Specimen analysis device, specimen analysis method and program

Abstract

To reduce a risk of accumulation of air bubbles in a flow path between a sampling nozzle and a fixed dispenser and formation of an air gap and reduce a risk of reduction in the analytical accuracy of a specimen.SOLUTION: A specimen analysis device includes a sampling nozzle, a fixed dispenser, a switching valve which switches the communication state of a flow path between the sampling nozzle and the fixed dispenser, a switching valve opening / closing instruction part and a fixed dispenser drive instruction part. The switching valve opening / closing instruction part controls the switching valve, the fixed dispenser drive instruction part performs a drawing instruction to the fixed dispenser in such a state that the connection between the sampling nozzle and the fixed dispenser in the flow path is shut down, the switching valve opening / closing instruction part controls the switching valve after the fixed dispenser draws liquid for discharge, the fixed dispenser drive instruction part performs a push-in instruction to the fixed dispenser in such a state that the sampling nozzle is connected to the fixed dispenser in the flow path, and the fixed dispenser pushes out the liquid for discharge to make it flow to the flow path, and discharges the liquid for discharge to the outside of the flow path.SELECTED DRAWING: Figure 7

Description

[Technical field]

[0001] The present invention relates to a sample analyzer, a sample analysis method, and a program. [Background technology]

[0002] Conventionally, there has been proposed an apparatus for analyzing components in blood by reacting blood with a reagent in a reaction vessel (see, for example, Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2012-21926 A Summary of the Invention [Problem to be solved by the invention]

[0004] In an apparatus for performing an immunoassay by reacting blood with an immunoassay reagent such as a CRP (C-reactive protein) reagent, the CRP reagent is aspirated from a reagent container through a sampling nozzle (hereinafter also simply referred to as a "nozzle") by the suction action of an immunoassay dispenser (hereinafter also referred to as a "CRP dispenser"). The CRP reagent is then discharged into a CRP chamber through the nozzle by the discharge action of the CRP dispenser. The flow path between the nozzle and the CRP dispenser is connected to a sample dispenser for aspirating and discharging blood through a plurality of valves (movable valves).

[0005] The flow path is usually filled with a diluent, and air bubbles are originally present in the flow path. Therefore, when the CRP dispenser repeatedly sucks and discharges the CRP reagent, the air bubbles accumulated in the flow path may combine and become an air gap that blocks the flow path. For example, if an air gap is formed in the flow path between the nozzle and the sample dispenser, when the sample dispenser sucks blood into the nozzle and then discharges it, the force pushing out the sucked blood is absorbed by the air gap. Therefore, the timing of the blood discharged from the nozzle is delayed, and it becomes impossible to discharge the specified amount of blood. As a result, a problem occurs in that the accuracy of blood analysis is reduced, for example, the measured value becomes low.

[0006] Such problems will not occur during normal use of the device, but may occur if an abnormality occurs in the valve, which is prone to trapping air bubbles (for example, leakage when shut off).

[0007] Patent Document 1 discloses that air bubbles are removed by performing a circulating operation in which the reagent sucked from the reagent container is returned to the reagent container. However, the configuration of Patent Document 1 has the possibility of an air gap being formed in the flow path from the valve to the nozzle, and there is room for improvement.

[0008] The present invention has been made to solve the above-mentioned problems, and its purpose is to provide a sample analysis device, a sample analysis method, and a program that can reduce the risk of air bubbles accumulating in the flow path between the sampling nozzle and the fixed-volume dispenser, resulting in the formation of an air gap, thereby reducing the risk of a decrease in the analytical accuracy of the sample (e.g., blood). [Means for solving the problem]

[0009] A sample analyzer according to one aspect of the present invention comprises a sampling nozzle, a fixed-volume dispenser which aspirates and dispenses liquid through the sampling nozzle, a switching valve which switches the communication state of a flow path between the sampling nozzle and the fixed-volume dispenser, a switching valve opening / closing instruction unit which instructs the switching valve to switch between open and closed, and a fixed-volume dispenser drive instruction unit which issues an instruction to drive the fixed-volume dispenser, wherein the switching valve opening / closing instruction unit controls the switching valve to block communication between the sampling nozzle and the fixed-volume dispenser in the flow path, the fixed-volume dispenser drive instruction unit issues an instruction to draw in liquid to the fixed-volume dispenser, and the fixed-volume dispenser draws in liquid to be dispensed inside, and then the switching valve opening / closing instruction unit controls the switching valve to connect the sampling nozzle to the fixed-volume dispenser in the flow path, the fixed-volume dispenser drive instruction unit issues an instruction to push in, and the fixed-volume dispenser pushes out the liquid to be dispensed and flows it into the flow path, and the liquid to be dispensed is discharged outside the flow path.

[0010] A sample analysis method according to another aspect of the present invention is a sample analysis method in a sample analyzer equipped with a fixed-volume dispenser which aspirates and dispenses liquid through a sampling nozzle, and a switching valve which switches the communication state of a flow path between the sampling nozzle and the fixed-volume dispenser, and includes a liquid drawing step in which the fixed-volume dispenser draws in liquid to be dispensed therein by (the switching valve opening / closing instruction unit) controlling the switching valve to block communication between the sampling nozzle and the fixed-volume dispenser in the flow path, and (the fixed-volume dispenser drive instruction unit) issuing an instruction to the fixed-volume dispenser to draw in liquid to be dispensed therein, and a liquid discharging step in which, after the liquid drawing step, the switching valve is controlled (by the switching valve opening / closing instruction unit) to connect the sampling nozzle and the fixed-volume dispenser in the flow path, and (the fixed-volume dispenser drive instruction unit) issues a push instruction to the fixed-volume dispenser to push out the liquid to be dispensed and flow it into the flow path, and the liquid to be dispensed is discharged outside the flow path.

