Specimen analysis device and specimen analysis method

Abstract

To generate a mixed state of a sample with a simple configuration prior to dispensing of the sample.SOLUTION: Suction discharge of a sample 68 by a nozzle 52 is repeated n times. Thereafter, the sample 68 is sucked into the nozzle 52, and the sucked sample is discharged into a cuvette that is a reaction container. Sample agitation and dispensing sample suction are performed at a same position. A nozzle tip 72 is replaced between sample agitation and subsequent sample suction.SELECTED DRAWING: Figure 2

Description

Technical Field

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

Background Art

[0002] A specimen analysis apparatus is an apparatus for analyzing blood, urine, etc. collected from a subject. As the specimen analysis apparatus, an immunoassay apparatus, a biochemical analysis apparatus, etc. are known.

[0003] In the analysis of blood, for example, blood collected from a subject is stored in a blood collection tube containing an anticoagulant. That blood is a specimen, and it is also called 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 specimen stirring performed immediately before dispensing the specimen from the original container to the reaction container.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Summary of the Invention

[0006] Prior to sample analysis, the sample from the original container is drawn into the nozzle, and the drawn sample is discharged from the nozzle into the reaction vessel. If a concentration gradient of the analyte is present in the original container during sample aspiration, the reliability of the analysis results will decrease.

[0007] The object of the present invention is to provide a specimen analyzer and specimen analyzer that can obtain highly reliable analytical results. Alternatively, it is to create a mixed state of specimens with a simple configuration prior to specimen aspiration. [Means for solving the problem]

[0008] The specimen analysis device according to the present invention is It consists of a nozzle body and a nozzle tip attached to it. The apparatus includes a nozzle and a control unit for controlling sample dispensing using the nozzle, the control unit for controlling sample agitation using the nozzle prior to controlling sample dispensing when agitation execution conditions are met, wherein in the sample dispensing, the sample in the source container transferred to the aspiration position is aspirated into the nozzle, the aspirated sample is discharged from the nozzle to the reaction vessel, the sample agitation includes n (where n is an integer of 1 or more) aspiration-discharge operations performed at the aspiration position, in each of the aspiration-discharge operations, the sample in the source container is aspirated into the nozzle, and the aspirated sample is discharged from the nozzle back into the source container. Furthermore, under the control of the control unit, a first nozzle tip replacement is performed for each sample to be dispensed, between the mixing of the sample and the subsequent dispensing of the sample, and a second nozzle tip replacement is performed after the dispensing of the sample. It is characterized by the following:

[0009] The specimen analysis method according to the present invention is It consists of a nozzle body and a nozzle tip attached to it.The process includes the steps of dispensing a sample using a nozzle, stirring the sample using the nozzle before dispensing the sample, and performing sample analysis after dispensing the sample, wherein in the sample dispensing, the sample in the original container transferred to the aspiration position is aspirated into the nozzle, and the aspirated sample is discharged from the nozzle into the reaction vessel, and the sample stirring includes n (where n is an integer of 1 or more) aspiration-discharge operations performed at the aspiration position, wherein in each aspiration-discharge operation, the sample in the original container is aspirated into the nozzle, and the aspirated sample is discharged from the nozzle into the original container. Furthermore, under the control of the control unit, a first nozzle tip replacement is performed for each sample to be dispensed, between the mixing of the sample and the subsequent dispensing of the sample, and a second nozzle tip replacement is performed after the dispensing of the sample. It is characterized by the following: [Effects of the Invention]

[0010] According to the present invention, a sample analysis apparatus and method can be provided that can obtain highly reliable analytical results. Alternatively, it is possible to create a mixed state of the sample with a simple configuration prior to sample aspiration. [Brief explanation of the drawing]

[0011] [Figure 1] This is a schematic diagram showing an analytical apparatus according to an embodiment. [Figure 2] This is a diagram illustrating suction and discharge control. [Figure 3] This figure shows an example of the configuration of the information processing unit. [Figure 4] This is a timing chart showing the first example of a stirring and dispensing operation. [Figure 5] This is a timing chart showing a second example of the stirring and dispensing operation. [Figure 6] This figure shows an example of the configuration of a management table. [Figure 7] This is a diagram illustrating the appropriate liquid volume range. [Figure 8] This is a flowchart showing the sample analysis method. [Figure 9] This is a flowchart (part 1) illustrating the stirring and dispensing process. [Figure 10] This is a flowchart (part 2) illustrating the stirring and dispensing process. [Figure 11]It is a schematic diagram showing a specimen analyzer according to a modified example. [Figure 12] It is a diagram showing a change in stirring execution conditions based on elapsed time. [Figure 13] It is a diagram showing a change in stirring execution conditions based on the amount of specimen and container type.

Mode for Carrying Out the Invention

[0012] Hereinafter, embodiments will be described based on the drawings.

[0013] (1) Outline of Embodiment The specimen analyzer according to the embodiment has a nozzle and a control unit. The control unit controls specimen dispensing using the nozzle. When the stirring execution conditions are satisfied, the control unit controls specimen stirring using the nozzle prior to controlling specimen dispensing. In specimen dispensing, the specimen in the original container transferred to the suction position is sucked into the nozzle, and the sucked specimen is discharged from the nozzle into the reaction container. Specimen stirring includes n (where n is an integer of 1 or more) suction and discharge operations performed at the suction position. In each suction and discharge operation, the specimen in the original container is sucked into the nozzle, and the sucked specimen is discharged from the nozzle into the original container.

[0014] According to the above configuration, when the stirring execution conditions are satisfied, specimen stirring is performed prior to specimen dispensing. As a result, a mixing state of the specimen occurs in the original container. That is, even if there was a concentration gradient of the analyte in the original container, it is eliminated. If sampling, that is, suction of the specimen for dispensing, is promptly performed after a uniform state of the specimen is formed, the analysis accuracy of the analyte can be improved, that is, the reliability of the analysis result of the analyte can be enhanced. Since it is specimen stirring using a nozzle, there is no need to provide special equipment, and the advantage of being able to perform specimen stirring using existing equipment can also be obtained.

