a configuration can be realized by using a diaphragm 143 as the in and out mechanism.

[0059] In this embodiment, the use of a diaphragm 143 as the insertion / removal mechanism is given as an example, but it is not necessarily limited to this. For example, a syringe may be used as the insertion / removal mechanism. Even when a syringe is used, it is possible to change the volume of the sensor container 142 in accordance with the change in the amount of reaction liquid remaining in the sensor container 142.

[0060] <Detection-related processing in cartridge 10> Next, an example of the flow of processing related to the detection of target molecules in cartridge 10 (hereinafter referred to as detection-related processing) will be explained using the flowchart in Figure 11. The flowchart in Figure 11 should be started, for example, when a sample potentially containing target molecules and antibody-coated magnetic beads (hereinafter referred to as the mixed solution) are delivered into the circulation channel 105. When the mixed solution is delivered into the circulation channel 105, the switching valves 110c, 110d, 110e, and 110f are assumed to be open, and the switching valves 110a, 110b, 110g, and 110h are assumed to be closed. The flowchart in Figure 11 will continue the explanation using the case where target molecules are present in the sample as an example. The amount of the mixed solution should be adjusted by adding buffer, etc., so that it reaches the specified amount as described above. The mixed solution can be introduced into the circulation channel 105 from the inlet provided in the circulation channel 105. The air trap 112 may be used as the inlet. In this case, for example, as in mechanism example 3, an air trap 112 can be used to introduce liquid into the circulation channel 105 from outside the circulation channel 105.

[0061] The flowchart in Figure 11 may also include, for example, the acceptance of an input to start the test in the assay device 20 as a start condition. In the following explanation, we will continue assuming that the assay device 20 controls the drive-controlled component of the cartridge 10. In the flowchart in Figure 11, we will continue the explanation assuming that the measurement of sensor drift has already started in the sensor area 104 where the reaction solution is sealed.

[0062] First, in step S1, the pump 111 is driven to circulate the mixture in the circulation channel 105. During this circulation, the target molecules contained in the sample bind to the antibody-coated magnetic beads. This binding causes the target molecules and antibody-coated magnetic beads to form a target bead complex. In S1, the switching valves 110c, 110d, 110e, and 110f are open, while the switching valves 110a, 110b, 110g, and 110h are closed.

[0063] In step S2, the magnetic force of the magnetic force unit 113 holds the antibody-coated magnetic beads in a specific region of the circulation channel 105. As a result, the target bead complex, including the antibody-coated magnetic beads, is also held in the specific region of the circulation channel 105. Then, in S2, the mixture is discharged as waste liquid to the waste liquid area 103 via the waste liquid channel 108. Since the target bead complex is held in a specific region of the circulation channel 105 by magnetic force, the discharged mixture does not contain the target bead complex. When discharging the mixture to the waste liquid area 103, the switching valve 110h is opened. After discharge, the switching valve 110h is closed. Discharging the mixture to the waste liquid area 103 can be done by driving the pump 111.

[0064] In step S3, the cleaning fluid is sent from the cleaning fluid holding area 102 to the circulation channel 105 via the cleaning fluid introduction channel 107. When the cleaning fluid is sent, the switching valve 110a is opened. After the fluid has been sent, the switching valve 110a is closed. The cleaning fluid can be sent to the circulation channel 105 by driving the pump 111. The amount of cleaning fluid sent to the circulation channel 105 should be the specified amount as described above. The amount of cleaning fluid sent to the circulation channel 105 can be adjusted, for example, by the timing of opening and closing the switching valve 110a.

[0065] In step S4, the cleaning solution is circulated in the circulation channel 105 by driving the pump 111. This circulation cleans the target bead complex and separates unreacted substances that do not form the target bead complex from it. Cleaning may be performed after releasing the magnetic hold of the target bead complex by the magnetic unit 113. Alternatively, cleaning may be performed while the magnetic hold of the target bead complex by the magnetic unit 113 continues. In S4, the switching valves 110c, 110d, 110e, and 110f are open, and the switching valves 110a, 110b, 110g, and 110h are closed.

