Cassette for protein or antibody chip, and inspection device in which said cassette is used

Abstract

A cassette (1) for a protein or antibody chip according to the present disclosure comprises: a storage chamber (6) for storing a chip; a port (104) for introducing a solution for the chip; a test sample introduction port (107); a test sample preparation chamber (120); a thin tube (127) that is inserted into the test sample introduction port (120), the thin tube (127) containing therein a test sample collected through capillary action; and a flow path (137) that connects the test sample introduction port (107) and the test sample preparation chamber (120).

Description

Cassette for Protein or Antibody Chip and Testing Apparatus Using the Cassette

[0001] The present invention relates to a cassette for a protein or antibody chip and a testing apparatus using the cassette.

[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, one or more proteins (antigens) or antibodies are immobilized on the chip, and one or more specific substances in the sample are detected and measured. By the measuring device, for example, the presence of a plurality of biomarkers in a sample can be measured simultaneously. Also, measurement of (multiple) 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.

[0004] International Publication No. 2020 / 175563

[0005] Biological samples such as blood are generally diluted and then applied onto a protein or antibody chip. In a conventional cassette, it is necessary for an examiner to dilute a biological sample, and operations such as transferring the diluted biological sample may become complicated. Also, there is a possibility that individual differences may occur in the test results due to an operator in dilution operations or the like.

[0006] An aspect of the present invention aims to provide a cassette for a protein or antibody chip, a testing apparatus using the cassette, etc., which are simple to operate and highly reproducible.

[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 a protein or antibody chip, comprising at least: a storage chamber for storing the chip; a solution inlet for the chip for introducing one or more detection reagents or washing solutions for the chip that communicate with the storage chamber; one or more test sample inlets that communicate with the storage chamber; a test sample preparation chamber for mixing a diluent and a test sample, disposed between the test sample inlet and the storage chamber; and a flow path connecting the test sample inlet and the test sample preparation chamber, for delivering the test sample from the test sample inlet to the test sample preparation chamber by capillary action.

[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.

[0009] This is a schematic front view of a cassette for a protein or antibody chip according to Embodiment 1 of the present invention. This is a schematic front view of a cassette for a protein or antibody chip according to Embodiment 2 of the present invention. This is a schematic front view of a cassette for a protein or antibody chip according to Embodiment 3 of the present invention. This diagram shows the mechanism by which a test sample is introduced into the storage chamber 6 when the capillary tube 127 is removable from the cassette. This diagram shows the mechanism by which a test sample is introduced into the storage chamber 6 when the capillary tube 127 is pre-attached to the cassette. This is a schematic front view of a cassette for a protein or antibody chip according to Embodiment 4 of the present invention. This is a schematic top view of a cassette for a protein or antibody chip according to Embodiment 5 of the present invention. This is a schematic front view of a cassette for a protein or antibody chip according to Embodiment 5 of the present invention. This is a schematic side view of cassettes 1201 to 1206 according to one aspect of the present invention. This is a schematic front view of a testing device according to Embodiment 6 of the present invention. This is a block diagram showing the main components of the testing system of the present invention. This diagram shows the mechanism by which a test sample is introduced into the storage chamber 6 when the capillary tube 127 is removable from the cassette and the connection part is a breaker seal.

[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 the cassette 1. The cassette 1 has a roughly rectangular shape.

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

[0012] As shown in Figure 1, the cassette 1 comprises a storage chamber 6 for storing chips, solution inlets 103-106 for chips (washing solution inlet 103, detection reagent inlets 104-106), a test sample inlet 107, and a drainage storage chamber 70. Each inlet 103-107 communicates with the storage chamber 6. The cassette body 2 of the cassette 1 is made of, for example, plastic. The cassette 1 may be used as a single-use item or for multiple uses.

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

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

[0015] Furthermore, an opening may be provided that penetrates the lid and communicates with the storage chamber 6 (internal space 61). By providing an opening, for example, the tip of the syringe barrel containing the diluted test sample, detection reagent, washing solution, etc., can be inserted into the opening to introduce the diluted test sample, detection reagent, washing solution, etc., onto the tip inside the storage chamber 6. There may be one or more openings.

[0016] <Chip> The chip stored in the storage chamber 6 is described as an allergen chip on which multiple allergens (antigen proteins) are immobilized. 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 Application Publication No. 2007-302745, Japanese Patent Application Publication No. 2015-025788, and Japanese Patent Application 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) on which capture antibodies are immobilized, or a protein chip (protein chip) on which proteins other than allergens are immobilized. It is preferable that the antibody chip or protein chip has multiple types of antibodies or proteins arranged as different spots (microarrayed) for each type of antibody or protein, as this enables simultaneous testing of multiple items.

