Inspection device, operation method for inspection device, and operation program for inspection device

Abstract

Provided are an inspection device, an operation method for the inspection device, and an operation program for the inspection device. The inspection device comprises: a nozzle in which a tip that comes into contact with a liquid containing a specimen and a reagent is replaceably attached to the leading end, and which repeatedly suctions and discharges a liquid in a container in which the liquid is stored, thereby stirring the liquid; and a processor which performs a control for correcting the position of the nozzle with respect to the container according to at least one of the position or the orientation of the container.

Description

Inspection device, operation method of inspection device, and operation program of inspection device

[0001] The technology of the present disclosure relates to an inspection device, an operation method for an inspection device, and an operation program for an inspection device.

[0002] Testing devices for testing samples are known. Among these testing devices, there are, for example, chemiluminescent enzyme immunoassay devices and fluorescent immunoassay devices, which optically detect a target substance in a sample by utilizing an antigen-antibody reaction between the target substance and a reagent. Chemiluminescent enzyme immunoassays involve reacting an antigen with a solid-phase antibody, then subjecting an enzyme-labeled antibody to a secondary reaction with the antigen, and then adding a chemiluminescent substrate to measure the luminescence intensity. Fluorescent immunoassays involve performing an antigen-antibody reaction using an enzyme-labeled antigen or antibody as a labeling substance, and then adding a fluorescent substrate to measure the fluorescence intensity.

[0003] In these testing devices, the liquid mixture of the specimen and reagent is agitated to reduce variations in the amount of detected light (see, for example, JP 2018-087786 A). For example, even if the amount of substance on which the luminescent substrate acts in the liquid is the same, comparing a state in which the substance is aggregated and solidified with a state in which the substance is dispersed results in differences in the surface area of ​​the substance on which the luminescent substrate acts, resulting in variations in the amount of detected light. Therefore, to reduce such variations in the amount of detected light, the liquid is agitated to disperse the substance contained in the specimen or reagent within the liquid.

[0004] As described in JP 2018-087786 A, stirring is performed using, for example, a nozzle that aspirates and discharges a liquid. Specifically, stirring is performed by repeatedly aspirating and discharging a liquid through the nozzle in a reaction vessel in which the sample and reagent are mixed.

[0005] When the stirring operation described in JP 2018-087786 A is performed using a common nozzle for different liquids, such as specimens or reagents, there is a concern about contamination between the different liquids. To prevent such contamination, a tip that comes into contact with the liquid is attached to the tip of the nozzle, and the tip is replaced for each liquid. The tip, like the nozzle, is cylindrical, and the stirring operation is performed while the tip is inserted into the liquid. In such a stirring operation, if too much liquid is aspirated into the tip, the liquid surface in the tip will reach the tip of the nozzle. Therefore, the amount of liquid aspirated into the tip is controlled to prevent the liquid from adhering to the nozzle.

[0006] However, even with tip replacement and controlled aspiration volume, contamination due to liquid adhering to the nozzle can still occur. One cause of this is misalignment of the tip as it enters the reaction vessel containing the liquid. For example, the tip descends vertically to enter the reaction vessel, but if the horizontal position of the tip's tip is misaligned from the center of the reaction vessel, a horizontal pressure difference occurs in the liquid flowing into the tip. This pressure difference increases the flow of the liquid flowing into the tip, which can cause the liquid to splash up inside the tip. If the liquid splashes up too much inside the tip, the liquid will adhere to the nozzle, resulting in contamination.

[0007] Japanese Patent Application Laid-Open No. 2018-087786 describes a technique for moving a nozzle to a discharge position where a high stirring effect is expected. However, Japanese Patent Application Laid-Open No. 2018-087786 does not describe the problem of suppressing contamination caused by liquid adhering to the nozzle when aspirating the liquid. Furthermore, the nozzle movement mechanism in Japanese Patent Application Laid-Open No. 2018-087786 corrects the nozzle position assuming that the position and orientation of the reaction vessel are appropriate, and does not consider what to do if the position or orientation of the reaction vessel is not appropriate.

[0008] The technology disclosed herein has been developed in consideration of the above circumstances, and provides an inspection device, an operating method for the inspection device, and an operating program for the inspection device that can suppress contamination caused by liquid sucked into the tip adhering to the nozzle even when at least one of the position and posture of the container is incorrect.

[0009] In order to achieve the above-mentioned object, the testing device of the present disclosure is a testing device for testing a sample, and is equipped with a nozzle having a replaceable tip attached to the tip that comes into contact with a liquid containing the sample and a reagent, the nozzle performing a liquid agitation operation by repeatedly suctioning and discharging the liquid within a container containing the liquid, and a processor that controls correction of the position of the nozzle relative to the container depending on at least one of the position and attitude of the container.

[0010] When correcting the position of the nozzle in a direction intersecting the direction in which the tip enters the container, the processor preferably performs correction to align the position of the tip tip with a target position at the bottom of the container as a reference.

[0011] In cases where the container is tilted relative to the tip's entry direction and the liquid level in the container changes due to the suction of the liquid, it is preferable that the processor corrects the position of the nozzle in a direction intersecting the entry direction while the liquid is being suctioned.

[0012] The processor preferably corrects the position of the tip end to follow the center position of the liquid surface in a direction intersecting the direction of entry, which center position changes depending on the height of the liquid surface.

[0013] When the container is tilted in the direction in which the tip enters and the liquid level in the container changes due to the suction of the liquid, it is preferable that the processor control the tip height to be lowered in accordance with the decrease in the liquid level.

[0014] With regard to the distance between the bottom of the container and the tip end, when the distance in the case of discharging is defined as a first distance and the distance in the case of suction is defined as a second distance, it is preferable that the second distance be larger than the first distance.

[0015] The specimen testing method is a testing method that optically detects the target substance by utilizing an antigen-antibody reaction between the target substance in the specimen and a reagent, and the stirring operation is preferably an operation that disperses the reagent and specimen in the liquid.

[0016] The reagent preferably comprises an antigen or antibody bound to a magnetic particle.

[0017] The operating method of the testing device relating to the disclosed technology is a method for operating a testing device that includes a nozzle having a replaceable tip attached to the tip that comes into contact with a liquid containing a sample and a reagent, and that performs a liquid agitation operation by repeatedly suctioning and discharging the liquid in a container containing the liquid, and a processor, wherein the processor controls to correct the position of the nozzle relative to the container depending on at least one of the position and attitude of the container.

[0018] The operating program of an inspection device relating to the technology of the present disclosure is an operating program of an inspection device that includes a nozzle having a replaceable tip attached to the end that comes into contact with a liquid containing a sample and a reagent, and that performs a liquid agitation operation by repeatedly suctioning and discharging the liquid within a container containing the liquid, and a processor, and causes the processor to execute control to correct the position of the nozzle relative to the container depending on at least one of the position and attitude of the container.

[0019] According to the technology disclosed herein, even if at least one of the position and posture of the container is not correct, contamination caused by the liquid aspirated into the tip adhering to the nozzle can be suppressed.

[0020] 1 is a diagram showing the overall configuration of an inspection device; FIG. 1 is a diagram showing the configuration of a cartridge; FIG. 2 is a diagram showing an inspection procedure; FIG. 3 is a diagram showing a stirring procedure; FIG. 4 is a diagram showing changes in pressure and clearance over time during stirring; FIG. 5 is a diagram showing how liquid splashes up in a tip; FIG. 6 is a diagram showing a configuration for correcting the position of a nozzle; FIG. 7 is a diagram showing an example of position correction when there is a positional deviation of a reaction cell; FIG. 8 is a diagram showing an example of nozzle position correction when the attitude of a reaction cell is tilted; FIG. 9 is a flowchart showing the processing procedure for nozzle position correction; FIG. 10 is a diagram showing a second embodiment in which the clearance during aspiration is made larger than during dispensing; FIG. 11 is a diagram showing changes in pressure and clearance over time during stirring operation of the second embodiment; FIG. 12 is a flowchart showing the processing procedure for nozzle position correction of the second embodiment; FIG. 13 is a diagram showing a third embodiment in which the nozzle position is corrected during aspiration; FIG. 14 is a diagram showing changes in pressure and clearance over time during stirring operation of the third embodiment; FIG. 15 is a flowchart showing the processing procedure for nozzle position control of the third embodiment in which the nozzle position is corrected during aspiration;

[0021] An inspection device according to an embodiment of the present disclosure will be described below with reference to the drawings. In each drawing, components indicated by the same reference numerals are the same components. Unless otherwise specified in the specification, each component is not limited to one, and may be present in multiple numbers.

