Cassette for protein or antibody chips, and testing apparatus using the cassette.

Abstract

To provide cassettes, etc., for protein or antibody chips that are easy to operate and highly reproducible. [Solution] The cassette for protein or antibody chips of the present disclosure comprises at least a storage chamber for storing the chip, a detection reagent inlet, a washing solution inlet, and a test sample inlet. The cassette further comprises a test sample preparation chamber, a flow path for transporting the test sample from the test sample inlet to the test sample preparation chamber by capillary action, and an on / off valve.

Description

Technical Field

[0006] , ,

[0001] The present invention relates to a cassette for a protein or antibody chip, and an inspection device using the cassette.

Background Art

[0002] In recent years, as a measuring device for measuring proteins or antibodies in a sample, development of a measuring device using a chip (substrate) such as a microarray chip has been underway. In the measuring device, a single or plural proteins (antigens) or antibodies are immobilized on the chip, and a single or plural specific substances in the sample are detected and measured. By the measuring device, for example, the presence of plural biomarkers in a sample can be measured simultaneously. Also, measurement of (plural) antibody titers in a sample is possible.

[0003] For example, Patent Document 1 discloses a cassette for a protein or antibody chip, which includes a storage chamber for storing the chip, and one or more syringes communicating with the storage chamber.

Prior Art Documents

Patent Documents

[0007] To solve the above problems, a cassette for a protein or antibody chip according to one aspect of the present invention is: A cassette for protein or antibody chips, A storage chamber for storing the above chip, A solution inlet for a chip, which is connected to the above storage chamber and allows the introduction of one or more detection reagents or cleaning solutions for chips, One or more inspection sample inlets communicating with the above storage chamber, A sample preparation chamber for mixing the diluent and the sample is located between the sample inlet and the storage chamber. The cassette comprises at least a channel that connects the above-mentioned sample inlet and the above-mentioned sample preparation chamber, and which delivers the sample from the sample inlet to the sample preparation chamber by capillary action. [Effects of the Invention]

[0008] According to one aspect of the present invention, a cassette for protein or antibody chips that is easy to operate and highly reproducible can be provided. [Brief explanation of the drawing]

[0009] [Figure 1] This is a schematic front view of a cassette for a protein or antibody chip according to Embodiment 1 of the present invention. [Figure 2] This is a schematic front view of a cassette for a protein or antibody chip according to Embodiment 2 of the present invention. [Figure 3] This is a schematic front view of a cassette for a protein or antibody chip according to Embodiment 3 of the present invention. [Figure 4] This diagram shows the mechanism by which the test sample is introduced into the storage chamber 6 when the capillary tube 127 is removable from the cassette. [Figure 5] This diagram shows the mechanism by which the test sample is introduced into the storage chamber 6 when the capillary tube 127 is pre-installed in the cassette. [Figure 6] This is a schematic front view of a cassette for a protein or antibody chip according to Embodiment 4 of the present invention. [Figure 7] This is a schematic top view of a cassette for a protein or antibody chip according to Embodiment 5 of the present invention. [Figure 8] This is a schematic front view of a cassette for a protein or antibody chip according to Embodiment 5 of the present invention. [Figure 9] This is a schematic side view of cassettes 1201 to 1206 according to one aspect of the present invention. [Figure 10] This is a schematic front view of an inspection device according to Embodiment 5 of the present invention. [Figure 11] This is a block diagram showing the main components of the inspection system of the present invention. [Modes for carrying out the invention]

[0010] [Embodiment 1] Based on Figure 1, a cassette 1 for a protein or antibody chip according to Embodiment 1 of the present invention (hereinafter sometimes simply referred to as "cassette") will be described. Figure 1 is a schematic front view of cassette 1. Cassette 1 has a roughly rectangular shape.

[0011] (Cassette 1) Cassette 1 is a cassette for detecting the target component in a test sample. Examples of test samples include liquid samples such as blood and urine. If the tip is an allergen tip as described later, the test sample is blood.

[0012] As shown in FIG. 1, the cassette 1 includes a storage chamber 6 for storing chips, solution inlets 103 to 107 for chips (a cleaning solution inlet 103, detection reagent inlets 104 to 106), a test sample inlet 107, and a drainage storage chamber 70. Each of the inlets 103 to 107 communicates with the storage chamber 6. The material of the cassette body 2 of the cassette 1 is, for example, plastic. The cassette 1 may be used as disposable or reused multiple times.

[0013] In the cassette according to Embodiment 1, each of the inlets 103 to 107 is arranged vertically above the storage chamber 6, and the drainage storage chamber 70 is arranged vertically below the storage chamber 6.

[0014] <Storage chamber 6> The storage chamber 6 includes an internal space 61 for storing chips. The storage chamber 6 is a recess formed in the front of the cassette 1 and is configured to be closed by a square lid (for example, made of translucent plastic). The chip is arranged (stored) on the bottom surface of the internal space 61 (the bottom of the storage chamber 6) with the lid open, and the lid is closed during use. The shape of the bottom surface of the storage chamber 6 is not particularly limited, but is preferably circular or elliptical from the viewpoint of good liquid drainage.

[0015] Further, an opening may be formed to penetrate the lid and communicate with the storage chamber 6 (the internal space 61 thereof). By providing the opening, for example, the tip of the syringe barrel storing a diluted test sample, a detection reagent, a cleaning solution, etc. can be inserted into the opening to introduce the diluted test sample, the detection reagent, and the cleaning solution onto the chip in the storage chamber 6. The opening may be one or plural.

[0016] <Chip> The chip stored in storage chamber 6 is described as an allergen chip with multiple allergens (antigen proteins) immobilized on it. For example, multiple types of allergens to be tested are arranged on the chip as different spots for each type of allergen. By arranging multiple types of allergens as different spots on the chip for each type of allergen, simultaneous testing of multiple items becomes possible. For example, an allergen chip may be created in which multiple types of allergens are arranged on the chip, and multiple spots are arranged for each type of allergen (microarray).

[0017] The shape of the chip is not limited as long as it is small enough to fit into the internal space 61 of the storage chamber 6, but from the viewpoint of good liquid drainage, it is preferably circular or oval in shape.

[0018] The surface of the chip may be subjected to conventional chemical treatments for substance immobilization in order to immobilize a substance (in this case, an allergen) onto the chip, or a substance immobilization agent may be pre-applied to it. Examples of substance immobilization agents include those disclosed in Japanese Patent Publication No. 4630817, Japanese Patent Publication No. 2007-302745, Japanese Patent Publication No. 2015-025788, and Japanese Patent Publication No. 2020-132803.

[0019] Although an allergen chip was used as an example of a chip, the chip may also be an antibody chip (e.g., an ELISA chip) with immobilized capture antibodies, or a protein chip (protein chip) with immobilized proteins other than allergens. For antibody chips or protein chips, it is preferable that multiple types of antibodies or proteins are arranged as different spots (microarrayed) for each type of antibody or protein, as this enables simultaneous testing of multiple items.

[0020] <Cleaning solution inlet 103> The cleaning fluid inlet 103 is an opening for introducing cleaning fluid for cleaning the tips into the storage chamber 6. The cleaning fluid inlet 103 and the storage chamber 6 are connected by flow paths 123 and 130. By opening the on / off valve 113 in the flow path 123, the cleaning fluid introduced from the cleaning fluid inlet 103 is introduced into the storage chamber 6. There may be one cleaning fluid inlet, or there may be two or more.

[0021] The cleaning fluid may be introduced into the storage chamber 6 from the cleaning fluid inlet 103 using a fluid delivery device. In this specification, a fluid delivery device refers to a device that delivers liquid by pressurization, such as a syringe or dropper, or by depressurization, such as suction, such as various fluid delivery pumps (diaphragm pumps, etc.).

[0022] When delivering liquid by pressurization using a syringe or dropper, the opening must be located in the direction of liquid flow (downstream). On the other hand, when delivering liquid by depressurization such as suction, the opening must be located in the opposite direction of liquid flow (upstream). A gas-liquid separation membrane may be present at the opening.

[0023] In order to miniaturize the cassette 1, the cleaning fluid may be introduced into the storage chamber 6 from the cleaning fluid inlet 103 by gravity without using a fluid delivery device. When introducing the cleaning fluid into the storage chamber 6 from the cleaning fluid inlet 103 by gravity, for example, the cleaning fluid may be introduced by covering the cleaning fluid inlet 103 with a seal and making a hole in the seal with a needle or the like. Hereinafter, in this specification, a seal that can be broken with a needle or the like will be referred to as a breaker seal.

