Analyte analysis device and analyte analysis method

Abstract

To solve the problem that when a long time has passed since an analyte was agitated, the analyte become insufficiently mixed.SOLUTION: In S14, an analyte is agitated using a nozzle. When it is determined in S16 that the time elapsed since agitation using the nozzle does not exceeded a predetermined time, in S18, analyte dispensing is performed using a nozzle. In S16, when it is determined that the time elapsed since agitation using the nozzle exceeds a predetermined time, steps S50 to S60 are performed. In S56, the analyte is manually re-agitated by an examiner. The analyte may be re-agitated using the nozzle instead of manually re-agitating the analyte.SELECTED DRAWING: Figure 9

Description

Technical Field

[0001] The present invention relates to a specimen analysis apparatus and a specimen analysis method, and particularly to specimen stirring before specimen dispensing.

Background Art

[0002] A specimen analysis apparatus is an apparatus that analyzes blood, urine, etc. collected from a subject. As specimen analysis apparatuses, an immunoassay apparatus, a biochemical analyzer, etc. are known.

[0003] When analyzing blood, for example, blood collected from a subject is stored in a blood collection tube containing an anticoagulant. The blood is a specimen, and it is also referred to as whole blood. In the whole blood in the blood collection tube or the whole blood transferred from the blood collection tube to another container, over time, blood cell components (red blood cells, white blood cells, etc.) settle to the lower part of the container. That is, a concentration gradient of blood cell components occurs in the blood collection tube or another container. When all or part of the analyte is contained in the blood cell components, if a part of such non-uniform whole blood is aspirated and analyzed, the reliability of the analysis result will decrease. Also, in specimens other than whole blood, if a concentration gradient occurs in a specific substance to be quantified, that is, the analyte, the same problem as above occurs. In order to eliminate the concentration gradient, it is necessary to stir the specimen.

[0004] Patent Documents 1 and 2 disclose a technique for stirring a specimen by repeating aspiration and discharge of the specimen. However, those patent documents do not disclose control based on the elapsed time after stirring the specimen by a nozzle.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0006] Prior to specimen analysis (typically quantification of an analyte), the specimen in the original container is aspirated into the nozzle (i.e., sampled), and the aspirated specimen is discharged from the nozzle into the reaction container. If a concentration gradient of the analyte occurs in the original container during sampling of the specimen, the reliability of the analysis results will decrease. Therefore, prior to sampling of the specimen, it is conceivable to stir the specimen using the nozzle to create a mixed state of the specimen. However, if the timing of actually sampling the specimen is delayed due to various circumstances after stirring the specimen, ultimately a concentration gradient of the analyte will occur in the specimen.

[0007] An object of the present invention is to improve the reliability of specimen analysis results. Alternatively, an object of the present invention is to prevent an insufficiently mixed specimen from being sampled.

Means for Solving the Problems

[0008] The specimen analysis apparatus according to the present invention includes a nozzle, a stirring control unit that controls stirring of the specimen in the original container by the nozzle, and a dispensing control unit that controls specimen dispensing for dispensing the specimen in the original container using the nozzle after stirring by the nozzle, wherein the dispensing control unit restricts implementation of the specimen dispensing based on the elapsed time after stirring by the nozzle.

[0009] The specimen analysis method according to the present invention includes a stirring control step of controlling stirring of the specimen in the original container by the nozzle, a dispensing control step of controlling specimen dispensing for dispensing the specimen in the original container using the nozzle after stirring by the nozzle, and an analysis step of performing specimen analysis after the specimen dispensing, wherein the dispensing control step includes a step of controlling implementation of the specimen dispensing based on the elapsed time after stirring by the nozzle.

Effects of the Invention

[0010] According to the present invention, the reliability of the specimen analysis result can be enhanced. Alternatively, according to the present invention, sampling of a specimen with insufficient mixing can be avoided.

Brief Description of the Drawings

[0011]

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Best Mode for Carrying Out the Invention

[0012] Hereinafter, embodiments will be described with reference to the drawings.

[0013] (1) Outline of Embodiment The specimen analyzer according to the embodiment has a nozzle, a stirring control unit, and a dispensing control unit. The stirring control unit controls the stirring of the specimen in the original container by the nozzle. The dispensing control unit controls the specimen dispensing for dispensing the specimen in the original container using the nozzle after the stirring by the nozzle. The dispensing control unit restricts the implementation of specimen dispensing based on the elapsed time after the stirring by the nozzle.

[0014] According to the above configuration, when the mixing state in the specimen becomes insufficient due to an increase in the elapsed time after the stirring by the nozzle, the implementation of specimen dispensing is restricted. Therefore, an opportunity to confirm the specimen state can be obtained, or an opportunity to reform the mixing state can be obtained. The above implementation restrictions include conditional implementation. For example, the implementation of specimen dispensing is permitted only when the specimen is re-stirred. A processor described later functions as the stirring control unit and the dispensing control unit.

[0015] The stirring by the nozzle consists of n suction and discharge operations. Here, n is an integer of 1 or more. In each suction and discharge operation, the specimen in the original container is sucked into the nozzle, and then the specimen in the nozzle is discharged into the original container. In the embodiment, the stirring by the nozzle is performed at the position where the specimen suction for specimen dispensing (that is, the sampling position) is performed. Even when the re-stirring by the nozzle is performed, the re-stirring is performed at the sampling position.

[0016] In an embodiment, the dispensing control unit includes a determination unit, a restriction unit, and a release unit. The determination unit determines an error based on the elapsed time after stirring by the nozzle. The restriction unit restricts the execution of sample dispensing when an error is determined. The release unit releases the restriction on the execution of sample dispensing when re-stirring of the sample in the original container is completed after the execution of sample dispensing has been restricted.

[0017] According to the above configuration, the mixing state of the sample is re-formed by re-stirring the sample, and then sampling of the sample is permitted. Therefore, it is possible to prevent a decrease in the accuracy of sample analysis caused by the concentration gradient of the analyte. Re-stirring of the sample includes re-stirring by the user and re-stirring by the nozzle. In addition, when an error is determined, it may be determined by the user (examiner) who visually recognizes the sample state that re-stirring is not necessary.

[0018] In an embodiment, the dispensing control unit includes a notification unit that provides information requesting the user to re-stir the sample in the original container when an error is determined. The release unit determines the completion of re-stirring based on a predetermined operation of the user after re-stirring. According to this configuration, it is possible to notify the user of the necessity of re-stirring the sample. It is recognized based on a predetermined operation that the user has performed re-stirring. Examples of the predetermined operation include an operation of a button, an input on a screen, and the like.

[0019] In an embodiment, the dispensing control unit determines an error based on the elapsed time after stirring by the nozzle. When an error is determined, the stirring control unit controls re-stirring of the sample in the original container by the nozzle. When an error is determined, the dispensing control unit controls sample dispensing after waiting for the completion of the re-stirring. According to this configuration, the burden on the user caused during re-stirring of the sample can be eliminated. The stirring conditions may be made different between the first stirring by the nozzle and the subsequent re-stirring by the nozzle. Whether further re-stirring is required may be determined based on the elapsed time after the re-stirring. In the re-stirring by the nozzle, stirring conditions different from those applied in the previous stirring by the nozzle may be applied. For example, the suction volume, discharge volume, stirring time, number of suction / discharge operations, etc. may be changed. The re-stirring conditions may be changed according to the degree to which the elapsed time after stirring by the nozzle exceeds the determination time. When sample dispensing is performed after waiting for the completion of the re-stirring, the start of the sample dispensing corresponds to the release of the restriction on the performance of the sample dispensing.

[0020] In an embodiment, the dispensing control unit determines a first error when the elapsed time after stirring by the nozzle exceeds a first determination time, and determines a second error when the elapsed time after re-stirring by the nozzle exceeds a second determination time. The first determination time and the second determination time can be set independently of each other. The first determination time and the second determination time may be made to coincide with each other, or they may be made different from each other. The first determination time and the second determination time may be adaptively set according to the situation. The re-stirring conditions when the first error is determined and the re-stirring conditions when the second error is determined may be made different from each other.