[0020] <Cleaning liquid inlet 103> The cleaning liquid inlet 103 is an opening for introducing cleaning liquid for cleaning the chips into the storage chamber 6. The cleaning liquid 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 liquid introduced from the cleaning liquid inlet 103 is introduced into the storage chamber 6. There may be one cleaning liquid 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, the 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 Ports 104-106> Detection reagent inlet ports 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 inlet ports, but if only one type of detection reagent is needed, one detection reagent inlet port is sufficient. If two types of detection reagents are used, two detection reagent inlet ports are sufficient. For example, when using the fluorescence method, one detection reagent inlet port is sufficient for cassette 1. Furthermore, when using a primary antibody, a labeled secondary antibody, and a chemiluminescent reagent as detection reagents, three detection reagent inlet ports are sufficient for cassette 1.

[0025] The detection reagent inlet 104 and the storage chamber 6 are connected by flow paths 124 and 130, the detection reagent inlet 105 and the storage chamber 6 are connected by flow paths 125 and 130, and the detection reagent inlet 106 and the storage chamber 6 are connected by flow paths 126 and 130. By opening the on / off valves 114 to 116 in flow paths 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 miniaturization of the 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 inspection sample inlet 107 is an opening for introducing the inspection sample into the storage chamber 6. Between the inspection sample inlet 107 and the storage chamber 6, there is an inspection sample preparation chamber 120 for storing the diluent. In this specification, when A is said to be placed 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 the 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 the 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 stored in the sample preparation chamber 120 beforehand. 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 the 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 inspected 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. It is also preferable to create a hydrophobic region at the connection point with the test sample preparation chamber 120, as this facilitates the adjustment of the amount of test sample introduced. Furthermore, the inner wall of the channel 127 may be coated with an anticoagulant.

[0035] The flow path (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 in 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 the cassette 1, at least one of the test sample, the cleaning liquid, and the 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, the cleaning liquid, and the detection reagent may be introduced into the storage chamber by gravity without using a liquid delivery device. Alternatively, the test sample, the cleaning liquid, and the 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 (stores the drainage) the liquid introduced into the storage chamber 6 as drainage after use. The drainage storage chamber 70 is provided below the storage chamber 6 in the vertical direction, 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. Further, the drainage storage chamber 70 communicates with an opening 170 via a flow path.

[0042] The drainage stored in the drainage storage chamber 70 can be absorbed by a water-absorbing material disposed in the drainage storage chamber 70.

[0043] The on-off valves provided in the cassette 1 can use on-off valves known in the art. For example, the on-off valve may be a breaker seal, a diaphragm of a diaphragm valve, or an actuator. In terms of ease of manufacturing the cassette and simplifying the structure, it is preferable that at least one of the on-off valves 113 to 117 is a breaker seal, and it is more preferable that the on-off valves 113 to 117 are breaker seals.

[0044] The cassette 1 according to Embodiment 1 is small-sized and can suppress the manufacturing cost. Further, the cassette 1 according to Embodiment 1 can reduce the amount of the test sample required. Also, the operation is simple and convenient. Also, the measurement of the target component can be performed quickly and accurately, enabling early diagnosis. Further, the cassette 1 according to Embodiment 1 can perform the introduction of the test sample, the reaction between the reagent and the test sample, the cleaning, and the measurement of the test sample after the reagent treatment within one cassette.

[0045] Furthermore, when the cassette 1 according to Embodiment 1 is installed in an inspection apparatus described later for inspection, miniaturization of the inspection apparatus can be achieved.

[0046] Also, an inspection kit including the cassette 1 and a chip is included as one aspect of the present invention. The inspection kit may further include, as necessary, 1) an instruction manual for the kit, 2) a detection reagent and a washing solution used for inspection, 3) a liquid delivery instrument such as a syringe and a suction pump, 4) a breaker seal, etc. The detection reagent and the washing solution may be filled in the liquid delivery instrument in advance, or may be filled (stored) in the liquid delivery instrument immediately before using the inspection kit. Also, the chip may be stored in the storage chamber 6 of the cassette 1 in advance, or may be stored in the storage chamber 6 immediately before using the inspection kit.

[0047] 〔Embodiment 2〕Next, based on FIG. 2, the cassette 1 according to Embodiment 2 of the present invention will be described. FIG. 2 is a front schematic view of the cassette 1 according to Embodiment 2. For the sake of convenience of explanation, members having the same functions as the members described in the above embodiment are given the same reference numerals, and the description thereof will not be repeated.