[0024] <Detection reagent inlet 104~106> The detection reagent inlets 104-106 are openings for introducing detection reagents for the chips, which are used to detect the target component in the test sample, into the storage chamber 6. In Figure 1, there are three detection reagent inlets, but if only one type of detection reagent is needed, one detection reagent inlet is sufficient. If two types of detection reagents are needed, two detection reagent inlets are sufficient. For example, when using the fluorescence method, cassette 1 only needs to have one detection reagent inlet. If primary antibody, labeled secondary antibody, and chemiluminescent reagent are used as detection reagents, cassette 1 only needs to have three detection reagent inlets.

[0025] The detection reagent inlet 104 and the storage chamber 6 are connected by channels 124 and 130, the detection reagent inlet 105 and the storage chamber 6 are connected by channels 125 and 130, and the detection reagent inlet 106 and the storage chamber 6 are connected by channels 126 and 130. By opening the on / off valves 114 to 116 in channels 124 to 126, the detection reagent introduced from the detection reagent inlets 104 to 106 is introduced into the storage chamber 6.

[0026] When the on-off valves 114 to 116 are closed, the detection reagent introduced from the detection reagent inlets 104 to 106 can remain in each inlet until the on-off valves 114 to 116 are opened.

[0027] Each detection reagent may be introduced into the storage chamber 6 from the detection reagent inlet using a pressurized or aspirated liquid delivery device. Alternatively, to allow for a smaller cassette 1, each detection reagent may be introduced into the storage chamber 6 from the detection reagent inlet by gravity without using a liquid delivery device. When introducing detection reagents into the storage chamber 6 from the detection reagent inlet by gravity, a breaker seal may be provided at the detection reagent inlet.

[0028] The cassette according to Embodiment 1 is provided with an inlet for the detection reagent and an inlet for the washing solution, but the inlets for the detection reagent and the washing solution may be the same. When the detection reagent and / or washing solution are introduced into the storage chamber 6 by gravity, it is preferable to provide separate inlets for the detection reagent and the washing solution in terms of washing efficiency.

[0029] <Inspection sample inlet 107> The sample inlet 107 is an opening for introducing the sample into the storage chamber 6. Between the sample inlet 107 and the storage chamber 6, there is a sample preparation chamber 120 for storing the diluent. In this specification, when A is said to be positioned between B and C, it does not prevent the presence of other members other than A between B and C.

[0030] The sample inlet 107 and the sample preparation chamber 120 are connected by a flow path 127, and the sample preparation chamber 120 and the storage chamber 6 are connected by flow paths 129 and 130. The sample, quantitatively measured and introduced from the sample inlet 107 by capillary action, is delivered to the sample preparation chamber 120 via flow path 127. There, the sample is diluted by mixing with a diluent in the sample preparation chamber 120. Next, the diluted sample is introduced into the storage chamber 6 by opening the on / off valve 117 in flow path 129.

[0031] Examples of diluents include those used in the present art for diluents of biological samples such as blood or urine (e.g., phosphate-buffered saline (PBS) or saline). The diluent may contain an anticoagulant.

[0032] To simplify the structure of the apparatus, the diluent may be pre-stored in the sample preparation chamber 120. Alternatively, an opening may be provided in the sample preparation chamber 120, and the diluent may be stored in the sample preparation chamber 120 through this opening using a liquid delivery device. There may be one or more openings. Alternatively, a diluent storage chamber may be provided in the cassette 1 for storing the diluent, and the diluent may be delivered from the diluent storage chamber to the sample preparation chamber 120 via a flow path. Providing a diluent storage chamber makes it easier to adjust the amount of diluent. A stirring mechanism such as vibration or shaking may also be provided.

[0033] The channel 127 is configured so that the sample to be tested is introduced into the internal space of the channel by capillary action. The inner diameter of the channel 127 may be, for example, 0.1 mm or more and 3 mm or less.

[0034] It is preferable that the inner wall of the channel 127 be hydrophilic, as this facilitates the introduction of the test sample into the cassette by capillary action, and that a hydrophobic region be created at the connection point with the test sample preparation chamber 120, as this facilitates the adjustment of the amount of test sample introduced. The inner wall of the channel 127 may also be coated with an anticoagulant.

[0035] The flow path (thin tube) 127 may be located inside the cassette 1 or outside the cassette 1. Furthermore, the flow path 127 may be removable from the cassette 1 or may be pre-installed in the cassette 1.

[0036] The opening 142 in the flow path 128 allows the solutions (test samples, test reagents, washing solutions) introduced from each inlet to be delivered to the storage chamber 6. The opening 142 may be connected to an area above the storage chamber 6 by installing a pipe, and multiple openings may be installed. A gas-liquid separation membrane may be provided at the opening 142. Alternatively, the liquids may be retained in the storage chamber 6 without using a gas-liquid separation membrane. Instead of the opening 142, a suction mechanism for delivering the solutions introduced from each inlet to the storage chamber 6 may be provided in the flow path 128.

[0037] Furthermore, a liquid delivery drive mechanism (for example, a diaphragm of a diaphragm pump) may be provided in the flow path 130 to facilitate the delivery of the solution introduced from each inlet to the storage chamber 6. A stirring mechanism such as vibration or shaking may be provided to facilitate each process in the storage chamber 6.

[0038] The cassette according to Embodiment 1 allows the test sample to be introduced into the cassette without prior dilution, making operation simple. Furthermore, by introducing the test sample into the cassette without prior dilution and automatically diluting and dispensing it within the cassette, highly reproducible test results can be obtained regardless of the operator's skill level.

[0039] Cassette 1 can deliver the solution introduced through each inlet to the storage chamber 6 by gravity, pressurization, or depressurization.

[0040] In terms of miniaturizing cassette 1, at least one of the test sample, washing solution, and detection reagent may be introduced into the storage chamber by gravity without using a liquid delivery device. Alternatively, at least two of the test sample, washing solution, and detection reagent may be introduced into the storage chamber by gravity without using a liquid delivery device. Alternatively, the test sample, washing solution, and detection reagent may be introduced into the storage chamber by gravity without using a liquid delivery device.

[0041] <Drainage storage chamber 70> The drainage storage chamber 70 holds the liquid introduced into the storage chamber 6 as drainage after use (stores the drainage). The drainage storage chamber 70 is located vertically below the storage chamber 6, and the drainage storage chamber 70 and the storage chamber 6 are connected by a flow path 128. By opening the on / off valve 118 in the flow path 128, the liquid introduced into the storage chamber 6 is stored in the drainage storage chamber 70. The drainage storage chamber 70 is also in communication with the opening 170 via the flow path.

[0042] The wastewater stored in the wastewater storage chamber 70 can be absorbed by the absorbent material placed inside the wastewater storage chamber 70.

[0043] The on-off valves provided in cassette 1 can be on-off valves known in the art. For example, the on-off valves may be breaker seals, diaphragms of diaphragm valves, or actuators. It is preferable that at least one of the on-off valves 113 to 117 be a breaker seal, and more preferably that all of the on-off valves 113 to 117 be breaker seals, as this makes the cassette easier to manufacture and simplifies the structure.

[0044] The cassette 1 according to Embodiment 1 is compact and can reduce manufacturing costs. Furthermore, the cassette 1 according to Embodiment 1 can reduce the amount of test sample required. It is also easy to operate. Moreover, it can measure the target component quickly and accurately, enabling early diagnosis. In addition, the cassette 1 according to Embodiment 1 allows for the introduction of the test sample, the reaction between the reagent and the test sample, washing, and measurement of the test sample after reagent treatment, all within a single cassette.

[0045] Furthermore, when the cassette 1 according to Embodiment 1 is installed in the inspection device described later and inspection is performed, the inspection device can be made smaller.

[0046] Furthermore, a test kit including cassette 1 and a chip is also included as one embodiment of the present invention. The test kit may also include, as necessary, 1) an instruction manual for the kit, 2) detection reagents and washing solutions to be used for testing, 3) liquid delivery equipment such as a syringe and aspiration pump, 4) a breaker seal, etc. The detection reagents and washing solutions may be pre-filled in the liquid delivery equipment, or they may be filled (stored) in the liquid delivery equipment immediately before using the test kit. The chip may also be pre-stored in the storage chamber 6 of cassette 1, or it may be stored in the storage chamber 6 immediately before using the test kit.

[0047] [Embodiment 2] Next, a cassette 1 according to Embodiment 2 of the present invention will be described based on Figure 2. Figure 2 is a schematic front view of the cassette 1 according to Embodiment 2. For the sake of convenience of explanation, components having the same function as those described in the above embodiments will be denoted by the same reference numerals, and their descriptions will not be repeated.

[0048] The cassette according to Embodiment 2 differs from Embodiment 1 in that a suction channel 227 is provided downstream of the test sample preparation chamber 120, downstream of the storage chamber 6, and downstream of the drainage storage chamber 70, which communicates with a suction mechanism (not shown) located outside the cassette. The suction mechanism communicates with the opening 230.