[0021] In an embodiment, the elapsed time after stirring by the nozzle is the time from a first reference time after the stirring by the nozzle is completed to a second reference time before starting the specimen dispensing. Examples of the first reference time include the nozzle tip discard timing, the end of a specific cycle time assigned for stirring by the nozzle, and the like. Examples of the second reference time include the current time as the error determination time, the nozzle tip mounting timing, the start of a specific cycle time assigned for specimen dispensing, the timing immediately before specimen aspiration, and the like. The specimen aspiration start timing may be used as the second reference time. In that case, desirably, the specimen aspiration start timing is predicted at a point in time before the specimen aspiration starts.

[0022] In an embodiment, the nozzle is composed of a nozzle body and a nozzle tip attached thereto. The nozzle tip is replaced after stirring by the nozzle. The specimen adheres to the inner and outer surfaces of the nozzle tip during stirring by the nozzle. If the nozzle tip is not replaced after stirring, the attached residual specimen may affect the specimen analysis accuracy. According to the above configuration, since the nozzle tip is replaced after stirring by the nozzle, a decrease in specimen analysis accuracy due to the residual specimen can be avoided. The nozzle tip for specimen stirring and the nozzle tip for specimen dispensing may be prepared separately, or they may be the same.

[0023] In an embodiment, after the implementation of specimen dispensing is restricted, the stirring control unit controls re-stirring of the specimen in the original container by the nozzle. After re-stirring by the nozzle, the nozzle tip is replaced again. According to this configuration, even when stirring by the nozzle is performed again, a decrease in specimen analysis accuracy due to the residual specimen can be avoided.

[0024] In an embodiment, in a multi-dispensing operation in which the dispensing control unit performs a plurality of specimen dispensings on the same specimen, the dispensing control unit determines an error based on the elapsed time after stirring by the nozzle, and thereby interrupts the multi-dispensing operation. According to this configuration, in the multi-dispensing operation, it is possible to avoid the occurrence of a situation in which a specimen in an insufficient mixing state becomes the object of dispensing. The multi-dispensing operation consists of a plurality of specimen dispensings continuously performed on the same specimen. The multi-dispensing operation includes a multi-dispensing operation related to multiple measurements and a multi-dispensing operation related to multi-item measurements.

[0025] In an embodiment, after interrupting the multi-dispensing operation, the stirring control unit controls re-stirring of the specimen in the original container by the nozzle. The dispensing control unit waits for the completion of the re-stirring by the nozzle and then resumes the multi-dispensing operation. According to this configuration, it is possible to resume specimen dispensing after reforming the mixing state of the specimen.

[0026] In an embodiment, when an error is determined, the dispensing control unit provides information to the user requesting re-stirring of the specimen in the original container. Further, the dispensing control unit determines the completion of re-stirring based on a predetermined operation of the user after re-stirring, and when the re-stirring is completed, releases the interruption of the multi-dispensing operation. According to this configuration, after waiting for the completion of re-stirring by the user, the interrupted multi-dispensing operation is resumed. Therefore, it is possible to guarantee a specimen mixing state equal to or higher than a certain level throughout the multi-dispensing operation.

[0027] In an embodiment, in a multi-dispensing operation in which the dispensing control unit performs a plurality of specimen dispensings on the same specimen, when it is predicted that the elapsed time after stirring by the nozzle exceeds the determination time during the multi-dispensing operation, the dispensing control unit determines an error in advance. When an error is determined in advance, re-stirring of the specimen in the original container by the nozzle is incorporated during the multi-dispensing operation. According to this configuration, when a poor specimen mixing state is predicted at the scheduling stage of the multi-dispensing operation, the content of the multi-dispensing operation is corrected. That is, re-stirring is incorporated during the multi-dispensing operation. Therefore, it is possible to perform necessary re-stirring in a timely manner during the process of performing the multi-dispensing operation.

[0028] In an embodiment, in a multi-dispensing operation in which the dispensing control unit performs multiple specimen dispensings on the same specimen, when it is predicted that the elapsed time after stirring by the nozzle exceeds the determination time during the multi-dispensing operation, an error is determined in advance. Further, when an error is determined in advance, the dispensing control unit provides information to the user requesting re-stirring of the specimen in the original container, and determines the completion of re-stirring based on a predetermined operation of the user after re-stirring. In this way, when an error is determined in advance, re-stirring by the user of the specimen in the original container is incorporated during the multi-dispensing operation. Therefore, it is possible to guarantee a specimen mixing state of a certain level or more throughout the multi-dispensing operation. In particular, since an error is determined in advance and re-stirring is incorporated in advance during the multi-dispensing operation, re-stirring by the user is performed in a timely manner, and it is possible to prevent the interruption of the multi-dispensing operation from being prolonged.

[0029] In an embodiment, in the stirring by the nozzle, the nozzle is conveyed up and down in accordance with the vertical movement of the liquid level of the specimen in the original container. By synchronizing the vertical movement of the nozzle with the vertical movement of the liquid level, it is possible to control the amount of entry of the nozzle into the specimen in the original container within a constant value or a certain range. For example, the amount of entry of the nozzle into the specimen in the original container in the stirring by the nozzle is in the range of 0.5 to 15 mm.

[0030] The specimen analyzer according to the embodiment includes a pressure sensor that detects the pressure inside the nozzle, and suction abnormality determination means that determines at least one of bubble suction, clogging, and leakage as a suction abnormality based on the output signal of the pressure sensor in the stirring by the nozzle, and error processing means that executes error processing when a suction abnormality is determined. According to this configuration, it is possible to avoid a situation in which the suction and discharge operation proceeds in a situation where there is a possibility that the mixing state of the specimen cannot be properly formed. In an embodiment, the processor functions as the suction abnormality determination means and the error processing means.

[0031] The specimen analysis apparatus according to the embodiment includes a height determination means for determining the height of the liquid surface of the specimen in the original container prior to stirring by the nozzle, and an error processing means for executing error processing when the height of the liquid surface is outside a predetermined height range. According to this configuration, it is possible to avoid a situation where the suction and discharge operation proceeds under a condition where appropriate stirring cannot be performed because the liquid volume is too large or too small. The concept of the height of the liquid surface includes the liquid volume. In the embodiment, the processor functions as the height determination means (liquid volume determination means) and the error processing means.

[0032] The specimen analysis method according to the embodiment includes a stirring control step, a dispensing control step, and an analysis step. In the stirring control step, the stirring by the nozzle for the specimen in the original container is controlled. In the dispensing control step, after the stirring by the nozzle, the specimen dispensing for dispensing the specimen in the original container using the nozzle is controlled. In the analysis step, the specimen analysis is performed after the specimen dispensing. The dispensing control step includes a step of controlling the execution of the specimen dispensing based on the elapsed time after the stirring by the nozzle.

[0033] Since the state of the specimen changes according to the elapsed time after the stirring by the nozzle, the execution of the specimen dispensing is controlled according to the change in the state of the specimen. Examples of the control of the execution of the specimen dispensing include not only the restriction of the execution of the specimen dispensing but also the change of the operation or conditions of the specimen dispensing. In the embodiment, when the elapsed time after the stirring by the nozzle exceeds the determination time, the specimen dispensing is restricted, the re-stirring of the specimen is performed, and the specimen dispensing is performed after waiting for the completion of the re-stirring.

[0034] (2) Details of the Embodiment FIG. 1 shows a specimen analysis apparatus 10 according to the embodiment. FIG. 1 schematically shows the upper surface of the specimen analysis apparatus 10. This specimen analysis apparatus 10 is an immunoassay apparatus that analyzes a specimen using an immune reaction, that is, an antigen-antibody reaction. Specifically, it is an immunoassay apparatus according to the chemiluminescent enzyme immunoassay (CLEIA). The technical matters described below may also be applied to a biochemical analyzer or the like.

[0035] In FIG. 1, the specimen analyzer 10 includes a specimen supply unit 12, a reaction unit 14, a reagent supply unit 16, a light detection unit 18, a cuvette supply unit 20, a substrate cooler 22, cuvette transfer mechanisms 24, 26, a specimen dispensing mechanism 28, reagent dispensing mechanisms 30, 32, and the like.

[0036] The specimen supply unit 12 has a turntable 33 as a rotating table. A holding hole group 34 is formed in the turntable 33, and the holding hole group 34 is composed of a plurality of holding holes 34a. In the illustrated example, the holding hole group 34 is composed of an outer holding hole row formed by a plurality of holding holes 34a arranged in a ring and an inner holding hole row formed by a plurality of holding holes 34a arranged in a ring. Each holding hole 34a is a portion for accommodating a specimen container as an original container. A specimen is accommodated in the specimen container.