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

[0049] The suction channel 227 includes a switch 222. A channel 221 exists between the switch 222 and the test sample preparation chamber 120. By switching the switch 222 and sucking air from the test sample preparation chamber 120 by the suction mechanism through the suction channel 221 and the suction channel 227, the test 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 drainage storage chamber 70. Channel 128 and switch 224 are connected by a suction channel 226. Switching between switch 222 and switch 224 and drawing air through the suction channels 226, 223, and 227 by a suction mechanism may facilitate 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 provided 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, an on / off valve, or a 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 with reference to Figure 3. Figure 3 is a schematic front view of a cassette 1 according to Embodiment 3. For the sake of convenience of explanation, the same reference numerals are used for components having the same function as those described in the above embodiments, 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, a 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] It is preferable that the inner wall of tube 127 be more hydrophilic than the inner wall of tube 133, as this facilitates the introduction of the test sample into the cassette by 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 sample acquisition by capillary action reaches 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] In the third embodiment, the cassette 1 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 for introducing the test sample into the storage chamber) Figure 4 shows the mechanism for introducing the test sample into the storage chamber when the tubular 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 and the connecting portion 111 that communicates with the inlet. To prevent the diluent in the sample preparation chamber 120 from leaking out of the cassette 1 when the capillary tube 127 is inserted into the sample inlet and the connecting portion 111, it is preferable that there is a flow path (space) 137 between the connecting portion 111 and the sample preparation chamber 120.

[0062] Figure 4(B) shows a capillary tube 127 containing the quantified test sample inserted into the test sample inlet and connection part 111. The test sample is present inside the capillary tube 127 due to capillary action. The amount of test sample in the capillary tube 127 can be adjusted by collecting it through capillary action. After the capillary tube 127 is inserted into the test sample inlet and connection part 111, 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 a suction mechanism outside the cassette through an opening 141 that does not touch the liquid surface. 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 by 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] Figure 12 shows the mechanism by which the test sample is introduced into the storage chamber when the tubular tube 127 is removable from the cassette 1. The test sample inlet 71 in Figure 12 is formed by a breaker seal.

[0070] Figure 12(A) shows the state before the capillary tube 127 is inserted into the sample inlet 71. To prevent the diluent 161 in the sample preparation chamber 120 from leaking out of the cassette 1 when the capillary tube 127 is inserted into the sample inlet 71, it is preferable that there is a flow path (space) 137 between the sample inlet 71 and the sample preparation chamber 120.

[0071] Figure 12(B) shows a capillary tube 127 containing the quantified test sample 140 inserted into the test sample inlet 71. The test sample is contained within the capillary tube 127 by capillary action. The amount of test sample in the capillary tube 127 can be adjusted by collecting it by capillary action. By inserting the capillary tube 127 into the test sample inlet 71, the breaker seal of the test sample inlet 71 is broken, and the capillary tube 127 is inserted into the test sample preparation chamber 120.

[0072] Figure 12(C) shows the state in which the test sample in the capillary tube 127 and the diluent 161 are mixed. After the capillary tube 127 is inserted into the test sample preparation chamber 120, the test sample in the capillary tube 127 is introduced into the test sample preparation chamber 120 by pressurization or depressurization by a liquid delivery device (not shown). Then, the test sample and the diluent 161 in the test sample preparation chamber 120 are mixed by pressurization or depressurization by the liquid delivery device, producing a diluted test sample 162. Then, by opening the on / off valve 117, the diluted test sample 162 is introduced into the lower storage chamber 6 by gravity or suction by a suction mechanism.

[0073] [Embodiment 4] Next, a cassette 1 according to Embodiment 4 of the present invention will be described with reference to Figure 6. Figure 6 is a schematic front view of a cassette 1 according to Embodiment 4. For the sake of convenience of explanation, the same reference numerals are used for components that have the same function as those described in the above embodiments, and their descriptions will not be repeated.

[0074] The cassette 1 according to Embodiment 4 differs from Embodiment 1 in that it is provided with a circulation passage 131 and an on / off valve 180 is provided in the passage 130.

[0075] The circulation channel 131 is provided to connect a channel 130 that connects the storage chamber 6 to each of the inlets 103 to 107, and a channel 128 that connects the drain storage chamber 70 to the storage chamber 6. The circulation channel 131 is also provided with on-off valves 158 and 159. On-off valves 180 and 158, and on-off valves 118 and 159 may be integrated into a single switch mechanism.