[0011] A program according to yet another aspect of the present invention is a program for causing a computer to execute the above-described sample analysis method. Effect of the Invention

[0012] According to the present invention, it is possible to reduce the risk of air bubbles accumulating in the flow path between the sampling nozzle and the fixed-volume dispenser, thereby reducing the risk of a decrease in the accuracy of sample analysis. [Brief description of the drawings]

[0013] [Figure 1] 1 is a perspective view showing the external configuration of a blood analyzer according to an embodiment of the present invention. [Diagram 2] FIG. 2 is an explanatory diagram illustrating a schematic internal configuration of the blood analyzer. [Diagram 3] FIG. 13 is an explanatory diagram showing a schematic diagram of blood being ejected into a BASO chamber through a nozzle while a BASO measurement reagent is being ejected from the side of the BASO chamber. [Figure 4] FIG. 2 is an explanatory diagram showing a flow path between a nozzle and a CRP fixed quantity dispenser in the blood analyzer. [Diagram 5] 4 is a flowchart showing the flow of operations in the blood analyzer. [Figure 6] 4 is a flowchart showing the flow of operations in the blood analyzer. [Figure 7] FIG. 2 is an explanatory diagram illustrating a schematic view of a main part of the blood analyzer. [Figure 8] FIG. 2 is an explanatory diagram illustrating a schematic view of a main part of the blood analyzer. [Figure 9] FIG. 2 is an explanatory diagram illustrating a schematic view of a main part of the blood analyzer. [Figure 10] FIG. 2 is an explanatory diagram illustrating a schematic view of a main part of the blood analyzer. [Figure 11] FIG. 2 is an explanatory diagram illustrating a schematic view of a main part of the blood analyzer. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Exemplary embodiments of the present invention will now be described with reference to the accompanying drawings. In the present embodiment, a blood analyzer, also called a whole blood cell and immune measuring apparatus, will be described as a sample analyzer.

[0015] [1. Overview of blood analyzers] 1 is a perspective view showing the external configuration of blood analyzer 1. Blood analyzer 1 has a display unit 3 on the upper front surface of device main body 2. Display unit 3 is configured, for example, with a liquid crystal display device with a touch panel, and displays blood analysis results, etc., and accepts input of various information by an operator (for example, a medical professional).

[0016] A specimen container loading section 4 is provided at the bottom of the device body 2. The specimen container 10 can be loaded into the device body 2 by opening the cover 4a of the specimen container loading section 4, setting a specimen container 10 containing a blood specimen (hereinafter also simply referred to as "blood"), and closing the cover 4a.

[0017] A reagent container loading section 5 is provided on the side of the device body 2. By opening the opening and closing door 5a of the reagent container loading section 5, containers containing reagents used in blood analysis (e.g., immunoassay reagents, blood cell measurement reagents, etc.) can be loaded.

[0018] 2. Internal structure of blood analyzer 2 is an explanatory diagram that shows a schematic diagram of the internal configuration of blood analyzer 1. Blood analyzer 1 includes immunomeasurement section 20. Immunomeasurement section 20 has a CRP chamber 21 (chamber for immunomeasurement). CRP chamber 21 is configured so that the CRP value can be optically measured according to the latex agglutination method.

[0019] A CRP reagent for immunoassay is discharged into the CRP chamber 21 through a sampling nozzle N (hereinafter also simply referred to as "nozzle N"). The CRP reagent includes an R1 reagent, an R2 reagent, and an R3 reagent. The R1 reagent is a hemolysis reagent, and is contained in an R1 reagent container 22. The R2 reagent is a buffer solution, and is contained in an R2 reagent container 23. The R3 reagent is a latex reagent, and is contained in an R3 reagent container 24. The CRP reagent is aspirated from each reagent container by the nozzle N and discharged into the CRP chamber 21.

[0020] Furthermore, blood is drawn from the specimen container 10 through a nozzle N and discharged into the CRP chamber 21. In the CRP chamber 21, the CRP reagent and the blood are mixed, stirred, and reacted with each other to perform an immunoassay (CRP measurement).

[0021] The above-mentioned suction and discharge of the CRP reagent, and the mixing of the CRP reagent and blood are performed by the piston movement of a CRP fixed-volume dispenser 25 (fixed-volume dispenser for immunoassay) whose flow path is connected to the CRP chamber 21 via an electromagnetic valve device 26. The piston movement of the fixed-volume dispenser refers to the retraction and extrusion motion of the piston relative to the syringe.

[0022] The nozzle N is held by a vertical movement mechanism 31 of the probe unit 30. The vertical movement mechanism 31 is held by a horizontal movement mechanism 32. By driving the vertical movement mechanism 31 and the horizontal movement mechanism 32, the nozzle N can be moved vertically and horizontally. This allows the nozzle N to be moved to positions above the specimen container 10, the CRP chamber 21, the CRP reagent containers (R1 reagent container 22, R2 reagent container 23, R3 reagent container 24), and each chamber of the blood cell counting and measuring section 40 described below, and also allows the nozzle N to be inserted and removed vertically relative to the specimen container 10, etc.

[0023] The probe unit 30 has a nozzle cleaner 33. The nozzle N is provided to penetrate the nozzle cleaner 33 in the vertical direction. By flowing a cleaning liquid or diluting liquid onto the outer circumferential surface and the tip (lower end) of the nozzle N through the nozzle cleaner 33, excess blood or reagent adhering to the outer circumferential surface, etc. can be washed away and removed.