[0037] In the embodiment, the specimen is whole blood. Other liquids collected from a living body may be used as the specimen. The specimen container (original container) is a blood collection tube containing whole blood or other container containing whole blood. For example, blood collected from a living body is accommodated in a blood collection tube containing an anticoagulant. In that case, the blood in the blood collection tube or the blood transferred from the blood collection tube to another container is the whole blood as the specimen. As is well known, whole blood contains blood cell components, and when whole blood is allowed to stand, the blood cell components settle. The sedimentation rate varies depending on the specimen.

[0038] In the specimen analyzer according to the embodiment, as will be described in detail later, specimen stirring is performed immediately before specimen dispensing. Specifically, the specimen stirring is stirring by the suction and discharge operation of the nozzle, that is, stirring by the nozzle. When the elapsed time after the first stirring by the nozzle increases, the user is required to re-stir the specimen. Instead of re-stirring by the user, re-stirring by the nozzle may be performed.

[0039] In the case of whole blood in a hemolytic state, depending on the degree of hemolysis, most of the analyte in the blood cell component may elute into the plasma. Therefore, depending on the degree of hemolysis, it may be determined whether specimen stirring is required immediately before specimen dispensing. The degree of hemolysis can be determined by measuring the hemoglobin value in the supernatant of the specimen. The degree of hemolysis may also be determined by analyzing an image obtained by imaging the specimen. On the other hand, depending on the degree of blood cell concentration, the erythrocyte sedimentation rate may slow down and the influence on the analysis may become small. Therefore, depending on the degree of blood cell concentration, it may be determined whether specimen stirring is required immediately before specimen dispensing. The degree of blood cell concentration can be determined by measuring the hematocrit value. As the hematocrit value, a measured value obtained by a known method (such as the microhematocrit method) may be used. The degree of sedimentation may also be determined by analyzing an image obtained by imaging the specimen.

[0040] By the manual operation of the user (examiner), each specimen container is inserted into each holding hole 34a. That is, each specimen container is installed. Usually, prior to the insertion of each specimen container, the specimen in the specimen container is stirred by repeatedly shaking the specimen container, that is, by repeatedly performing mixing by inversion. Any number of specimen containers can be installed with respect to the specimen supply unit 12. The timing of installing each specimen container can also be arbitrarily determined by the examiner.

[0041] Prior to the installation of the specimen container, the button 36 is operated by the examiner. Thereby, the operation of the specimen supply unit 12 is temporarily interrupted, and a state in which the specimen supply unit 12 can receive the specimen container is formed. After the installation of the specimen container, the button 36 is operated again by the user. Thereby, the operation of the specimen supply unit 12 resumes. A virtual button replacing the button 36 may be displayed on a touch screen panel or the like. The button 38 is operated when it is desired to rotate the turntable 33. The button 36 and the button 38 may be integrated.

[0042] The specimen supply unit 12 is provided with a barcode reader (BCR) (not shown). By the BCR, the content of the barcode label attached to each specimen container held by the holding hole group 34 is read. Thereby, specimen information such as specimen ID is read for each specimen. Based on the specimen ID, subject information, analysis items, specimen container type, etc. are specified.

[0043] The reaction unit 14 has a turntable 39 as a turntable. A holding hole group 40 is formed in the turntable 39, and the holding hole group 40 is composed of a plurality of holding holes 40a. In the illustrated example, the holding hole group 40 is composed of an outer holding hole row composed of a plurality of holding holes 40a arranged in a ring and an inner holding hole row composed of a plurality of holding holes 40a arranged in a ring. Each holding hole 40a is a portion for accommodating a cuvette as a reaction vessel. Reagents and specimens are injected stepwise into each cuvette. Thereby, an immunoreaction occurs in each cuvette.

[0044] In the embodiment, for example, the specimen is measured based on the so-called two-step method. The two-step method includes a first immunoreaction step using a first reagent containing a first antibody, a second immunoreaction step using a second reagent containing a second antibody, an enzyme reaction step using a substrate (substrate solution), and a light detection step. In the reaction unit 14, the first immunoreaction step, the second immunoreaction step, and the enzyme reaction step are carried out. Also, in the reaction unit 14, a stirring step, a B / F washing step, etc. are carried out. In FIG. 1, the illustration of the mechanism of the reaction unit 14 is omitted. Note that the stirring method in the reaction unit 14 is a vortex stirring method in which the cuvette is swirled to generate a vortex in the cuvette.

[0045] The reagent supply unit 16 has a reagent tank 41 as a rotating cold storage. The reagent tank 41 houses a reagent bottle row 42 and a reagent bottle row 44. The reagent bottle row 42 and the reagent bottle row 44 are each composed of a plurality of reagent bottles. Each reagent bottle contains a reagent. Reagent dispensing mechanisms 30 and 32 are provided adjacent to the reagent supply unit 16 and the reaction unit 14. The reagent dispensing mechanism 30 has a pivoting arm 60 and a nozzle 62 provided at the tip of the arm 60. The reagent dispensing mechanism 32 has a pivoting arm 64 and a nozzle 65 provided at the tip of the arm 64. The nozzles 62 and 65 are non-replaceable nozzles, that is, cleaning type nozzles. By the reagent dispensing mechanisms 30 and 32, a specific reagent is aspirated and the aspirated reagent is discharged into a specific cuvette.

[0046] The light detection unit 18 is a unit that detects luminescence generated in the cuvette after the enzymatic reaction. Based on the detection value, the concentration etc. of the analyte is calculated. When transferring the cuvette, the cuvette transfer mechanisms 24 and 26 function. In FIG. 1, the reference numerals 56 and 58 each indicate a disposal unit. Used cuvettes and used nozzle tips are discarded in the disposal unit.

[0047] In the illustrated configuration example, the specimen dispensing mechanism 28 has a rail mechanism 46, a slide base 48, an arm 50, a nozzle 52, etc. The rail mechanism 46 has rails extending in a direction inclined with respect to the left-right direction and the depth direction of the apparatus. The slide base 48 slides along the rails (see reference numeral 53). The base end portion of the arm 50 is rotatably held by the slide base 48, and the nozzle 52 is disposed at the tip end portion of the arm 50.

[0048] The nozzle 52 is composed of a nozzle body and a nozzle tip. The nozzle tip is detachably attached to the nozzle body. The nozzle body is made of metal, and the nozzle tip is made of a resin having transparency, semi-transparency or non-transparency. The nozzle tip is replaced after specimen dispensing. In the embodiment, the nozzle tip is also replaced even after agitation by the nozzle.

[0049] In the sample supply unit 12, a first suction position (outer suction position) and a second suction position (inner suction position) are defined. At each suction position, in addition to performing sample suction for dispensing, stirring of the sample is also performed. The stirring of the sample will be described in detail later.

[0050] The movement area of the nozzle 52 is enlarged by the combination of the sliding movement of the slide base 48 and the turning movement of the arm 50. Under the control of the control unit described later, during sample dispensing, the sample in the sample container (original container) at the suction position (the first suction position or the second suction position) is sucked by the nozzle 52, and the sucked sample is discharged from the nozzle 52 into a specific cuvette on the reaction unit 14. The discharge destination position may be fixedly determined or may be dynamically changed. In the embodiment, after the first reagent is dispensed into the cuvette, the sample is discharged into the cuvette. When the sample is discharged, the sample and the first reagent are mixed together.

[0051] The sample dispensing mechanism 28 shown in FIG. 1 is an example, and other mechanisms may be adopted as the sample dispensing mechanism 28. For example, a sample dispensing mechanism 28 without the rail mechanism 46 may be adopted, or a sample dispensing mechanism provided with an X rail and a Y rail may be adopted.

[0052] The tip rack 54 is a member that holds a plurality of nozzle tips. When replacing the nozzle tip, the used nozzle tip is removed from the nozzle body and discarded. Then, the tip of the nozzle body is inserted into the upper opening of the nozzle tip selected from the tip rack 54. Thereby, a new nozzle tip is attached to the nozzle body. The tip rack is replaced by a tip rack replacement mechanism (not shown).

[0053] The aspiration and discharge control will be described with reference to FIG. 2. The specimen dispensing mechanism has a nozzle transfer mechanism 28A. The nozzle transfer mechanism 28A is composed of the rail mechanism, slide base, arm, etc. that have been described above. A syringe pump 76 is fixed to the arm. The syringe pump 76 has a syringe and a piston, and generates aspiration pressure and discharge pressure. Other types of pumps may be used.