[0022] FIG. 1 is a schematic diagram showing the overall configuration of a testing device 10 according to an embodiment of the present disclosure. The testing device 10 is a testing device that tests a specimen 22 collected from a living body, and as an example, is an immunoanalyzer based on the principle of chemiluminescent enzyme immunoassay. As is well known, chemiluminescent enzyme immunoassay is a testing method that optically detects a test target substance A (see FIG. 3 ) in the specimen 22 by utilizing an antigen-antibody reaction between the test target substance A and a reagent. The test target substance A is a target substance that is the subject of testing, and is an example of a "target substance" according to the technology of the present disclosure.

[0023] The testing device 10 uses, as an example, a cartridge RC containing a reagent. The cartridge RC is an example of a cartridge used to perform a test based on chemiluminescent enzyme immunoassay. The reagent contains an antigen or antibody that reacts with the test target substance A. Because different reagents are used for different types of test target substance A, cartridges RC are prepared for each measurement item corresponding to the type of test target substance A. In the testing device 10, a cartridge RC is selected according to the measurement item. The cartridge RC is integrally provided with a reaction vessel that reacts the specimen 22 with the reagent, as described below.

[0024] The testing device 10 includes a dispensing mechanism 12, a photodetector 50, a processor 16, a memory 17, a touch panel display 18, and a camera 62. A specimen 22 is loaded into the testing device 10 while being contained in a specimen collection container 20.

[0025] The dispensing mechanism 12 includes a nozzle 12A that aspirates or discharges a liquid such as a specimen 22 or a reagent, and a pump 12B that applies aspirating pressure and discharging pressure to the nozzle 12A. The pump 12B is, for example, a syringe pump that generates aspirating pressure and discharging pressure by reciprocating a plunger inserted into a cylinder connected to the nozzle 12A within the cylinder. The pump 12B is, for example, driven by a pulse motor.

[0026] The dispensing mechanism 12 is equipped with a movement mechanism 12E (see FIG. 7) that moves the nozzle 12A in the horizontal and vertical directions. In this example, the vertical direction is the Z direction, and the direction along the X-Y plane is the horizontal direction. The dispensing mechanism 12 moves the nozzle 12A to a target position using the movement mechanism 12E, and at the target position, causes the nozzle 12A to perform suction or discharge via the pump 12B. The movement mechanism 12E includes an elevation mechanism that raises and lowers the nozzle 12A in the vertical direction, and a horizontal movement mechanism that moves the nozzle 12A in the horizontal direction, each of which is equipped with a drive motor that generates a drive force and a transmission mechanism consisting of a belt, gears, or the like that transmits the drive force.

[0027] A tip 12C that comes into contact with a liquid containing a specimen 22 or a reagent is replaceably attached to the tip 12D of the nozzle 12A. Like the nozzle 12A, the tip 12C is cylindrical and tapered. The tip 12C is single-use and is replaced, for example, for each different specimen 22 or each different reagent measurement item. As described below, the liquid aspirated by the nozzle 12A is retained within the tip 12C and controlled so as not to reach the tip 12D of the nozzle 12A. This prevents contamination between different specimens 22 or different reagents. The testing device 10 is also equipped with a stocker 29 that accommodates multiple tips 12C. The nozzle 12A is provided with a mechanism for attaching and detaching the tips 12C (not shown). The dispensing mechanism 12 moves the nozzle 12A to the location of the stocker 29 and attaches an unused tip 12C to the tip 12D of the nozzle 12A. The used tip 12C is removed from the nozzle 12A and discarded, for example, in a disposal unit (not shown).

[0028] The dispensing mechanism 12 acquires the specimen 22 from the specimen collection container 20 and dispenses the acquired specimen 22 into the cartridge RC. The dispensing mechanism 12 also mixes the specimen 22 with a portion of the reagent contained in the cartridge RC. The dispensing mechanism 12 also functions as a stirring mechanism that stirs the liquid in which the specimen 22 and the reagent are mixed.

[0029] The inspection device 10 also includes a transport mechanism that transports the cartridge RC horizontally along the X-Y plane. The transport mechanism, for example, is composed of a pair of rails 23 that guide the cartridge RC in the transport direction, as well as a transport belt and a drive motor. The cartridge RC is set in the transport mechanism with both ends in the Y direction engaged with a pair of rails 23 extending in the X direction, and suspended from the rails 23. The cartridge RC is transported in the X direction along the rails 23 while set on the rails 23. When the cartridge RC is transported to a predetermined location in the transport path, various processes (such as a reaction process and a detection process) included in the inspection procedure, which will be described later, are executed.

[0030] The camera 62 is, for example, an image acquisition unit for monitoring the attachment state of the chip 12C to the nozzle 12A. The camera 62 also functions as an image acquisition unit for acquiring an image 66 (see FIG. 7) for monitoring the position and posture of the cartridge RC set in the transport mechanism. The camera 62 is, for example, an optical camera having an image sensor and an optical system for forming an image on an imaging plane. The image sensor is, for example, a CMOS (Complementary Metal Oxide Semiconductor) image sensor or a CCD (Charge Coupled Device) image sensor.

[0031] In the cartridge RC, each process, such as a reaction process between the specimen 22 and the reagent, is carried out in accordance with the testing procedure, and finally, an optical detection process for the test target substance A is carried out by the photodetector 50. The photodetector 50 receives chemiluminescence L (see FIG. 3) emitted in accordance with the reaction state between the specimen 22 and the reagent, and measures the concentration of the test target substance A in the specimen 22 in accordance with the amount of received light. The photodetector 50 is composed of a photomultiplier tube, a photodiode, or the like.

[0032] The processor 16 comprehensively controls each part of the inspection device 10. The processor 16 is composed of, for example, a CPU (Central Processing Unit) 16A and a memory 17. The memory 17 stores a program 26 executed by the CPU 16A and reference information 27. The program 26 is an operating program that causes the general-purpose CPU 16A to function as the processor 16 that controls the inspection device 10. The reference information 27 includes setting information that is set in advance to perform various controls.

[0033] The processor 16 controls the operation of the dispensing mechanism 12, which includes a movement mechanism for the pump 12B and the nozzle 12A. The reference information 27 includes, as setting information, stirring operation conditions 27A, which are operating conditions when the dispensing mechanism 12 stirs a liquid. The processor 16 controls the operation of the pump 12B in accordance with the stirring operation conditions 27A. The stirring operation conditions 27A also include information for controlling the position of the nozzle 12A, which will be described later.

[0034] The processor 16 also acquires information on the amount of chemiluminescent light L detected by the photodetector 50, and calculates the concentration of the test target substance A based on the information on the amount of light. The reference information 27 stores information indicating the correspondence between the amount of chemiluminescent light L detected by the photodetector 50 and the amount of the test target substance A. The correspondence is stored, for example, as a calibration curve expressed as a function. The correspondence may also be in the form of a table. The processor 16 calculates the amount of the test target substance A, for example, from the amount of chemiluminescent light L acquired from the photodetector 50 and the calibration curve stored in the memory 17. Then, since the amount of the specimen 22 is known, the concentration of the test target substance A is calculated from the calculated amount of the test target substance A. The processor 16 outputs the concentration of the test target substance A as the test result.

[0035] The touch panel display 18 displays an operation screen and accepts operation instructions, such as an instruction to start an examination, through user operations on the operation screen. The touch panel display 18 also displays information such as examination results.