[0015] It is possible to have different locations for sample mixing (mixing position) and sample aspiration during sample dispensing (dispensing aspiration position, sampling position). However, in that case, it is necessary to transfer the original container between sample mixing and sample aspiration, which requires time or a separate process. In the above configuration, since the mixing position and the dispensing aspiration position are the same, sample aspiration can be performed quickly after sample mixing. As will be described later, the nozzle tip may be changed between sample mixing and sample aspiration. Since the time required for nozzle tip change is usually short, even in that case, it is possible to aspiration a sample that is in a mixed state.

[0016] For example, if a long time has passed since the original container was installed in its designated position within the sample analyzer, and the viscosity of the settled components has become very high, or if the original container contains a large amount of sample, repeated aspiration and discharge by the nozzle may not adequately mix the sample. In such cases, it is desirable to supplement or substitute manual mixing or mixing by other methods. Also, depending on the type or condition of the sample, mixing may not be necessary. Considering various situations, the above configuration is designed to perform sample mixing by the nozzle only when the conditions for mixing are met. Sample mixing by the nozzle may be performed after manual mixing or mixing by other methods has been performed.

[0017] The sample analyzer according to this embodiment operates according to cycle times. Sample mixing and sample dispensing are performed for each cycle time unit, or for each cycle time. A cycle time is the basic unit of operation on the time axis, and in the sample analyzer, each piece of equipment operates according to the cycle time. A cycle time unit consists of multiple cycle times that are arranged in time.

[0018] In one embodiment, the control unit measures the elapsed time from a reference time determined based on the installation of the original container to the time of determination before sample stirring is started, and controls the operation of the nozzle based on the elapsed time.

[0019] Generally, before the original container is placed on the sample analyzer, it is manually stirred. After the original container is placed, sedimentation and aggregation of specific components proceed within the container. The degree of sample change depends on the elapsed time, but the elapsed time actually varies depending on various conditions (number of samples, presence or absence of interruptions, etc.). Therefore, in the above configuration, the elapsed time is measured and the nozzle operation is controlled based on the elapsed time. The time when the original container is placed may be used as the reference time, or a predetermined time after the original container is placed may be used as the reference time. The start of the aspiration process may be used as the determination time, or the time immediately before the start of aspiration may be used as the determination time. Even when the sample container rack is placed on the sample analyzer, the reference time and determination time may be determined as appropriate.

[0020] In this embodiment, the control unit determines an error without allowing the nozzle to agitate the sample if the elapsed time exceeds a predetermined time. Alternatively, the control unit changes the sample agitation conditions according to the elapsed time. For example, the control unit changes n according to the elapsed time. Based on the error determination, measures such as manual sample agitation can be taken. Increasing n as the elapsed time increases reduces the possibility of insufficient agitation. Other parameters, such as the suction discharge volume, may also be changed.

[0021] In one embodiment, the nozzle consists of a nozzle body and a nozzle tip attached thereto. The nozzle tip is replaced between sample mixing and sample dispensing.

[0022] During sample mixing, sample residue adheres to the inner and outer surfaces of the nozzle tip. This residual sample may affect analytical accuracy. By replacing the nozzle tip after sample mixing is complete, sample dispensing can be performed using a new nozzle tip, thus avoiding problems caused by residual sample. Both sample mixing and sample dispensing may be performed using a single type of nozzle tip. A separate nozzle tip may be used for sample mixing and a different nozzle tip for sample dispensing. Using a single type of nozzle tip can reduce costs. Providing a dedicated nozzle tip for sample mixing can improve mixing efficiency. It is also possible to use a washable nozzle for both sample mixing and sample dispensing.

[0023] The stirring execution conditions may include a liquid volume condition. The liquid volume condition is a condition that the amount of sample in the original container must satisfy. The stirring execution conditions may include a container condition. The container condition is a condition that the original container must satisfy. The stirring execution conditions may include a sample type condition. The sample type condition is a condition that the type of sample in the original container must satisfy. The stirring execution conditions may include a sample state condition. The sample state condition is a condition that the state of the sample in the original container must satisfy. Examples of sample state conditions include hemolysis conditions and blood cell concentration conditions. The hemolysis condition is a condition that the degree of hemolysis in the sample must satisfy when the sample in the original container is whole blood. The blood cell concentration condition is a condition that the degree of blood cell concentration in the sample must satisfy when the sample in the original container is whole blood. Multiple conditions may be included in the stirring execution conditions, and stirring may be performed only when all of those conditions are satisfied.

[0024] In this embodiment, during sample agitation, the nozzle is transported up and down in accordance with the vertical movement of the liquid surface of the sample in the original container. By synchronizing the vertical movement of the nozzle with the vertical movement of the liquid surface, it becomes possible to control the amount of nozzle penetration into the sample in the original container to a constant value or within a certain range. For example, the amount of nozzle penetration into the sample in the original container during each suction / discharge operation is within the range of 0.5–15 mm.

[0025] In this embodiment, a pressure sensor is provided to detect the pressure inside the nozzle. During sample mixing, at least one of the following is determined as an aspiration abnormality based on the output signal of the pressure sensor: air bubble aspiration, clogging, and leakage. Error processing is performed when an aspiration abnormality is detected. This configuration makes it possible to avoid situations in which the aspiration and dispensing operation proceeds even when there is a risk that the sample may not be properly mixed. In this embodiment, the processor functions as both an aspiration abnormality detection means and an error processing means.

[0026] In this embodiment, the liquid level of the sample in the original container is determined prior to sample agitation. Error processing is performed if the liquid level is outside a predetermined height range. This configuration prevents situations where the aspiration and dispensing operation proceeds when proper sample agitation is not possible due to an excessive or insufficient liquid volume. The concept of liquid level height includes the liquid volume. In this embodiment, the processor functions as both a liquid volume suitability determination means and an error processing means.

[0027] The sample analysis method according to this embodiment comprises a dispensing step, a stirring step, and an analysis step. The dispensing step is a step in which a sample is dispensed using a nozzle. The stirring step is a step performed before sample dispensing, in which the sample is stirred using a nozzle. The analysis step is a step in which sample analysis is performed after sample dispensing. In sample dispensing, the sample in the original container, which has been transferred to the aspiration position, is drawn into the nozzle, and the drawn sample is discharged from the nozzle into the reaction vessel. Sample stirring includes n (where n is an integer of 1 or more) aspiration-discharge operations performed at the aspiration position. In each aspiration-discharge operation, the sample in the original container is drawn into the nozzle, and the drawn sample is discharged from the nozzle into the original container.