[0024] The blood analyzer 1 includes a blood cell counting and measuring unit 40. The blood cell counting and measuring unit 40 has a BASO chamber 41, a LMNE chamber 42, an RBC chamber 43, and a WBC chamber 44 as chambers for measuring blood cells.

[0025] The BASO chamber 41 is provided for counting basophils contained in white blood cells. The LMNE chamber 42 is provided for counting lymphocytes, monocytes, neutrophils, and eosinophils contained in white blood cells. The RBC chamber 43 is provided for counting red blood cells (RBC) and platelets (PLT). The WBC chamber 44 is provided for counting white blood cells (WBC) and analyzing hemoglobin (HGB) (for measuring the concentration).

[0026] Blood is suctioned from the specimen container 10 and discharged into each chamber of the blood cell counting and measuring section 40 via nozzle N by the piston movement of sample dispenser 60. Blood cell counting reagent is discharged from the side of each chamber of the blood cell counting and measuring section 40 by reagent dispenser 70 (see FIG. 4). A reagent dispenser 70 is provided corresponding to each reagent (BASO measurement reagent (e.g., basophil hemolyzing agent), LMNE measurement reagent (e.g., eosinophil measurement reagent), washing solution, hemolyzing agent, diluent).

[0027] 3 is a schematic diagram showing how blood BL is discharged into the BASO chamber 41 through a nozzle N while the BASO measurement reagent Rb is discharged from the side of the BASO chamber 41 through a conduit 41a. As shown in the figure, by mixing the BASO measurement reagent Rb with the blood BL while flowing the BASO measurement reagent Rb along the inner peripheral surface of the BASO chamber 41, uniform mixing can be achieved and erroneous measurements due to blood viscosity can be prevented.

[0028] 2, the blood cell counting and measuring unit 40 further includes a washing chamber 45. The washing chamber 45 is provided to receive the washing liquid that flows when the nozzle N is washed, the liquid remaining in each chamber of the immunoassay unit 20 and the blood cell counting and measuring unit 40, the dilution liquid used to wash the flow path between the nozzle N and the CRP fixed dispenser 25 described below, and the like. The washing liquid and the like received in the washing chamber 45 are sent to a waste liquid container 52 via an electromagnetic valve device 50 and a discharge pump 51.

[0029] The operation of each part of the blood analyzer 1 is controlled by the control unit 100. The control unit 100 includes a solenoid valve opening / closing instruction unit 101 and a fixed-volume dispenser drive instruction unit 102. The solenoid valve opening / closing instruction unit 101 issues instructions to switch between open and closed states to each solenoid valve (including the solenoid valves constituting each of the solenoid valve devices 26 and 50). The fixed-volume dispenser drive instruction unit 102 issues drive instructions to each fixed-volume dispenser (CRP fixed-volume dispenser 25, sample fixed-volume dispenser 60, reagent fixed-volume dispenser 70). In addition, the operation of the probe unit 30 is also controlled by the control unit 100. The control unit 100 is composed of a central processing unit (computer) called a CPU (Central Processing Unit), and operates according to an operating program.

[0030] [3. Flow path between the nozzle and the CRP dispenser] 4 is an explanatory diagram showing a flow path FP between the nozzle N and the CRP fixed quantity dispenser 25 in the blood analyzer 1. As shown in the figure, the CRP fixed quantity dispenser 25 is fluidly connected to the nozzle N via the flow path FP. The flow path FP includes a first flow path FP1 and a second flow path FP2.

[0031] The first flow path FP1 is a flow path between the nozzle N and a first valve V1 included in the solenoid valve device 50. A sample dispenser 60 is disposed midway along the first flow path FP1. A sensor 61 for detecting a reagent is disposed along the first flow path FP1 between the nozzle N and the sample dispenser 60. The nozzle N, the sample dispenser 60, the sensor 61, and the nozzle cleaner 33 are attached to a carriage (not shown) of the probe unit 30 (see FIG. 2), and can be moved together by the drive of the vertical movement mechanism 31 and the horizontal movement mechanism 32.

[0032] The first flow path FP1 and the second flow path FP2 are connected via a first valve V1. The first valve V1 switches the first flow path FP1 and the second flow path FP2 between a communicated state and a blocked state. The communication refers to a state in which the two are connected and liquid can flow from one to the other (can flow). On the other hand, the blocking of the communication refers to a state in which the connection between the two is cut off and liquid cannot flow from one to the other (cannot flow).

[0033] The second flow path FP2 is a flow path between the first valve V1 and the CRP fixed pipetting device 25. In the second flow path FP2, a second valve V2 is disposed between the first valve V1 and the CRP fixed pipetting device 25. The second valve V2 switches between a state in which the first valve V1 and the CRP fixed pipetting device 25 are in communication with each other and a state in which the communication with each other is blocked.

[0034] CRP chamber 21 is connected to second valve V2 via branch 27 and third valve V3. Branch 27 and second valve V2 are switched between a connected state and a disconnected state by third valve V3. In addition, a valve for switching the connected state is disposed at a predetermined position of the flow path in blood analyzer 1.

[0035] Each valve (including first valve V1, second valve V2, and third valve V3) in blood analyzer 1 is configured as a solenoid valve that is turned on and off by a control signal (open / close instruction signal) from control unit 100 (particularly solenoid valve open / close instruction unit 101 (see FIG. 2)). The solenoid valve is configured as a three-way valve with three inlets and outlets for liquid (connections to piping in three directions) or a two-way valve with two inlets and outlets for liquid (connections to piping in two directions).