[0049] The suction channel 227 is equipped with a switch 222. A channel 221 exists between the switch 222 and the sample preparation chamber 120. By switching the switch 222 and drawing air from the sample preparation chamber 120 via the suction channel 221 and suction channel 227 using the suction mechanism, the sample collected by capillary action and the diluent are mixed.

[0050] The suction channel 227 also includes a switch 224 via a switch 222. A channel 223 exists between switch 222 and switch 224. A channel 225 exists between switch 224 and the drain storage chamber 70. Channel 128 and switch 224 are connected by a suction channel 226. Switches 222 and 224 can be switched to draw air in through suction channels 226, 223, and 227 using a suction mechanism, thereby facilitating the introduction of the solutions introduced from each inlet 103 to 107 into the storage chamber 6.

[0051] Furthermore, by opening the on / off valve 118 and communicating with the opening 230 via the suction passages 227, 223, and 225, the liquid introduced into the storage chamber 6 is stored in the drainage storage chamber 70.

[0052] Switches 222 and 224 may be equipped with two or more on-off valves to control the airflow through each passage. Alternatively, by providing multiple suction mechanisms and switches within the inspection device 200 described later, the suction passages 221, 225, and 226 may communicate directly with the suction mechanism (not shown) rather than through the suction passage 227.

[0053] In Figure 2, a flow path 226 and an opening 142 are provided, but if a flow path 226 is provided, the opening 142 does not need to be provided. A switch, on / off valve, or gas-liquid separation membrane (not shown) may be provided at the connection point between the suction flow paths 221, 225, and 226 and 120, 70, and 128 respectively to prevent liquid from entering the suction flow path.

[0054] [Embodiment 3] Next, a cassette 1 according to Embodiment 3 of the present invention will be described based on Figure 3. Figure 3 is a schematic front view of the cassette 1 according to Embodiment 3. For the sake of convenience of explanation, components having the same function as those described in the above embodiments will be denoted by the same reference numerals, and their descriptions will not be repeated.

[0055] In the cassette according to Embodiment 3, the capillary tube 127 is inserted into the test sample inlet 107 from outside the cassette 1, which is a difference from Embodiment 1.

[0056] Another difference from Embodiment 1 is that it is equipped with a circulation channel 134 which includes on-off valves 156 and 157 and a liquid delivery mechanism (for example, the diaphragm of a diaphragm pump) 151. Both ends of the circulation channel 134 are in communication with the test sample preparation chamber 120. By driving the liquid delivery mechanism 151 provided in the circulation channel 134 and opening the on-off valves 156 and 157, mixing of the test sample and the diluent in the test sample preparation chamber 120 is promoted.

[0057] The inner wall of tube 127 is preferably more hydrophilic than the inner wall of tube 133, as this facilitates the introduction of the test sample into the cassette due to capillary action and makes it easier to adjust the amount of test sample introduced. The inner wall of tube 127 may also be coated with an anticoagulant. Even if tube 127 is removable, tube 133 in the cassette is hydrophobic. Furthermore, a hydrophobic region may be formed to quantitatively collect the test sample by capillary action. This ensures that the sample is taken up by capillary action only up to the hydrophilic surface, allowing for the collection of a fixed amount of test sample.

[0058] A certain amount of the collected test sample is sent to the test sample preparation room 120, where it is mixed with a diluent and further diluted in a circulation circuit. Then, by opening the on / off valve 117, the diluted sample is introduced into the storage room 6.

[0059] The cassette 1 according to Embodiment 3 may have an opening at the top of the drainage storage chamber 70 for draining liquid from the storage chamber 6 to the drainage storage chamber 70.

[0060] (Mechanism by which the test sample is introduced into the storage chamber) Figure 4 shows the mechanism by which the test sample is introduced into the storage chamber when the capillary tube 127 is removable from the cassette 1.

[0061] Figure 4(A) shows the state before the capillary tube 127 is inserted into the sample inlet 107.

[0062] Figure 4(B) shows a capillary tube 127 containing the quantified test sample inserted into the test sample inlet 107. After the capillary tube 127 is inserted into the test sample inlet 107, the test sample inside the capillary tube 127 is introduced into the test sample preparation chamber 120 by pressurizing or depressurizing with a liquid delivery device (not shown). Then, the test sample and the diluent in the test sample preparation chamber 120 are mixed by pressurizing or depressurizing with the liquid delivery device.

[0063] Figure 4(C) shows the state in which the test sample and diluent are mixed in the capillary tube 127. By opening the on / off valve 117, the mixture of the test sample and diluent is introduced into the lower storage chamber 6 by gravity or by suction using a suction mechanism.

[0064] Figure 5 shows the mechanism by which the test sample is introduced into the storage chamber when the capillary tube 127 is pre-attached to the cassette 1. Note that the explanation in Figure 5 describes a cassette in which a suction mechanism is connected to the test sample preparation chamber 120 via an opening 141, and in which the diluent is not pre-stored in the test sample preparation chamber 120.

[0065] Figure 5(A) shows the state before the test sample is stored in the capillary tube 127. The diluent is stored in the diluent storage chamber 160, and a flow path 136 is provided between the diluent storage chamber 160 and the test sample preparation chamber 120.

[0066] Figure 5(B) shows the sample being collected inside the capillary tube 127 by capillary action. The sample is quantitatively collected by making the inside of the tube at the connection part 111 hydrophobic. Subsequently, the sample inside the capillary tube 127 is introduced into the sample preparation chamber 120 by drawing air through the opening 141, which does not touch the liquid surface, using a suction mechanism outside the cassette. At the same time, the on / off valve 153 in the flow path 136 is opened, and the diluent in the diluent storage chamber 160 is introduced into the sample preparation chamber 120 by suction from the opening 141 using the suction mechanism outside the cassette, and mixed.

[0067] Figure 5(C) shows the state in which the test sample and diluent are mixed in the capillary tube 127. The diluted test sample 162 is stored in the test sample preparation chamber 120.

[0068] Figure 5(D) shows the state after the diluted test sample 162 has been introduced into the storage chamber 6. The on / off valve 117 is opened, and the diluted test sample 162 is delivered into the storage chamber 6 by a suction mechanism (not shown).

[0069] [Embodiment 4] Next, a cassette 1 according to Embodiment 4 of the present invention will be described based on Figure 6. Figure 6 is a schematic front view of the cassette 1 according to Embodiment 4. For the sake of convenience of explanation, components having the same function as those described in the above embodiments will be denoted by the same reference numerals, and their descriptions will not be repeated.

[0070] The cassette 1 according to Embodiment 4 differs from Embodiment 1 in that it is provided with a circulation channel 131 and an on / off valve 180 is provided in the channel 130.

[0071] The circulation channel 131 is provided to connect the channel 130 connecting the storage chamber 6 to each inlet 103-107 and the channel 128 connecting the drain storage chamber 70 to the storage chamber 6. The circulation channel 131 is also provided with on-off valves 158 and 159. Note that on-off valves 180 and 158, and on-off valves 118 and 159 may be integrated into a single switch mechanism.

[0072] By driving the liquid delivery mechanism 119 (for example, the diaphragm of a diaphragm pump) provided in the circulation channel 131, the on-off valves 158 and 159 are opened, and the on-off valves 180 and 118 are closed, thereby circulating the liquid introduced into the storage chamber 6 via the circulation channel 131. By providing the circulation channel 131, the amount of washing liquid and / or detection reagent can be reduced, and the reaction and washing process times can be shortened.

[0073] The cassette 1 according to Embodiment 4 may have an opening at the top of the drainage storage chamber 70 that does not come into contact with the liquid in the drainage storage chamber 70, in order to drain the liquid from the storage chamber 6 to the drainage storage chamber 70.

[0074] [Embodiment 5] Next, a cassette 1 according to Embodiment 5 of the present invention will be described based on Figure 7. Figure 7 is a schematic top view of the cassette 1 according to Embodiment 5. For the sake of convenience of explanation, components having the same function as those described in the above embodiments will be denoted by the same reference numerals, and their descriptions will not be repeated.

[0075] This embodiment differs from Embodiment 1 in that the syringe (liquid delivery device) 3 for the washing solution and the liquid delivery devices 4 and 5 for the detection reagent are connected to the storage chamber 6. It also differs from Embodiment 1 in that the on / off valve 117 is not provided.

[0076] Furthermore, this embodiment differs from Embodiment 1 in that an opening 62 is provided in the storage chamber 6 to introduce the solution introduced from each inlet into the storage chamber 6, while an opening 142 is not provided. A gas-liquid separation membrane may be provided at the opening 62.