[0028] According to the method described above, sample mixing is performed using a nozzle immediately before dispensing the sample for analysis. This means that the sample is sampled only after its homogeneity or uniformity has been ensured, thereby increasing the reliability of the analysis results for the analyte. Another advantage is that there is no need to install complex equipment for sample mixing, and sample mixing can be performed using existing equipment. Furthermore, in the case of whole blood, for example, if the hemocytosis rate in the sample is slow or the degree of hemolysis is above a certain level, mixing may not be necessary depending on the type of analyte, and sample mixing by nozzle may be omitted.

[0029] In this embodiment, the sample is whole blood. The mixing process is applied to all samples as long as the mixing conditions are met. However, the necessity of mixing may be determined on a sample-by-sample basis. Examples of sample types include serum, plasma, urine, sweat, saliva, etc.

[0030] (2) Details of the embodiment Figure 1 shows a sample analyzer 10 according to an embodiment. Figure 1 schematically shows the top surface of the sample analyzer 10. This sample analyzer 10 is an immunoassay device that analyzes a sample using an immune reaction, that is, an antigen-antibody reaction, and specifically, it is an immunoassay device that follows the chemiluminescent enzyme immunoassay (CLEIA). The technical matters described below may also be applied to biochemical analyzers, etc.

[0031] In Figure 1, the sample analyzer 10 includes a sample supply unit 12, a reaction unit 14, a reagent supply unit 16, a photodetector unit 18, a cuvette supply unit 20, a substrate cooler 22, cuvette transfer mechanisms 24, 26, a sample dispensing mechanism 28, a reagent dispensing mechanism 30, 32, etc.

[0032] The sample supply unit 12 has a turntable 33 as a rotating platform. The turntable 33 has a group of retaining holes 34, which consists of a plurality of retaining holes 34a. In the illustrated example, the group of retaining holes 34 consists of an outer row of retaining holes 34a arranged in an annular shape, and an inner row of retaining holes 34a arranged in an annular shape. Each retaining hole 34a is a part that accommodates a sample container as the original container. A sample is contained inside the sample container.

[0033] In this embodiment, the sample is whole blood. Other fluids collected from a living organism may also be used as the sample. The sample container (original container) is a blood collection tube containing whole blood or another container containing whole blood. For example, blood collected from a living organism is contained in a blood collection tube containing an anticoagulant. In this case, the blood in the blood collection tube or the blood transferred from the blood collection tube to another container is the whole blood used as the sample. As is well known, whole blood contains blood cell components, and when whole blood is left to stand, the blood cell components settle. The settling rate varies depending on the sample.

[0034] In the case of hemolyzed whole blood, depending on the degree of hemolysis, a large portion of the analyte in the blood cell components may be eluted into the plasma. Therefore, in the embodiment, as described later, the necessity of mixing the sample with a nozzle is determined by the degree of hemolysis. The degree of hemolysis can be determined by measuring the hemoglobin value of the supernatant portion of the sample. The degree of hemolysis may also be determined by analyzing images obtained by imaging the sample. On the other hand, depending on the blood cell concentration, the erythrocyte sedimentation rate may slow down, reducing its impact on the analysis. Therefore, the necessity of mixing the sample with a nozzle may also be determined by the blood cell concentration. The blood cell concentration can be determined by measuring the hematocrit value. As the hematocrit value, a measurement value obtained by a known method (such as the microhematocrit method) may be used. The degree of sedimentation may also be determined by analyzing images obtained by imaging the sample.

[0035] Each sample container is inserted into each holding hole 34a by the inspector's manual operation. In other words, each sample container is placed. Typically, prior to inserting each sample container, the sample inside is agitated by repeatedly shaking the container, that is, by repeatedly inverting it. Any number of sample containers can be placed in the sample supply unit 12. The timing of placing each sample container can also be determined arbitrarily by the inspector.

[0036] Prior to placing the sample container, the examiner operates button 36. This temporarily interrupts the operation of the sample supply unit 12, creating a state in the sample supply unit 12 where it can accept the sample container. After placing the sample container, the examiner operates button 36 again. This resumes the operation of the sample supply unit 12. A virtual button may be displayed on a touchscreen panel or the like to replace button 36. Button 38 is operated when the turntable 33 is to be rotated. Buttons 36 and 38 may be integrated.

[0037] The sample supply unit 12 is equipped with a barcode reader (BCR), which is not shown. The BCR reads the contents of the barcode labels attached to each sample container held by the holding hole group 34. This allows sample information such as the sample ID to be read for each sample. Based on the sample ID, subject information, analysis items, sample container type, etc., are identified.

[0038] The reaction unit 14 has a turntable 39 as a rotating platform. The turntable 39 has a group of retaining holes 40 formed therein, which consists of a plurality of retaining holes 40a. In the illustrated example, the group of retaining holes 40 consists of an outer row of retaining holes 40a arranged in a ring shape, and an inner row of retaining holes 40a arranged in a ring shape. Each retaining hole 40a is a part that accommodates a cuvette as a reaction vessel. Reagents and samples are injected into each cuvette in stages. This causes an immunoassay to occur in each cuvette.

[0039] In this embodiment, for example, the sample is measured based on a so-called two-step method. The two-step method includes a first immunoassay step using a first reagent containing a first antibody, a second immunoassay step using a second reagent containing a second antibody, an enzymatic reaction step using a substrate (substrate solution), and a photodetection step. The first immunoassay step, the second immunoassay step, and the enzymatic reaction step are carried out in the reaction unit 14. In addition, a stirring step, a B / F washing step, etc. are carried out in the reaction unit 14. In Figure 1, the mechanism of the reaction unit 14 is not shown. The stirring method in the reaction unit 14 is a vortex stirring method in which a cuvette is rotated to create a vortex inside the cuvette.