[0066] In step S5, the magnetic force of the magnetic force unit 113 holds the target bead complex in a specific region of the circulation channel 105. Then, in S5, the cleaning liquid used for cleaning is discharged as waste liquid to the waste liquid area 103 via the waste liquid channel 108. Since the target bead complex is held in a specific region of the circulation channel 105 by magnetic force, the target bead complex is not included in the discharged cleaning liquid. When the cleaning liquid is discharged to the waste liquid area 103, the switching valve 110h is opened. After discharge, the switching valve 110h is closed. Discharge of the cleaning liquid to the waste liquid area 103 can be done by driving the pump 111.

[0067] In step S6, a buffer containing the aptamer enzyme fusion (hereinafter referred to as aptamer enzyme solution) is delivered from the labeled substance holding area 101 to the circulation channel 105 via the labeled substance introduction channel 106. The target bead complex is held in the circulation channel 105 through which the aptamer enzyme solution is delivered by the magnetic force of the magnetic force unit 113. The amount of aptamer enzyme solution is the predetermined amount as described above. When delivering the aptamer enzyme solution, the switching valve 110b is opened. After delivery, the switching valve 110b is closed. The delivery of the aptamer enzyme solution to the circulation channel 105 can be done by driving the pump 111.

[0068] In step S7, the pump 111 is driven to circulate the aptamer enzyme solution and the target bead complex within the circulation channel 105. This circulation is performed after releasing the magnetic hold of the target bead complex by the magnetic force of the magnetic unit 113. During this circulation, the aptamer enzyme fusion and the target bead complex bind together. This binding creates a sandwich complex between the aptamer enzyme fusion and the target bead complex. In S7, the switching valves 110c, 110d, 110e, and 110f are open, while the switching valves 110a, 110b, 110g, and 110h are closed.

[0069] In step S8, the magnetic force of the magnetic unit 113 holds the antibody-coated magnetic beads in a specific region of the circulation channel 105. This also holds the sandwich complex containing the antibody-coated magnetic beads in the specific region of the circulation channel 105. Then, in S8, the aptamer enzyme solution is discharged as waste liquid to the waste liquid area 103 via the waste liquid channel 108. Since the sandwich complex is held in a specific region of the circulation channel 105 by magnetic force, the discharged aptamer enzyme solution does not contain the sandwich complex. When discharging the aptamer enzyme solution to the waste liquid area 103, the switching valve 110h is opened. After discharge, the switching valve 110h is closed. Discharging the aptamer enzyme solution to the waste liquid area 103 can be done by driving the pump 111.

[0070] In step S9, the cleaning solution is sent from the cleaning solution holding area 102 to the circulation channel 105 via the cleaning solution introduction channel 107, similar to S4. In step S10, the cleaning solution is circulated in the circulation channel 105 by driving the pump 111, similar to S5. This circulation cleans the sandwich complex and separates unreacted substances that do not form the sandwich complex from it. In step S11, the magnetic force of the magnetic force unit 113 holds the sandwich complex in a specific region of the circulation channel 105. Then, in S11, the cleaning solution used for cleaning is discharged as waste liquid to the waste liquid area 103 via the waste liquid channel 108. Since the sandwich complex is held in a specific region of the circulation channel 105 by magnetic force, the discharged cleaning solution does not contain the sandwich complex.

[0071] In step S12, if the sandwich complex has been washed two or more times (YES in S12), proceed to step S13. On the other hand, if the sandwich complex has been washed less than two times (NO in S12), proceed to S9 and repeat the process.