[0076] 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 time of the reaction process and washing process can be shortened.

[0077] 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.

[0078] [Embodiment 5] Next, a cassette 1 according to Embodiment 5 of the present invention will be described with reference to Figure 7. Figure 7 is a schematic top view of the cassette 1 according to Embodiment 5. For the sake of convenience of explanation, the same reference numerals are used for components having the same function as those described in the above embodiments, and their descriptions will not be repeated.

[0079] 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.

[0080] 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 in the opening 62.

[0081] In the cassette according to Embodiment 5, the test sample is introduced into the test sample preparation chamber 120 from the test sample inlet 107 using capillary action. 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 sucked in via the flow path 129, thereby introducing the test sample into the test sample preparation chamber 120. The test sample introduced into the test sample preparation chamber 120 is then introduced into the storage chamber 6 via the flow path 129 and through the end of the passage 71b.

[0082] <Syringes (liquid delivery channels) 3, 4, 5> In Figure 7, syringe 3 is a liquid delivery device for the washing solution, and syringes 4 and 5 are liquid delivery devices for the detection reagent. Syringe 3 contains a cleaning solution for the tip, which is used to wash the tip. Syringes 4 and 5 contain detection reagents for the tip, which are used to detect the target component in the test sample.

[0083] 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.

[0084] 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.

[0085] 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.

[0086] 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.

[0087] Furthermore, a dropper may be used instead of a syringe as a liquid delivery device. It is preferable to use a syringe to introduce a large amount of liquid into the storage chamber 6 of the washing solution because it allows for easy introduction of a large quantity of liquid. It is preferable to use a dropper when introducing a detection reagent or a diluted solution of the test sample into the storage chamber 6. The dropper will be described later. The arrangement of syringes or droppers connected to the ends of the passages will be described later.

[0088] 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, cassette 1 only needs to contain one syringe of the fluorescently labeled antibody for detection. If primary antibody, labeled secondary antibody, and chemiluminescent reagent are used as detection reagents, the cassette should contain three syringes for the detection reagents.

[0089] 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 in communication 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.

[0090] 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 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).

[0091] In this specification, "driving the plunger" includes both pushing the plunger out and pulling the plunger out.

[0092] 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 (the length direction of the cassette 1). The syringe may be arranged along the z-direction (the height direction of the 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 the washing solution or detection reagent.

[0093] Figure 9 is a schematic side view of cassettes 1201 to 1206 according to one embodiment of the present invention.

[0094] In the cassette 1201, the y-direction of the cassette is 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.

[0095] The 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.

[0096] The cassette 1203 has its y-direction approximately parallel to the horizontal direction, and the storage chamber 6 and the 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 the drain storage chamber 70.

[0097] The cassette 1204 has its y-direction approximately parallel to the horizontal direction, and the storage chamber 6 and the 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 the drain storage chamber 70.

[0098] The 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.

[0099] The cassette 1206 has its y-direction approximately parallel to the horizontal direction. The solution inlet 101 and the drainage storage chamber 70 are located vertically below the storage chamber 6.

[0100] [Embodiment 6] 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 the inspection device according to Embodiment 6. For the sake of convenience of explanation, the same reference numerals are used for components having the same function as those described in the above embodiments, and their descriptions will not be repeated.

[0101] (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 chips are 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) provided on 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.

[0102] <Plunger drive units 12, 15> The plunger drive units 12 and 15 are provided 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 provided on the upper surface of the inspection chamber 16. The plunger drive unit 12 drives the plunger 3a of the syringe 3, and the plunger drive unit 15 drives the plunger 5a of the syringe 5. The number of plunger drive units of the inspection device 200 can be changed depending on the number of syringes provided 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 personal computer that communicates 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.

[0103] <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.

[0104] 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.

[0105] <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 in order to efficiently carry out the reaction and washing.

[0106] 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.

[0107] 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.

[0108] 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.

[0109] [Modified Example] The inspection device 210 in Figure 10 is a modified example 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.

[0110] 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 (liquid delivery device) to be driven. Therefore, in this case, it becomes unnecessary to provide multiple plunger (or dropper pump) drive units.

[0111] 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.

[0112] Furthermore, the inspection devices 200 and 210 in Figure 10 may be modified to include the cassettes 1201 to 1206 in Figure 9.

[0113] (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.

[0114] <1. Testing Method Using Cassette 1 According to Embodiment 5> The testing method using Cassette 1 According to Embodiment 5 will be described below with reference to Figure 7. The following description of the testing method describes the case in which the antibody reagent is stored in syringe 4, the luminescent reagent is stored in syringe 5, and blood is used as the test sample.