[0040] The reagent supply unit 16 has a reagent tank 41 which serves as a rotating cooler. The reagent tank 41 houses reagent bottle rows 42 and reagent bottle rows 44. Each reagent bottle row 42 and reagent bottle row 44 consists of multiple 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. Reagent dispensing mechanism 30 has a rotating arm 60 and a nozzle 62 provided at the tip of arm 60. Reagent dispensing mechanism 32 has a rotating arm 64 and a nozzle 65 provided at the tip of arm 64. Nozzles 62 and 65 are non-replaceable nozzles, i.e., washable nozzles. A specific reagent is drawn in by the reagent dispensing mechanisms 30 and 32, and the drawn reagent is discharged into a specific cuvette.

[0041] The photodetector 18 is a unit that detects the light emission generated in the cuvette after the enzymatic reaction. Based on the detected value, the concentration of the analyte is calculated. The cuvette transfer mechanisms 24 and 26 function when the cuvette is transferred. In Figure 1, reference numerals 56 and 58 indicate the waste section. Used cuvettes and used nozzle tips are discarded in the waste section.

[0042] The sample dispensing mechanism 28, in the illustrated configuration example, includes a rail mechanism 46, a slide base 48, an arm 50, a nozzle 52, etc. The rail mechanism 46 has rails that extend in a direction inclined with respect to the left-right direction and the depth direction of the device. The slide base 48 slides along these rails (see reference numeral 53). The base end of the arm 50 is rotatably held by the slide base 48, and the nozzle 52 is positioned at the tip of the arm 50.

[0043] The nozzle 52 consists 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 transparent, translucent, or opaque resin. The nozzle tip is replaced after sample aspiration. In some embodiments, the nozzle tip is also replaced after the sample has been agitated by the nozzle.

[0044] In the sample supply unit 12, a first aspiration position (external aspiration position) and a second aspiration position (internal aspiration position) are defined. At each aspiration position, sample aspiration for dispensing is performed, as well as sample mixing. Sample mixing will be described in detail later.

[0045] The sliding motion of the slide base 48 and the rotational motion of the arm 50 combine to expand the movement area of ​​the nozzle 52. Under the control of the control unit described later, during sample dispensing, the sample in the sample container (original container) at the aspiration position (first aspiration position or second aspiration position) is aspirated by the nozzle 52, and the aspirated sample is discharged from the nozzle 52 into a specific cuvette on the reaction unit 14. The discharge destination position may be fixed or dynamically changed. In this embodiment, the sample is discharged into the cuvette after the first reagent has been dispensed into it. The sample and the first reagent mix together when the sample is discharged.

[0046] The sample dispensing mechanism 28 shown in Figure 1 is just one example, and other mechanisms may be used as the sample dispensing mechanism 28. For example, a sample dispensing mechanism 28 without a rail mechanism 46 may be used, or a sample dispensing mechanism equipped with X-rails and Y-rails may be used.

[0047] The tip rack 54 is a component that holds multiple nozzle tips. When replacing a 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 a nozzle tip selected from the tip rack 54. This attaches a new nozzle tip to the nozzle body. The tip rack is replaced by a tip rack replacement mechanism (not shown).

[0048] Aspiration and discharge control will be explained using Figure 2. The sample dispensing mechanism has a nozzle transport mechanism 28A. The nozzle transport mechanism 28A is composed of a rail mechanism, slide base, arm, etc., as already described. 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.

[0049] The nozzle 52 is held by the nozzle transport mechanism 28A. The nozzle transport mechanism 28A allows the nozzle 52 to be moved freely in the vertical and horizontal directions. As already described, the nozzle 52 consists of a nozzle body 70 and a nozzle tip 72. The nozzle body 70 can also be called a sample rod. Figure 2 shows a sample container 66 that has been transported to the aspiration position in the sample supply unit 12 and is stopped at the aspiration position. A sample (whole blood) 68 is contained inside it.

[0050] A tube 74 is provided between the nozzle body 70 and the syringe pump 76, and the suction pressure and discharge pressure are transmitted via the air inside 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 inside the tube 74. This pressure indicates the pressure inside the nozzle 52. The detection signal from the pressure sensor 78 is output to the information processing unit 80.

[0051] The information processing unit 80 is comprised 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, the information processing unit 80 is connected to a timer 82, an input device 84, a display device 86, and a communication device 88. The information processing unit 80 has a storage unit, but it is not shown in Figure 2.

[0052] Timer 82 measures the elapsed time from the reference time to the determination time for each sample container. The information processing unit 80 itself may also have a timing function. The reference time is, for example, the time when the sample container is placed on the sample supply unit and the barcode label on the sample container is read to identify its sample ID. The reference time may be the time when the sample container is placed on the unit, or another timing related to sample placement. The determination time is, for example, the start of a specific cycle time assigned to the dispensing process. Another timing related to sample aspiration may also be the determination time. The elapsed time is used as one piece of information to estimate the sedimentation rate of blood cell components in the sample container 66. That is, the elapsed time is used as information to determine whether the sample is in a state suitable for mixing with the nozzle 52.

[0053] The input device 84 may consist of buttons, switches, touch panels, pointing devices, keyboards, etc. The display device 86 may consist of liquid crystal displays, organic EL display devices, etc. The communication device 88 functions when the information processing unit 80 exchanges data with the host computer via the network.

[0054] In this embodiment, if the conditions for agitation are met, the sample is agitated immediately before dispensing. Specifically, the nozzle is moved above the sample container 66 in the aspiration position, and then the nozzle 52 is lowered. In the lowered state, air is continuously supplied into the nozzle 52 by the action of the syringe pump 76. The pressure sensor 78 detects the increase in air pressure when the tip of the nozzle 52 comes into contact with the liquid surface of the sample 68 and the tip opening is sealed. Based on the output signal from the pressure sensor 78, the information processing unit 80 determines the height of the liquid surface and calculates the liquid volume from that height. Incidentally, the type of sample container 66 can be identified based on the sample ID, and the type of sample container 66 is referenced when calculating the liquid volume.