[0054] The nozzle 52 is held by the nozzle transfer mechanism 28A. The nozzle transfer mechanism 28A can move the nozzle 52 freely in the vertical and horizontal directions. The nozzle 52 is composed of a nozzle body 70 and a nozzle tip 72 as described above. The nozzle body 70 can also be referred to as a sample rod. In FIG. 2, a specimen container 67 that has been transferred to the aspiration position in the specimen supply unit 12 and stopped at the aspiration position is shown. A specimen (whole blood) 68 is contained therein.

[0055] A tube 74 is provided between the nozzle body 70 and the syringe pump 76, and the aspiration pressure and discharge pressure are transmitted through the air in the tube 74. A pressure sensor 78 is provided in the middle of the tube 74. The pressure sensor 78 detects the pressure of the air in the tube 74. That pressure indicates the pressure in the nozzle 52. The detection signal from the pressure sensor 78 is output to the information processing unit 80.

[0056] The information processing unit 80 is composed of, for example, a computer equipped with a processor. The information processing unit 80 functions as a control unit, an arithmetic unit, etc. In the illustrated configuration example, a timer 82, an input device 84, a display 86, and a communicator 88 are connected to the information processing unit 80. The information processing unit 80 has a storage unit, but its illustration is omitted in FIG. 2.

[0057] Timer 82 is for measuring the elapsed time after sample agitation, specifically, for measuring the elapsed time from the first reference time after sample agitation to the second reference time before the start of sample aspiration (sample sampling for sample dispensing). The elapsed time is used as reference information for estimating the sedimentation rate of blood cell components in the sample container 67. That is, the information is for confirming that the sample is in a mixed state during sample sampling or for determining the necessity of re-agitating the sample. The information processing unit 80 itself may perform a timing function.

[0058] Note that the timer 82 may measure the elapsed time from the reference time after sample installation to the reference time before the start of sample sampling. Based on the elapsed time, the necessity of sample agitation immediately before sample sampling may be determined.

[0059] The input device 84 can be composed of a button, a switch, a touch panel, a pointing device, a keyboard, etc. The display 86 can be composed of a liquid crystal display, an organic EL display device, etc. The communicator 88 functions when the information processing unit 80 exchanges data with a host computer via a network.

[0060] In the embodiment, when the agitation condition is satisfied, sample agitation is performed prior to sample dispensing. This will be specifically described. The nozzle 52 is transferred above the sample container 67 at the suction position, and then the nozzle 52 is lowered. In the lowered state, air is continuously fed into the nozzle 52 by the action of the syringe pump 76. When the tip of the nozzle 52 contacts the liquid surface of the sample 68 and the air pressure rise at the time when the tip opening is blocked is detected by the pressure sensor 78. Based on the output signal from the pressure sensor 78, the information processing unit 80 specifies the height of the liquid surface and calculates the liquid volume from the height. Incidentally, the type of the sample container 67 can be specified based on the sample ID, and the type of the sample container 67 is referred to when calculating the liquid volume.

[0061] After the liquid level is detected, the sample is sucked into the nozzle tip 72 by the action of the syringe pump 76. During the suction process, the nozzle 52 is conveyed downward as the liquid level drops. Thereby, the amount of entry of the nozzle tip 72 into the sample 68 is maintained constant. When a predetermined amount of suction is completed, the descent of the nozzle 52 and the sample suction are stopped. Immediately thereafter, or after a certain temporary waiting time, the nozzle 52 is pulled upward, and sample discharge is performed by the action of the syringe pump 76. During the discharge process, the nozzle 52 is conveyed upward as the liquid level rises. Thereby, the amount of entry of the nozzle tip 72 into the sample 68 is maintained constant.

[0062] For example, as the amount of entry of the nozzle tip 72, a value within the range of 0.5 to 15 mm is selected. The lower limit of the range is determined from the viewpoint of avoiding air suction by the nozzle tip 72. The upper limit of the range is determined from the viewpoint of avoiding contact of the tip of the nozzle tip 72 with the inner bottom surface of the sample container 67, and is also determined from the viewpoint of suppressing the amount of sample adhering to the outer surface of the nozzle tip 72. Preferably, as the amount of entry of the nozzle tip 72, a value within the range of 1 to 4 mm is selected. All the numerical values given in this specification are merely examples. After the discharge is completed, with the above-mentioned amount of entry maintained, the ascent of the nozzle 52 and the sample discharge are stopped.

[0063] The above suction operation and discharge operation are repeatedly executed. The sample agitation consists of n suction and discharge operations. An arbitrary value can be specified in advance as the repetition number n. n is, for example, an integer of 1 or more, and values such as 5, 6, or 7 may be specified as n. The maximum number of repetitions that can be executed within one cycle time may be specified as n. n may be adaptively varied according to various conditions. When nozzle-based re-agitation is selected as the re-agitation method, that re-agitation also consists of a plurality of suction and discharge operations, similar to the first agitation. The agitation conditions (for example, the number of suction and discharge operations) in the first agitation and the agitation conditions (for example, the number of suction and discharge operations) in the re-agitation are set independently of each other.

[0064] As described above, in the agitation by the nozzle, the nozzle is vertically conveyed in accordance with the vertical movement of the liquid surface of the specimen. In other words, the nozzle moves vertically following and synchronizing with the vertical movement of the liquid surface of the specimen. In the process, the amount of entry of the nozzle into the specimen is set relatively small and is maintained. This can reduce the adhesion of the specimen to the outer surface of the nozzle and enable stable and reliable agitation of the specimen.

[0065] After the agitation by the nozzle is completed, after the nozzle tip is exchanged, specimen sampling for specimen dispensing is performed. As a result, a predetermined amount of the specimen is accommodated in the nozzle tip 72. While maintaining the accommodation state, the nozzle 52 is pulled upward and conveyed to the cuvette which is the discharge destination. By exchanging the nozzle tip, it is possible to avoid the problem of deterioration of the measurement accuracy due to the residual specimen adhering to the inner and outer surfaces of the nozzle tip 72. When such a problem does not occur or can be ignored, the nozzle tip exchange may be omitted. The specimen container 67 shown in FIG. 2 is an example, and various containers can be used as the specimen container.

[0066] By continuously performing specimen agitation and specimen sampling at the same position (sampling position), it becomes possible to quickly accommodate the specimen in the nozzle tip after specimen agitation. When the blood cell components are sedimented in whole blood, it is possible to use the whole blood with the blood cell component concentration made uniform as the sampling target by agitating the whole blood.

[0067] In the embodiment, if the specimen sampling cannot be performed promptly after the specimen agitation, an error is determined and the start of specimen dispensing is restricted. In that case, the user is notified of the necessity of manually re-agitating the specimen. After manually re-agitating the specimen, when the user makes a predetermined input, the restriction on the implementation of specimen dispensing is released and it becomes possible to start the implementation of specimen dispensing. As already described, instead of re-agitation by the examiner, re-agitation by the nozzle may be performed.

[0068] As reasons why sample sampling cannot be promptly performed after sample agitation, an increase in elapsed time due to nozzle tip mounting errors, incomplete preparation at the dispensing destination, etc. can be cited. When such circumstances occur, re-agitation of the sample is required or carried out prior to sample dispensing. Even when the elapsed time increases due to repetition of the dispensing operation in multiple measurements or repetition of the dispensing operation in multi-item measurements, re-agitation of the sample is required or carried out. Multiple measurements mean multiple measurements of the same analysis item for one sample. Multi-item measurements mean measurements of multiple analysis items for one sample. In both multiple measurements and multi-item measurements, since multiple dispensings are carried out for one sample, a certain amount of time is required until the last dispensing is completed, and during that process, the mixing state tends to become insufficient. The control of the implementation of sample dispensing based on the elapsed time will be described in detail later.

[0069] FIG. 3 shows a configuration example of the information processing unit 80. In FIG. 3, elements similar to those shown in FIG. 2 are denoted by the same reference numerals, and their descriptions are omitted. The information processing unit 80 includes a processor 90. The processor 90 is constituted by, for example, a CPU that executes a program.