[0115] Step (S1): Storing the allergen chip into the storage chamber 6. The allergen chip, which has multiple allergens (antigen proteins) fixed to it, is stored in the storage chamber 6 of the cassette 1. On the chip, multiple types of allergens to be tested are arranged as different spots for each type of allergen.

[0116] Step (S2): Storing the detection reagent and washing solution. The enzyme-labeled (detection) antibody reagent and the luminescent 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 test sample preparation room 120 beforehand.

[0117] Step (S3): After steps (S1) to (S2), the cassette 1 filled with the test reagents, washing solution, and diluent may be stored until use.

[0118] Step (S4): After step (S3) of introducing blood into the blood sample preparation room 120, (for example, at the testing site) blood is introduced into the blood sample preparation room 120 via the flow path 127 of the cassette 1 by capillary action from the blood sample inlet 107 and mixed with the diluent in the blood sample preparation room 120.

[0119] Step (S5): Installation of Cassette 1 into the Inspection Device 200. Cassette 1, which contains the test reagent and washing solution that have been diluted by introducing blood through capillary action, is placed in the cassette receiver 13 of the Inspection Device 200.

[0120] Step (S6): After the installation of the diluted blood sample into the storage chamber 6 in step (S5) on the testing device 200, the diluted blood (diluted blood sample) is introduced into the storage chamber 6 by an aspiration mechanism (not shown) by opening an 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.

[0121] Step (S7): After step (S6) of the reaction between the allergen and the diluted blood sample, the allergen on the tip is reacted with the serum antibody in the diluted blood sample in an antigen-antibody reaction. 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.

[0122] Step (S8): After step (S7) of removing the diluted blood sample from the storage chamber 6, the drainage is moved to the drainage 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 storage chamber 70.

[0123] Step (S9): After step (S8) of introducing the cleaning solution into the storage chamber 6, 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 stirring with the shaking mechanism or vibration mechanism.

[0124] Step (S10): After step (S9) of removing the wastewater from the storage chamber 6, 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 (S9) and (S10) may be repeated multiple times as necessary.

[0125] Step (S11): After step (S10) of introducing the detection antibody reagent into the storage chamber 6, the plunger 4a of the syringe 4 is driven in the y-axis direction by a plunger drive unit (not shown), and the detection antibody reagent (for example, enzyme-labeled secondary antibody) in the syringe 4 is introduced into the storage chamber 6.

[0126] Step (S12): After step (S11) of the reaction between the tip-adsorbed serum antibody and the labeled detection antibody, 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.

[0127] Step (S13): After step (S12) of introducing the cleaning solution into the storage chamber 6, 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 stirring with the shaking mechanism or vibration mechanism.

[0128] Step (S14): After step (S13) of removing the wastewater from the storage chamber 6, 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 (S13) and (S14) may be repeated multiple times as necessary.

[0129] Step (S15): After step (S14) of introducing the luminescent reagent into the storage chamber 6, the plunger drive unit 15 drives the plunger 5a of the syringe 5 in the y-axis direction to introduce the luminescent reagent in the syringe 5 into the storage chamber 6.

[0130] Step (S16): 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.

[0131] Step (S17): After step (S16) of measuring the luminescence intensity, 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 the fluorescence method is used, the fluorescence intensity can be directly captured as an image of the chip without adding a luminescent reagent, and the obtained image can be quantified using analysis software.

[0132] <2. Testing Method Using Cassette 1 According to Embodiment 2 (Sandwich Method)> The following describes a testing method using Cassette 1 according to Embodiment 2, using a sandwich method in which multiple antibodies are immobilized on the chip, with reference to Figure 2. The following description of the testing method describes a testing method using a primary antibody reagent, a secondary antibody reagent, and a luminescent reagent as test reagents, and using blood as the test sample.

[0133] Step (S21): Storing the antibody chip into the storage chamber 6. The antibody chip, on which multiple capture antibodies are immobilized, is stored in the storage chamber 6 of the cassette 1. Multiple types of capture antibodies to be tested are arranged on the chip as different spots for each type of capture antibody.

[0134] Step (S22): Introduction of blood into the blood sample preparation room 120. After the storage of the antibody chip in the storage room 6 in step (S21) above, blood is introduced into the blood sample preparation room 120 via the flow path through the blood sample inlet 107 by capillary action (for example, at the testing site).

[0135] Step (S23): After step (S22) of installing cassette 1 into the inspection device 200, cassette 1 is placed in the cassette receiver of the inspection device 200.