[0055] After detecting the liquid level, the syringe pump 76 draws the sample into the nozzle tip 72. During this aspiration process, the nozzle 52 is moved downward as the liquid level drops. This maintains a constant amount of nozzle tip 72 entering the sample 68. When a predetermined amount of sample has been aspirationed, the descent of the nozzle 52 and sample aspiration are stopped. Immediately thereafter, or after a certain waiting period, the nozzle 52 is pulled upward, and the syringe pump 76 dispenses the sample. During this dispensing process, the nozzle 52 is moved upward as the liquid level rises. This maintains a constant amount of nozzle tip 72 entering the sample 68.

[0056] For example, the insertion depth of the nozzle tip 72 is selected to be within the range of 0.5-15 mm. The lower limit of this range is determined from the viewpoint of avoiding air aspiration by the nozzle tip 72. The upper limit of this 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 66, and also from the viewpoint of suppressing the amount of sample adhering to the outer surface of the nozzle tip 72. Preferably, the insertion depth of the nozzle tip 72 is selected to be within the range of 1-4 mm. All values ​​listed in this specification are merely examples. After dispensing is complete, the rise of the nozzle 52 and sample dispensing are stopped while the above insertion depth is maintained.

[0057] The above suction and discharge operations are performed repeatedly. Sample agitation consists of n suction and discharge operations. The number of repetitions n can be specified in advance as any value. n is, for example, an integer of 1 or more, and may be specified as a number such as 5, 6, or 7. The maximum number of repetitions that can be performed within one cycle time may also be specified as n. n may be adaptively varied depending on various conditions. This will be described later. As described above, in sample agitation, the nozzle is transported up and down in accordance with the up and down movement of the sample's liquid surface. In other words, the nozzle moves up and down in accordance with and synchronized with the up and down movement of the sample's liquid surface. During this process, the amount of nozzle penetration into the sample is set to be relatively small and is maintained. This reduces the amount of sample adhering to the outer surface of the nozzle and enables stable and reliable sample agitation.

[0058] After the sample agitation is complete, the nozzle tip is replaced, and then the aspiration operation described above is performed. This fills the nozzle tip 72 with a predetermined amount of sample. While maintaining this filled state, the nozzle 52 is pulled upward and transported to the cuvette, which is the discharge destination. Replacing the nozzle tip avoids the problem of reduced measurement accuracy due to residual sample adhering to the inner and outer surfaces of the nozzle tip 72. If such a problem does not occur or can be ignored, the nozzle tip replacement may be omitted. The sample container 66 shown in Figure 2 is just one example, and various containers can be used as sample containers.

[0059] By performing sample agitation and sample aspiration consecutively at the same aspiration position, it becomes possible to quickly contain the sample in the nozzle tip after sample agitation. Even when blood cell components have settled in whole blood, sample agitation is applied to the whole blood, making it possible to sample whole blood with a uniform concentration of blood cell components.

[0060] Figure 3 shows an example configuration of the information processing unit 80. In Figure 3, elements similar to those shown in Figure 2 are denoted by the same reference numerals, and their descriptions are omitted. The information processing unit 80 has a processor 90. The processor 90 is composed of, for example, a CPU that executes programs.

[0061] Figure 3 shows the multiple functions performed by the processor 90 represented by multiple blocks. The processor 90 functions as an operation control unit (error processing unit) 94, an excess determination unit 96, a bubble aspiration determination unit 98, a blockage determination unit 100, etc. The processor 90 determines whether or not the stirring execution conditions have been met. Examples of stirring execution conditions include a condition that the elapsed time has not exceeded a predetermined time, a condition that the sample volume is within a predetermined range, a condition that the sample container is not shaped in a way that makes it unsuitable for stirring, a condition that the degree of hemolysis is lower than a predetermined level, a condition that the degree of hemocyte sedimentation is less than a predetermined level, etc. In Figure 3, the function that performs the determination related to elapsed time is explicitly shown as the excess determination unit 96. A storage unit 92 is connected to the processor 90. The storage unit 92 stores a management table 102. The processor 90 performs control, calculations, etc. based on the management table 102.

[0062] The excess determination unit 96 determines whether the elapsed time for each sample has exceeded a predetermined time (reference time). If an excess is determined, the operation control unit 94 performs error processing. For example, the excess is reported to the examiner, and manual stirring of the sample container is prompted. After manual stirring, the sample container is returned to the sample supply unit. Subsequently, the sample container may be processed preferentially. Multiple reference times may be set to be compared with the elapsed time. For example, if the elapsed time does not exceed the first reference time, stirring may be omitted and sampling may be performed; if the elapsed time exceeds the first reference time but does not exceed the second reference time, stirring may be performed and sampling may be performed; and if the elapsed time exceeds the second reference time, error processing may be performed.

[0063] The bubble aspiration detection unit 98 determines bubble aspiration based on the detection signal from the pressure sensor. For example, if bubbles are present on the surface of the sample liquid, and the unit mistakenly identifies the surface of the bubbles as the liquid surface, only the bubbles will be sucked into the nozzle tip. This is determined by the bubble aspiration detection unit 98. If bubble aspiration is detected, error processing is performed and the user is notified accordingly.

[0064] The blockage detection unit 100 determines blockages based on detection signals from the pressure sensor. For example, if a blockage occurs inside the nozzle tip during suction, the pressure inside the nozzle tip rises rapidly. A blockage is determined based on this pressure change. If a blockage is detected, error processing is performed, and the user is notified accordingly.

[0065] In addition to the above, other monitoring and other determinations may be performed to ensure proper sample mixing and dispensing. The processor 90 according to this embodiment performs various determinations and various error processing. For example, the entry of air into the suction path, including the inside of the nozzle tip (i.e., a leak) may be determined. A leak can be determined based on a detection signal from a pressure sensor. Air bubble aspiration, blockage, and leak can all be considered suction abnormalities. Other suction abnormalities may also be determined. A camera may be connected to the processor 90. The camera captures the sample state before or during sample mixing, and by analyzing the obtained image, errors may be determined, or the sample mixing execution conditions may be changed. As will be explained later, prior to sample mixing, it is determined whether or not the liquid level of the sample is within a predetermined height range. Error processing is performed if the liquid level of the sample is outside the predetermined height range.