[0036] A flow path (e.g., flow path FP in FIG. 4) inside blood analyzer 1 is usually filled with a liquid such as a diluent. This allows, for example, the piston movement of CRP fixed-volume dispenser 25 to aspirate and discharge the CRP reagent through flow path FP.

[0037] Due to the structure of each valve arranged in the flow path FP, air bubbles tend to accumulate in each valve, and therefore air bubbles exist in the flow path FP. When the CRP dispenser 25 repeatedly sucks and dispenses the CRP reagent, the air bubbles accumulated in the flow path FP are bound together, which may become an air gap that hinders the sample dispenser 60 from discharging blood. In this embodiment, the CRP dispenser 25 is used to fill the flow path FP with a liquid for discharging (e.g., diluent) at a predetermined timing and discharge it from the nozzle N, thereby preventing the formation of an air gap in the flow path FP. The operation of the blood analyzer 1 of this embodiment, including the operation of discharging the diluent, will be described below.

[0038] [4. Operation] 5 and 6 are flow charts showing the flow of operations in blood analyzer 1. Also, FIGS. 7 to 11 are explanatory diagrams that typically show the main parts of blood analyzer 1. Blood analyzer 1 has the following operation modes: DIFF+CRP mode (a mode in which both blood cell counting including 5-part differential white blood cell counting and immunoassays are performed), DIFF mode (a mode in which only blood cell counting including 5-part differential white blood cell counting is performed), CBC+CRP mode (a mode in which both blood cell counting other than 5-part differential white blood cell counting and immunoassays are performed), and CBC mode (a mode in which only blood cell counting other than 5-part differential white blood cell counting is performed). Here, as an example, a case will be described in which blood analyzer 1 operates in DIFF+CRP mode under the control of control unit 100.

[0039] When blood analyzer 1 operates in DIFF mode, only the steps shown in the dashed boxes in Figures 5 and 6 are performed. That is, the steps shown in the solid boxes in Figures 6 and 7 are steps related to CRP measurement. Also, the CBC+CRP mode and CBC mode are the same as the DIFF+CRP mode and DIFF mode, except that the operations (steps) related to the BASO and LMNE measurements are not performed.

[0040] The movement of the nozzle N when aspirating and dispensing blood and CRP reagent is performed at appropriate timing by the above-mentioned probe unit 30, but since this is not the essence of the present invention, detailed description of the movement of the nozzle N will be omitted below. Also, the main control unit for each valve is the solenoid valve opening / closing instruction unit 101, and the main control unit for each fixed-volume dispenser is the fixed-volume dispenser drive instruction unit 102, but detailed description of these units will be omitted to avoid redundant description.

[0041] First, the specimen for CRP measurement is dispensed and stirred (S1). Specifically, the first valve V1 and the second valve V2 shown in Fig. 7 are appropriately controlled to allow flow through the flow path FP between the nozzle N and the CRP fixed dispenser 25. In this state, the R1 reagent is aspirated from the R1 reagent container 22 through the nozzle N by the aspirating operation of the CRP fixed dispenser 25. The aspirated amount of the R1 reagent is, for example, 100 μL.

[0042] Next, the first valve V1 is appropriately controlled to make the flow path FP non-flowable. Then, as shown in FIG. 8, blood for immunoassay is aspirated from the specimen container 10 through the nozzle N by the suction operation of the sample dispenser 60. The amount of blood aspirated is, for example, 8 μL. Thereafter, the first valve V1 and the second valve V2 are appropriately controlled to make the flow path FP flowable. In this state, the aspirated blood and R1 reagent are discharged from the nozzle N to the CRP chamber 21 by the discharge operation of the CRP dispenser 25.

[0043] Next, the second valve V2 and the third valve V3 (see FIG. 9) are appropriately controlled to allow flow through the flow path between the CRP chamber 21 and the CRP fixed-volume dispenser 25 via the branching section 27, the third valve V3, and the second valve V2. In this state, the blood and the R1 reagent are stirred in the CRP chamber 21 by the piston movement of the CRP fixed-volume dispenser 25. The second valve V2 and the third valve V3 constitute the solenoid valve device 26 shown in FIG.

[0044] Thereafter, in the cleaning chamber 45 shown in FIG. 2, the nozzle N is cleaned with the diluent (S2). For example, while appropriately controlling a predetermined valve (including the first valve V1) located in the flow path between the first flow path FP1 and the reagent dispenser 70 (see FIG. 7), the diluent drawn from the buffer tank 80 is caused to flow into the inside of the nozzle N through the first flow path FP1 by the reagent dispenser 70. The reagent dispenser 70 also causes the diluent to flow onto the outer circumferential surface of the nozzle N through the nozzle cleaner 33. This cleans the inside and outer circumferential surface of the nozzle N. The diluent after cleaning the outer circumferential surface of the nozzle N is discharged into the waste liquid container 52 (see FIG. 2) through the discharge pump 51, which is a drainage unit.

[0045] Next, the first valve V1 is appropriately controlled to make the flow path FP non-flowable. Then, as shown in FIG. 8, the suction operation of the sample dispenser 60 causes blood for blood cell count measurement to be sucked from the specimen container 10 through the nozzle N (S3). The amount of blood sucked is, for example, 33 μL. Next, the discharge operation of the sample dispenser 60 performs a discard dispensation in which a portion of the sucked blood is discharged into the washing chamber 45 in preparation for the next dispensation of the remaining blood (S4). By the discard dispensation, for example, dirty blood located at the tip of the nozzle N is discharged and discarded. The amount of blood discharged is, for example, 3 μL.