[0036] The specimen 22 is, for example, a body fluid such as blood collected from a living organism. When the specimen 22 is blood, it may be any of whole blood, plasma, serum, etc. Furthermore, a centrifuge may be provided within the testing device 10 to extract plasma or serum from whole blood. Furthermore, the test target substance A that may be contained in the specimen 22 may be an antigen, an antibody, a protein, a low molecular weight compound, etc. The specimen 22 is not limited to blood, and may be any substance collected from a living organism, such as urine or a body fluid.

[0037] The specimen collection containers 20 containing the collected specimens 22 are loaded into the testing device 10. A plurality of specimen collection containers 20 may be loaded into the testing device 10 at once so that tests for a plurality of different specimens 22 can be processed consecutively.

[0038] The cartridge RC is a single-use type that is discarded after use with one specimen 22. The cartridge RC contains, for example, all reagents necessary for testing the specimen 22.

[0039] For example, the testing device 10 can be loaded with a plurality of cartridges RC of the same or different types. It can also be loaded with a plurality of specimen collection containers 20. This makes it possible to continuously test a plurality of different specimens 22, and also to continuously test the same specimen 22 for a plurality of measurement items.

[0040] FIG. 2 is a schematic diagram showing an example of a cartridge RC, with FIG. 2(A) showing a top view of the cartridge RC and FIG. 2(B) showing a front view of the cartridge RC. The cartridge RC includes a plate-shaped connecting portion 35 with five openings 30-34 and five cylindrical cells R0-R4 extending downward from each of the openings 30-34. The cartridge RC is configured such that the multiple cells R0-R4 are integrated by the connecting portion 35. As an example, the multiple cells R0-R4 are arranged in the Y direction, which is perpendicular to the X direction, which is the transport direction of the cartridge RC. Of the multiple cells R0-R4, cells R0 and R1, located at both ends, are longer than the other cells R2-R4. Cell R0 is the longest. Before use, the openings 30-34 of the cartridge RC are covered with a sealing film (not shown).

[0041] Cell R0 functions as a reaction vessel for the specimen 22 and reagents. Cell R0 will be referred to as reaction cell R0 below. Reaction cell R0 contains, as one of the reagents, a plurality of magnetic particles MB modified with a first binding substance B1, which is an antigen or antibody that specifically binds to the test target substance A. As an example, the magnetic particles MB are contained in a solid-phase state by being sealed in gelatin G. Specimen 22 is dispensed into reaction cell R0, and the specimen 22 and various reagents are mixed in reaction cell R0. For example, when the magnetic particles MB are spherical, their diameter is approximately 0.1 to 10 μm, preferably 0.1 to 5 μm, and more preferably 1 to 3 μm.

[0042] Cell R1 contains a buffer solution 36. Cell R2 contains a labeled reagent 37 containing a label S modified with a second binding substance B2 that specifically binds to the test substance A. Cell R3 contains a first luminescent reagent 38, and cell R4 contains a second luminescent reagent 39. In this example, the label S is an enzyme, and the label S emits light in the presence of the first luminescent reagent 38 and the second luminescent reagent 39. When it is not necessary to distinguish between the liquids, the buffer solution 36 in cell R1, the labeled reagent 37 in cell R2, the first luminescent reagent 38 in cell R3, and the second luminescent reagent 39 in cell R4 will be simply referred to as reagents 36 to 39.

[0043] The first binding substance B1 and second binding substance B2 that specifically bind to the test target substance A are, for example, an antibody to the antigen when the test target substance A is an antigen, or an antigen to the antibody when the test target substance A is an antibody. Furthermore, when the test target substance A is a protein or a low molecular weight compound, the first binding substance B1 and second binding substance B2 are an aptamer to the protein or low molecular weight compound, etc. The first binding substance B1 and second binding substance B2 may be the same or different.

[0044] The test procedure based on the chemiluminescent enzyme immunoassay of this example will now be described with reference to Fig. 3. Fig. 3 shows a schematic diagram of the reaction when the test target substance A is contained in the specimen 22.

[0045] The reaction cell R0 contains magnetic particles MB modified with a first binding substance B1 in advance, and a buffer solution 36 is dispensed into the reaction cell R0 before dispensing the sample 22. In this state, the sample 22 is dispensed into the reaction cell R0 (step ST11).

[0046] As described above, the magnetic particles MB are sealed in the reaction cell R0 by gelatin G. The gelatin G is melted by heating with a heater (not shown), and the liquefied gelatin G is sucked and removed by the dispensing mechanism 12. Before the specimen 22 and buffer solution 36 are dispensed, only the magnetic particles MB remain in the reaction cell R0 due to the suction of the gelatin G. In this case, more specifically, to improve the dispersion effect of the magnetic particles MB by stirring (described later), a process is performed to collect the magnetic particles MB at the bottom of the reaction cell R0, including the magnetic particles MB adhering to the side walls of the reaction cell R0. In this state, the buffer solution 36 and specimen 22 are dispensed into the reaction cell R0.

[0047] In the reaction cell R0, the magnetic particles MB, the specimen 22, and the buffer solution 36 are mixed, and a first reaction occurs in which the test substance A in the specimen 22 specifically binds to the first binding substance B1 (step ST12). In this first reaction, the test substance A in the specimen 22 binds to the first binding substance B1, and the test substance A is captured by the magnetic particles MB via the first binding substance B1.

[0048] Next, a first washing process (so-called B (Bound) / F (Free) separation) is performed to remove unreacted components other than the test substance A captured by the magnetic particles MB (step ST13). A magnet 48 is placed near the outside of the reaction cell R0, and the reaction solution after the first reaction is discharged while the magnetic particles MB are collected on the inner wall surface of the reaction cell R0. Thereafter, a washing solution 40 is dispensed into the reaction cell R0. In step ST13 in FIG. 3 , the double-headed arrows pointing up and down above the reaction cell R0 schematically illustrate the dispensing of the washing solution 40 into the reaction cell R0 and the dispensing of the washing solution 40 from the reaction cell R0. In the first washing process, the dispensing and dispensing of the washing solution 40 are repeated multiple times. The dispensing of the washing solution 40 from the reaction cell R0 is also performed while the magnet 48 is placed near the outside of the reaction cell R0 and the magnetic particles MB are collected on the inner wall surface of the reaction cell R0.

[0049] After the first washing process, a labeled reagent 37 is dispensed into the reaction cell R0 (step ST14). The labeled reagent 37 contains a second binding substance B2 that specifically binds to the test target substance A and that has been labeled S.

[0050] In the reaction cell R0, a second reaction occurs in which the test target substance A captured by the magnetic particles MB specifically binds to the second binding substance B2 (step ST15), thereby attaching the label S to the test target substance A via the second binding substance B2.

[0051] Next, a second washing process (B / F separation) is carried out (step ST16) to remove unreacted components other than the second binding substance B2 bound to the test target substance A captured by the magnetic particles MB in the labeled reagent 37. The second washing process (step ST16) is carried out in the same manner as the first washing process (step ST13).

[0052] Thereafter, a first luminescent reagent 38 and a second luminescent reagent 39 are added to the reaction cell R0 (step ST17). The label S is an enzyme, which generates chemiluminescence L in the presence of the first luminescent reagent 38 and the second luminescent reagent 39, which contain a luminescent substrate. Then, in step ST18, the chemiluminescence L is detected to detect the test target substance A. The test procedure is as described above.

[0053] Here, in the first reaction, the dispensing mechanism 12 agitates the liquid containing the specimen 22 in the reaction cell R0 by repeatedly aspirating and dispensing the liquid. This agitation disperses the magnetic particles MB within the liquid. Comparing a state in which the magnetic particles MB are aggregated and solidified with a state in which they are dispersed, the surface area on which the first luminescent reagent 38 and the second luminescent reagent 39 act changes. If the dispersion state of the magnetic particles MB becomes uneven, variations in the amount of detected light will occur between tests, even if the concentration of the test substance A contained in the specimen 22 is the same. Because the dispersion state of the magnetic particles MB within the liquid can be made uniform by agitation, variations in the amount of detected light of the chemiluminescent light L are suppressed.