[0066] Figure 4 shows a timing chart of the first example of a stirring and dispensing operation. (A) shows the i-th cycle time, the (i+1)th cycle time, and the (i+2)th cycle time. i is an integer greater than or equal to 1. (B) shows the processing for the j-th sample and the (j+1)th sample. j is an integer greater than or equal to 1. For the j-th sample, the stirring operation is performed within the i-th cycle time, and the dispensing operation is performed within the subsequent (i+1)th cycle time. On the other hand, for the (j+1)th sample, the stirring operation is performed within the (i+2)th cycle time, and the dispensing operation is performed within the subsequent (i+3)th cycle time. In this first example, the stirring operation and the dispensing operation are performed for each cycle time unit 200 consisting of two consecutive cycle times.

[0067] In Figure 4, Tx represents the elapsed time for the j-th sample. The elapsed time Tx is the time between the reference time T1 and the judgment time T2. Error handling is performed if the elapsed time Tx exceeds a predetermined time. The elapsed time for each sample is compared with the predetermined time.

[0068] Figure 5 shows a timing chart of a second example of the stirring and dispensing operation. (A) shows the i-th cycle time and the (i+1)th cycle time. (B) shows the processing for the j-th sample and the (j+1)th sample. For the j-th sample, the stirring and dispensing operations are performed sequentially within the i-th cycle time. On the other hand, for the (j+1)th sample, the stirring and dispensing operations are performed sequentially within the (i+1)th cycle time. Thus, in the second stirring and dispensing operation, the stirring and dispensing operations are performed for each cycle time. Other stirring and dispensing operations besides the first and second examples shown in Figures 4 and 5 may also be adopted.

[0069] Figure 6 shows an example of the configuration of a management table. The illustrated management table 102 has multiple records 104 corresponding to multiple samples. Each record 104 includes information 106 that identifies the location of the sample container, information 108 that identifies the sample ID, information 110 that represents the sample type, information 112 that represents the analysis item, and further includes information 114 that represents the time (start of elapsed time) identified at the reference time. The elapsed time is calculated based on the information 114.

[0070] Figure 7 illustrates the appropriate range for sample volume. (A) shows the appropriate range 122 defined for the sample container 116. Specifically, an upper limit 118 and a lower limit 120 are defined for the sample container 116, and the range between these is the appropriate range 122. If the liquid level is within the appropriate range 122, that is, if the sample volume is within a certain range, sample stirring is permitted. If the liquid level is not within the appropriate range 122, in particular if the liquid level is above the upper limit 118, sample stirring will not be performed, and error processing will be executed. In that case, manual sample stirring will be prompted. Error processing will also be executed if the sample volume is below the lower limit 120. In that case, the user will be notified of insufficient sample volume.

[0071] In Figure 7, (B) shows the appropriate range 132 defined for the sample container 124. Specifically, the sample container 124 is held by the adapter 126. An upper limit 128 and a lower limit 130 are defined for the sample container 124, and the range between them is the appropriate range 132. Similarly, if the liquid level is within the appropriate range 132, sample agitation is permitted. If the liquid level is not within the appropriate range 132, sample agitation is not performed, and error handling is performed.

[0072] Figure 8 shows the entire sample analysis process as a flowchart. This flowchart assumes a two-step method that includes two immunoassay steps.

[0073] In S10, the sample container is placed on the sample supply unit. In S12, the barcode attached to the sample container is read by a barcode reader. This identifies the sample ID, and a query is performed to the host computer using that sample ID. Alternatively, the sample ID may be identified using the sample placement location information instead of using the barcode. S14 is a waiting process, in which case the samples are in a waiting state.

[0074] If the conditions for agitation are met, sample agitation is performed in S16. That is, the aspiration and dispensing operation is repeated n times. In S18, sample dispensing is performed. Specifically, the sample in the sample container is aspirated by the nozzle, and the aspirated sample is dispensed from the nozzle into the cuvette.

[0075] S20 is usually performed before sample dispensing. In S20, the first reagent is aspirated by the reagent dispensing nozzle and discharged into the cuvette. In S18, when the sample is discharged from the nozzle into the cuvette, a mixture of the first reagent and the sample is created within the cuvette.

[0076] In S22, the mixture in the cuvette is stirred. S24 shows the primary immunoassay step. After S24, B / F washing is performed in S26. Then, in S28, the second reagent is dispensed into the cuvette using the reagent dispensing nozzle. In S30, the liquid in the cuvette is stirred. S32 shows the secondary immunoassay step. In S34, B / F washing is performed.

[0077] In S38, the substrate is dispensed into the cuvette. A substrate dispensing nozzle is used for this purpose. In S40, the liquid in the cuvette is stirred. S42 shows the enzyme reaction step. In S44, the luminescence generated in the cuvette is measured. In S46, the concentration of the analyte is calculated based on the amount of luminescence. Also in S46, the measurement results are output.

[0078] The stirring and dispensing process A1 in Figure 8 will be described in detail using Figures 9 and 10. Figure 9 is a flowchart (part 1) showing the stirring and dispensing process, and Figure 10 is a flowchart (part 2) showing the stirring and dispensing process. These also illustrate the control performed by the processor.

[0079] In Figure 9, at S50, the barcode attached to the sample container mounted on the sample supply unit is read by a barcode reader. This identifies the sample ID, and based on that sample ID, the sample type and container type are identified. At S50, the measurement of the elapsed time from the reference time begins.

[0080] In S52, based on the identified sample type, it is determined whether the sample in the sample container is subject to agitation. If the sample is not subject to agitation, other processes for sample analysis are applied in S54. If the identified sample type is whole blood, the state of the sample in the sample container is determined in S55. For example, it is determined whether the sample is hemolyzed based on the hemoglobin value and color of the supernatant portion of the sample. Specifically, the hemoglobin value of the supernatant portion is measured, and then compared to a threshold (predetermined value). If the hemoglobin value exceeds the threshold, it is determined that the sample is hemolyzed. The hemolyzed state may also be determined by the color of the supernatant portion. If a hemolyzed state is determined, other processes for sample analysis are applied in S54. The state of the sample may also be determined from the degree (degree or rate) of hemocyte sedimentation.