[0046] Next, dispensing for the first dilution is performed (S5). Specifically, while the diluent is discharged from the side of the WBC chamber 44 by the reagent dispenser 70, blood is discharged from the nozzle N into the WBC chamber 44 by the discharging operation of the sample dispenser 60. The amount of blood discharged at this time is, for example, 10 μL.

[0047] 10, a first valve unit U1, a second valve unit U2, and a third valve unit U3 are disposed at predetermined positions in the flow path connecting a reagent dispenser 70 that dispenses the diluent and the blood cell counting and measuring section 40. By appropriately controlling the valves included in the first valve unit U1 and the second valve unit U2, the diluent is dispensed from the reagent dispenser 70 to the WBC chamber 44 via the path indicated by the thick line in the figure.

[0048] Next, dispensing and measurement for white blood cell classification measurement are performed (S6). Specifically, while the reagent dispenser 70 dispenses the BASO measurement reagent from the side of the BASO chamber 41, the dispensing operation of the sample dispenser 60 dispenses blood from the nozzle N into the BASO chamber 41. The amount of blood dispensed at this time is, for example, 5 μL. Furthermore, while the reagent dispenser 70 dispenses the LMNE measurement reagent from the side of the LMNE chamber 42, the dispensing operation of the sample dispenser 60 dispenses blood from the nozzle N into the LMNE chamber 42. The amount of blood dispensed at this time is, for example, 12.5 μL. Then, the BASO measurement is performed in the BASO chamber 41.

[0049] Next, the valve included in the third valve unit U3 in FIG. 10 is appropriately controlled to perform secondary dilution (S7). Specifically, after a part of the blood in the WBC chamber 44 is transferred to the flow path for RBC measurement, a hemolytic agent for WBC and HGB measurement is injected into the blood remaining in the WBC chamber 44. Then, the blood transferred to the flow path is discharged into the RBC chamber 43 together with the diluent previously filled in the flow path for RBC measurement. Next, the reagent dispenser 70 discharges the diluent from the side of the LMNE chamber 42, and then a dedicated dispenser (not shown) transfers the liquid in the LMNE chamber 42 to a flow cell (not shown) in preparation for LMNE measurement in the flow cell. During this time, HGB measurement is performed in the WBC chamber 44.

[0050] Thereafter, WBC measurement is performed in the WBC chamber 44, RBC and PLT measurements are performed in the RBC chamber 43, and LMNE measurement is performed in the flow cell (S8).

[0051] Furthermore, after S6, the CRP measurement reagent is dispensed (S9). Specifically, the first valve V1 and the second valve V2 (see FIG. 7) are appropriately controlled to put the flow path FP in a flowing state, and the R2 reagent is aspirated from the R2 reagent container 23 via the nozzle N by the suction operation of the CRP fixed dispenser 25. The amount of R2 reagent aspirated is, for example, 100 μL. Then, after the nozzle N is raised from the liquid level of the R2 reagent container 23, a predetermined amount (100 μL) of the R2 reagent in the nozzle N is further aspirated by the suction operation of the CRP fixed dispenser 25 while being detected by the sensor 61. That is, the R2 reagent and air are aspirated by the nozzle N.

[0052] By detecting the R2 reagent (buffer solution) as a representative of the CRP reagents with the sensor 61, it is possible to detect (determine) whether the CRP reagent in each reagent container has run out. This allows the CRP reagent to be replenished as necessary. The R2 reagent is less likely to foam than the R1 and R3 reagents, and is therefore useful in accurately detecting whether the CRP reagent has run out.

[0053] The above step in S9 corresponds to a reagent aspirating step in which the CRP reagent is aspirated from the CRP reagent container by the nozzle N using the CRP dispenser 25 until the sensor 61 arranged in the flow path FP detects that a predetermined amount (e.g., 100 μL) of CRP reagent (particularly R2 reagent) has been aspirated.

[0054] Thereafter, the aspirated R2 reagent is discharged from the nozzle N into the CRP chamber 21 by the discharge operation of the CRP fixed dispenser 25. This step corresponds to a reagent discharge step in which the CRP fixed dispenser 25 discharges a predetermined amount of CRP reagent into the CRP chamber 21.

[0055] In parallel with S8 described above, the following CRP measurement reagent is dispensed and stirred (S10). Specifically, the second valve V2 and the third valve V3 (see FIG. 9) are appropriately controlled, and the previously discharged blood and R1 reagent and the R2 reagent are stirred in the CRP chamber 21 by the piston movement of the CRP fixed dispenser 25. Next, the first valve V1 and the second valve V2 (see FIG. 7) are appropriately controlled to put the flow path FP into a circulating state, and the R3 reagent is aspirated from the R3 reagent container 24 through the nozzle N by the suction operation of the CRP fixed dispenser 25, and then the aspirated R3 reagent is discharged from the nozzle N to the CRP chamber 21 by the discharge operation of the CRP fixed dispenser 25. The amount of R3 reagent aspirated at this time is, for example, 200 μL. Thereafter, the second valve V2 and the third valve V3 (see FIG. 9) are appropriately controlled, and the piston movement of the CRP fixed dispenser 25 causes the blood, R1 reagent, R2 reagent, and R3 reagent that have been previously discharged to be mixed in the CRP chamber 21.

[0056] Next, the liquid remaining in each chamber for blood cell counting is discharged as waste liquid, and then a diluent is introduced into each chamber (except for the BASO chamber 41) to wash each chamber (S11). Note that since the BASO measurement is completed before the measurement of WBC, etc., the BASO chamber 41 is washed before the washing of the other chambers (for example, after S7).