[0054] 4 shows a processing procedure from the sample dispensing in step ST11 to the stirring operation in the first reaction in step ST12. This series of processing is performed by the dispensing mechanism 12, which operates under the control of the processor 16.

[0055] First, as a premise, before dispensing the specimen 22, as described above, the gelatin G in the reaction cell R0 is melted and removed, and further, the buffer solution 36 is dispensed into the reaction cell R0. In dispensing the specimen, the dispensing mechanism 12 attaches the tip 12C to the tip 12D of the nozzle 12A, and then aspirates the specimen 22 from the specimen collection container 20.

[0056] The dispensing mechanism 12 moves the nozzle 12A horizontally to the position of the reaction cell R0 of the cartridge RC (the cell position in FIG. 4 ) while holding the aspirated sample 22 in the tip 12C. Then, in bottom position detection, the dispensing mechanism 12 first lowers the nozzle 12A in the Z direction toward the bottom of the reaction cell R0. The Z direction is the approach direction in which the tip 12C approaches the reaction cell R0, and is an example of the "approach direction" according to the technology of the present disclosure. The horizontal direction is an example of the "direction intersecting the approach direction" according to the technology of the present disclosure.

[0057] The processor 16 detects the bottom position of the reaction cell R0 while controlling the operation of the dispensing mechanism 12. Bottom position detection is performed, for example, by the following configuration using a reflective photosensor 12H. Specifically, the nozzle 12A is attached to a support member 12F extending in the Z direction so as to be freely slidable in the Z direction, and is biased toward the lower end of the sliding range by a spring 12G. As a result, when the leading end of the tip 12C hits the bottom of the reaction cell R0, the nozzle 12A receives a reaction force from the bottom through the tip 12C and slides upward relative to the support member 12F. The photosensor 12H is provided on the support member 12F, and faces the nozzle 12A when the nozzle 12A slides upward a predetermined distance from its initial position on the lower end of the support member 12F.

[0058] Therefore, when the support member 12F and nozzle 12A descent, causing the tip 12C to hit the bottom, and the resulting reaction force causes the nozzle 12A to slide a predetermined distance, the amount of light received by the photosensor 12H changes due to light blocking by the nozzle 12A. The processor 16 monitors the amount of descent of the support member 12F from the descent start position where the support member 12F begins to descent until the amount of light received by the photosensor 12H changes, based on the amount of rotation of the drive motor. The processor 16 detects the amount of rotation of the drive motor corresponding to this amount of descent of the support member 12F, i.e., the amount of rotation of the drive motor indicating how much the drive motor needs to rotate from the descent start position of the support member 12F until the tip of the tip 12C reaches the bottom of the reaction cell R0, as the bottom position of the reaction cell R0.

[0059] The method for detecting the bottom position is not limited to the method using the photosensor 12H. For example, the bottom position may be detected using a force sensor that outputs an electrical signal based on the reaction force caused by contact between the tip of the tip 12C and the bottom of the reaction cell R0. Also, the sliding of the nozzle 12A may be detected by a microswitch instead of the photosensor 12H.

[0060] The stirring is performed, for example, while a preset clearance DC is maintained between the bottom of the reaction cell R0 and the tip of the tip 12 C. The bottom position of the reaction cell R0 is detected as a reference position for maintaining the clearance DC of the tip 12 C.

[0061] After the bottom position detection is completed, the dispensing mechanism 12 raises the tip 12C from the bottom of the reaction cell R0 and moves it to the dispensing position, which is, for example, a position where the tip of the tip 12C is slightly inserted into the buffer solution 36. At the dispensing position, the dispensing mechanism 12 applies a dispensing pressure to the nozzle 12A via the pump 12B, dispensing the sample 22 aspirated into the tip 12C into the buffer solution 36.

[0062] After dispensing the sample 22, the dispensing mechanism 12 raises the nozzle 12A, raising the tip of the tip 12C in the buffer solution 36 above the liquid surface of the buffer solution 36. The dispensing mechanism 12 then dispenses any liquid remaining in the tip 12C. This opens the tip 12C to the atmosphere. The purpose of opening the tip 12C to the atmosphere is as follows. For example, the pulse motor switches its excitation pattern between when aspirating the sample 22 and when stirring the liquid. The excitation pattern is switched by changing the current flowing through the electromagnet coil to switch the strength of the magnetic flux generated by the electromagnet. When switching such excitation patterns, if liquid remains in the tip 12C, the minute driving of the pulse motor may cause the liquid in the tip 12C to be ejected or sucked. The opening to the atmosphere is performed to prevent unintended ejection or sucking of liquid that occurs when switching the excitation pattern of the pulse motor. Note that the opening to the atmosphere is performed, for example, by a solenoid valve provided separately from the pulse motor.

[0063] After the release to the atmosphere is completed, the dispensing mechanism 12 lowers the nozzle 12A and moves it to the stirring position. The stirring position is a position where a predetermined distance, a clearance DC, is secured between the bottom of the reaction cell R0 and the tip of the tip 12C. The clearance DC is set to, for example, about 0.5 mm.

[0064] At this stirring position, the dispensing mechanism 12 performs a stirring operation in which the liquid in the reaction cell R0 is repeatedly sucked in and discharged, thereby stirring the liquid and dispersing the magnetic particles MB in the liquid.

[0065] 5, Fig. 5(A) shows the change over time in the pressure applied to the nozzle 12A during the agitation operation, and Fig. 5(B) shows the change over time in the clearance DC during the agitation operation. As shown in Fig. 5(A), when the nozzle 12A agitates the liquid, the processor 16 repeatedly performs control to alternately apply suction pressure and discharge pressure to the nozzle 12A multiple times. As a result, as shown in Fig. 5(A), a suction period SP during which suction pressure is applied to the nozzle 12A and a discharge period DP during which discharge pressure is applied to the nozzle 12A are repeated multiple times.

[0066] An example of pressure control applied to such nozzle 12A is performed as follows. As described above, pump 12B is driven by a pulse motor. The amount of rotation of a pulse motor is determined according to the number of drive pulses input, and the greater the number of pulses input per unit time, the faster the rotation speed. When pump 12B is driven by such a pulse motor, the greater the number of pulses per unit time, the higher the pressure generated by pump 12B. Because the positive and negative pressures are reversed during suction and discharge, processor 16 switches between suction and discharge by reversing the direction of rotation of the pulse motor.

[0067] 5B, in this example, the clearance DC during the stirring operation is constant throughout the suction period SP and the discharge period DP. That is, the height, which is the position of the nozzle 12A in the Z direction, does not change during the stirring operation. As described above, the specific value of the clearance DC is, for example, about 0.5 mm.

[0068] The details of such pressure control and height control of the nozzle 12A are set in the agitation operation conditions 27A. The processor 16 controls the agitation operation based on the agitation operation conditions 27A.

[0069] When the nozzle 12A stirs the liquid in the reaction cell R0, if the horizontal position (X direction in FIG. 6) of the tip E of the tip 12C is at the center of the reaction cell R0, as shown in FIG. 6A, no horizontal pressure difference occurs in the liquid flowing into the tip 12C. Therefore, in this case, the flow of the liquid flowing into the tip 12C (shown by hatching in FIG. 6A) is relatively small. On the other hand, as shown in FIG. 6B, if the horizontal position of the tip E of the tip 12C is shifted from the center of the reaction cell R0, a horizontal pressure difference occurs in the liquid flowing into the tip 12C. When such a pressure difference occurs, the flow of the liquid flowing into the tip 12C (shown by hatching in FIG. 6B) increases, which may cause the liquid to splash up toward the nozzle 12A within the tip 12C. If the liquid splashes up significantly within the tip 12C, the liquid will adhere to the tip 12D of the nozzle 12A. Unlike the chip 12C, the nozzle 12A is shared among different liquids (such as the specimen 22), which can lead to contamination. In Fig. 6, the degree of liquid flow within the chip 12C is shown schematically by the magnitude of change in the liquid surface.

