JP5432391B2 - Sample analyzer and sample analysis method - Google Patents

Description

  The present invention relates to a sample analyzer and a sample analysis method for analyzing a predetermined component in a sample such as blood and urine.

  2. Description of the Related Art Conventionally, many sample analyzers have been developed that measure the size of predetermined component particles in a sample such as blood or urine and analyze the distribution state thereof. Especially in blood analyzers that detect the distribution of red blood cells, white blood cells, platelets, etc. in blood, the size of red blood cells is 7-8 μm, whereas the size of platelets is relatively small, 1-4 μm. The size of red blood cells and platelets was measured by using a sample obtained by diluting the extracted blood for an electric resistance measuring instrument and an optical measuring instrument, respectively.

  However, the size of relatively small red blood cells, pulverized red blood cells, and the like may be a relatively small size equivalent to that of platelets. In this case, erythrocytes and platelets cannot be accurately distinguished only by the size of the predetermined component particles in the specimen.

  Therefore, in Patent Document 1, by measuring the platelet size with each of the electrical resistance measuring instrument and the optical measuring instrument and determining the reliability of each measurement result, the measurement result with the higher reliability is obtained. A particle analyzer to be used is disclosed. In particular, with an optical measuring instrument, it is possible to more accurately measure particles having a size that matches the optical sensitivity of the particles, and the reliability of the measurement results is increased.

JP 2000-275163 A

  However, since the particle analyzer disclosed in Patent Document 1 uses two types of measuring devices, the same specimen is distributed to always prepare two types of measurement samples, and each measurement sample is used. It was necessary to carry out measurement with an electrical resistance measuring instrument and an optical measuring instrument. Accordingly, there is a problem that it is difficult to reduce the analysis cost because the cost of the reagent for preparation, the number of measurement steps, etc. are simply doubled.

  The present invention has been made in view of such circumstances, and by judging the necessity of re-detection according to reliability, it is possible to avoid unnecessary preparation of a measurement sample and to analyze components having different sizes. An object of the present invention is to provide a sample analyzer and a sample analysis method capable of accurately performing the above.

The sample analyzer according to the first invention to achieve the above object, the specimen a first measurement sample containing a first reagent, a second measurement sample containing the analyte and the second reagent, and the analyte and a third reagent A sample preparation unit for preparing a third measurement sample including: a first flow cell; and a first measurement cell for detecting a predetermined component contained in the first measurement sample. A first detection unit having a voltage measurement unit for measuring a voltage change at the time of passing, a second flow cell for detecting a predetermined component contained in the second measurement sample or the third measurement sample, A light emitting unit that irradiates light to the second measurement sample or the third measurement sample that passes through the two flow cells, and a light receiving unit that receives light from the second measurement sample or the third measurement sample irradiated with the light. a second detecting section, a predetermined of said first measurement sample And a control unit which correspondingly has detected the result makes a reliable determination of whether the previous SL control section, as a result of detecting a predetermined component of the first measurement sample by said first detector If but unreliable, the predetermined component of the control the operation of the sample preparation unit, adjustment made by said third measurement sample to prepare the third measurement sample on the basis of the same said analyte, said second It detects using a detection part, It is characterized by the above-mentioned.

Further, the sample analysis method according to the second aspect of the invention is to detect a predetermined component in the first measurement sample including the sample and the first reagent by the electric detection unit, and in the second measurement sample including the sample and the second reagent. Analyzing method capable of detecting a predetermined component in the optical detection unit and detecting the predetermined component in the third measurement sample including the third reagent different from the sample and the second reagent in the optical detection unit Because
When the result of detecting the predetermined component in the first measurement sample by the electrical detection unit is not reliable, the third measurement sample is prepared based on the same specimen as the first measurement sample, and the prepared A predetermined component in the third measurement sample is detected using the optical detection unit .