[0077] In the cassette according to Embodiment 5, the test sample is introduced into the test sample preparation chamber 120 from the opening 107 using capillary action. Furthermore, for example, a suction mechanism (not shown) is connected to the flow path 129 and mixed with the diluent in the test sample preparation chamber 120, and the air in the cassette 1 is drawn in via the flow path 129, thereby introducing the test sample into the test sample preparation chamber 120.

[0078] <Syringe (liquid delivery channel) 3, 4, 5> In Figure 7, syringe 3 is a fluid delivery device for the washing solution, and syringes 4 and 5 are fluid delivery devices for the detection reagents. Syringe 3 contains a washing solution for cleaning the tip. Syringes 4 and 5 contain detection reagents for the tip, which are used to detect the target component in the test sample.

[0079] In Figure 7, the syringes of syringes 3, 4, and 5 are integrated with the cassette body 2. That is, the syringes of syringes 3, 4, and 5 are configured as holes provided in the base (cassette body 2) in which the storage chamber 6 is formed. Each syringe is formed in a direction along the y-direction of the cassette 1. Each syringe of syringe 3 is provided near opposing long end faces in the cassette 1, and each extends from right to left on the plane of Figure 7. As a result, the tips of the syringes of syringe 3 are positioned to straddle the storage chamber 6. The passage 31 extends in the y-direction to connect the tips of the syringes of syringe 3 and the internal space 61 of the storage chamber 6, and then curves in the x-direction (towards the inside of the cassette 1). The volume of syringe 3 is, for example, in the range of 0.1 mL or more and 10 mL or less.

[0080] The syringes of syringes 4 and 5 each extend inward from near the center of the same short end face in cassette 1, from left to right on the plane of the paper in Figure 7. As a result, the tips of the syringes of syringes 4 and 5 are positioned facing the storage chamber 6. The passages 41 and 51 each extend in the y-direction to connect the tips of the syringes of syringes 4 and 5 to the internal space 61 of the storage chamber 6. The volumes of syringes 4 and 5 are, for example, in the range of 0.001 mL or more and 1 mL or less.

[0081] In Figure 7, syringe 3 is positioned opposite syringes 4 and 5, but syringes 3, 4 and 5 may be positioned on the same end face of cassette 1, or the cassette may be circular and the syringes may be positioned radially.

[0082] The shape of the syringe is not particularly limited as long as it allows for the inflow and outflow of the solution, and commercially available syringes may be used. Examples of syringe shapes include cylindrical shapes.

[0083] Furthermore, a dropper may be used instead of a syringe as a liquid delivery device. It is preferable to use a syringe to introduce the washing solution into the storage chamber 6, as this allows for easy introduction of large quantities of liquid. It is preferable to use a dropper when introducing the detection reagent or the diluted solution of the test sample into the storage chamber 6. The dropper will be described later. The placement of syringes or droppers connected to the ends of the passage will be described later.

[0084] In Figure 7, there are two syringes containing detection reagents for the chips. However, if only one type of detection reagent is needed, one syringe is sufficient. Conversely, if three or more types of detection reagents are used, three or more syringes may be provided. For example, when using the fluorescence method, one syringe of fluorescently labeled antibody for detection reagent is sufficient in cassette 1. Also, when using primary antibody, labeled secondary antibody, and chemiluminescent reagent as detection reagents, three syringes for detection reagents should be provided in the cassette.

[0085] For ease of operation and to shorten measurement time, it is preferable to pre-store the detection reagent in syringes 4 and 5. The method of introducing the detection reagent into syringes 4 and 5 is not particularly limited, but for example, the detection reagent may be introduced into syringes 4 and 5 from openings 9 and 10 for the detection reagent and stored in syringes 4 and 5. Openings 9 and 10 may each communicate with syringes 4 and 5. Alternatively, the detection reagent may be pre-stored in syringes 4 and 5 when inserting plungers 4a and 5a. Syringes 4 and 5 are each communicated with the ends 41a and 51a of the passages. By driving plungers 4a and / or 5a, the detection reagent is pushed out from inside syringes 4 and / or 5 and introduced into the storage chamber 6 through passages 41 and / or 51 and the ends 41b and / or 51b of the passages.

[0086] For ease of operation and to shorten measurement time, it is preferable to pre-store the cleaning solution in syringe 3. The method of introducing the cleaning solution into syringe 3 is not particularly limited, but for example, the cleaning solution may be introduced into syringe 3 from the opening 11 for the cleaning solution and stored in syringe 3. The opening 11 may be in communication with syringe 3. Alternatively, the cleaning solution may be pre-stored in syringe 3 when inserting plunger 3a. Syringe 3 is also in communication with the end 31a of the passage. By driving plunger 3a, the cleaning solution is pushed out from inside syringe 3 and introduced into storage chamber 6 through passage 31 and the end 31b of the passage. Examples of cleaning solutions include physiological saline and buffer solutions such as phosphate buffer (PBS).

[0087] In this specification, "driving the plunger" includes both pushing the plunger out and pulling the plunger out.

[0088] Figures 8, 1101-1105, are schematic front views of the cassette for the protein or antibody chip shown in Figure 7. The outer parts of cassettes 1101-1105 correspond to the plunger or dropper pump section that contacts the plunger drive unit. The liquid delivery devices 3 and 5 are arranged along the y-direction (length direction of cassette 1). The syringe may be arranged along the z-direction (height direction of cassette 1) as shown in 1102. The dropper or syringe may be arranged at an angle to the z-direction as shown in 1103. Also, as shown in 1104 and 1105, the tip of the liquid delivery device may be appropriately deformed and positioned at the optimal location on the chip for introducing washing solution or detection reagent.

[0089] Figure 9 is a schematic side view of cassettes 1201 to 1206 according to one embodiment of the present invention.

[0090] Cassette 1201 has its y-direction approximately parallel to the horizontal direction, and the solution inlet 101 (including the washing solution inlet 103, detection reagent inlets 104-106, and test sample inlet 107), storage chamber 6, and drainage storage chamber 70 are arranged in a straight line along the horizontal direction.

[0091] Cassette 1202 has its y-direction approximately parallel to the vertical direction, and the solution inlet 101, storage chamber 6, and drain storage chamber 70 are arranged in a straight line along the vertical direction.

[0092] Cassette 1203 has its y-direction approximately parallel to the horizontal direction, and the storage chamber 6 and drain storage chamber 70 are arranged in a straight line along the horizontal direction. The solution inlet 101 is located vertically above the storage chamber 6 and drain storage chamber 70.

[0093] Cassette 1204 has its y-direction approximately parallel to the horizontal direction, and the storage chamber 6 and drain storage chamber 70 are arranged in a straight line along the horizontal direction. The solution inlet 101 is located vertically below the storage chamber 6 and drain storage chamber 70.

[0094] Cassette 1205 has its y-direction approximately parallel to the horizontal direction. The solution inlet 101 is located vertically above the storage chamber 6, and the drainage storage chamber 70 is located vertically above the storage chamber 6.

[0095] Cassette 1206 has its y-direction approximately parallel to the horizontal direction. The solution inlet 101 and drainage storage chamber 70 are located vertically below the storage chamber 6.

[0096] [Embodiment 7] Next, an inspection device 200 according to Embodiment 6 of the present invention will be described with reference to Figure 10. Figure 10 is a schematic front view of an inspection device according to Embodiment 7. For the sake of convenience of explanation, components having the same function as those described in the above embodiments will be denoted by the same reference numerals, and their descriptions will not be repeated.

[0097] (Inspection device 200) As shown in Figure 10, the inspection device 200 includes a cassette receiver 13 for attaching a cassette 1 according to Embodiment 5, in which a chip is stored in a storage chamber 6; liquid delivery device drive units (plunger drive units) 12 and 15 for driving the liquid delivery devices (plungers 3a and 5a of syringes 3 and 5) of the cassette 1 in the y-axis direction; a cassette tilting mechanism 14 (sometimes abbreviated as "mechanism 14") for tilting the cassette 1 from the horizontal direction; and an inspection chamber 16 for housing the cassette 1. By using the above cassette 1, the inspection device 200 can be miniaturized, and manufacturing costs can be reduced.

[0098] <Plunger drive unit 12, 15> The plunger drive units 12 and 15 are located on the side of the inspection chamber 16. When the plunger drive units 12 and 15 are arranged along the z-direction (height direction of the cassette 1), they may be located on the top surface of the inspection chamber 16. The plunger drive unit 12 drives the plunger 3a of syringe 3, and the plunger drive unit 15 drives the plunger 5a of syringe 5. The number of plunger drive units in the inspection device 200 can be changed depending on the number of syringes contained in the cassette 1. Alternatively, one plunger drive unit may drive the plungers of multiple syringes. The plunger drive units 12 and 15 may be operated, for example, by a computer communicating with the inspection device 200. Additionally, a member for connecting to the tip of the syringe plunger may be provided at the tip of the plunger drive unit.