[0070] 7, the processor 16 controls the position of the nozzle 12A relative to the reaction cell R0 in accordance with at least one of the position and posture of the reaction cell R0, thereby suppressing the splashing of the liquid in the tip 12C. That is, the processor 16 suppresses the splashing of the liquid by eliminating the positional deviation of the tip E of the tip 12C relative to the reaction cell R0, which causes the splashing of the liquid.

[0071] Specifically, the processor 16 acquires an image 66 of the reaction cell R0 captured by the camera 62 and detects the position and orientation of the reaction cell R0 by analyzing the image 66. The processor 16 then derives a correction amount for correcting the position of the nozzle 12A based on at least one of the detected position and orientation. The processor 16 corrects the position of the nozzle 12A relative to the reaction cell R0 via the moving mechanism 12E based on the derived correction amount.

[0072] In this example, the cartridge RC is set in the transport mechanism while being suspended from rails 23 extending in the X direction. In this example, positional deviation of the cartridge RC occurs mainly in the X direction along the rails 23, and positional deviation in the Y direction is negligible. Therefore, in this example, an example will be described in which the processor 16 corrects only the positional deviation of the nozzle 12A in the X direction.

[0073] As shown in FIG. 8 , for example, a reference position (shown by a two-dot chain line in FIG. 8 ), which is the appropriate position of reaction cell R0 when performing a stirring operation, is set in advance. The processor 16 detects the amount of positional deviation of the actual reaction cell R0 (shown by a solid line in FIG. 8 ) from this reference position based on the image 66. In FIG. 8 , CC0 is the center of the bottom of the reaction cell R0 in the X direction when the reaction cell R0 is at the reference position, and CC is the horizontal center of the bottom of the actual reaction cell R0. If the X direction position of the actual reaction cell R0 is deviated from the reference position, a positional deviation of ΔCC occurs between CC0 and CC. The processor 16 detects this positional deviation ΔCC from the image 66. The reference position of the reaction cell R0 is set, for example, as a template image in the reference information 27. The processor 16 detects the position and orientation of the actual reaction cell R0 from the image 66 using an image analysis method such as contour extraction, and outputs the detected result as an image analysis result. The processor 16 then compares the image analysis results based on the image 66 with the template image to detect the positional misalignment amount ΔCC. The processor 16 then derives the amount of correction for the horizontal position of the nozzle 12A based on the detected positional misalignment amount ΔCC.

[0074] When the reaction cell R0 is at the reference position, as shown in FIG. 8A, the tip E of the tip 12C can be aligned with the center CC0 of the reaction cell R0 by moving the tip E of the tip 12C to position T0, which corresponds to the center CC0 in the X direction. Therefore, if there is a positional deviation of ΔCC between the actual reaction cell R0 and the reference position, the processor 16 determines the X-direction movement amount of the nozzle 12A by taking into account the movement amount assumed when the reaction cell R0 is at the reference position and a correction amount ΔE corresponding to the positional deviation ΔCC. For example, the movement amount of the nozzle 12A to position T0 is also set in the reference information 27, and the processor 16 determines the movement amount of the nozzle 12A by adding or subtracting the correction amount ΔE from the movement amount to position T0. This allows the tip E of the tip 12C to be aligned with the position corresponding to the center CC in the X direction of the actual reaction cell R0, as shown in FIG. 8B. After correcting the position of nozzle 12A in the X direction in this manner, processor 16 lowers nozzle 12A along the Z direction, causing tip 12C to enter reaction cell R0 and move to a stirring position within reaction cell R0.

[0075] The example shown in Figure 9 is an example in which the attitude of the reaction cell R0 is tilted. In Figure 8, the cylindrical axis in the depth direction of the reaction cell R0 coincides with the Z direction. In contrast, in Figure 9, the cylindrical axis of the reaction cell R0 is tilted with respect to the Z direction. α indicates the tilt angle with respect to the Z direction. As shown in Figure 6, mixing is performed by inserting the tip 12C into the reaction cell R0 and bringing it close to the bottom of the reaction cell R0. Therefore, even when the attitude of the reaction cell R0 is tilted, the processor 16 corrects the position of the nozzle 12A in the X direction so as to align the center CC of the bottom of the reaction cell R0 with the tip E of the tip 12C. That is, the processor 16 calculates the correction amount ΔE for the position of T0 corresponding to the center CC0 when the reaction cell R0 shown in Figure 9(A) is positioned at the reference position without tilt, and determines the movement amount. Then, as shown in Figure 9(B), a correction is performed to align the position of the tip E of the tip 12C with the center CC of the bottom, which is an example of the target position in the reaction cell R0.

[0076] The processor 16 can also detect the attitude of the reaction cell R0, for example, by comparing the image analysis results of the image 66 with a template image. More specifically, the processor 16 detects the tilt angle α with respect to the Z direction as the attitude of the reaction cell R0.

[0077] The operation of the above configuration will be described with reference to the flowchart of the processing procedure for the stirring operation shown in Fig. 10 as an example. First, for example, after opening to the atmosphere as shown in Fig. 4, in step S1100, the processor 16 acquires an image 66 of the reaction cell R0. In step S1200, the processor 16 performs image analysis of the image 66. Then, in step S1300, based on the image analysis results, the processor 16 derives a correction amount for the X-direction position of the nozzle 12A in accordance with the position and orientation of the reaction cell R0.

[0078] In step S1400, the processor 16 moves the nozzle 12A in the X direction using the movement mechanism 12E according to the correction amount. For example, as shown in FIG. 8B, if the center CC of the actual bottom of the reaction cell R0 is shifted by ΔCC from the reference position CC0, the processor 16 moves the tip E of the tip 12C in the X direction based on the correction amount ΔE corresponding to the positional shift ΔCC. After adjusting the position of the nozzle 12A in the X direction in this manner, in step S1500, the processor 16 lowers the nozzle 12A in the Z direction toward the stirring position, as shown in FIG. 4. The amount of movement to the stirring position is derived by detecting the bottom position of the reaction cell R0. At the stirring position, a clearance DC is secured between the tip 12C and the bottom of the reaction cell R0. In this state, the process proceeds to step S1600, where the processor 16 applies pressure to the nozzle 12A to initiate a stirring operation that repeatedly suctions and dispenses liquid.

[0079] Because the X-direction position of the nozzle 12A has been corrected, the tip E of the tip 12C is aligned with the center CC of the bottom of the reaction cell R0 at the stirring position. Therefore, the liquid in the reaction cell R0 is stirred in the state shown in Figure 6(A), which suppresses the flow of liquid in the tip 12C caused by the horizontal pressure difference and suppresses the splashing of liquid toward the tip 12D of the nozzle 12A. As a result, adhesion of the liquid to the nozzle 12A is suppressed, and contamination caused by the adhesion of the liquid is also suppressed.

[0080] After starting the stirring operation, in step S1700, the processor 16 determines, for example, whether a termination condition is satisfied. If the determination result is negative (N in step S1700), the stirring operation continues. If the determination result is positive (Y in step S1700), the process proceeds to step S1800, where the stirring operation is terminated. The termination condition may be, for example, that the number of repeated suction and discharge cycles reaches a specified number.

[0081] As described above, the testing device 10 relating to the technology of the present disclosure comprises a nozzle 12A having a replaceable tip attached to the tip thereof a tip 12C that comes into contact with a liquid containing a sample 22 and a reagent, the nozzle 12A performing a liquid agitation operation by repeatedly suctioning and discharging the liquid within a reaction cell R0 (an example of a container) containing the liquid, and a processor 16 that controls correction of the position of the nozzle 12A relative to the reaction cell R0 according to at least one of the position and attitude of the reaction cell R0.

[0082] This makes it possible to prevent contamination caused by the liquid aspirated into the tip 12C adhering to the nozzle 12A even if at least one of the position and posture of the container is not correct.