According to the above configuration, when the detection result of the predetermined component by the first detection unit is unreliable , the operation of the sample preparation unit is controlled so as to prepare the measurement sample again based on the same specimen. A new measurement sample may be prepared only when it is necessary to redetect the component. Therefore, the preparation reagent can be saved and the increase in the number of measurement steps can be minimized. Further, upon detection of a predetermined component in the measurement sample that is prepared again by using the second detector, even have field if such have first detection result is reliable, the reliability The detection result which has can be obtained.

It is a block diagram which shows the structure of the sample analyzer which concerns on Embodiment 1 of this invention. It is a perspective view which shows the internal structure of the analyzer main body which concerns on Embodiment 1 of this invention. It is a front view which shows the internal structure of the analyzer main body which concerns on Embodiment 1 of this invention. FIG. 2 is a fluid circuit diagram of the analyzer main body according to the first embodiment. FIG. 2 is a fluid circuit diagram of the analyzer main body according to the first embodiment. FIG. 2 is a fluid circuit diagram of the analyzer main body according to the first embodiment. FIG. 2 is a fluid circuit diagram of the analyzer main body according to the first embodiment. It is a block diagram which shows the structure of the calculation display apparatus which concerns on Embodiment 1 of this invention. It is a schematic diagram which shows the principal part structure of the 1st measurement part which is an electrical resistance type measuring device. It is a schematic diagram which shows the structure of the 3rd measurement part which is an optical measuring device. It is a flowchart which shows the process sequence of CPU of the calculation display apparatus of the sample analyzer which concerns on Embodiment 1 of this invention. It is an illustration figure of the reliability judgment based on a histogram. It is an illustration figure of the histogram based on the measurement data of PLT measurement. It is a flowchart which shows the procedure of the reliability judgment process of CPU of the calculation display apparatus of the sample analyzer which concerns on Embodiment 1 of this invention. It is an illustration figure of the scattergram which shows the PLT remeasurement result in the sample analyzer which concerns on Embodiment 1 of this invention. It is a flowchart which shows the process sequence of CPU of the calculation display apparatus of the sample analyzer which concerns on Embodiment 2 of this invention. It is a flowchart which shows the procedure of the reliability judgment process of CPU of the calculation display apparatus of the sample analyzer which concerns on Embodiment 2 of this invention. It is an illustration figure of the scattergram which shows the result of the 1st PLT measurement in the 3rd measurement part in the sample analyzer which concerns on Embodiment 2 of this invention. It is another example of a scattergram showing the result of the first PLT measurement by the third measurement unit in the sample analyzer according to Embodiment 2 of the present invention. It is an illustration figure of the scattergram which shows the result of the 2nd PLT measurement in the 3rd measurement part in the sample analyzer which concerns on Embodiment 2 of this invention.

  Hereinafter, in the present embodiment, a blood analyzer that analyzes blood is taken as an example of the sample analyzer, and will be specifically described based on the drawings.

(Embodiment 1)
FIG. 1 is a block diagram showing the configuration of the sample analyzer according to Embodiment 1 of the present invention. The sample analyzer according to the first embodiment of the present invention is configured by connecting the analyzer main body 1 and the calculation display device 2 so that data communication is possible. The calculation display device 2 is installed with sample analysis software for performing operations of the analyzer main body 1, various settings relating to analysis, display of analysis results, and the like, and through data communication with the analyzer main body 1, An instruction can be given to the analyzer main body 1 and measurement data can be received from the analyzer main body 1.

  2 is a perspective view showing the internal configuration of the analyzer main body 1 according to Embodiment 1 of the present invention. FIG. 3 is a front view showing the internal configuration of the analyzer main body 1 according to Embodiment 1 of the present invention. FIG. The analyzer main body 1 is a blood analyzer that performs analysis (measurement, analysis, etc.) of blood (specimen) stored in a blood collection tube 3 that is a sealed container (initial storage container for a measurement sample). A sample setting unit for setting the sample at a predetermined position in the analyzer main body 1, a sample preparation unit for preparing a measurement sample by quantifying and diluting the blood in the blood collection tube 3, and the diluted blood Measurement units D1, D2, and D3 are provided.