[0081] In S56, it is determined whether the sample container is suitable for stirring based on the container type. For example, if the sample container is a large container, it is determined that the sample container is not suitable for stirring. In that case, error processing is performed in S58, and the user, who is the tester, is notified of the error.

[0082] In S56, if it is determined that the sample container is suitable for stirring, in S60 the stirring execution conditions are set. For example, the number of suction / discharge repetitions n, suction volume, suction speed, temporary waiting time after suction, discharge volume, discharge speed, temporary waiting time after discharge, nozzle descent speed, nozzle rise speed, etc. are set. S62 indicates the waiting process. This corresponds to S14 shown in Figure 8.

[0083] In S64, it is determined whether the elapsed time from the reference time to the time of judgment has exceeded a predetermined time. If the elapsed time has exceeded the predetermined time, error processing is performed in S66. In this case, the user is notified of the error and is prompted to manually mix the sample. If it is determined in S64 that the elapsed time has not exceeded the predetermined time, in S68 the nozzle tip is attached to the nozzle body, and in S70 the nozzle is positioned above the aspiration position.

[0084] In Figure 10, at S72, the nozzle descent begins. At S74, it is determined that the nozzle tip has reached the liquid level. At S76, the sample volume is calculated from the liquid level, and it is determined whether the sample volume is within the appropriate range. However, it is also possible to directly determine whether the sample volume is within the appropriate range from the liquid level. If the sample volume falls outside the appropriate range, i.e., if the sample volume is inappropriate, error processing is performed at S78, and the error is notified to the user. In that case, the stirring execution conditions are not met. If it is determined at S76 that the sample volume is appropriate, the processes from S80 onward are executed. In this embodiment, the nozzle descent is temporarily stopped at the time of liquid level detection, but it is also possible to start suction without stopping the nozzle descent.

[0085] In S80, suction by the nozzle begins, and simultaneously, the nozzle starts to descend. In S82, the nozzle descends in accordance with the decrease in the liquid level. When a predetermined amount of sample has been aspirated, in S84, suction of the sample stops, and the descent of the nozzle also stops. After a brief waiting period, in S86, discharge of the sample begins, and the nozzle starts to rise. In S88, the nozzle rises in accordance with the increase in the liquid level. In S90, discharge of the sample ends, and the nozzle stops rising.

[0086] In S92, it is determined whether the number of repetitions nx of suction and discharge has reached the set value n. If it has not, nx is incremented by 1, and the processes from S80 onward are executed again. A temporary waiting period is provided before the execution of S80. The initial value of nx is 1, and n is given as an integer of 1 or greater.

[0087] In S92, if it is determined that n suction and discharge operations have been completed, in S100, the nozzle is transported to the tip disposal area, where the nozzle tip is removed from the nozzle body. In S102, a new nozzle tip is attached to the nozzle body. In S104, the nozzle is transported above the suction position.

[0088] In S106, the nozzle descent begins, and in S108, it is determined that the tip of the nozzle has reached the liquid surface. In this embodiment, the nozzle descent is stopped at this point, but it may be allowed to continue descending. In S110, sample aspiration and nozzle descent begin, and in S112, the nozzle descent follows the decrease in the liquid surface. When a predetermined amount of sample has been aspirated, in S114, sample aspiration and nozzle descent are stopped. After a temporary waiting period, in S116, the nozzle is pulled upward. The nozzle is then transported to the cuvette for discharge. In S118, the sample is discharged from the nozzle into the cuvette. In S120, the used nozzle tip is removed and discarded.

[0089] S96 indicates a step to monitor for abnormal suction during the suction process. Specifically, in S96, air bubble suction and blockage are detected. S98 indicates a step to monitor for abnormal discharge during the discharge process. Specifically, in S98, blockage is detected. S122 indicates a step to monitor for abnormal suction during the suction process. Specifically, in S122, air bubble suction and blockage are detected, similar to S96.

[0090] Figure 11 shows a modified sample analyzer. In Figure 11, elements similar to those shown in Figure 1 are denoted by the same reference numerals. The sample analyzer 10A consists of a main unit 134 and a rack transport table 136 attached thereto. The main unit 134 is equipped with a sample dispensing mechanism 28. The sample dispensing mechanism 28 has a rail mechanism 46, a slide base 48, an arm 50, and a nozzle 52.

[0091] Individual racks are transported on the rack transport platform 136. Reference numeral 140 indicates a row of sample container racks set by the user (hereinafter, sample container racks will be simply referred to as racks). Reference numeral 142 indicates the rack being processed. Reference numeral 144 indicates a row of reprocessable racks 144 located within the buffer area. Reference numeral 146 indicates a row of discharged racks 146. Each rack holds multiple sample containers.

[0092] The samples in the individual sample containers held in the rack 142 are to be dispensed. In other words, the position of each sample container corresponds to the aspiration position where the stirring and dispensing aspiration operations are performed. The nozzle transport mechanism in the sample dispensing mechanism 28 sequentially positions the nozzle 52 at each aspiration position.

[0093] In the modified sample analyzer 10A, for example, samples in the sample supply unit 12 are processed preferentially, and then each sample in each rack is processed. However, control may be implemented so that each sample in each rack is processed preferentially.

[0094] As shown in Figure 12, the stirring conditions may be changed based on the elapsed time 148. For example, the number of suction discharges (n) 150 may be set based on the elapsed time 148. In that case, the larger the elapsed time 148, the greater the number of suction discharges (n) may be increased. The suction discharge speed 152 may also be set based on the elapsed time 148.

[0095] As shown in Figure 13, the number of aspiration / discharge cycles (n) 156 may be changed based on the sample volume / sample condition / container type 154 (where " / " means "or"). For example, the number of aspiration / discharge cycles (n) 156 may be increased as the sample volume increases or the container size increases. The aspiration / discharge speed 158, aspiration / discharge volume 160, amount entering the liquid surface 162, waiting time from the end of aspiration to the start of discharging (or waiting time from the end of discharging to the start of aspiration) 164, the horizontal position of the nozzle in the sample container 166, etc. may be changed based on the sample volume / sample condition / container type 154. Similarly, the aspiration / discharge speed 158, aspiration / discharge volume 160, amount entering the liquid surface 162, waiting time from the end of aspiration to the start of discharging (or waiting time from the end of discharging to the start of aspiration) 164, the horizontal position of the nozzle in the sample container 166, etc. may be changed based on the nozzle tip capacity and the type of sample.