[0099] <Cassette tilting mechanism 14> The mechanism 14 shown in Figure 10 is installed on the bottom surface of the inspection chamber 16. A cassette holder 13 is provided on the top surface of the mechanism 14. The cassette 1 is tilted from the horizontal by changing the height of both ends of the mechanism 14. For example, the mechanism 14 may be configured to tilt the cassette 1 from the horizontal by moving the height position of one or both ends of the cassette holder 13.

[0100] In addition to the cassette tilting mechanism 14, a cassette rotation mechanism (not shown) may also be provided. By rotating the cassette rotation mechanism, the plunger (or dropper pump) drive unit 12 or 15 can be made into a single unit and moved to the vicinity of the plunger (or dropper pump) of the syringe (liquid delivery device) to be driven. Alternatively, by rotating the side wall of the inspection device 200 that constitutes the side of the inspection chamber 16, the plunger (or dropper pump) drive unit 12 or 15 can be made into a single unit and moved to the vicinity of the plunger (or dropper pump) of the syringe (liquid delivery device) to be driven. Therefore, if a cassette rotation mechanism is provided or the side wall of the inspection device 200 is rotated, it becomes unnecessary to provide multiple plunger (or dropper pump) drive units.

[0101] <Other components> The inspection device 200 may have, for example, an imaging unit that acquires an image of the luminescence of the chip after treatment with a luminescent reagent. The imaging unit is preferably located on the upper surface of the inspection chamber 16, but may also be located on the lower surface. The inspection device 200 may also have a temperature control unit that maintains the temperature inside the inspection chamber 16 at a predetermined temperature. The temperature inside the inspection chamber is preferably maintained at around 30°C to 45°C, and more preferably at around 35°C to 40°C. Furthermore, it is desirable to have a shaking mechanism or vibration mechanism to efficiently carry out the reaction and washing.

[0102] The inspection device 200 may include an on-off valve adjustment mechanism for adjusting the opening and closing of the on-off valve. For example, it may include a drive unit for a diaphragm valve.

[0103] When using a cassette equipped with a breaker seal, the inspection device 200 may be equipped with a breaking mechanism for breaking the breaker seal. It may also be equipped with a cleaning mechanism for cleaning the breaking mechanism.

[0104] When using a cassette equipped with a suction mechanism, the inspection device 200 may also be equipped with a suction drive mechanism for driving the suction mechanism and switch mechanism. When using a cassette equipped with a liquid delivery mechanism and valve mechanism, the cassette may be equipped with a roller-type or finger-type drive unit for driving the diaphragm inside the cassette.

[0105] [Differentiation] The inspection device 210 in Figure 10 is a modified version of the inspection device 200. The cassette 1 in the inspection device 210 differs from the inspection device 200 in that the syringes (liquid delivery devices) 3 and 5 are arranged along the z direction (height direction of the cassette 1), as shown in the cassette 1104 in Figure 9, and the tips of the syringes (liquid delivery devices) are deformed.

[0106] Furthermore, the system may also include a plunger (or dropper pump) rotating unit 22 that rotates the plunger (or dropper pump) drive unit 12. By rotating the plunger (or dropper pump) rotating unit 22, the plunger (or dropper pump) drive unit 12 or 15 can be made into a single unit and moved directly above the syringe (fluid delivery device) to be driven. Therefore, in this case, it becomes unnecessary to provide multiple plunger (or dropper pump) drive units.

[0107] The inspection devices 200 and 210 in Figure 10 are equipped with cassettes according to Embodiment 5, but they may be modified to be equipped with cassettes according to Embodiments 1 to 4, for example.

[0108] Furthermore, the inspection devices 200 and 210 in Figure 10 may be modified to include cassettes 1201 to 1206 in Figure 9.

[0109] (Testing method) Next, a testing method using the cassette of this embodiment will be described. The following description will focus on a testing method using two types of detection reagents, but the number of detection reagents may be one or three or more. Furthermore, the chip will be described as an allergen chip or antibody chip on which multiple allergens (antigen proteins) or antibodies are immobilized.

[0110] <1. Inspection method using cassette 1 according to Embodiment 5> The following description of the testing method using cassette 1 according to Embodiment 5 will be explained with reference to Figure 7. The following description of the testing method is for the case where the antibody reagent is stored in syringe 4, the luminescent reagent is stored in syringe 5, and blood is used as the test sample.

[0111] Step (S1): Storage of allergen chip into storage chamber 6 An allergen chip, which has multiple allergens (antigen proteins) immobilized on it, is stored in the storage chamber 6 of cassette 1. On the chip, multiple types of allergens to be tested are arranged as different spots, one for each type of allergen.

[0112] Step (S2): Storage of detection reagent and washing solution The enzyme-labeled (detection) antibody reagent and the luminescence reagent are stored in syringes 4 and 5 for the detection reagent, respectively. The washing solution is stored in syringe 3 for the washing solution. The order in which the detection reagent and washing solution are stored is not particularly limited. Step (S2) may be performed before or after step (S1). The diluent is stored in the sample preparation room 120 beforehand.

[0113] Step (S3): Storage of cassette 1 filled with test reagents, washing solution, and diluent. After steps (S1) and (S2), cassette 1, filled with the test reagents, washing solution, and diluent, may be stored until use.

[0114] Step (S4): Introduction of blood sample into the blood test sample preparation room 120 After step (S3), blood is introduced into the sample preparation chamber 120 via the flow path 127 of the cassette 1 by capillary action (for example, at the testing site) through the sample inlet 107 and mixed with the diluent in the sample preparation chamber 120.

[0115] Step (S5): Installation of cassette 1 into inspection device 200 Cassette 1, containing the diluted test reagent and washing solution, is placed in the cassette receiver 13 of the testing device 200, after blood has been introduced and diluted by capillary action.

[0116] Step (S6): Introduction of diluted blood sample into storage chamber 6 After installation in the inspection device 200 in step (S5), the diluted blood (diluted blood sample) is introduced into the storage chamber 6 by an aspiration mechanism (not shown) by opening the on / off valve (not shown) in the flow path 129. Before introducing the diluted blood sample into the storage chamber 6, the plunger 3a of the syringe 3 may be driven in the y-axis direction by the plunger drive unit 12 to introduce a portion of the washing solution in the syringe 3 into the storage chamber 6, thereby washing or immersing the tip in advance.

[0117] Step (S7): Reaction of allergen with diluted blood sample After step (S6), the allergen on the chip is subjected to an antigen-antibody reaction with the serum antibody in the diluted blood sample. For example, the testing device 200 may be equipped with a temperature control unit or a stirring mechanism to maintain the testing chamber 16 of the testing device 200 at a predetermined temperature. By maintaining the temperature of the testing chamber 16 at a predetermined temperature with the temperature control unit and stirring with the stirring mechanism, the reaction between the allergen and the serum antibody can be promoted.

[0118] Step (S8): Removal of diluted blood sample from storage chamber 6 After step (S7), the drainage liquid is moved to the drainage liquid storage chamber 70 by tilting the cassette 1 horizontally or by a suction mechanism (not shown), and absorbed by the absorbent material placed in the drainage liquid storage chamber 70.

[0119] Step (S9): Introduction of cleaning solution into storage chamber 6 After step (S8), the plunger drive unit 12 drives the plunger 3a of the syringe 3 in the y-axis direction, introducing a portion of the cleaning solution in the syringe 3 into the storage chamber 6. Then, the tip is cleaned. If necessary, the cassette 1 may be tilted from the horizontal direction by the mechanism 14. By tilting the cassette 1 from the horizontal direction, the cleaning solution can be distributed throughout the entire tip. Furthermore, the cleaning efficiency can be promoted by agitating or vibrating the solution.

[0120] Step (S10): Removal of drained fluid from storage chamber 6 After step (S9), the drained liquid is moved to the drained liquid storage chamber 70 by tilting the cassette 1 horizontally or by a suction mechanism (not shown), and absorbed by the absorbent material placed in the drained liquid storage chamber 70. Steps (S6) and (S7) may be repeated multiple times as necessary.

[0121] Step (S11): Introduction of detection antibody reagent into storage chamber 6 After step (S10), the plunger drive unit 19 (not shown) drives the plunger 4a of the syringe 4 in the y-axis direction, introducing the detection antibody reagent (e.g., enzyme-labeled secondary antibody) in the syringe 4 into the storage chamber 6.