[0072] In step S13, the diaphragm 143 is driven to move the reaction liquid sealed in the sensor container 142 into and out of the circulation channel 105. In S13, the switching valve 110g is opened and the switching valve 110h is closed. In S13, the diaphragm 143 is driven in the order of the discharge step and the suction step described above. In the discharge step, the reaction liquid sealed in the sensor container 142 is sent via the sensor channel 109 to the area in the circulation channel 105 where the sandwich complex is held. In the suction step, the magnetic force holding the sandwich complex by the magnetic force of the magnetic force unit 113 is released. Then, the reaction liquid that had flowed out from the sensor container 142 to the circulation channel 105 is sucked back into the sensor container 142. At this time, the sandwich complex is also sucked into the sensor container 142 along with the reaction liquid.

[0073] In step S14, the sensor chip 141 performs sensing based on the substance produced by the reaction between the enzyme contained in the sandwich complex and the reaction solution. In this embodiment, the voltage corresponding to the concentration of hydrogen ions generated by the hydrolysis reaction of p-nitrophenyl phosphate and water using ALP as a catalyst is sensed. In S14, the sensor chip 141 should output the ratio of the voltage measured by sensor drift as the sensing result (see Figure 12). Figure 12 is a diagram showing an example of the time change of the voltage measured by the sensor chip 141. As shown in Figure 12, the voltage is also measured during the sensor drift stage. Therefore, the sensor chip 141 improves the measurement accuracy by outputting the ratio of the voltage measured by sensor drift as the sensing result. The assay device 20 can then quantify the target molecule from the sensing result of the sensor chip 141.

[0074] The flowchart in Figure 11 shows an example configuration where cleaning in S4 is performed only once, but this is not necessarily the only configuration. For example, a configuration in which cleaning is repeated multiple times, similar to the cleaning in S10, is also possible.

[0075] <Summary of Embodiment 1> According to the configuration of Embodiment 1, the binding of the target molecule to the target bead complex and aptamer enzyme fusion, and the washing of unreacted substances, are performed in the circulation channel 105. Since the liquid is circulated in the circulation channel 105, the target molecule, target bead complex, and aptamer enzyme fusion are more easily agitated in the circulation channel 105. Therefore, the opportunity for binding of the target molecule to the target bead complex and aptamer enzyme fusion is increased. Consequently, it becomes possible to increase the proportion of binding between the target molecule and the target bead complex and aptamer enzyme fusion. The circulation channel 105 is tubular, and air bubbles mixed in the liquid within the circulation channel 105 may circulate within the circulation channel 105 together with the target molecule, target bead complex, and aptamer enzyme fusion. In contrast, according to the configuration of Embodiment 1, it is possible to remove or capture air bubbles from the liquid using the air trap 112. Therefore, the air trap 112 reduces the amount of time that the target molecule, target bead complex, and aptamer enzyme fusion remain in contact with air bubbles, thus reducing the likelihood of inhibition of binding and washing. As a result, even when binding and washing of the target molecule and its binding target are performed within the flow channel, it becomes possible to facilitate the binding of the target molecule within the flow channel while reducing the inhibition of target molecule binding and washing due to the introduction of air bubbles into the flow channel.

[0076] (Embodiment 2) Embodiment 1 shows a configuration in which an insertion / removal mechanism is used in the sensor area 104, but it is not necessarily limited to this. For example, the configuration of Embodiment 2 below may also be used. Below, an example of the configuration of Embodiment 2 will be described with reference to a figure. The inspection system 1 of Embodiment 2 is the same as the inspection system 1 of Embodiment 1, except that the cartridge 10 has a sensor area 114 instead of a sensor area 104.

[0077] The sensor area 114 is similar to the sensor area 104 of Embodiment 1, except for a few differences. These differences will be explained below. An example of the schematic configuration of the sensor area 114 will be explained using Figure 13. As shown in Figure 13, the sensor area 114 includes a flow path 1141, a sensor chip 1142, and a magnetic force unit 1143.

[0078] The flow path 1141 is a flow path in which the sensor chip 1142 is provided. For the flow path 1141, for example, a tubular resin can be used. For the flow path 1141, a silicone tube can be used. The flow path 1141 can be made into a loop shape, for example, so that the liquid flowing in from the sensor flow path 109 returns to the sensor flow path 109. In addition, a container for holding the reaction liquid as described in Embodiment 1 (hereinafter referred to as the reaction liquid holding container) can be connected to the flow path 1141. The connection between the reaction liquid holding container and the flow path 1141 can be switched by a valve similar to the switching valve 110.