[0057] Meanwhile, in the CRP chamber 21, CRP measurement is performed (S12; immunoassay step). That is, blood aspirated by the nozzle N from the specimen container 10 by the sample dispenser 60 and discharged into the CRP chamber 21 and CRP reagent aspirated by the nozzle N from the CRP reagent container by the CRP dispenser 25 and discharged into the CRP chamber 21 are mixed inside the CRP chamber 21 to perform the CRP measurement.

[0058] During the CRP measurement in S12, the diluent is discharged through the flow path FP shown in FIG. 7 (S13). More specifically, as shown in FIG. 11, the second valve V2 is controlled to block communication between the nozzle N in the flow path FP (see FIG. 7) and the CRP dispenser 25 (S13-1). Then, the third valve V3 is controlled to connect the liquid suction path FP3 and the second flow path FP2 through the second valve V2 (S13-2). This brings the CRP dispenser 25 and the buffer tank 80 into communication with each other through the liquid suction path FP3 and a part of the second flow path FP2. The above "part of the second flow path FP2" refers to a partial flow path FP2-1 between the second valve V2 and the CRP dispenser 25, which is included in the second flow path FP2. The liquid suction path FP3 has a first suction path FP3-1 that connects the second valve V2 and the third valve V3, and a second suction path FP3-2 that connects the third valve V3 and the buffer tank 80.

[0059] In this state, when the piston of the CRP fixed dispenser 25 is retracted, the diluent in the buffer tank 80 merges with the second flow path FP2 via the second suction path FP3-2 and the first suction path FP3-1, flows through the partial flow path FP2-1 and is drawn into the inside of the CRP fixed dispenser 25 (S13-3). At this time, the second valve V2 and the third valve V3 (solenoid valve device 26) can be said to constitute a junction that merges the diluent with the second flow path FP2 via the second suction path FP3-2 and the first suction path FP3-1.

[0060] Thereafter, the first valve V1 and the second valve V2 (see FIG. 7) are appropriately controlled to bring the flow path FP into communication (S13-4), and in this state, the piston of the CRP fixed-point dispenser 25 is pushed in. This causes the diluent inside the CRP fixed-point dispenser 25 to be discharged to the outside (into the washing chamber 45) via the second flow path FP2 and the first flow path FP1 (S13-5).

[0061] That is, in S13, the solenoid valve opening / closing instruction unit 101 controls the second valve V2 and the third valve V3 to cut off communication between the nozzle N and the CRP fixed dispenser 25 in the flow path FP, and the fixed dispenser drive instruction unit 102 issues a drawing instruction to the CRP fixed dispenser 25, so that the CRP fixed dispenser 25 draws in the diluent as the liquid for discharge (S13-1 to S13-3; liquid drawing step). After that, the solenoid valve opening / closing instruction unit 101 controls the first valve V1 and the second valve V2 to connect the nozzle N and the CRP fixed dispenser 25 in the flow path FP, and the fixed dispenser drive instruction unit 102 issues a push instruction to the CRP fixed dispenser 25, so that the CRP fixed dispenser 25 pushes out the diluent and flows it into the flow path FP, and the diluent is discharged to the outside of the flow path FP (S13-4 to S13-5; liquid discharging step).

[0062] Next, in the cleaning chamber 45, the nozzle N is cleaned with a cleaning liquid (S14). More specifically, while appropriately controlling a predetermined valve located in the flow path between the first flow path FP1 and the reagent dispenser 70, the cleaning liquid drawn in from a cleaning liquid storage container (not shown) by the reagent dispenser 70 is caused to flow into the inside of the nozzle N through the first flow path FP1. Also, while appropriately controlling a predetermined valve located in the flow path between the nozzle cleaner 33 and the reagent dispenser 70, the cleaning liquid drawn in from the cleaning liquid storage container by the reagent dispenser 70 is caused to flow onto the outer circumferential surface of the nozzle N through the nozzle cleaner 33. This cleans the inside and outer circumferential surface of the nozzle N. Since the cleaning liquid is used to clean the nozzle N, a higher cleaning effect can be obtained than in S2, in which cleaning is performed using a diluting liquid.

[0063] Finally, post-processing after the CRP measurement is performed (S15). For example, a cleaning solution is introduced into the CRP chamber 21 by the reagent dispenser 70 to clean the CRP chamber 21. The waste liquid after cleaning is discharged into the waste liquid container 52, and the series of processes is completed.

[0064] As described above, in this embodiment, in the step of S13, air bubbles present in the flow path FP between the nozzle N and the CRP fixed dispenser 25 are discharged by discharging the diluent through the flow path FP. This reduces the risk of air bubbles accumulating in the flow path FP. Therefore, it is possible to reduce the risk that air bubbles will gather somewhere in the flow path FP (for example, between the nozzle N and the sample fixed dispenser 60) and form an air gap. As a result, in S5 to S6, it is possible to reduce the risk that the timing of the blood discharge operation by the sample fixed dispenser 60 will be delayed due to the air gap, and the risk of a decrease in the accuracy of blood analysis can be reduced.

[0065] In particular, when the flow path FP provided inside the blood analyzer 1 is curved so as to be convex toward the upper side in the height direction, it is desirable to position the first valve V1 at the upper part (convex part) of the curved flow path FP. In this case, even if air bubbles accumulate near the first valve V1 and an air gap is formed (in the unlikely event that air bubbles accumulate near the first valve V1), the air gap will not easily be drawn into the CRP fixed amount dispenser 25 (because it is lighter than the liquid in the flow path FP).

[0066] Furthermore, the liquid discharge step S13 is performed between the start and end of the CRP measurement step (immunoassay step) S12 (see FIG. 6). Since the diluent is discharged in S13 in parallel with the CRP measurement in S12, the time between CRP measurements can be effectively utilized to prevent the formation of air gaps.