[0070] In FIG. 3, a plurality of functions exhibited by the processor 90 are represented by a plurality of blocks. The processor 90 functions as a control unit 94, a bubble suction determination unit 98, a clogging determination unit 100, etc. The control unit 94 functions as an agitation control unit 210 and a dispensing control unit 212. The dispensing control unit 212 functions as a determination unit 214, a notification unit 216, a restriction unit 218, and a release unit 220.

[0071] The stirring control unit 210 determines whether the stirring conditions are satisfied, and controls the sample stirring using the nozzle when the stirring conditions are satisfied. As the stirring conditions, there are conditions that require the sample volume to be within a predetermined range, conditions that require the sample container not to have a shape unsuitable for stirring (for example, a large sample container), conditions that require the degree of hemolysis to be lower than a predetermined level, conditions that require the degree of blood sedimentation to be smaller than a predetermined level, and the like. The stirring conditions may include a condition that requires the elapsed time after the sample is installed not to exceed a predetermined time. When re-stirring by the nozzle is performed, the re-stirring is controlled by the stirring control unit 210.

[0072] The dispensing control unit 212 controls sample dispensing and related operations. Usually, sample dispensing is performed immediately after sample stirring. When sample dispensing cannot be performed immediately after sample stirring due to various reasons, the determination unit 214, the notification unit 216, the restriction unit 218, and the release unit 220 function.

[0073] Specifically, the determination unit 214 determines an error when the elapsed time from the first reference time after sample stirring to the second reference time before the start of sample sampling exceeds a predetermined time (determination time). That is, the determination unit 214 determines the necessity of re-stirring. When an error is determined, the notification unit 216 notifies the examiner of the necessity of re-stirring. For example, information requesting re-stirring (re-stirring request) is displayed on the screen of the display. The restriction unit 218 restricts (specifically, prohibits) the start of sample sampling when an error is determined. This can avoid a situation where dispensing and analysis are performed on a sample that is highly likely to have a concentration gradient of the measurement target substance.

[0074] In accordance with the above notification, the user takes out the specimen container to be stirred from the specimen supply unit. When taking out the specimen container, a button for taking out is operated beforehand. After taking out the specimen container, by repeatedly shaking the specimen container, that is, by repeatedly inverting the specimen container, a mixed state of the specimen is formed. Then, the specimen container is returned to the specimen supply unit. After the specimen container is reinstalled, the above button is operated again. In addition, after taking out the specimen container, even if it is determined by the user who has confirmed the specimen state that re-stirring is not necessary, the above button is also operated again.

[0075] In the embodiment, information about the specimen to be re-stirred is displayed on the display. By referring to the information, the re-stirring target can be identified. It is also possible that a plurality of specimens are each a re-stirring target. Before taking out the specimen container and after reinstalling the specimen container, the button displayed on the display may be operated.

[0076] When there is a button operation after reinstallation, the release unit 220 releases the restriction on the implementation of specimen dispensing. Thereby, the implementation of specimen dispensing is started. If necessary, the elapsed time is also managed after re-stirring. When the elapsed time exceeds a predetermined time (judgment time), an error is judged by the judgment unit 214, and further re-stirring is required. When multiple dispenses are performed on the same specimen, desirably, for each dispense, it is judged whether re-stirring is necessary based on the elapsed time after the previous specimen stirring. Note that a plurality of judgment times to be compared with the elapsed time may be set. In that case, the stirring conditions may be changed according to the exceeded judgment time. For example, when the elapsed time exceeds the first judgment time, re-stirring by the nozzle is performed, and when the elapsed time exceeds the second judgment time, manual re-stirring may be required. Here, the second judgment time is longer than the first judgment time.

[0077] A storage unit 92 is connected to the processor 90. A management table 102 is stored in the storage unit 92. Based on the management table 102, the processor 90 performs control, calculation, etc.

[0078] The bubble suction determination unit 98 determines bubble suction based on the detection signal from the pressure sensor. For example, in a situation where there are bubbles on the liquid surface of the specimen, if the surface of the bubbles is misrecognized as the liquid surface, only the bubbles are sucked into the nozzle tip. This is determined by the bubble suction determination unit 98. When bubble suction is determined, error processing is executed and the user is notified of the error.

[0079] The clogging determination unit 100 determines clogging based on the detection signal from the pressure sensor. For example, when clogging occurs inside the nozzle tip during suction, the pressure inside the nozzle tip rises rapidly. Clogging is determined based on this pressure change. When clogging is determined, error processing is executed and the user is notified of the error.

[0080] In addition to the above, other monitoring and other determinations may be performed to appropriately perform specimen stirring and specimen dispensing. The processor 90 according to the embodiment executes various determinations and various error processes. For example, entry of air (i.e., leakage) into the suction path including the inside of the nozzle tip may be determined. Leakage can be determined based on the detection signal from the pressure sensor. Bubble suction, clogging, and leakage can all be referred to as suction abnormalities. Other suction abnormalities may be determined. A camera may be connected to the processor 90. The state of the specimen before or during specimen stirring is photographed by the camera, and an error may be determined or the specimen stirring conditions may be changed by analyzing the obtained image. Prior to specimen stirring, it may be determined whether the liquid level height of the specimen is within a predetermined height range. Error processing may be executed when the liquid level height of the specimen is outside the predetermined height range.

[0081] Figure 4 shows a first example of the stirring and dispensing operation as a timing chart. (A) shows a plurality of consecutive cycle times. Specifically, it shows the cycle times from the i-th to the (i + 3)-th. i is an integer of 1 or more. (B) shows the processing for a plurality of specimens. Specifically, it shows the processing for the j-th specimen and the processing for the (j + 1)-th specimen. j is an integer of 1 or more. One cycle time is determined, for example, within the range of 5 seconds to 30 seconds, and it may be set to 15 seconds.

[0082] For the j-th specimen, the stirring operation 201 is executed within the i-th cycle time, and then the dispensing operation 202 is executed within the subsequent (i + 1)-th cycle time. On the other hand, for the (j + 1)-th specimen, the stirring operation 203 is executed within the (i + 2)-th cycle time, and then the dispensing operation 204 is executed within the subsequent (i + 3)-th cycle time. In this first example, basically, for each cycle time unit 200 consisting of two consecutive cycle times, the stirring operation and the dispensing operation are executed.

[0083] Figure 5 shows the error processing in the first example of the stirring and dispensing operation. After the stirring operation 201 for the j-th specimen, as indicated by reference numeral 223, for some reason, the start of the next dispensing operation 202A is delayed. When the elapsed time Tx from the first reference time t1 to the second reference time t2 exceeds the determination time T1 corresponding to the threshold value, as indicated by reference numeral 224, an error is determined. Accordingly, the execution of the next dispensing operation 202A is restricted, and a stirring request is output to the user.

[0084] For example, the first reference time t1 may be determined as the timing when the nozzle tip is discarded after stirring. The first reference time t1 may be determined as the end of the cycle time to which the stirring operation 201 is assigned. The second reference time t2 may be determined as the timing when the nozzle tip is attached prior to the start of dispensing. The second reference time t2 may be determined as the start of the cycle time to which the dispensing operation 202A is assigned. The second reference time t2 may be the current time, that is, the determination time.

[0085] When the dispensing for the j-th sample is restricted, the execution of the dispensing operation 202A at the cycle time i + 3 is restricted, that is, the dispensing operation 202A is not executed at the cycle time i + 3. After the sample is manually stirred, the above restriction is released, and then the dispensing operation 202A is executed.

[0086] When an error is determined because the elapsed time exceeds the determination time, although the processing of the sample related to the error is in an interrupted state, for each unprocessed sample, dispensing is executed unless an error is determined for it. When all dispensing is completed, the removal of the sample container related to the error, etc. is permitted. However, the removal of the sample container related to the error, etc. may be permitted at the time when the error is determined.

[0087] In FIG. 6, a second example of the stirring and dispensing operation is shown as a timing chart. (A) shows a plurality of cycle times, specifically, the i-th cycle time and the (i + 1)-th cycle time. (B) shows the processing for a plurality of samples, specifically, the processing for the j-th sample and the processing for the (j + 1)-th sample. For the j-th sample, the stirring operation 201 and the dispensing operation 202 are sequentially executed within the i-th cycle time. On the other hand, for the (j + 1)-th sample, the stirring operation 203 and the dispensing operation 204 are sequentially executed within the (i + 1)-th cycle time. Thus, in the second stirring and dispensing operation, basically, the stirring operation and the dispensing operation are executed for each cycle time.