[0083] Furthermore, when correcting the position of the nozzle 12A in a direction (for example, the horizontal X direction) intersecting with the approach direction (for example, the vertical Z direction) in which the tip 12C approaches the reaction cell R0, the processor 16 performs a correction to align the position of the tip E of the tip 12C with reference to a target position (for example, the center CC) at the bottom of the reaction cell R0. From the viewpoint of suppressing contamination, it is preferable to align the position of the tip E of the tip 12C in the direction intersecting with the approach direction of the tip 12C with reference to a target position (for example, the center CC) at the bottom of the reaction cell R0.

[0084] This is because, as described above, the stirring position is close to the bottom of the reaction cell R0. In this way, by correcting the position of the tip E of the tip 12C based on the target position at the bottom of the reaction cell R0, the tip E of the tip 12C can be corrected to an appropriate position even if the reaction cell R0 is tilted. As a result, contamination can be suppressed more effectively than when the target position at the bottom is not used as the reference.

[0085] In the above embodiment, the test method for the specimen 22 is a test method that optically detects a target substance (e.g., test target substance A) in the specimen 22 by utilizing an antigen-antibody reaction between the target substance and a reagent, and the stirring operation is an operation that disperses the reagent and specimen 22 in the liquid. The stirring operation can homogenize the dispersion state of the reagent and specimen 22 in the liquid, thereby suppressing unevenness in the amount of light. The technology disclosed herein is particularly effective in the case of a test method that involves such a stirring operation.

[0086] In the above embodiment, the reagent contains an antigen or antibody bound to magnetic particles MB. Magnetic particles MB may be prone to agglomeration, making stirring highly necessary. The technology of the present disclosure is particularly effective in testing methods that require such stirring operations.

[0087] Furthermore, in the above embodiment, the horizontal center CC of the bottom of the reaction cell R0 includes an allowable error. For example, the center CC may be within a range of approximately ±10% based on the exact center position. Furthermore, although the entry direction of the tip 12C is shown as the vertical Z direction, the entry direction may also be tilted as long as the liquid in the reaction cell R0 does not spill. Accordingly, the direction in which the position of the nozzle 12A is corrected may also be tilted relative to the horizontal direction.

[0088] 11 shows an example in which, for the clearance DC between the bottom of the reaction cell R0 and the tip E of the tip 12C, when the clearance DC in the case of discharging is DC1, which is an example of a first distance, and the clearance DC in the case of suction is DC2, which is an example of a second distance, DC2 is larger than DC1. In other words, this is an example in which the height of the tip 12C in the case of suction is higher than the height of the tip 12C in the case of discharging.

[0089] If the clearance DC is narrow during suction, a horizontal pressure difference is likely to occur in the liquid flowing into the tip 12 C, which tends to increase the splashing of the liquid inside the tip 12 C. Therefore, by widening the clearance DC during suction compared to when discharging, it is possible to suppress the splashing of the liquid.

[0090] In the first embodiment, as shown in Fig. 5, the clearance DC of the tip 12C was constant during the stirring operation. However, in the second embodiment, as shown in Fig. 12, the processor 16 changes the height of the tip 12C and the clearance DC by controlling the height of the nozzle 12A during the stirring operation. Specifically, during the suction period SP shown in Fig. 12(A), the processor 16 sets the clearance DC to DC2 by moving the height of the tip 12C to a suction position that is higher than the discharge position, as shown in Fig. 12(B). In contrast, during the discharge period DP shown in Fig. 12(A), the processor 16 sets the clearance DC to DC1 by moving the height of the tip 12C to a discharge position that is lower than the suction position, as shown in Fig. 12(B).

[0091] A flowchart showing the processing procedure of the stirring operation of the second embodiment is shown in Fig. 13. The difference from the processing procedure of the first embodiment shown in Fig. 10 is that after the stirring operation is started in step S1600, position control of the nozzle 12A is executed in step S1610 during the stirring operation. The rest is the same as in the first embodiment shown in Fig. 10.

[0092] FIG. 14 shows the procedure for controlling the position of the nozzle 12A in step S1610A, which is executed as step S1610 in the second embodiment. In step S1610A, the processor 16 first determines whether or not the suction period SP is in progress in step S1620. If the suction period SP is in progress (Y in step S1620), the process proceeds to step S1630. In step S1630, the processor 16 raises the height of the nozzle 12A along the Z direction to move the height of the tip 12C to the suction position. This ensures that DC2 is secured as the clearance DC for the tip E of the tip 12C. The processor 16 applies suction pressure to the nozzle 12A at this position to perform a suction operation. Then, in step S1640, the processor 16 determines whether or not the suction period SP has ended and the discharge period DP has begun. If the determination result is positive (Y in step S1640), the process proceeds to step S1650. In step S1650, the processor 16 moves the nozzle 12A down along the Z direction to move the height of the tip 12C to the ejection position, and causes the nozzle 12A to perform the ejection operation.

[0093] [Third Embodiment] In the first and second embodiments, the height of the tip 12C was constant during aspiration, as shown in the changes in the clearance DC over time in Fig. 5 and Fig. 12. In contrast, in the testing device 10 of the third embodiment, as shown in Fig. 15, when the reaction cell R0 is tilted with respect to the Z direction, which is the direction in which the tip 12C enters, and the height h of the liquid level LS of the liquid in the reaction cell R0 changes due to the aspiration of the liquid, the processor 16 performs control to lower the height of the tip 12C in accordance with the decrease in the height h of the liquid level LS.

[0094] This is expected to have the effect of suppressing splashing of the liquid in the tip 12C even when an appropriate clearance DC cannot be secured between the bottom of the reaction cell R0, which is an example of a container, and the tip of the tip 12C due to the inclination of the reaction cell R0 in the Z direction. The reason is as follows.

[0095] First, when the reaction cell R0 is tilted, the reason why an appropriate clearance DC cannot be ensured is that the tip E of the tip 12C slides due to the tilt of the bottom during bottom position detection as shown in FIG. 4 . As described above, bottom position detection is performed by lowering the tip 12C in the Z direction and pressing the tip E of the tip 12C against the bottom. In this case, if the bottom is tilted, the tip 12C, which is lowered straight in the Z direction, will slide in the X direction along the tilt. This may cause the processor 16 to erroneously detect a position deeper than the actual bottom position. This tendency is particularly noticeable in reaction cells R0, which often have curved bottoms.

[0096] As described above, the bottom position of the reaction cell R0 is detected as a reference position for ensuring the clearance DC. Therefore, if an error occurs between the accurate bottom position and the actually detected bottom position, for example, a clearance DC of 0.5 mm should be ensured, but in reality only a clearance DC of 0.2 mm can be ensured.

[0097] Thus, if the amount of liquid aspirated is increased without ensuring an appropriate clearance DC, the liquid in the tip 12C may splash up significantly, resulting in adhesion of the liquid to the nozzle 12A. For example, in an experiment using a tip 12C capable of aspirating approximately 100 μL of liquid, no liquid adhesion occurred even when aspirating 50 μL or more with a clearance DC of 0.5 mm. In contrast, when only a clearance DC of 0.2 mm was ensured, aspirating 50 μL or more resulted in significant liquid splashing, resulting in adhesion of the liquid to the nozzle 12A. Since the amount of liquid in the reaction cell R0 is large at the beginning of the aspiration period SP, performing aspiration without ensuring an appropriate clearance DC may result in a large amount of aspirated liquid, potentially resulting in adhesion of the liquid. The amount of liquid in the reaction cell R0 varies depending on the measurement item. When the amount of liquid is large, a larger amount of aspirated liquid is required for agitation, making the risk of liquid adhesion more pronounced.

[0098] 15 and 16, the processor 16 increases the height of the tip 12C at the beginning of the suction period SP to ensure a large clearance DC, and then lowers the position of the tip 12C as the liquid level LS decreases with the progress of suction, so that the tip 12C approaches the bottom near the end of the suction period SP. Figures 15(A) to 15(D) show how the height h of the liquid level LS decreases from h1 to h2, h3, and h4 as suction progresses.