[0067] In this embodiment, the reagent aspirating step and the reagent discharging step shown in S9 are performed before the step S12. In the reagent aspirating step, the CRP fixed dispenser 25 aspirates the CRP reagent until the sensor 61 detects the aspirating of a predetermined amount of the CRP reagent (particularly the R2 reagent), and therefore the aspirated CRP reagent may flow from the first flow path FP1 to the second flow path FP2 via the first valve V1. When such a movement of the CRP reagent (at a large movement amount) occurs, air bubbles are accumulated in the flow path FP, and an air gap is likely to be formed. Therefore, the effect of this embodiment, which can reduce the risk of air bubbles accumulating in the flow path FP and reduce the risk of an air gap being formed, is very effective in the case where the CRP reagent is aspirated until the aspirating of a predetermined amount is detected and then discharged into the CRP chamber 21.

[0068] Moreover, steps S3 to S8 in this embodiment correspond to a blood cell measurement step. In the blood cell measurement step, blood is aspirated from the specimen container 10 by the nozzle N using the sample dispenser 60 and discharged into the blood cell measurement chambers (BASO chamber 41, LMNE chamber 42, RBC chamber 43, WBC chamber 44) and a blood cell measurement reagent is discharged into the blood cell measurement chamber by the reagent dispenser 70, and mixed inside the blood cell measurement chamber to perform measurement.

[0069] If an air gap is formed in the flow path FP due to the accumulation of air bubbles, it will be difficult for the sample dispenser 60 to discharge a specified amount of blood, which will have an effect particularly on the blood cell measurement process. Therefore, the effect of this embodiment, which can reduce the risk of air bubbles accumulating in the flow path FP and the risk of air gaps being formed, is extremely effective when performing the blood cell measurement process.

[0070] In this embodiment, the diluent is used as the liquid to be discharged by the CRP dispenser 25 into the flow path FP. The diluent is generally used in blood analyzers such as blood cell counters. By using such a diluent as the liquid to be discharged, the formation of an air gap in the flow path FP can be eliminated, so there is no need to use a dedicated liquid for eliminating the formation of an air gap, and the diluent can be effectively used. In addition, the diluent used in the above-mentioned S2, S5, S7, and S11 and the diluent used in S13 are both supplied from the same buffer tank 80 (where the diluent is replenished from the diluent container). In this way, the diluent can be effectively used in terms of using the same diluent for all of the washing of the nozzle N, dilution of blood, and removal of air bubbles.

[0071] In this embodiment, in S13, the diluent pushed out from the CRP fixed dispenser 25 into the flow path FP is discharged from the nozzle N, but for example, a branch path may be provided in the middle of the flow path FP (a valve is disposed at the branch point) and the diluent may be discharged from the branch path to the outside of the flow path FP. However, in this case, it is necessary to newly install a branch path and a valve, so in terms of simplifying the configuration, it is desirable for the CRP fixed dispenser 25 to discharge the diluent as the discharge liquid from the nozzle N.

[0072] [5. About the Program] The blood analyzer 1 of the present embodiment can be configured by a computer in which an operating program (application software) is installed. The computer (for example, the control unit 100 as a CPU) reads and executes the above program, thereby operating each unit of the blood analyzer 1 to execute each of the above-mentioned processes (each step). Such a program is acquired, for example, by downloading it from an external source via a network, and stored in a memory in the control unit 100. The program may be recorded in a computer-readable recording medium such as a CD-ROM (Compact Disk-Read Only Memory), and the program may be read from the recording medium and stored in the memory. That is, the program of the present embodiment is a program for causing a computer to execute the above-mentioned blood analysis method of the present embodiment. The recording medium of the present embodiment is a computer-readable recording medium in which the above program is recorded.

[0073] [6. Supplementary Information] In S13, instead of the dilution liquid, other liquids such as a cleaning liquid may be used as the ejection liquid flowing through the flow path FP.

[0074] In this embodiment, an example has been described in which each valve (including the first valve V1, the second valve V2, and the third valve V3) in the blood analyzer 1 is configured with a solenoid valve, but each valve may be configured with a switching valve other than a solenoid valve. Therefore, the above-mentioned solenoid valve opening / closing instruction unit 101 can also be called a switching valve opening / closing instruction unit.

[0075] When the CRP reagent is aspirated into the flow path FP by the CRP fixed pipette 25, in order to prevent the aspirated CRP reagent from mixing with the diluent originally present in the flow path FP, the CRP reagent is aspirated by the CRP fixed pipette 25 with an air gap between it and the diluent. Note that since the CRP fixed pipette 25 is larger than the sample fixed pipette 60, even if the air gap exists in the flow path FP, it is possible to eject a specified amount of CRP reagent from the nozzle N by the pushing action of the CRP fixed pipette 25.

[0076] In this embodiment, the blood analyzer 1 that uses blood as a sample and analyzes blood has been described as an example of a sample analyzer, but the sample analyzer is not limited to the blood analyzer 1. For example, the configuration and method described in this embodiment can also be applied to an analyzer that uses body fluids such as plasma, serum, saliva, urine, lymphatic fluid, and cerebrospinal fluid as a sample.

[0077] In this embodiment, the risk of air gaps being formed in the flow path FP due to the discharge of diluent by the drawing-in and pushing-out operations of the CRP dispenser 25 is reduced. However, drawing in and pushing out of the diluent into the flow path FP may be performed by another dispenser (sample dispenser 60, reagent dispenser 70). In other words, if there is a risk of air gaps being formed in the flow path FP when the other dispenser repeatedly draws in and ejects liquid (including specimens and reagents), the formation of air gaps can be reduced by having the other dispenser draw in and push out the diluent into the flow path FP.