[0136] Step (S24): The dilution switch 222 in the sample preparation chamber 120 is switched, connecting the sample preparation chamber 120 to the opening 230 via the flow paths 221 and 227. As a result, the diluent in the sample preparation chamber 120 and the blood are mixed by suction from a suction mechanism (not shown) connected to the opening 230.

[0137] Step (S25): The diluted blood sample is introduced into the storage chamber 6 by opening the on / off valve 117 in the introduction channel 129 for the diluted blood sample into the storage chamber 6. 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 channel 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.

[0138] 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 and the (antigen) protein in the diluted blood sample to react as an antigen-antibody 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. The antigen-antibody reaction can be promoted 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.

[0139] Step (S27): After step (S26) of removing the diluted blood sample from the storage chamber 6, 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 diluted blood sample from the storage chamber 6 to the drainage storage chamber 70. After moving the diluted blood sample 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.

[0140] Step (S28): After step (S27) of introducing the cleaning solution into the storage chamber 6, the cleaning solution is introduced into the storage chamber 6 from the cleaning solution 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 passages 226, 223 and 227 in the flow path 128, and the introduction of the cleaning solution into the storage chamber 6 can be promoted by suction from the suction mechanism (not shown) of the inspection device 200.

[0141] Step (S29): After step (S28) of removing the cleaning fluid from the storage chamber 6, 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.

[0142] Step (S30): After step (S29) of introducing the primary antibody reagent into the storage chamber 6, 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.

[0143] Step (S31): After the reaction step (S30) with the primary antibody, 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 a shaking mechanism or vibration mechanism, the reaction with the primary antibody can be promoted.

[0144] Step (S32): After step (S31) of removing the primary antibody reagent from the storage chamber 6, 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 suction channels 225, 223 and 227. This moves the primary antibody reagent waste from the storage chamber 6 to the drain storage chamber 70. After the primary antibody reagent waste 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.

[0145] After step (S32), steps (S28) and (S29) above are performed to carry out washing and drainage.

[0146] Furthermore, 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.

[0147] Step (S33): After washing and draining following step (S32) of introducing the secondary antibody reagent into the storage chamber 6, 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.

[0148] Step (S34): After the reaction step (S33) with the secondary antibody, 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.

[0149] Step (S35): After step (S34) of removing the secondary antibody reagent from the storage chamber 6, 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 waste from the storage chamber 6 to the drain storage chamber 70. After moving the secondary antibody reagent waste 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.

[0150] After step (S35), steps (S28) and (S29) above are performed to carry out washing and drainage.

[0151] Step (S36): After the step of introducing the luminescent reagent into the storage chamber 6 (S35), washing and draining are performed, and then the on / off valve 116 is opened to introduce the luminescent reagent into the storage chamber 6 from the detection reagent inlet 106. 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.

[0152] 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. Testing method using cassette 1 according to Embodiment 4> The testing method using cassette 1 according to Embodiment 4 will be described below with reference to Figure 6. For the sake of explanation, the same reference numerals will be used for steps that are the same as those described in the above testing method, and their explanations will not be repeated. The following description of the testing method is for cases where blood is used as the test sample.

[0153] Step (S131): Introduction and dilution of blood into the blood sample preparation chamber 120. After the storage of the allergen chip in the storage chamber 6 in step (S1) above, blood is introduced into the blood sample preparation chamber 120 via the flow path 127 by capillary action from the blood sample inlet 107 and mixed with the diluent in the blood sample preparation chamber 120.

[0154] Step (S132): After step (S131) ​​of installing cassette 1 into the inspection device 200, cassette 1 is placed in the cassette receiver of the inspection device 200 (for example, at the inspection site).

[0155] Step (S133): The diluted blood sample is introduced into the storage chamber 6 by opening the on / off valve 117 in the introduction channel 129 for the diluted blood sample into the storage chamber 6.

[0156] Step (S134): After the reaction step (S133) between the allergen and serum antibody, the cassette 1 is incubated to allow the allergen on the chip to react with the serum antibody in the blood. 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 antibody can be promoted.

[0157] Step (S135): The diluted blood sample is moved to the drain storage chamber 70 by opening the drain valve 118 for the diluted blood sample from the storage chamber 6. After the diluted blood sample has been moved to the drain storage chamber 70, the valve 118 is closed.

[0158] Step (S136): After step (S135) of introducing the cleaning solution into the storage chamber 6, the cleaning solution is introduced into the storage chamber 6 from the cleaning solution 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.

[0159] 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.