[0079] The sensor chip 1142 performs sensing in the same manner as the sensor chip 141 in Embodiment 1. The sensor chip 1142 is provided within the flow channel 1141. The magnetic force unit 1143 holds the antibody-coated magnetic beads in the liquid flowing through the flow channel 1141 near the sensor chip 1142 within the flow channel 1141 using magnetic force. The magnetic force unit 1143 may be provided outside the flow channel 1141, near the sensor chip 1142. The magnetic force unit 1143 may hold and release the antibody-coated magnetic beads in the same manner as the magnetic force unit 113.

[0080] In Embodiment 2, instead of the process at S13 in the flowchart of Figure 11 of Embodiment 1, the following process may be performed, for example. First, the transport liquid is sent from the circulation channel 105 to the channel 1141 via the sensor channel 109. For the transport liquid, for example, the cleaning liquid from the cleaning liquid holding area 102 may be used. This transport is performed after releasing the magnetic force holding of the sandwich composite by the magnetic force unit 113. In addition, during this transport, the magnetic force unit 1143 holds the sandwich composite near the sensor chip 1142 in the channel 1141. Co in Figure 13 indicates the sandwich composite held near the sensor chip 1142.

[0081] Next, the reaction liquid is transferred from the reaction liquid holding container to the flow path 1141. This transfer is performed after releasing the magnetic force holding the sandwich complex by the magnetic force unit 113. This transfer of the reaction liquid (see RL in Figure 13) sends the transport liquid out of the flow path 1141 and replaces the liquid near the sensor chip 1142 with the reaction liquid. Then, within the flow path 1141, the sensor chip 1142 performs sensing based on the substance produced by the reaction between the enzyme contained in the sandwich complex Co and the reaction liquid RL. The transport liquid sent out of the flow path 1141 can be discharged to the waste liquid area 103 via, for example, the sensor flow path 109 and the waste liquid flow path 108. In this case, the switching valves 110e and 110f should be closed and the switching valves 110g and 110h should be opened.

[0082] (Embodiment 3) In the embodiment described above, a configuration using a cartridge 10 that can be attached to and detached from the assay device 20 was shown, but the invention is not necessarily limited to this. For example, the assay device 20 may perform the functions that the cartridge 10 provides. Alternatively, the assay device 20 may perform some of the functions that the cartridge 10 provides. For example, the assay device 20 may perform the functions of the sensor areas 104 and 114 instead of the cartridge 10.

[0083] (Disclosed technical ideas) This specification discloses several technical concepts, as set forth in the following paragraphs. Some paragraphs may be written in a multiple dependent form, where subsequent paragraphs alternately refer to preceding paragraphs. Furthermore, some paragraphs may be written in a multiple dependent form, referring to other multiple dependent forms. These paragraphs written in multiple dependent forms define several technical concepts.

[0084] (Technical thought 1) An assay device used to detect target molecules, The system includes a pre-treatment (100) in which the target molecule is bonded to a detection material for detecting the target molecule, and any unreacted substances that were not bonded are separated by a washing solution. The aforementioned pre-processing unit, The place where the coupling and cleaning are performed includes a circulation channel (105), which is a tubular channel for circulating the liquid used for the coupling and cleaning, An assay apparatus comprising a bubble removal mechanism (112, 112a, 112b, 112c, 112d, 112e, 112f) that removes or captures bubbles mixed in the liquid introduced into the circulation channel by utilizing the difference in properties between the liquid and the gas.