[0099] 16, FIG. 16(A) shows the change over time in the pressure applied to the nozzle 12A during the stirring operation, and FIG. 16(B) shows the change over time in the clearance DC. As shown in FIG. 16(B), during the suction period SP, the processor 16 changes the clearance DC. The initial suction position of the tip 12C is set to a height that ensures a relatively large DC21. The processor 16 gradually decreases the clearance DC from DC21 to DC22, DC23, and DC24 by lowering the height of the tip 12C in accordance with the decrease in the height h of the liquid level LS. Note that the height of the tip 12C is set so that the tip E of the tip 12C is below the liquid level LS to prevent air from being sucked in during suction.

[0100] By controlling the height of the tip 12C in this manner, as shown in FIG. 15A, a relatively large clearance DC of DC21 is ensured at the beginning of the suction period SP. Even when considering errors due to erroneous detection of the bottom position, there is a margin in the clearance DC, so there is little concern about splashing up even if the suction volume is large. On the other hand, near the end of the suction period SP, the tip 12C approaches the bottom, and the clearance DC also becomes small, like DC24. However, near the end of the suction period SP, suction is almost complete, so the suction volume is small. Therefore, even if an appropriate clearance DC is not ensured due to erroneous detection of the bottom position, splashing up of the liquid in the tip 12C can be suppressed.

[0101] Furthermore, in the third embodiment, when the reaction cell R0 is inclined with respect to the Z direction, which is the direction of entry of the tip 12C, and the height h of the liquid surface LS of the liquid in the reaction cell R0 changes due to the suction of the liquid, the processor 16 corrects the position of the nozzle 12A in the X direction, which is the direction intersecting the Z direction, while the liquid is being suctioned.

[0102] As shown in FIG. 8, when the reaction cell R0 is not tilted with respect to the Z direction, even if the height h of the liquid surface LS in the Z direction changes, the center position of the liquid surface LS in the X direction does not change.

[0103] In contrast, as shown in Figure 15, when the reaction cell R0 is tilted with respect to the Z direction, the center position CS of the liquid level LS in the X direction also changes in accordance with changes in the height h of the liquid level LS. As shown as an example in Figure 15, when the height h of the liquid level LS gradually decreases in the order of h1, h2, h3, and h4, the center position CS of the liquid level LS in the X direction also changes in the order of Csh1, Csh2, Csh3, and Csh4. ΔS shown in Figure 15 indicates the amount of positional deviation in the X direction between the center CC of the bottom of the reaction cell R0 in the X direction and the center position CS of the liquid level LS in the X direction. ΔS also changes in the order of ΔS1, ΔS2, ΔS3, and ΔS4 in accordance with changes in the center position CS of the liquid level LS in the X direction from Csh1 to Csh2, Csh3, and Csh4. In the example shown in FIG. 15, as the height h of the liquid level LS decreases, the central position CS approaches the center CC of the bottom, and as a result, ΔS becomes smaller.

[0104] In this way, when the reaction cell R0 is tilted with respect to the Z direction, the center position CS of the liquid level LS in the X direction also changes according to the change in the height h of the liquid level LS. Therefore, the processor 16 corrects the position of the nozzle 12A in the X direction while aspirating the liquid, thereby making it possible to correct the position of the tip E of the tip 12C to an appropriate position according to the change in the height h of the liquid level LS.

[0105] More specifically, the processor 16 performs a correction to make the position of the tip E of the chip 12C follow the central position CS of the liquid level LS in the X direction that intersects the Z direction, which changes depending on the height h of the liquid level LS.

[0106] The effect of having the tip E of the tip 12C follow the center position CS of the liquid level LS is as follows: When the reaction cell R0 is tilted, by appropriately ensuring the clearance between the sidewall of the reaction cell R0 and the nozzle regardless of the height of the nozzle 12A, splashing of the liquid caused by the pressure difference in the horizontal X direction can be suppressed. In other words, by having the tip E of the tip 12C follow the center position CS of the liquid level LS, the distance between the tip E and the sidewall of the reaction cell R0 can be made equal in both directions in the X direction, even if the liquid level LS changes. This suppresses the pressure difference in the liquid flowing into the tip 12C from the X direction, which is expected to have the effect of suppressing splashing of the liquid in the tip 12C.

[0107] FIG. 17 is a flowchart showing the procedure for controlling the position of the nozzle 12A executed in the third embodiment. In the third embodiment, step S1610B shown in FIG. 17 is executed as step S1610 shown in FIG. 13. Step S1610B shown in FIG. 17 differs from step S1610A of the second embodiment shown in FIG. 14 in the steps between step S1620 and step S1640. First, when the suction period SP starts, in step S1631, the processor 16 moves the height of the tip 12C to the initial suction position. The initial suction position is the position where DC21 is secured as the clearance DC in FIGS. 15 and 16. The processor 16 starts suction from this position. Then, in step S1632, the processor 16 lowers the height of the tip 12C in accordance with the decrease in the height h of the liquid level LS. As a result, a relatively large clearance DC21 is secured as the clearance DC at the beginning of the suction period SP, so there is ample clearance DC even when errors in bottom position detection are taken into account. Therefore, although the suction volume increases at the beginning of the suction period SP, a generous clearance DC is secured, suppressing adhesion of liquid to the nozzle 12A. Furthermore, at the end of the suction period SP, the clearance DC decreases to DC24, but the suction volume is also small, so there is little concern about liquid adhesion.

[0108] Next, in step S1633, the processor 16 causes the position of the tip E of the tip 12C to follow the center position CS, which changes depending on the height h of the liquid level LS. This suppresses the pressure difference in the X direction, even when the height h of the liquid level LS changes, thereby suppressing adhesion of the liquid. The processor 16 causes the tip 12C to follow the center position CS as the height of the liquid level LS decreases, but in the final stage shown in FIG. 15(D), a correction is made to align the tip E of the tip 12C with a position corresponding to the center CC of the reaction cell R0.

[0109] In this way, in the position control of the nozzle 12A during suction in the third embodiment, both the height of the chip 12C in the Z direction and the position of the chip 12C in the X direction are controlled.

[0110] [Fourth Embodiment] In the third embodiment shown in Figure 16, the processor 16 controls the position of the nozzle 12A during aspiration by controlling both the height of the tip 12C in the Z direction and the position of the tip 12C in the X direction. In contrast, in the fourth embodiment shown in Figure 18, the position of the nozzle 12A during aspiration is controlled by controlling only the height of the tip 12C in the Z direction. That is, as shown in Figures 18(A) to 18(D), the distance ΔF in the X direction between the tip E of the tip 12C and the center CC of the reaction cell R0 remains constant regardless of the change in ΔS from ΔS1 to ΔS4. If the change in the center position CS of the liquid level LS is slight, correcting the X direction position of the tip 12C during aspiration is permissible because it does not significantly affect the effect of suppressing liquid adhesion.

[0111] In the fourth embodiment, the effect of controlling the height of the tip 12C during suction can be obtained, as in the third embodiment. Furthermore, since the position control of the nozzle 12A is limited to height control, the process is simple.

[0112] Furthermore, in each of the above embodiments, the horizontal position of the nozzle 12A is corrected only in the X direction, but if correction is also required in the Y direction, correction may be performed in the Y direction.

[0113] In the above embodiment, the testing device 10 employing a testing method based on the chemiluminescent enzyme immunoassay method has been described as an example, but the technology of the present disclosure may also be applied to testing devices employing other testing methods. The technology of the present disclosure is effective for testing devices employing testing methods that require agitation of a liquid containing a specimen and a reagent and that require suppression of contamination caused by liquid adhesion to the nozzle.

[0114] In the above embodiment, the processor 16 can be any of various processors having the following hardware structures.

[0115] Various types of processors include CPUs, programmable logic devices (PLDs), dedicated electrical circuits, etc. As is well known, a CPU is a general-purpose processor that executes software (programs) and functions as various processing units. A PLD is a processor such as an FPGA (Field Programmable Gate Array) whose circuit configuration can be changed after manufacturing. A dedicated electrical circuit is a processor such as an ASIC (Application Specific Integrated Circuit) that has a circuit configuration designed specifically to execute specific processing.