[0122] Step (S12): Reaction of tip-adsorbed serum antibody with labeled detection antibody After step (S11), the tip-adsorbed serum antibody in the diluted blood sample is reacted with the labeled detection antibody. For example, the testing device 200 may be equipped with a temperature control unit, a shaking mechanism, or a vibration mechanism to maintain the testing chamber 16 of the testing device 200 at a predetermined temperature. By maintaining the temperature of the testing chamber 16 at a predetermined temperature with the temperature control unit and stirring with the shaking mechanism or vibration mechanism, the reaction between the tip-adsorbed serum antibody and the labeled detection antibody can be promoted.

[0123] Step (S13): Introduction of cleaning fluid into storage chamber 6 After step (S12), the plunger drive unit 12 drives the plunger 3a of the syringe 3 in the y-axis direction, introducing a portion of the cleaning solution in the syringe 3 into the storage chamber 6. Then, the tip is cleaned. If necessary, the cassette 1 may be tilted from the horizontal direction by the mechanism 14. By tilting the cassette 1 from the horizontal direction, the cleaning solution can be distributed throughout the entire tip. Furthermore, the cleaning efficiency can be promoted by agitating or vibrating the solution.

[0124] Step (S14): Removal of drainage fluid from storage chamber 6 After step (S13), the cassette 1 is tilted horizontally or by a suction mechanism (not shown) to move the wastewater into the wastewater storage chamber 70, where it is absorbed by the absorbent material placed in the wastewater storage chamber 70. Steps (S10) and (S11) may be repeated multiple times as needed.

[0125] Step (S15): Introduction of luminescent reagent into storage chamber 6 After step (S14), the plunger drive unit 15 drives the plunger 5a of the syringe 5 in the y-axis direction, introducing the luminescent reagent in the syringe 5 into the storage chamber 6.

[0126] Step (S16): Biochemical reaction with luminescent reagent After step (S15), the enzyme that labels the detection antibody is reacted with the luminescent reagent. For example, the testing device 200 may be equipped with a temperature control unit to maintain the testing chamber 16 of the testing device 200 at a predetermined temperature. The temperature control unit can maintain the temperature of the testing chamber 16 at a predetermined temperature and promote the biochemical reaction.

[0127] Step (S17): Measurement of luminescence intensity After step (S16), the luminescence intensity of the chip is measured. The luminescence intensity can be measured, for example, by capturing an image of the chip and quantifying the obtained image using analysis software. If using the fluorescence method, the fluorescence intensity can be measured by directly capturing an image of the chip without adding a luminescent reagent and quantifying the obtained image using analysis software.

[0128] <2. Inspection method using cassette 1 according to Embodiment 2 (sandwich method)> The following describes a testing method using cassette 1 according to Embodiment 2, which employs a sandwich method in which multiple antibodies are immobilized on an antibody chip, with reference to Figure 2. The following description of the testing method describes a method using a primary antibody reagent, a secondary antibody reagent, and a luminescent reagent as the test reagents, and using blood as the test sample.

[0129] Step (S21): Storage of antibody chip into storage chamber 6 An antibody chip containing multiple immobilized capture antibodies is placed in the storage chamber 6 of cassette 1. On the chip, multiple types of capture antibodies to be tested are arranged as different spots, one for each type of capture antibody.

[0130] Step (S22): Introduction of blood sample into the blood test sample preparation room 120 After the antibody chip is placed in the storage chamber 6 in step (S22) described above, blood is introduced into the sample preparation chamber 120 via the flow path through the sample inlet 107 by capillary action (for example, at the testing site).

[0131] Step (S23): Installation of cassette 1 into inspection device 200 After step (S22), cassette 1 is placed in the cassette receiver of the inspection device 200.

[0132] Step (S24): Dilution in the test sample preparation room 120 Switch 222 is switched to connect the sample preparation chamber 120 to the opening 230 via the flow paths 221 and 227. As a result, the diluent and blood in the sample preparation chamber 120 are mixed by suction from a suction mechanism (not shown) connected to the opening 230.

[0133] Introduction of diluted blood sample into storage chamber 6 Step (S25): Introduction of diluted blood sample into storage chamber 6 The diluted blood sample is introduced into the storage chamber 6 by opening the on / off valve 117 in the flow path 129. Switches 222 and 224 can be switched to connect the storage chamber 6 to the opening 230 via the suction flow paths 226, 223, and 227 in the flow path 128, and the introduction of the diluted blood sample into the storage chamber 6 may be facilitated by suction using the suction mechanism (not shown) of the testing device 200. A portion of the washing solution may be introduced into the storage chamber 6 to wash or soak the tip in advance.

[0134] Step (S26): Reaction of antibody with (antigen) protein in diluted blood sample After step (S25), incubation is performed to allow the capture antibody on the chip to react with the (antigen) protein in the diluted blood sample for a certain period of time. For example, the testing device 200 may be equipped with a temperature control unit or a shaking mechanism to maintain the testing chamber 16 of the testing device 200 at a predetermined temperature. By maintaining the temperature of the testing chamber 16 at a predetermined temperature with the temperature control unit and stirring with the shaking mechanism or vibration mechanism, the antigen-antibody reaction can be promoted.

[0135] Step (S27): Removal of diluted blood sample from storage chamber 6 After step (S26), the on-off valve 118 is opened, and switches 222 and 224 are switched to connect the drainage storage chamber 70 to the opening 230 via the suction passages 225, 223 and 227. This moves the diluted blood sample from the storage chamber 6 to the drainage storage chamber 70. After the diluted blood sample has been moved to the drainage storage chamber 70, switches 222 and 224 are switched to block the connection between the drainage storage chamber 70 and the opening 230, and the on-off valve 118 is closed.

[0136] Step (S28): Introduction of cleaning fluid into storage chamber 6 After step (S27), the cleaning fluid is introduced into the storage chamber 6 from the cleaning fluid inlet 103 by opening the on / off valve 113. Then the tip is cleaned. The cleaning efficiency can be promoted by stirring with a shaking mechanism or vibration mechanism. Switches 222 and 224 can be switched to connect the storage chamber 6 to the opening 230 via suction channels 226, 223 and 227 in the flow path 128, and the introduction of the cleaning fluid into the storage chamber 6 can be promoted by suction from the suction mechanism (not shown) of the inspection device 200.

[0137] Step (S29): Removal of cleaning fluid from storage chamber 6 After step (S28), the on-off valve 118 is opened, and switches 222 and 224 are switched to connect the drainage storage chamber 70 to the opening 230 via the suction passages 225, 223 and 227. This moves the cleaning drainage from the storage chamber 6 to the drainage storage chamber 70. After the cleaning drainage has been moved to the drainage storage chamber 70, switches 222 and 224 are switched to block the connection between the drainage storage chamber 70 and the opening 230, and the on-off valve 118 is closed.

[0138] Step (S30): Introduction of primary antibody reagent into storage chamber 6 After step (S29), the primary antibody reagent is introduced into the storage chamber 6 from the detection reagent inlet 104 by opening the on / off valve 114. Alternatively, switches 222 and 224 may be switched to connect the storage chamber 6 to the opening 230 via the suction channels 226, 223, and 227 in the flow path 128, and the introduction of the primary antibody reagent into the storage chamber 6 may be facilitated by suction using the suction mechanism (not shown) of the testing device 200.

[0139] Step (S31): Reaction with primary antibody After step (S30), the primary antibody in the reagent is reacted. For example, the testing device 200 may be equipped with a temperature control unit or a stirring mechanism to maintain the testing chamber 16 of the testing device 200 at a predetermined temperature. By maintaining the temperature of the testing chamber 16 at a predetermined temperature with the temperature control unit and stirring with the shaking mechanism or vibration mechanism, the reaction with the primary antibody can be promoted.

[0140] Step (S32): Removal of primary antibody reagent from storage chamber 6 After step (S31), the on-off valve 118 is opened, and switches 222 and 224 are switched to connect the drainage storage chamber 70 to the opening 230 via the suction channels 225, 223 and 227. This moves the primary antibody reagent drainage from the storage chamber 6 to the drainage storage chamber 70. After the primary antibody reagent drainage has been moved to the drainage storage chamber 70, switches 222 and 224 are switched to block the connection between the drainage storage chamber 70 and the opening 230, and the on-off valve 118 is closed.

[0141] After step (S32), steps (S28) and (S29) above are performed to carry out washing and drainage.

[0142] If the primary antibody is enzyme-labeled, the luminescence reagent can be added and the emission intensity measured without going through the next steps (S33) and (S34). Also, if the primary antibody is fluorescently labeled, the fluorescence intensity can be measured immediately.

[0143] Step (S33): Introduction of secondary antibody reagent into storage chamber 6 After washing and draining following step (S32), the secondary antibody reagent is introduced into the storage chamber 6 from the detection reagent inlet 105 by opening the on / off valve 115. Alternatively, switches 222 and 224 may be switched to connect the storage chamber 6 to the opening 230 via the suction channels 226, 223, and 227 in the flow path 128, and the introduction of the secondary antibody reagent into the storage chamber 6 may be facilitated by suction using the suction mechanism (not shown) of the testing device 200.