[0088] FIG. 7 shows error processing in a second example of the stirring and dispensing operation. After the stirring operation 201 for the j-th specimen, for some reason, as indicated by reference numeral 223A, the start of the next dispensing operation 202A is delayed. If the elapsed time Tx from the first reference time t1 to the second reference time t2 exceeds the determination time T1, an error is determined as indicated by reference numeral 224A. Accordingly, the start of the next dispensing operation 202A is restricted, and a stirring request is output to the user.

[0089] If the dispensing for the j-th specimen is restricted, the implementation of the dispensing operation 202A at cycle time i + 3 is restricted, that is, the dispensing operation 202A is not performed at cycle time i + 3. After the specimen is manually stirred, the above restriction is released, and then the dispensing operation 202A is performed.

[0090] Note that also in this second example, as in the first example, when an error is determined because the elapsed time exceeds the determination time, although the processing of the specimen related to the error is interrupted, the dispensing is continuously performed for the unprocessed specimens for which no error is determined. When all the dispensing is completed, the removal of the specimen container related to the error is permitted.

[0091] FIG. 8 shows a configuration example of a management table referred to by the control unit. The illustrated management table 102 has a plurality of records 104 corresponding to a plurality of specimens. Each record 104 includes information 106 for specifying the position of the specimen container, information 108 for specifying the specimen ID, information 110 representing the specimen type, information 112 representing the analysis item, and further includes information 114 representing the time (start period of the elapsed time) specified at the first reference time. The elapsed time is calculated based on the information 114.

[0092] FIG. 9 shows a first embodiment of the specimen analysis method as a flowchart. The flowchart is premised on a two-step method including two immunoreaction steps. A1 indicates a part specific to the first embodiment.

[0093] In S10, an examiner mounts a specimen container on the specimen supply unit. In S11, the barcode attached to the specimen container is read by a barcode reader. Thereby, the specimen ID is identified, and an inquiry to the host computer is executed using the specimen ID. Note that the specimen ID may be identified using the specimen mounting position information without using a barcode. S12 is a standby process, and the specimens are in a waiting state.

[0094] When the stirring conditions are satisfied, specimen stirring is performed. Specifically, first, in S13, a nozzle tip is attached to the nozzle body. Next, in S14, n suction and discharge operations on the specimen are repeatedly executed. Thereby, a mixed state of the specimen is formed. In S15, the nozzle tip is removed from the nozzle body and discarded. In S15, a first reference time is specified, and measurement of the elapsed time from the first reference time is started.

[0095] In S16, prior to specimen dispensing, it is determined whether the elapsed time from the first reference time to the second reference time exceeds the determination time. For example, the determination time is set so that the occurrence of a non-ignorable concentration gradient for the measurement target substance can be determined. The case where the elapsed time exceeds the determination time will be described later.

[0096] When the elapsed time does not exceed the determination time, in S18, specimen dispensing is performed. Specifically, a nozzle tip is attached to the nozzle body, the specimen in the specimen container, which is the original container, is sucked by the nozzle tip, and the sucked specimen is discharged from the nozzle tip into the cuvette. When no further dispensing of the specimen is required, the nozzle tip is removed from the nozzle body and discarded.

[0097] S20 is usually executed prior to specimen dispensing. In S20, the first reagent is sucked by a reagent dispensing nozzle, and the sucked first reagent is discharged into the cuvette. In S18, when the specimen is discharged from the nozzle into the cuvette, a mixed state of the first reagent and the specimen occurs in the cuvette.

[0098] In S22, the mixed solution in the cuvette is stirred. S24 indicates the primary immune reaction step. After S24, B / F washing is performed in S26. Then, in S28, a second reagent is dispensed into the cuvette using a reagent dispensing nozzle. In S30, the liquid in the cuvette is stirred. S32 indicates the secondary immune reaction step. In S34, B / F washing is performed.

[0099] In S38, a substrate is dispensed into the cuvette. In that case, a nozzle for substrate dispensing is used. In S40, the liquid in the cuvette is stirred. S42 indicates the enzyme reaction step. In S44, the luminescence generated in the cuvette is measured. In S46, the concentration of the analyte substance, etc. is calculated based on the amount of luminescence. Also, in S46, the measurement result is output.

[0100] On the other hand, in S16 above, if it is determined that the elapsed time exceeds the determination time, an error is determined in S50. In S52, the dispensing for the specimen related to the error is restricted (i.e., prohibited). Then, in S54, the user is notified that manual stirring of the specimen is required. In S56, the user performs a stirring operation on the specimen. In that case, generally, the specimen container is repeatedly inverted. Thereby, the mixing state of the specimen is reformed. Note that prior to the stirring operation, a button for stopping the operation of the specimen supply unit, etc. is operated. After the completion of the stirring operation, a button for restarting the operation of the specimen supply unit, etc. is operated.

[0101] In S58, based on the signal generated by the operation of the restart button or other input information, the completion of the stirring operation is recognized. Then, in S60, the restriction on the implementation of the start of dispensing is released. That is, the specimen dispensing in S18 is permitted. In S58, if the completion of the stirring operation cannot be confirmed, error processing is executed.

[0102] After the restriction is released, the elapsed time from the release time may be measured, and it may be determined in S16 whether the elapsed time exceeds the determination time (see B in FIG. 9). When dispensing is performed multiple times on the same specimen, the elapsed time from the previous stirring is measured each time dispensing is performed, and it is determined in S16 whether the elapsed time exceeds the determination time (see C in FIG. 9). When the elapsed time exceeds the determination time, each step after S50 is performed as described above.

[0103] According to the first embodiment described above, since the stirring operation can be performed while visually observing the specimen, it is possible to surely form a mixed state of the specimen. Prior to the stirring operation, if the state of the specimen is confirmed and no concentration gradient of blood cell components is present in the specimen, the stirring operation may be postponed. In the first embodiment, the above-described dispensing control unit controls the execution of S18, and also controls the execution of S50, S52, S54, S58, and S60.

[0104] FIG. 10 shows an example of an image displayed in the process of analyzing a specimen. The image includes a table 230. The table 230 has a plurality of rows 232, and each row 232 corresponds to each specimen. Each row 232 includes information 234 indicating the position of the specimen, information 236 specifying the specimen ID, information 240 indicating the analysis item, information 242 indicating the presence or absence of a stirring request, information 244 indicating the current status, and the like.

[0105] For example, when the user sequentially stirs a plurality of specimens for which stirring is required, the buttons 246 and 248 are sequentially operated by the user. When the user has stirred all of the plurality of specimens for which stirring is required, the button 250 may be operated by the user. According to the table 230 shown in FIG. 10, it is possible to clearly recognize whether manual stirring is required for each specimen.

[0106] FIG. 11 shows a second embodiment of the specimen analysis method as a flowchart. The flowchart is also premised on a two-step method including two immunoreaction steps, but the illustration of the steps after the specimen dispensing S18 is omitted. A2 indicates a part specific to the second embodiment, and the explanation will be centered around this part.

[0107] In S16, when it is determined that the elapsed time exceeds the determination time, an error is determined in S50, and the specimen dispensing is restricted (i.e., prohibited) in S52. Thereafter, automatic remixing of the specimen using the nozzle is performed. Specifically, in S63, the nozzle tip is attached to the nozzle body, and in S64, the specimen is automatically remixed by repeating the aspiration and discharge operations n times. In S65, the nozzle tip is removed from the nozzle body. In S60, the restriction on the implementation of the dispensing is released. The restriction on the implementation of the dispensing may be released immediately after S14.

[0108] According to the second embodiment, compared with the first embodiment, the burden on the examiner can be significantly reduced. On the other hand, when bubbles are likely to be generated in the specimen container due to repeated agitation of the specimen by the nozzle, the adoption of the above-described first embodiment is desirable.

[0109] Note that the conditions for specimen agitation performed in S14 and the conditions for specimen agitation performed in S64 may be the same or different. Examples of the agitation conditions include the number of aspiration and discharge repetitions, the aspiration volume, the aspiration speed, the temporary waiting time after aspiration, the discharge volume, the discharge speed, the temporary waiting time after discharge, the nozzle lowering speed, the nozzle rising speed, and the like. The agitation conditions may be adaptively set according to the specimen. In the second embodiment, the above-described dispensing control unit controls the execution of S18, and also controls the execution of S50, S52, and S60. The above-described agitation control unit controls the execution of S14, and also controls the execution of S63, S64, and S65.