[0085] (Technical thought 2) The assay apparatus described in Technical Concept 1, A sensor (141) that performs sensing based on a substance produced by the reaction between the aforementioned detection material and the reaction liquid, The sensor unit (104) includes a sensor container (142) which is a container on which the aforementioned sensor is provided, The aforementioned sensor unit is The sensor container is equipped with an inlet / outlet mechanism (143) for inletting and outleting the reaction liquid sealed in the sensor container into the circulation channel, The aforementioned inlet / outlet mechanism is an assay apparatus that draws the composite of the target molecule and the detection material, obtained by the coupling and after washing, from the circulation channel into the sensor container by moving the reaction liquid sealed in the sensor container in and out of the circulation channel.

[0086] (Technical Thought 3) The assay apparatus described in Technical Concept 2, The sensor container is an assay apparatus in which the volume of the sensor container changes in accordance with the change in the amount of reaction liquid remaining in the sensor container when the reaction liquid sealed in the sensor container is moved in and out of the circulation channel by the insertion and removal mechanism.

[0087] (Technical Thought 4) An assay apparatus according to any one of the technical ideas described in items 1 to 3, The bubble removal mechanism (112a) has one or more sets of outlets (1121) from which the liquid circulating in the circulation channel flows out, recesses (1122) that receive and collect the liquid flowing out from the outlets, and inlets (1123) that allow the liquid collected in the recesses to flow into the circulation channel. An assay apparatus in which, in the set of the outlet, the recess, and the inlet, the outlet is provided above the inlet in the height direction.

[0088] (Technical Thought 5) An assay apparatus according to any one of the technical ideas described in items 1 to 3, The aforementioned circulation channel is at least partially curved, The bubble removal mechanism (112f) is an assay apparatus having a chamber structure in which a part of the circulation channel is provided as an bulge on the outer circumference of the arc-shaped portion of the circulation channel.

[0089] (Technical Thought 6) An assay apparatus according to any one of the technical ideas described in items 1 to 3, The bubble removal mechanism (112e) is an assay apparatus comprising a plurality of columnar structures having irregularities on their surfaces, provided inside the circulation channel.

[0090] (Technical Thought 7) An assay apparatus according to any one of the technical ideas described in items 1 to 3, The aforementioned bubble removal mechanism (112b, 112c, 112d) is an assay apparatus having a chamber structure in which a part of the circulation channel is provided as an inflation on the upper side in the height direction.

[0091] (Technical Thought 8) The assay apparatus described in Technical Concept 7, An assay apparatus having a bubble vent (1124) on the upper side in the height direction of the chamber structure.

[0092] (Technical Thought 9) An assay apparatus as described in Technical Idea 7 or 8, The assay apparatus is provided with a chamber structure that divides the space in the height direction by a permeable membrane (1125) having selective permeability that prevents the liquid from passing through but allows the bubbles to pass through, wherein the space in the chamber structure above the permeable membrane in the height direction is a layer of gas.

[0093] This disclosure is not limited to the embodiments described above, and various modifications are possible within the scope of the claims. Embodiments obtained by appropriately combining the technical means disclosed in different embodiments are also included in the technical scope of this disclosure. [Explanation of Symbols]

[0094] 1 Inspection system, 10 Cartridge (assay device), 20 Assay device, 100 Pre-processing section, 104 Sensor area (sensor section), 105 Circulation channel, 112, 112a, 112b, 112c, 112d, 112e, 112f Air trap (bubble removal mechanism), 141 Sensor tip (sensor), 142 Sensor container, 143 Diaphragm (insertion / removal mechanism), 1121 Outlet, 1122 Recess, 1123 Inlet, 1124 Outlet, 1125 Permeable membrane

Claims

1. An assay device used to detect target molecules, The system includes a pre-treatment (100) in which the target molecule is bonded to a detection material for detecting the target molecule, and any unreacted substances that were not bonded are separated by a washing solution. The aforementioned pre-processing unit, The place where the coupling and cleaning are performed includes a circulation channel (105), which is a tubular channel for circulating the liquid used for the coupling and cleaning, An assay apparatus comprising a bubble removal mechanism (112, 112a, 112b, 112c, 112d, 112e, 112f) that removes or captures bubbles mixed in the liquid introduced into the circulation channel from the liquid by utilizing the difference in properties between the liquid and the gas.