[0144] Step (S34): Reaction with secondary antibody After step (S33), the secondary antibody in the reagent is reacted. For example, the testing device 200 may be equipped with a temperature control unit or a stirring mechanism to maintain the testing chamber 16 of the testing device 200 at a predetermined temperature. By maintaining the temperature of the testing chamber 16 at a predetermined temperature with the temperature control unit and stirring with a shaking mechanism or vibration mechanism, the reaction with the secondary antibody can be promoted.

[0145] Step (S35): Removal of secondary antibody reagent from storage chamber 6 After step (S34), the on-off valve 118 is opened, and switches 222 and 224 are switched to connect the drain storage chamber 70 to the opening 230 via the flow paths 225, 223 and 227. This moves the secondary antibody reagent drain from the storage chamber 6 to the drain storage chamber 70. After the secondary antibody reagent drain has been moved to the drain storage chamber 70, switches 222 and 224 are switched to block the connection between the drain storage chamber 70 and the opening 230, and the on-off valve 118 is closed.

[0146] After step (S35), steps (S28) and (S29) above are performed to carry out washing and drainage.

[0147] Step (S36): Introduction of luminescent reagent into storage chamber 6 After washing and draining following step (S35), the luminescent reagent is introduced into the storage chamber 6 from the detection reagent inlet 106 by opening the on / off valve 116. Alternatively, switches 222 and 224 may be switched to connect the storage chamber 6 to the opening 230 via the suction channels 226, 223, and 227 in the flow path 128, and the introduction of the luminescent reagent into the storage chamber 6 may be facilitated by suction using the suction mechanism (not shown) of the inspection device 200.

[0148] After step (S36), steps (S16: biochemical reaction with luminescent reagent) and (S17: measurement of luminescence intensity) are performed. If the secondary antibody is fluorescently labeled, the steps from step (S36: introduction of luminescent reagent into storage chamber 6) onwards can be omitted, and the fluorescence intensity can be measured immediately. <3. Inspection method using cassette 1 according to Embodiment 4> The following describes the testing method using cassette 1 according to Embodiment 4, with reference to Figure 6. For the sake of clarity, the same reference numerals are used for steps that were described in the above testing method, and their descriptions will not be repeated. The following description of the testing method describes the testing method when blood is used as the test sample.

[0149] Step (S131): Introduction and dilution of blood into the blood sample preparation room 120. After the allergen chip is placed in the storage chamber 6 in step (S1) described above, blood is introduced into the sample preparation chamber 120 via the flow path 127 through the sample inlet 107 by capillary action and mixed with the diluent in the sample preparation chamber 120.

[0150] Step (S132): Installation of cassette 1 into inspection device 200 After step (S131), cassette 1 is placed in the cassette receiver of the inspection device 200 (for example, at the inspection site).

[0151] Step (S133): Introduction of diluted blood sample into storage chamber 6 By opening the on / off valve 117 in the flow path 129, the diluted blood sample is introduced into the storage chamber 6.

[0152] Step (S134): Reaction between allergen and serum antibody After step (S133), cassette 1 is incubated to allow the allergen on the chip to react with serum antibodies in the blood in an antigen-antibody reaction. For example, the testing device 200 may be equipped with a temperature control unit or a shaking mechanism to maintain the testing chamber 16 of the testing device 200 at a predetermined temperature. By maintaining the temperature of the testing chamber 16 at a predetermined temperature with the temperature control unit and stirring with a circulation circuit, shaking mechanism, or vibration mechanism, the reaction between the allergen and serum antibodies can be promoted.

[0153] Step (S135): Drainage of diluted blood sample from storage chamber 6. By opening the on / off valve 118, the diluted blood sample is moved to the drainage storage chamber 70. After the diluted blood sample has been moved to the drainage storage chamber 70, the on / off valve 118 is closed.

[0154] Step (S136): Introduction of cleaning fluid into storage chamber 6 After step (S135), the cleaning fluid is introduced into the storage chamber 6 from the cleaning fluid inlet 103 by opening the on / off valve 113. Then the tip is cleaned. Furthermore, the cleaning efficiency can be promoted by stirring with a circulation circuit, shaking mechanism, or vibration mechanism.

[0155] The cleaning of the tip may be accelerated by circulating the cleaning fluid through the circulation channel 131 by driving the liquid delivery mechanism 119.

[0156] Step (S137): Removal of cleaning fluid from storage chamber 6 After step (S136), the on-off valve 118 is opened to move the cleaning wastewater into the wastewater storage chamber 70. Steps (S136) and (S137) may be repeated multiple times as needed. After the cleaning wastewater has been moved into the wastewater storage chamber 70, the on-off valve 118 is closed.

[0157] Step (S138): Introduction of detection antibody reagent into storage chamber 6 After step (S137), the detection antibody reagent (for example, enzyme-labeled secondary antibody) is introduced into the storage chamber 6 from the detection reagent inlet 104 by opening the on / off valve 114.

[0158] After step (S138), step (S12) above (reaction between the tip-adsorbed serum antibody and the labeled detection antibody) is performed.

[0159] Step (S139): Removal of detection antibody reagent from storage chamber 6 By opening the on / off valve 118, the diluted blood sample is moved to the drainage storage chamber 70. After the detection antibody reagent has been moved to the drainage storage chamber 70, the on / off valve 118 is closed.

[0160] Step (S140): Introduction of cleaning fluid into storage chamber 6 The cleaning solution is introduced into the storage chamber 6 from the cleaning solution inlet 103 to clean the tips. Furthermore, the cleaning efficiency can be promoted by agitating the solution using a circulation circuit, shaking mechanism, or vibration mechanism.

[0161] The cleaning of the tip may be accelerated by circulating the cleaning fluid through the circulation channel 131 by driving the liquid delivery mechanism 119.

[0162] Step (S141): Removal of cleaning fluid from storage chamber 6 After step (S140), the cleaning wastewater is moved to the wastewater storage chamber 70 by opening the on-off valve 118. Steps (S140) and (S141) may be repeated multiple times as necessary. After the cleaning wastewater has been moved to the wastewater storage chamber 70, the on-off valve 118 is closed.

[0163] Step (S142): Introduction of luminescent reagent into storage chamber 6 After step (S141), the luminescent reagent is introduced into the storage chamber 6 from the detection reagent inlet 105 by opening the on / off valve 115.

[0164] After step (S142), the above steps (S16: biochemical reaction with luminescent reagent) and (S17: measurement of luminescence intensity) are carried out.

[0165] (Inspection System 500) Next, the inspection system 500 will be described with reference to Figure 11. Figure 11 is a block diagram showing the main components of the inspection system 500. The inspection system 500 comprises the inspection device 200 and a personal computer (PC) 300. The inspection system 500 can automatically perform tasks such as loading the inspection sample, injecting detection reagents into the cassette 1, cleaning the tip, and measuring the luminescence intensity. Furthermore, it is easy to operate and does not require specialized staff; anyone can operate it.

[0166] The inspection device and the PC may be separate devices, or the PC may be integrated into the inspection device, making the inspection device and the PC a single unit.

[0167] <pc300> Referring to Figure 11, the PC300 will be described. The PC300 comprises a communication unit 301 and a control unit 302. The control unit 302 also functions as a tilt instruction unit 303 or a drive instruction unit 304 by executing a program stored in the control unit 302, for example. The communication unit 301, tilt instruction unit 303, and drive instruction unit 304 will be described below.

[0168] The PC300 executes instructions for a program, which is software that implements each function. The PC300 includes, for example, one or more processors and a computer-readable recording medium that stores the program. The object of the present invention is achieved in the PC300 when the processor reads the program from the recording medium and executes it. As the processor, for example, a CPU (Central Processing Unit) can be used. As the recording medium, a "tangible medium that is not temporary," such as ROM (Read Only Memory), can be used, as well as tape, disk, card, semiconductor memory, programmable logic circuit, etc. It may also further include RAM (Random Access Memory) for deploying the program. Furthermore, the program may be supplied to the PC300 via any transmission medium capable of transmitting the program (such as a communication network or broadcast wave). In one aspect of the present invention, the program can also be realized in the form of a data signal embedded in a carrier wave, which is embodied by electronic transmission.

[0169] <Communications Department 301> The communication unit 301 communicates with the inspection device 200. For example, it transmits the instructions from the tilt instruction unit 303 or the drive instruction unit 304 to the inspection device 200.

[0170] <Incline instruction section 303> The tilt indicator unit 303 changes the height of one or both ends of the cassette tilt mechanism 14 to tilt the cassette receiver 13 of the inspection device 200 from the horizontal direction.