[0110] FIG. 12 shows a third embodiment of the specimen analysis method as a flowchart. The flowchart is also premised on a two-step method including two immunoreaction steps, but the illustration of the steps after the specimen dispensing S18 is omitted. A3 indicates a part specific to the third embodiment, and the explanation will be centered around this part.

[0111] In S16, when it is determined that the elapsed time exceeds the determination time, an error is determined in S50, and specimen dispensing is restricted (i.e., prohibited) in S52. In S66, a remixing method is selected. The remixing method may be selected by the user, or may be automatically selected according to predetermined selection conditions. For example, the remixing method may be automatically selected based on information such as the specimen type, specimen state, and specimen volume.

[0112] In S66, when manual remixing is selected, a notification requesting it is displayed on the display in S68. Accordingly, remixing of the specimen by the examiner is performed in S70. In S72, completion of the remixing of the specimen is confirmed.

[0113] On the other hand, in S66, when nozzle-based remixing is selected, a nozzle tip is attached to the nozzle body in S74, and n suction and discharge operations on the specimen are performed in S76. Thereby, the specimen is remixed. The nozzle tip is removed from the nozzle body in S78. In S60, the restriction on the execution of dispensing is released. Thereafter, specimen dispensing is performed in S18.

[0114] According to the third embodiment, it is possible to select an appropriate remixing method according to the specimen. In the third embodiment, the above-described dispensing control unit controls the execution of S18, and also controls the execution of S50, S52, S68, S72, and S60. The above-described stirring control unit controls the execution of S14, and also controls the execution of S74, S76, and S78. Regarding S66, its execution is controlled by either the dispensing control unit or the stirring control unit.

[0115] Next, the aliquoting operation will be described with reference to FIGS. 13 to 16. FIGS. 13 and 14 show the aliquoting operation in multiple measurements, and FIGS. 15 and 16 show the aliquoting operation in multi-item measurements. In each figure, (A) shows a plurality of cycle times in time sequence, and (B) shows the processing for a plurality of specimens.

[0116] In FIG. 13, after the stirring operation 300 and the first aliquoting operation 301 for the j-th specimen are performed, for some reason, as indicated by reference numeral 302, the execution of the second aliquoting operation 303A is delayed. As a result, the elapsed time Tx from the first reference time t1 to the second reference time t2 exceeds the determination time T1. In this case, the execution of the aliquoting operation 302A at the (i + 3)-th cycle time is restricted, that is, canceled, and as indicated by reference numeral 304, the re-stirring operation 305 is performed at the (i + 4)-th cycle time. That is, the suction and discharge operation by the nozzle is repeatedly executed at the (i + 4)-th cycle time. Thereafter, the second aliquoting operation 303 is performed at the (i + 5)-th cycle time. That is, as indicated by reference numeral 306, the aliquoting operation assigned to the (i + 3)-th cycle time in the scheduling stage is performed at the (i + 5)-th cycle time after re-stirring. By thus determining the necessity of re-stirring during the aliquoting operation and incorporating the re-stirring operation into the aliquoting operation, it becomes possible to make the state of the specimen to be aliquoted appropriate in each specimen aliquoting.

[0117] In the operation example shown in FIG. 13, instead of re-stirring by the nozzle, re-stirring by the user may be performed. For example, when the elapsed time Tx exceeds the determination time T1, an error is determined and an interruption of the aliquoting operation is determined. Based on the error, information requesting the user to re-stir the sample in the original container is provided. For re-stirring, a temporary interruption of the aliquoting operation is determined. Completion of the re-stirring is determined based on a predetermined operation of the user after the re-stirring. Based on that determination, the interruption of the aliquoting operation is released, that is, the aliquoting operation is restarted. In that case, the aliquoting control unit functions as an error determination unit, an information notification unit, an operation restriction unit, a restriction release unit, etc.

[0118] As shown in FIG. 14, at the stage of scheduling for multiple measurements, the necessity of re-stirring during the aliquoting operation may be determined in advance, and a re-stirring operation may be pre-assigned during the aliquoting operation. Specifically, in the example shown in FIG. 14, when three aliquoting operations are continuous, it is predicted in advance that the elapsed time Tx from the first stirring will exceed the determination time T1. As indicated by reference numeral 304, according to that prediction, a re-stirring operation 314 by the nozzle is incorporated between the second aliquoting operation 313 and the third aliquoting operation 315. As a result, for the j-th sample, from the i-th cycle time to the i + 4-th cycle time, a stirring operation 311, a first aliquoting operation 312, a second aliquoting operation 313, a re-stirring operation 314, and a third aliquoting operation 315 are sequentially performed. According to the operation example shown in FIG. 14, it is possible to perform re-stirring of the sample in a timely and smooth manner during the aliquoting operation.

[0119] In the operation example shown in FIG. 14, instead of re-stirring by the nozzle, re-stirring by the user may be performed. For example, when it is predicted in advance that the elapsed time Tx exceeds the determination time T1, an error may be determined in advance, and during the dispensing operation, re-stirring by the user may be incorporated. Specifically, based on the error determined in advance, information for requesting the user to re-stir the sample in the original container is provided at an appropriate timing. For re-stirring, a temporary interruption of the dispensing operation is determined. Completion of the re-stirring is determined based on a predetermined operation of the user after the re-stirring. Based on that determination, the interruption of the dispensing operation is released, that is, the dispensing operation is resumed. Also in that case, the dispensing control unit functions as a determination unit, a notification unit, a restriction unit, a release unit, etc.

[0120] In FIG. 15, for the j-th sample, after the stirring operation 320 is performed, the dispensing operation 321 for the test item a1 is being performed. Thereafter, as indicated by reference numeral 322, due to some reason, the implementation of the dispensing operation 323A for the test item a2 is delayed. As a result, the elapsed time Tx from the first reference time t1 to the second reference time t2 exceeds the determination time T1. In this case, the implementation of the dispensing operation 323A at the (i + 3)-th cycle time is restricted, that is, canceled, and as indicated by reference numeral 324, the re-stirring operation 325 is performed at the (i + 4)-th cycle time. That is, the suction and discharge operation by the nozzle is repeatedly executed at the (i + 4)-th cycle time. Thereafter, the dispensing operation 323 for the test item a2 is performed at the (i + 5)-th cycle time. That is, as indicated by reference numeral 326, the dispensing operation assigned to the (i + 3)-th cycle time in the scheduling stage is performed at the (i + 5)-th cycle time after re-stirring. By thus determining the necessity of re-stirring during the dispensing operation and incorporating the re-stirring operation into the dispensing operation, it becomes possible to make the state of the sample to be dispensed appropriate in each sample dispensing. In the operation example shown in FIG. 15, instead of re-stirring by the nozzle, re-stirring by the user may be performed.

[0121] As shown in FIG. 16, at the stage of scheduling for multi-item measurement, the necessity of re-stirring during the aliquoting operation may be determined in advance, and a re-stirring operation may be pre-assigned during the aliquoting operation. Specifically, in the example shown in FIG. 16, when three consecutive aliquoting operations are performed, it is predicted in advance that the elapsed time Tx from the first stirring exceeds the determination time T1. As indicated by reference numeral 330, according to this prediction, a re-stirring operation 334 by the nozzle is incorporated between the aliquoting operation 333 for the test item a2 and the aliquoting operation 335 for the test item a3. As a result, for the j-th specimen, the stirring operation 331, the aliquoting operation 332, the aliquoting operation 333, the re-stirring operation 334, and the aliquoting operation 335 are sequentially performed from the i-th cycle time to the (i + 4)-th cycle time. According to the operation example shown in FIG. 16, it is possible to perform timely and smooth re-stirring of the specimen during the aliquoting operation. In the operation example shown in FIG. 16, instead of re-stirring by the nozzle, re-stirring by the user may be performed.

[0122] FIG. 17 shows a specimen analyzer according to a modified example. In FIG. 17, the same elements as those shown in FIG. 1 are denoted by the same reference numerals. The specimen analyzer 10A includes an apparatus main body 134 and a rack transfer table 136 attached thereto. The apparatus main body 134 is provided with a specimen aliquoting mechanism 28. The specimen aliquoting mechanism 28 has a rail mechanism 46, a slide base 48, an arm 50, and a nozzle 52.