[0096] According to the above embodiment, when the stirring conditions are met, the sample is stirred prior to dispensing, and a mixed state of the sample is formed in the original container. Since the sample can then be sampled, the accuracy of the analysis of the analyte can be improved. There is no need to set up special equipment for stirring the sample; it can be stirred using existing equipment. In this embodiment, since the stirring position and the aspiration position for dispensing are the same, the sample can be aspirationed immediately after stirring. [Explanation of Symbols]

[0097] 10 Sample analyzer, 12 Sample supply unit, 14 Reaction unit, 16 Reagent supply unit, 18 Photodetector, 28 Sample 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.

Claims

1. A nozzle comprising a nozzle body and a nozzle tip attached thereto, A control unit for controlling sample dispensing using the nozzle, comprising: a control unit that controls sample stirring using the nozzle prior to controlling sample dispensing when stirring execution conditions are met; Includes, In the aforementioned sample dispensing, the sample in the original container, which has been transferred to the aspiration position, is aspirated into the nozzle, and the aspirated sample is discharged from the nozzle into the reaction vessel. The sample stirring includes n (where n is an integer of 1 or more) aspiration and discharging operations performed at the aspiration position, In each of the above-mentioned aspiration and dispensing operations, the sample in the original container is drawn into the nozzle, and the drawn-in sample is discharged from the nozzle into the original container. Under the control of the control unit, a first nozzle tip replacement is performed for each sample to be dispensed, between the mixing of the sample and the subsequent dispensing of the sample, and a second nozzle tip replacement is performed after the dispensing of the sample. A specimen analyzer characterized by the following features.

2. In the specimen analyzer according to claim 1, The sample analyzer operates according to the cycle time. The sample stirring and sample dispensing are performed for each cycle time unit consisting of multiple cycle times, or for each cycle time. A specimen analyzer characterized by the following features.

3. In the specimen analyzer according to claim 1, The control unit, The elapsed time from the reference time determined based on the installation of the original container to the time of determination before the start of sample stirring is measured. The operation of the nozzle is controlled based on the elapsed time. A specimen analyzer characterized by the following features.

4. In the specimen analyzer according to claim 3, The control unit determines an error without causing the nozzle to agitate the sample if the elapsed time exceeds a predetermined time. A specimen analyzer characterized by the following features.

5. In the specimen analyzer according to claim 3, The control unit changes the conditions for stirring the sample according to the elapsed time. A specimen analyzer characterized by the following features.

6. In the specimen analyzer according to claim 5, The control unit changes n according to the elapsed time. A specimen analyzer characterized by the following features.

7. In the specimen analyzer according to claim 1, In the first nozzle tip replacement and the second nozzle tip replacement, the used nozzle tip is replaced with an unused nozzle tip of the same type. A specimen analyzer characterized by the following features.

8. In the specimen analyzer according to claim 1, The aforementioned stirring conditions include liquid volume conditions. The aforementioned liquid volume condition is a condition that must be met by the amount of sample in the original container. A specimen analyzer characterized by the following features.

9. A nozzle and A control unit for controlling sample dispensing using the nozzle, comprising: a control unit that controls sample stirring using the nozzle prior to controlling sample dispensing when stirring execution conditions are met; Includes, In the aforementioned sample dispensing, the sample in the original container, which has been transferred to the aspiration position, is aspirated into the nozzle, and the aspirated sample is discharged from the nozzle into the reaction vessel. The sample stirring includes n (where n is an integer of 1 or more) aspiration and discharging operations performed at the aspiration position, In each of the above-mentioned aspiration and dispensing operations, the sample in the original container is drawn into the nozzle, and the drawn-in sample is discharged from the nozzle into the original container. The aforementioned stirring conditions include container conditions. The aforementioned container conditions are the conditions that the original container must satisfy. A specimen analyzer characterized by the following features.

10. In the specimen analyzer according to claim 1, The aforementioned stirring conditions include sample state conditions. The aforementioned sample condition is the condition that the sample in the original container must satisfy. A specimen analyzer characterized by the following features.

11. In the specimen analyzer according to claim 1, During the sample stirring process, the nozzle is moved up and down in accordance with the vertical movement of the liquid surface of the sample in the original container. A specimen analyzer characterized by the following features.

12. In the specimen analyzer according to claim 1, The amount of insertion of the nozzle into the sample in the original container during each of the aforementioned suction and discharge operations is in the range of 0.5 to 15 mm. A specimen analyzer characterized by the following features.

13. In the specimen analyzer according to claim 1, A pressure sensor for detecting the pressure inside the nozzle, In the sample stirring process, means for determining that at least one of the following is an aspiration abnormality: air bubble aspiration, blockage, and leak, based on the output signal of the pressure sensor, A means for executing error processing when the aforementioned suction abnormality is detected, A specimen analyzer characterized by including [a specific component].

14. In the specimen analyzer according to claim 1, A means for determining the height of the liquid level of the sample in the original container prior to stirring the sample, Means for executing error processing when the liquid level is outside a predetermined height range, A specimen analyzer characterized by including [a specific component].

15. A step of dispensing a sample using a nozzle comprising a nozzle body and a nozzle tip attached thereto, A step of performing sample agitation using the nozzle before dispensing the sample, The process involves performing sample analysis after dispensing the aforementioned sample, Includes, In the aforementioned sample dispensing, the sample in the original container, which has been transferred to the aspiration position, is aspirated into the nozzle, and the aspirated sample is discharged from the nozzle into the reaction vessel. The sample stirring includes n (where n is an integer of 1 or more) aspiration / discharge operations performed at the aspiration position. In each of the above-mentioned aspiration and dispensing operations, the sample in the original container is drawn into the nozzle, and the aspirated sample is discharged from the nozzle into the original container. For each sample to be dispensed, a first nozzle tip replacement is performed between the mixing of the sample and the subsequent dispensing of the sample, and a second nozzle tip replacement is performed after the dispensing of the sample. A method for analyzing a specimen characterized by the following features.

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