[0171] <Drive instruction unit 304> The drive instruction unit 304 drives the plunger drive units 12 and 15 of the inspection device 200 to drive the plungers of each syringe. It also drives the drive units of the diaphragm pump and diaphragm valve.

[0172] <Control Unit 302> The control unit 302 may function as a shaking instruction unit, a constant temperature instruction unit, or an imaging instruction unit. The shaking instruction unit shakes the shaking unit of the inspection device 200. The constant temperature instruction unit sets the temperature controlled by the temperature control unit of the inspection device to a predetermined temperature and maintains that predetermined temperature. The imaging instruction unit drives the imaging unit of the inspection device 200 to image the chip after the light emission processing.

[0173] As shown in Figure 11, the inspection device 200 comprises a communication unit 201 and a control unit 202. The control unit 202 functions as a tilt operation unit 203 or a drive operation unit 204 by, for example, executing a program recorded within the control unit 202. The communication unit 201, the tilt operation unit 203, and the drive operation unit 204 will be described below.

[0174] <Communications Department 201> The communication unit 201 communicates with the PC 300. For example, it receives instructions from the PC 300 regarding the tilt instruction unit 303 or the drive instruction unit 304.

[0175] <Tilt operation unit 203> The tilt operation unit 203 changes the height of one or both ends of the cassette tilt mechanism 14 based on the instructions from the tilt instruction unit 303 of the PC 300, thereby tilting the cassette receiver 13 of the inspection device 200 from the horizontal direction.

[0176] <Drive operation unit 204> The drive operation unit 204 drives the plunger drive units 12 and 15 of the inspection device 200 to drive the plungers of each syringe, based on the instructions from the drive instruction unit 304 of the PC 300.

[0177] <Control Unit 202> The control unit 202 may function as a shaking instruction unit, a constant temperature instruction unit, or an imaging instruction unit. The shaking instruction unit shakes the shaking unit (not shown) of the inspection device 200 based on the instructions of the shaking instruction unit of the PC 300. The constant temperature instruction unit sets the temperature controlled by the temperature control unit of the inspection device to a predetermined temperature and maintains that predetermined temperature based on the instructions of the constant temperature instruction unit of the PC 300. The imaging instruction unit drives the imaging unit (not shown) of the inspection device 200 to image the chip after the light emission processing based on the instructions of the shaking instruction unit of the PC 300.

[0178] (summary) In summary, the present invention incorporates the following features in order to solve the above-mentioned problems. <1> A cassette for protein or antibody chips, A storage chamber for storing the above chip, A solution inlet for a chip, which is connected to the above storage chamber and allows the introduction of one or more detection reagents or cleaning solutions for chips, One or more inspection sample inlets communicating with the above storage chamber, A sample preparation chamber for mixing the diluent and the sample is located between the sample inlet and the storage chamber. A cassette comprising at least a flow path connecting the above-mentioned sample inlet and the above-mentioned sample preparation chamber, which delivers the sample from the sample inlet to the sample preparation chamber by capillary action. <2> The above tip has a solution inlet that is further equipped with one or more liquid delivery devices, The above-mentioned liquid delivery device contains a cleaning solution for the tip or a detection reagent for the tip, and comprises at least a first liquid delivery device containing the cleaning solution for the tip and a second liquid delivery device containing the detection reagent for the tip. <1> The cassette mentioned above. <3> At least one of the above-mentioned test sample, washing solution, and detection reagent is introduced into the storage chamber by gravity. <1> The cassette mentioned above. <4> The above storage chamber is further equipped with a circulation channel for circulating the liquid introduced into it. <1> ~ <3> The cassette listed in one of the following. <5> The above-mentioned diluent is stored in the above-mentioned cassette. <1> ~ <4> The cassette listed in one of the following. <6> The above chip is stored in the above storage chamber. <1> ~ <5> The cassette listed in one of the following. <7> The system further comprises a drainage storage chamber for holding the liquid introduced into the storage chamber as drainage, and an on / off valve positioned in a flow path connecting the storage chamber and the drainage storage chamber. <1> ~ <6> The cassette listed in one of the following. <8> The above-mentioned fluid delivery device is configured to be detachable. <2> , <4> ~ <6> The cassette listed in one of the following. <9> A portion of the above-mentioned liquid transfer device is configured as a hole provided in the base body in which the above-mentioned storage chamber is formed. <2> , <4> ~ <6> The cassette listed in one of the following. <10> <1> ~ <9> An inspection device that uses a cassette described in any one of the above, comprising a cassette receiver for attaching the cassette. <11> The cassette further includes a plunger drive unit for driving the plunger of the fluid delivery device, <10> The inspection device described above.

[0179] The present invention 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 the present invention. Furthermore, new technical features can be formed by combining the technical means disclosed in each embodiment. [Industrial applicability]

[0180] This invention can, for example, analyze and measure clinical specimens and can be used in life science research and medical applications. [Explanation of symbols]

[0181] 1, 1101~1105, 1201~1204 Cassettes 2 Cassette Units 3. Syringe for washing solution 3a, 4a, 5a plungers 4, 5 Syringe for detection reagent 6. Storage Room 9, 10 Openings for detection reagents 11. Opening for cleaning solution 12, 15 Plunger drive unit 13 Cassette receiver 14. Cassette tilt mechanism 16. Laboratory 20 chips 22 Plunger Rotating Part Aisles 31, 41, and 51 31a, 41a, 51a Ends of the passageway 31b, 41b, 51b Ends of the passageway 61 Interior space 62, 141, 142, 230 aperture 70 Drainage storage room 101 Solution Inlet 103 Cleaning solution inlet 104-106 Detection reagent inlet 107 Sample Inlet 111, connection part 113-118, 153, 156-159, 180 Shut-off valves 119, 151 Fluid delivery mechanism 120 Laboratory Sample Preparation Room 121 Dilution Chamber Channels 123-126, 128-132, 134, 136 133 Capillary 127 Flow channels (small tubes) 160 Dilution Solution Storage Room 161 Diluent 162 Diluted test sample 170 Drainage outlet (opening) 200, 210 Inspection equipment 220, 221, 223, 225~227 suction flow path 222, 224 switches 300 PC 201, 301 Communications Department 202, 302 Control Unit 203, 303 Tilt indicator 204, 304 Drive Indicator Unit 500 Inspection Systems

Claims

1. A cassette for protein or antibody chips, A storage chamber for storing the above chip, A solution inlet for a chip, which is connected to the above storage chamber and allows the introduction of one or more detection reagents or cleaning solutions for chips, One or more inspection sample inlets communicating with the above storage chamber, A sample preparation chamber for mixing the diluent and the sample is located between the sample inlet and the storage chamber. A tubular tube containing the above-mentioned test sample collected by capillary action is inserted into the above-mentioned test sample inlet, A flow path connecting the above-mentioned sample inlet and the above-mentioned sample preparation chamber, comprising at least a flow path for transferring the sample inside the capillary tube, collected by capillary action, from the sample inlet to the sample preparation chamber under pressurized or depressurized conditions, The above-mentioned diluent is stored in advance in the above-mentioned sample preparation chamber, or in a cassette stored in a diluent storage chamber connected to the above-mentioned sample preparation chamber via a flow path.

2. The above tip has a solution inlet that is further equipped with one or more liquid delivery devices, The above liquid delivery device contains either a cleaning solution for the tip or a detection reagent for the tip. The cassette according to claim 1, comprising at least a first liquid dispensing device storing a cleaning solution for the tip, and a second liquid dispensing device storing a detection reagent for the tip.

3. The cassette according to claim 1, further comprising a liquid delivery device for introducing the test sample in the capillary tube into the test sample preparation chamber by pressurization or depressurization.

4. The cassette according to claim 1, further comprising a circulation channel for circulating the liquid introduced into the above-mentioned storage chamber.

5. The cassette according to claim 1, wherein the above-mentioned diluent is stored in the cassette.

6. The cassette according to claim 1, wherein the above-mentioned chip is stored in the above-mentioned storage chamber.

7. A drainage storage chamber that holds the liquid introduced into the above storage chamber as drainage, The cassette according to claim 1, further comprising an on-off valve disposed in a flow path connecting the above-mentioned storage chamber and the above-mentioned drainage storage chamber.

8. The cassette according to claim 2, wherein the above-mentioned liquid delivery device is configured to be detachable.

9. The cassette according to claim 2, wherein a part of the above-mentioned liquid delivery device is configured as a hole provided in the base body in which the above-mentioned storage chamber is formed.

10. An inspection device using a cassette according to any one of claims 1 to 9, An inspection device comprising a cassette holder for attaching the above-mentioned cassette.

11. The inspection apparatus according to claim 10, further comprising a liquid delivery device drive unit for driving a liquid delivery device provided in the above-mentioned cassette.

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