[0123] Individual racks are transported on the rack transfer table 136. Reference numeral 140 indicates a specimen container rack row set by the user (hereinafter, the specimen container rack is simply referred to as a rack). Reference numeral 142 indicates a rack to be processed. Reference numeral 144 indicates a reprocessable rack row 144 in the buffer area. Reference numeral 146 indicates an ejected rack row 146. Each rack holds a plurality of specimen containers.

[0124] The specimens in the individual specimen containers held in the rack 142 are to be dispensed. In other words, the positions of the individual specimen containers correspond to the suction positions where the stirring operation and the sampling operation are performed. The nozzle transfer mechanism in the specimen dispensing mechanism 28 sequentially positions the nozzle 52 at each suction position.

[0125] In the specimen analyzer 10A according to the modification, for example, the specimens in the specimen supply unit 12 are preferentially processed, and then the specimens in each rack are processed. However, the control may be performed so that the specimens in each rack are preferentially processed.

[0126] Also in the specimen analyzer 10A according to the modification, specimen stirring by the nozzle is performed prior to specimen dispensing. When the elapsed time after specimen stirring exceeds a predetermined time, re-stirring by the nozzle is performed on the specimen to be dispensed. Therefore, it is possible to ensure sampling of the specimens in a mixed state.

[0127] According to the embodiment, when the mixing state becomes insufficient in the specimen due to an increase in the elapsed time after specimen stirring, the implementation of specimen dispensing is restricted and then re-stirring of the specimen is performed. As a result, the mixing state of the specimen is reformed and then the specimen is sampled. Therefore, the specimen analysis accuracy can be improved, or in other words, the reliability of the specimen analysis result can be improved.

Description of Reference Numerals

[0128] 10 Specimen analyzer, 12 Specimen supply unit, 14 Reaction unit, 16 Reagent supply unit, 18 Light detection unit, 28 Specimen dispensing mechanism, 30, 32 Reagent dispensing mechanism, 46 Rail mechanism, 48 Slide base, 50 Arm, 52 Nozzle, 70 Nozzle body, 72 Nozzle tip, 78 Pressure sensor, 80 Information processing unit, 82 Timer, 90 Processor, 94 Control unit, 210 Stirring control unit, 212 Dispensing control unit, 214 Determination unit, 216 Notification unit, 218 Restriction unit, 220 Release unit.

Claims

1. A nozzle, a stirring control unit that controls stirring of a specimen in a source container by the nozzle, a dispensing control unit that controls specimen dispensing for dispensing the specimen in the source container using the nozzle after stirring by the nozzle, comprising: wherein the dispensing control unit restricts implementation of the specimen dispensing based on the elapsed time after stirring by the nozzle, a specimen analysis apparatus characterized by this.

2. In the specimen analysis apparatus according to Claim 1, the dispensing control unit includes a determination unit that determines an error based on the elapsed time after stirring by the nozzle, a restriction unit that restricts implementation of the specimen dispensing when the error is determined, and a release unit that releases the restriction on implementation of the specimen dispensing when re-stirring of the specimen in the source container is completed, a specimen analysis apparatus characterized by this.

3. In the specimen analysis apparatus according to Claim 2, the dispensing control unit includes a notification unit that provides information requesting re-stirring of the specimen in the source container to the user when the error is determined, and the release unit determines completion of the re-stirring based on a predetermined operation of the user after the re-stirring, a specimen analysis apparatus characterized by this.

4. In the specimen analysis apparatus according to Claim 1, the dispensing control unit determines an error based on the elapsed time after stirring by the nozzle, the stirring control unit controls re-stirring of the specimen in the source container by the nozzle when the error is determined, and the dispensing control unit controls the specimen dispensing after waiting for completion of the re-stirring when the error is determined, a specimen analysis apparatus characterized by this.

5. In the specimen analysis apparatus according to Claim 4, the stirring control unit applies stirring conditions different from those applied in stirring by the nozzle in the re-stirring by the nozzle, a specimen analysis apparatus characterized by this.

6. In the specimen analysis apparatus according to Claim 4, the dispensing control unit determines a first error as the error when the elapsed time after stirring by the nozzle exceeds a first determination time, and determines a second error when the elapsed time after re-stirring by the nozzle exceeds a second determination time, wherein the first determination time and the second determination time are each independently set, a specimen analysis apparatus characterized by this.

7. In the specimen analysis apparatus according to Claim 1, The elapsed time after stirring by the nozzle is the time from a first reference time after the stirring by the nozzle is completed to a second reference time before the start of the specimen dispensing. A specimen analyzer characterized by this. **Claim 8** In the specimen analyzer according to claim 1, the nozzle is composed of a nozzle body and a nozzle tip attached thereto, the nozzle tip is replaced after stirring by the nozzle, A specimen analyzer characterized by this. **Claim 9** In the specimen analyzer according to claim 8, the stirring control unit controls re-stirring of the specimen in the original container by the nozzle after the implementation of the specimen dispensing is restricted, the nozzle tip is replaced again after re-stirring by the nozzle, A specimen analyzer characterized by this. **Claim 10** In the specimen analyzer according to claim 1, in a multi-dispensing operation in which the dispensing control unit performs specimen dispensing a plurality of times on the same specimen, an error is determined based on the elapsed time after stirring by the nozzle, and thereby the multi-dispensing operation is interrupted. A specimen analyzer characterized by this. **Claim 11** In the specimen analyzer according to claim 10, the stirring control unit controls re-stirring of the specimen in the original container by the nozzle after the interruption of the multi-dispensing operation, the dispensing control unit waits for the completion of re-stirring by the nozzle and then resumes the multi-dispensing operation. A specimen analyzer characterized by this. **Claim 12** In the specimen analyzer according to claim 10, the dispensing control unit, when the error is determined, provides information requesting re-stirring of the specimen in the original container to the user, determines the completion of the re-stirring based on a predetermined operation of the user after the re-stirring, when the re-stirring is completed, releases the interruption of the multi-dispensing operation. A specimen analyzer characterized by this. **Claim 13** In the specimen analyzer according to claim 1, in a multi-dispensing operation in which the dispensing control unit performs specimen dispensing a plurality of times on the same specimen, when it is predicted that the elapsed time after stirring by the nozzle exceeds a determination time during the multi-dispensing operation, an error is determined in advance, when the error is determined in advance, re-stirring of the specimen in the original container by the nozzle is incorporated during the multi-dispensing operation. A specimen analyzer characterized by this. **Claim 14** In the specimen analyzer according to claim 1, the dispensing control unit, In a multi-dispensing operation of performing multiple dispenses of the same sample, when it is predicted that the elapsed time after stirring by the nozzle during the multi-dispensing operation exceeds the determination time, an error is determined in advance. When the error is determined in advance, information requesting re-stirring of the sample in the original container is provided to the user. Based on a predetermined operation of the user after the re-stirring, completion of the re-stirring is determined. When the error is determined in advance, re-stirring by the user of the sample in the original container is incorporated during the multi-dispensing operation. A sample analyzer characterized by the above.

15. In the sample analyzer according to claim 1, In the stirring by the nozzle, the nozzle is conveyed up and down in accordance with the vertical movement of the liquid level of the sample in the original container. A sample analyzer characterized by the above.

16. In the sample analyzer according to claim 1, The amount of entry of the nozzle into the sample in the original container during the stirring by the nozzle is in the range of 0.5 to 15 mm. A sample analyzer characterized by the above.

17. In the sample analyzer according to claim 1, A pressure sensor for detecting the pressure inside the nozzle, In the stirring by the nozzle, means for determining at least one of bubble suction, clogging, and leakage as suction abnormality based on the output signal of the pressure sensor, Means for executing error processing when the suction abnormality is determined. A sample analyzer characterized by including the above.

18. In the sample analyzer according to claim 1, Means for determining the height of the liquid level of the sample in the original container prior to the stirring by the nozzle, Means for executing error processing when the height of the liquid level is outside a predetermined height range. A sample analyzer characterized by including the above.

19. A stirring control step for controlling stirring of the sample in the original container by the nozzle, A dispensing control step for controlling sample dispensing for dispensing the sample in the original container using the nozzle after the stirring by the nozzle, An analysis step for performing sample analysis after the sample dispensing. Including, The dispensing control step includes a step of controlling the execution of the sample dispensing based on the elapsed time after the stirring by the nozzle. A sample analysis method characterized by the above.

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