2. The assay apparatus according to claim 1, A sensor (141) that performs sensing based on a substance produced by the reaction between the detection material and the reaction solution, The sensor unit (104) includes a sensor container (142) which is a container on which the aforementioned sensor is provided, The aforementioned sensor unit is The sensor container is equipped with an inlet / outlet mechanism (143) for inletting and outleting the reaction liquid sealed in the sensor container into the circulation channel, The aforementioned inlet / outlet mechanism is an assay apparatus that draws the composite of the target molecule and the detection material, obtained by the coupling and after washing, from the circulation channel into the sensor container by moving the reaction liquid sealed in the sensor container in and out of the circulation channel.

3. The assay apparatus according to claim 2, The sensor container is an assay apparatus in which the volume of the sensor container changes in accordance with the change in the amount of reaction liquid remaining in the sensor container when the reaction liquid sealed in the sensor container is moved in and out of the circulation channel by the insertion and removal mechanism.

4. An assay apparatus according to any one of claims 1 to 3, The bubble removal mechanism (112a) has one or more sets of outlets (1121) from which the liquid circulating in the circulation channel flows out, recesses (1122) for receiving and accumulating the liquid flowing out from the outlets, and inlets (1123) for allowing the liquid accumulated in the recesses to flow into the circulation channel. An assay apparatus in which, in the set of the outlet, the recess, and the inlet, the outlet is provided above the inlet in the height direction.

5. An assay apparatus according to any one of claims 1 to 3, The aforementioned circulation channel is at least partially curved, The bubble removal mechanism (112f) is an assay apparatus having a chamber structure in which a part of the circulation channel is provided as a bulge on the outer circumference of the arc-shaped portion of the circulation channel.

6. An assay apparatus according to any one of claims 1 to 3, The bubble removal mechanism (112e) is an assay apparatus comprising a plurality of columnar structures having irregularities on their surfaces, provided inside the circulation channel.

7. An assay apparatus according to any one of claims 1 to 3, The assay apparatus is a chamber structure in which the bubble removal mechanism (112b, 112c, 112d) is provided with a portion of the circulation channel bulging upwards in the height direction.

8. The assay apparatus according to claim 7, An assay apparatus having a bubble vent (1124) on the upper side in the height direction of the chamber structure.

9. The assay apparatus according to claim 7, The assay apparatus is provided with a chamber structure that divides the space in the height direction, having a permeable membrane (1125) that is impermeable to the liquid but permeable to the bubbles, and the space in the chamber structure above the permeable membrane in the height direction is a layer of gas.

10. A target molecule testing method used to detect a target molecule, The process includes a pretreatment step for detecting the target molecule, in which the target molecule is bonded to a detection material for detecting the target molecule, and any unreacted substances that were not bonded are separated by a washing solution. The aforementioned pretreatment step includes: In the place where the coupling and cleaning are performed, in a circulation channel (105) which is a tubular channel for circulating the liquid used for coupling and cleaning, a circulation step of circulating the liquid is performed. A method for inspecting target molecules, comprising a bubble removal step of removing or capturing bubbles mixed in the liquid introduced into the circulation channel by a bubble removal mechanism (112, 112a, 112b, 112c, 112d, 112e, 112f) that removes or captures bubbles from the liquid by utilizing the difference in properties between the liquid and the gas.

11. A method for testing a target molecule according to claim 10, A method for inspecting a target molecule, comprising a sensor unit (104) comprising a sensor (141) that performs sensing based on a substance produced by a reaction between the detection material and a reaction liquid, a sensor container (142) which is a container in which the sensor is provided, and an inlet / outlet mechanism (143) that inlets and outlets the reaction liquid sealed in the sensor container into the circulation channel, wherein the inlet / outlet mechanism of the sensor unit (104) is used to inlet and outlet the reaction liquid sealed in the sensor container into the circulation channel, thereby drawing the composite of the target molecule and the detection material after washing, obtained by the bonding, from the circulation channel into the sensor container.

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