[0160] Step (S137): After step (S136) of removing the cleaning fluid from the storage chamber 6, the cleaning drainage fluid is moved to the drainage storage chamber 70 by opening the on-off valve 118. Steps (S136) and (S137) may be repeated multiple times as necessary. After the cleaning drainage fluid has been moved to the drainage storage chamber 70, the on-off valve 118 is closed.

[0161] Step (S138): After step (S137) of introducing the detection antibody reagent into the storage chamber 6, 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.

[0162] After step (S138), step (S12) (reaction between the tip-adsorbed serum antibody and the labeled detection antibody) is performed.

[0163] Step (S139): The diluted blood sample is moved to the drain storage chamber 70 by opening the removal valve 118 for the detection antibody reagent from the storage chamber 6. After the detection antibody reagent has been moved to the drain storage chamber 70, the valve 118 is closed.

[0164] Step (S140): Introduction of cleaning solution into storage chamber 6. The cleaning solution is introduced into the storage chamber 6 from the cleaning solution inlet 103 to clean the chips. Furthermore, the cleaning efficiency can be promoted by stirring with a circulation circuit, shaking mechanism, or vibration mechanism.

[0165] 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.

[0166] Step (S141): After step (S140) of removing the cleaning fluid from the storage chamber 6, the cleaning drain is moved to the drain storage chamber 70 by opening the on-off valve 118. Steps (S140) and (S141) may be repeated multiple times as necessary. After the cleaning drain has been moved to the drain storage chamber 70, the on-off valve 118 is closed.

[0167] Step (S142): After step (S141) of introducing the luminescent reagent into the storage chamber 6, the on / off valve 115 is opened to introduce the luminescent reagent into the storage chamber 6 from the detection reagent inlet 105.

[0168] After step (S142), the above steps (S16: biochemical reaction with luminescent reagent) and (S17: measurement of luminescence intensity) are carried out.

[0169] (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 into the cassette 1, injecting detection reagents into the cassette 1, cleaning the chip, and measuring the luminescence intensity. Furthermore, it is easy to operate and does not require specialized staff; anyone can operate it.

[0170] 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.

[0171] <PC300> The PC300 will be described with reference to Figure 11. 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, the tilt instruction unit 303, and the drive instruction unit 304 will be described below.

[0172] The PC 300 executes instructions for a program, which is software that implements each function. The PC 300 includes, for example, one or more processors and a computer-readable recording medium that stores the program. The objective of the present invention is achieved in the PC 300 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 PC 300 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.

[0173] <Communication Unit 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.

[0174] <Tilting instruction unit 303> The tilting instruction unit 303 instructs the inspection device 200 to tilt the cassette receiver 13 of the inspection device 200 from the horizontal direction by changing the height of one or both ends of the cassette tilting mechanism 14.

[0175] <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.

[0176] <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.

[0177] 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 executing a program recorded in the control unit 202, for example. The communication unit 201, the tilt operation unit 203, and the drive operation unit 204 will be described below.

[0178] <Communication Unit 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 of the PC 300.

[0179] <Tilting Operation Unit 203> The tilting operation unit 203 changes the height of one or both ends of the cassette tilting mechanism 14 based on the instructions from the tilting instruction unit 303 of the PC 300, thereby tilting the cassette receiver 13 of the inspection device 200 from the horizontal direction.

[0180] <Drive Operation Unit 204> Based on the instructions from the drive instruction unit 304 of the PC 300, 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.

[0181] <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 imaging instruction unit of the PC 300.