[0078] Although the embodiment of the present invention has been described above, the scope of the present invention is not limited to this, and the invention can be expanded or modified without departing from the spirit of the invention. [Industrial Applicability]

[0079] The present invention can be used in, for example, a blood analyzer that performs blood counting and immunoassay. [Explanation of symbols]

[0080] 1. Blood analyzer (sample analyzer) 10 Sample container 20 Immunoassay Department 21 CRP chamber 22 R1 Reagent Container 23 R2 Reagent Container 24 R3 Reagent Container 25 CRP fixer (fixer for immunoassay) 60 Sample dispenser 61 Sensors 70 Reagent dispenser 101 Solenoid valve opening / closing instruction unit (switching valve opening / closing instruction unit) 102 Fixed-rate dispenser drive instruction unit FP flow path FP1 First flow path FP2 Second flow path FP3 Liquid suction path FP3-1 1st suction path (liquid suction path) FP3-2 2nd suction path (liquid suction path) N nozzle (sampling nozzle) V1 First valve (switching valve) V2 Second valve (switching valve) V3 3rd valve (switching valve)

Claims

1. A sampling nozzle; A fixed-volume dispenser that aspirates and dispenses liquid through the sampling nozzle; A switching valve for switching the communication state of the flow path between the sampling nozzle and the fixed-rate dispenser; a switching valve opening / closing instruction unit that instructs the switching valve to switch between opening and closing; A fixed-rate injection device drive instruction unit that issues drive instructions to the fixed-rate injection device, The switching valve opening / closing instruction unit controls the switching valve to block communication between the sampling nozzle and the fixed pipette in the flow path, and the fixed pipette drive instruction unit issues a drawing instruction to the fixed pipette, and the fixed pipette draws the liquid to be discharged into itself, A sample analysis device in which the switching valve opening / closing instruction unit controls the switching valve to connect the sampling nozzle and the fixed-volume dispenser in the flow path, and the fixed-volume dispenser drive instruction unit issues a pushing instruction to the fixed-volume dispenser, causing the fixed-volume dispenser to push out the discharge liquid and flow it into the flow path, and then discharging the discharge liquid outside the flow path.

2. The sample analyzer according to claim 1 , wherein the fixed-volume dispenser discharges the liquid to be discharged from the sampling nozzle.

3. further comprising a sensor disposed in the flow path; The sample analyzer of claim 1 or 2, wherein the dispenser drive instruction unit causes the dispenser to aspirate the reagent until the sensor detects that a predetermined amount of reagent has been aspirated, and then causes the dispenser to eject the predetermined amount of reagent into the chamber.

4. The sample analyzer according to claim 1 , wherein the liquid to be discharged is a diluting liquid.

5. The sample analyzer according to claim 1 or 2, wherein the fixed-volume dispenser is a fixed-volume dispenser for immunoassay.

6. A sample analysis method for a sample analyzer including a fixed-volume dispenser that aspirates and dispenses liquid through a sampling nozzle, and a switching valve that switches the communication state of a flow path between the sampling nozzle and the fixed-volume dispenser, a liquid drawing step in which the fixed pipette draws the liquid to be discharged into it by controlling the switching valve to block communication between the sampling nozzle and the fixed pipette in the flow path and issuing a drawing instruction to the fixed pipette; a liquid discharge step in which, after the liquid drawing step, the switching valve is controlled to connect the sampling nozzle and the fixed-volume dispenser in the flow path, and a push command is given to the fixed-volume dispenser, causing the fixed-volume dispenser to push out the discharge liquid and flow it into the flow path, and then discharging the discharge liquid outside the flow path.

7. The sample analysis method according to claim 6, wherein in the liquid discharging step, the constant volume dispenser discharges the liquid to be discharged from the sampling nozzle.

8. 8. The sample analysis method according to claim 6, wherein the dispenser is a dispenser for immunoassay.

9. The method further includes an immunoassay step of mixing blood, which is aspirated from a specimen container through the sampling nozzle and discharged into the immunoassay chamber by a sample dispenser located midway through the flow path, and an immunoassay reagent, which is aspirated from an immunoassay reagent container through the sampling nozzle and discharged into the immunoassay chamber by the immunoassay dispenser, inside the immunoassay chamber, to perform the immunoassay; The sample analyzing method according to claim 8 , wherein the liquid drawing step and the liquid discharging step are performed between the start and end of the immunoassay step.

10. 10. The sample analysis method according to claim 9, further comprising a blood cell measurement step of mixing blood aspirated from the specimen container by the sampling nozzle and discharged into the blood cell measurement chamber by the sample dispenser with a blood cell measurement reagent discharged into the blood cell measurement chamber by a reagent dispenser inside the blood cell measurement chamber, and performing a measurement.

11. Before the immunoassay step, a reagent aspirating step of aspirating the immunoassay reagent from the immunoassay reagent container with the sampling nozzle by the immunoassay fixed-quantity dispenser until a sensor disposed in the flow path detects that a predetermined amount of the immunoassay reagent has been aspirated; 10. The sample analysis method according to claim 9, further comprising a reagent discharging step of discharging the predetermined amount of the immunoassay reagent into the immunoassay chamber using the immunoassay dispenser.

12. The sample analysis method according to claim 6 or 7, wherein a dilution liquid is used as the liquid to be discharged.

13. A program for causing a computer to execute the sample analysis method described in claim 6 or 7.

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