[0116] A single processing unit may be configured with one of these various processors, or may be configured with a combination of two or more processors of the same or different types (e.g., multiple FPGAs, or a combination of a CPU and an FPGA). Multiple processing units may also be configured with a single processor. Examples of multiple processing units configured with a single processor include: a first configuration in which a single processor is configured with a combination of one or more CPUs and software, and this processor functions as multiple processing units; and a second configuration in which a processor is used that realizes the functions of an entire system including multiple processing units on a single IC chip, as typified by a system-on-chip (SoC). In this way, the various processing units are configured with one or more of the above-mentioned various processors as a hardware structure.

[0117] Furthermore, more specifically, the hardware structure of these various processors can be an electric circuit that combines circuit elements such as semiconductor elements.

[0118] The technology of the present disclosure is not limited to the above-described embodiments, and various configurations may be adopted without departing from the spirit of the technology of the present disclosure. The program of the present disclosure can be provided as a program product. The program product includes all types of products for providing a program. For example, the program product includes a program provided via a network such as the Internet, and a non-transitory computer-readable recording medium such as a CD-ROM or DVD on which the program is stored.

[0119] The above-described description and illustrations are a detailed explanation of the parts related to the technology of the present disclosure and are merely an example of the technology of the present disclosure. For example, the above description of the configuration, functions, actions, and effects is an explanation of an example of the configuration, functions, actions, and effects of the parts related to the technology of the present disclosure. Therefore, it goes without saying that unnecessary parts may be deleted, new elements may be added, or replacements may be made to the above-described description and illustrations within the scope of the gist of the technology of the present disclosure. Furthermore, to avoid confusion and facilitate understanding of the parts related to the technology of the present disclosure, the above-described description and illustrations omit explanations of common technical knowledge that do not require particular explanation to enable the implementation of the technology of the present disclosure.

[0120] The disclosure of Japanese Patent Application No. 2024-018863, filed on February 9, 2024, is incorporated herein by reference in its entirety. All documents, patent applications, and technical standards mentioned herein are incorporated herein by reference to the same extent as if each individual document, patent application, and technical standard was specifically and individually indicated to be incorporated by reference.

[0121] The above description allows the understanding of the following technologies. [Supplementary Item 1] A testing device for testing a sample, comprising: a nozzle having a replaceable tip attached to its tip that comes into contact with a liquid containing a sample and a reagent, the nozzle agitating the liquid in a container containing the liquid by repeatedly aspirating and dispensing the liquid; and a processor that controls correction of the position of the nozzle relative to the container in accordance with at least one of the position and attitude of the container. [Supplementary Item 2] The testing device described in Supplementary Item 1, wherein, when correcting the position of the nozzle in a direction intersecting an entry direction of the tip into the container, the processor performs correction to align the position of the tip's tip with a target position at the bottom of the container as a reference. [Supplementary Item 3] The testing device described in Supplementary Item 1 or Supplementary Item 2, wherein, when the container is tilted with respect to the entry direction of the tip and the height of the liquid level in the container changes due to aspirating the liquid, the processor corrects the position of the nozzle in the direction intersecting the entry direction while aspirating the liquid. [Supplementary Item 4] The inspection device according to Supplementary Item 3, wherein the processor corrects the position of the tip end to follow the center position of the liquid level in a direction intersecting the direction of entry, which center position changes according to the height of the liquid level. [Supplementary Item 5] The inspection device according to any one of Supplementary Items 1 to 4, wherein, in a case where the container is tilted with respect to the direction of entry of the tip and the height of the liquid level in the container changes due to suction of the liquid, the processor controls to lower the height of the tip according to the decrease in the height of the liquid level. [Supplementary Item 6] The inspection device according to any one of Supplementary Items 1 to 5, wherein, with respect to the distance between the bottom of the container and the tip end of the tip, the distance in the case of dispensing is defined as a first distance and the distance in the case of suction is defined as a second distance, the second distance is larger than the first distance. [Supplementary Item 7] The testing device according to any one of Supplementary Items 1 to 6, wherein the method for testing a specimen is a testing method for optically detecting a target substance in the specimen by utilizing an antigen-antibody reaction between the target substance and a reagent, and the stirring operation is an operation for dispersing the reagent and the specimen in the liquid. [Supplementary Item 8] The testing device according to Supplementary Item 7, wherein the reagent includes an antigen or antibody bound to magnetic particles.[Supplementary Item 14] A method for operating an inspection device comprising: a nozzle having a replaceable tip attached to its tip that comes into contact with a liquid containing a specimen and a reagent, the nozzle performing a liquid agitation operation by repeatedly aspirating and discharging the liquid in a container containing the liquid; and a processor, wherein the processor performs control to correct the position of the nozzle with respect to the container in accordance with at least one of the position and attitude of the container. [Supplementary Item 15] An operation program for an inspection device comprising: a nozzle having a replaceable tip attached to its tip that comes into contact with a liquid containing a specimen and a reagent, the nozzle performing a liquid agitation operation by repeatedly aspirating and dispensing the liquid in a container containing the liquid; and a processor, wherein the operation program for an inspection device causes the processor to execute control to correct the position of the nozzle with respect to the container in accordance with at least one of the position and attitude of the container.

Claims

1. A testing device for testing a specimen, comprising: a nozzle having a replaceable tip attached to the tip thereof, which comes into contact with a liquid containing the specimen and a reagent, and which agitates the liquid by repeatedly suctioning and discharging the liquid within a container containing the liquid; and a processor which controls the correction of the position of the nozzle relative to the container in accordance with at least one of the position and attitude of the container.

2. The inspection device according to claim 1, wherein when correcting the position of the nozzle in a direction intersecting the direction in which the tip enters the container, the processor performs a correction to align the position of the tip of the tip with a target position at the bottom of the container as a reference.

3. The inspection device according to claim 1, wherein, when the container is tilted relative to the direction of entry of the tip and the height of the liquid surface in the container changes due to the suction of the liquid, the processor corrects the position of the nozzle in a direction intersecting the direction of entry while the liquid is being suctioned.

4. The inspection device according to claim 3, wherein the processor corrects the position of the tip of the tip to follow the center position of the liquid surface in a direction intersecting the entry direction, the center position changing depending on the height of the liquid surface.

5. The inspection device according to claim 1, wherein when the container is tilted relative to the direction in which the tip is inserted and the liquid level in the container changes due to the suction of the liquid, the processor controls the tip to be lowered in accordance with the decrease in the liquid level.

6. The inspection device according to claim 1, wherein, with respect to the distance between the bottom of the container and the tip of the tip, when the distance in the case of discharging is defined as a first distance and when the distance in the case of suction is defined as a second distance, the second distance is larger than the first distance.

7. The testing device according to claim 1, wherein the method for testing the specimen is a testing method for optically detecting the target substance in the specimen by utilizing an antigen-antibody reaction between the target substance in the specimen and the reagent, and the stirring operation is an operation for dispersing the reagent and the specimen in the liquid.

8. The testing device according to claim 7, wherein the reagent contains an antigen or antibody bound to magnetic particles.

9. A method for operating an inspection device comprising: a nozzle having a replaceable tip attached to the tip thereof that comes into contact with a liquid containing a specimen and a reagent, the nozzle agitating the liquid by repeatedly suctioning and discharging the liquid within a container containing the liquid; and a processor, wherein the processor controls to correct the position of the nozzle relative to the container according to at least one of the position and attitude of the container.

10. An operating program for an inspection device comprising a nozzle having a replaceable tip attached to the tip that comes into contact with a liquid containing a specimen and a reagent, the nozzle agitating the liquid by repeatedly suctioning and discharging the liquid in a container containing the liquid, and a processor, the operating program for an inspection device causing the processor to execute control to correct the position of the nozzle relative to the container depending on at least one of the position and attitude of the container.

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