[0182] (Summary) To summarize the above, the present invention has the following features in order to solve the above problems. <1> A cassette for a protein or antibody chip, comprising: a storage chamber for storing the chip; a solution inlet for the chip for introducing one or more detection reagents or washing solutions for the chip that communicate with the storage chamber; one or more test sample inlets that communicate with the storage chamber; a test sample preparation chamber disposed between the test sample inlet and the storage chamber for mixing a diluent and a test sample; and a flow path connecting the test sample inlet and the test sample preparation chamber, for delivering the test sample from the test sample inlet to the test sample preparation chamber by capillary action. <2> The cassette according to <1>, wherein the solution inlet for the chip further comprises one or more liquid delivery devices, the liquid delivery device storing the washing solution for the chip or the detection reagent for the chip, and comprising at least a first liquid delivery device storing the washing solution for the chip and a second liquid delivery device storing the detection reagent for the chip. <3> The cassette according to <1>, wherein at least one of the above-mentioned test sample, washing solution, and detection reagent is introduced into the storage chamber by gravity. <4> The cassette according to any one of <1> to <3>, further comprising a circulation channel for circulating the liquid introduced into the storage chamber. <5> The cassette according to any one of <1> to <4>, wherein the diluent is stored in the cassette. <6> The cassette according to any one of <1> to <5>, wherein the tip is stored in the storage chamber. <7> The cassette according to any one of <1> to <6>, further comprising a drain storage chamber for holding the liquid introduced into the storage chamber as drainage, and an on / off valve disposed in a channel connecting the storage chamber and the drain storage chamber. <8> The cassette according to any one of <2>, <4> to <6>, wherein the liquid delivery device is configured to be detachable. <9> The cassette according to any one of <2>, <4> to <6>, wherein a part of the liquid supply device is configured as a hole provided in the base in which the storage chamber is formed. <10> An inspection device that uses the cassette according to any one of <1> to <9>, comprising a cassette receiver for attaching the cassette.<11> The inspection apparatus according to <10>, further comprising a plunger drive unit for driving a plunger of a liquid delivery device provided in the cassette. <12> A cassette for a protein or antibody chip, comprising at least: a storage chamber for storing the chip; a solution inlet for a chip for introducing one or more detection reagents or washing solutions for a chip that communicate with the storage chamber; one or more test sample inlets that communicate with the storage chamber; a test sample preparation chamber disposed between the test sample inlet and the storage chamber for mixing a diluent and a test sample; a capillary tube inserted into the test sample inlet containing the test sample collected by capillary action; and a flow path connecting the test sample inlet and the test sample preparation chamber, the flow path for delivering the test sample inside the capillary tube collected by capillary action from the test sample inlet to the test sample preparation chamber under pressure or depressurization. <13> The cassette according to <12>, 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.

[0183] 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.

[0184] This invention can, for example, analyze and measure clinical specimens and can be used in life science research and medical applications.

[0185] 1, 1101-1105, 1201-1206 Cassette 2 Cassette body 3 Syringe for washing solution 3a, 4a, 5a Plunger 4, 5 Syringe for detection reagent 6 Storage chamber 9, 10 Opening for detection reagent 11 Opening for washing solution 12, 15 Plunger drive unit 13 Cassette holder 14 Cassette tilting mechanism 16 Test chamber 20 Tip 22 Plunger rotating part 31, 41, 51 Passageway 31a, 41a, 51a End of passageway 31b, 41b, 51b, 71b End of passageway 61 Internal space 62, 141, 142, 230 Opening 70 Drainage storage chamber 101 Solution inlet 103 Washing solution inlet 104-106 Detection reagent inlet 71, 107 111 Inspection sample inlet, 113-118, 153, 156-159, 180 On / off valves, 119, 151 Fluid delivery mechanism, 120 Inspection sample preparation chamber, 123-126, 128-130, 134, 136, 137 Flow path, 127 Flow path (tube), 131 Circulation flow path, 133 Tube, 140 Inspection sample, 160 Diluent storage chamber, 161 Diluent, 162 Diluted inspection sample, 170 Drainage outlet (opening), 200, 210 Inspection device, 221, 223, 225-227 Suction flow path, 222, 224 Switch, 300 PC, 201, 301 Communication unit, 202, 302 Control unit, 203 Inclination operation unit, 303 Inclination indicator unit, 204 Drive operation unit 304 Drive instruction unit 500 Inspection system

Claims

1. A cassette for protein or antibody chips, comprising at least: a storage chamber for storing the chip; a solution inlet for chips for introducing one or more detection reagents or washing solutions for chips that communicate with the storage chamber; one or more test sample inlets that communicate with the storage chamber; a test sample preparation chamber disposed between the test sample inlet and the storage chamber for mixing a diluent and a test sample; a capillary tube inserted into the test sample inlet containing the test sample collected by capillary action; and a flow path connecting the test sample inlet and the test sample preparation chamber, the flow path for transferring the test sample inside the capillary tube collected by capillary action from the test sample inlet to the test sample preparation chamber under pressure or depressurization.

2. The cassette according to claim 1, further comprising one or more liquid dispensing devices having a solution inlet for the above-mentioned tip, wherein the liquid dispensing devices store a cleaning solution for the tip or a detection reagent for the tip, and the liquid dispensing devices comprising at least a first liquid dispensing device storing the cleaning solution for the tip and a second liquid dispensing device storing the 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. The cassette according to claim 1, further comprising: a drainage storage chamber for holding the liquid introduced into the storage chamber as drainage liquid; and an on / off valve disposed in a flow path connecting the storage chamber and the 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 liquid delivery device is configured as a hole provided in the base body in which the storage chamber is formed.

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

Images