  The sample preparation unit sucks a predetermined amount of blood from the inside of the blood collection tube 3 to obtain a first mixing chamber (first storage container: HGB / RBC chamber) MC1, a second mixing chamber (second storage container: WBC chamber) MC2, The third mixing chamber (third storage container: RET chamber) MC3, or the fourth mixing chamber (fourth storage container: PLT chamber) MC4 is a part for preparing samples for various analyzes by mixing with reagents, A plug 3a that seals the inside of the blood collection tube 3 is punctured, and a suction tube (aspiration unit) 14 that sucks the sample in the blood collection tube 3; a horizontal drive unit that moves the suction tube 14 horizontally; and a suction tube 14 And a vertical drive unit that moves vertically. The horizontal drive unit includes a stepping motor (horizontal drive unit motor) 69 as a drive source, and the vertical drive unit includes a stepping motor (vertical drive unit motor) 68 as a drive source. The suction tube 14 is not particularly limited as long as it has a channel extending in the longitudinal direction inside and a suction port for sucking a sample or air is formed near the tip.

  4 and 5 are fluid circuit diagrams of the analyzer main body 1 according to the first embodiment. As shown in FIGS. 4 and 5, the analyzer main body 1 can be provided with a reagent container for containing a reagent, and the reagent container can be connected to a fluid circuit. . Specifically, the reagent container used in the first embodiment is a diluent container EPK-V for storing the diluent (washing liquid) EPK, and a hemoglobin hemolyzing agent for storing the hemoglobin hemolyzing agent SLS. A container SLS-V, a leukocyte classification hemolyzing agent container (common reagent container) FFD-V for containing a leukocyte classification hemolyzing agent FFD for lysing red blood cells, and a leukocyte classification for containing a leukocyte classification staining solution FFS This is a staining liquid container (dedicated reagent container) FFS-V.

  FIG. 6 is a fluid circuit diagram including the chamber MC3 for RET measurement of the analyzer main body 1 according to the first embodiment. Similar to FIGS. 4 and 5, the analyzer main body 1 can be provided with a reagent container for containing the reagent, and the reagent container can be connected to the fluid circuit. A fluid circuit including the chamber MC3 for RET measurement includes a reticulocyte staining solution container RES-V for storing a staining solution RES for staining reticulocytes, and a dilution solution RED for measuring reticulocytes. A reticulocyte diluent container RED-V is provided.

  FIG. 7 is a fluid circuit diagram including the chamber MC4 for PLT measurement of the analyzer main body 1 according to the first embodiment. Similar to FIGS. 4 and 5, the analyzer main body 1 can be provided with a reagent container for containing the reagent, and the reagent container can be connected to the fluid circuit. The fluid circuit including the chamber MC4 for PLT measurement includes a platelet staining liquid container PLS-V for storing a staining liquid PLS for staining platelets, and a dilution for platelets for storing a dilution liquid PLD for platelet measurement. A liquid container PLD-V is provided. In the platelet staining liquid container PLS-V, for example, Nile blue is accommodated as a staining liquid.

  As a sample supply unit for supplying a sample from the blood collection tube 3 to the first mixing chamber MC1 and / or the second mixing chamber MC2, a suction tube 14, a whole blood suction syringe pump SP1, and a sample supply syringe pump SP2 are provided. ing. The suction tube 14 moves to the first mixing chamber MC1 and the second mixing chamber MC2 in a state where a predetermined amount of whole blood sample is sucked from the blood collection tube 3 by the whole blood suction syringe pump SP1 and the sample supply syringe pump SP2. Then, a predetermined amount of whole blood sample is distributed and supplied to the first mixing chamber MC1 and the second mixing chamber MC2, respectively, by the whole blood suction syringe pump SP1 and the sample supply syringe pump SP2. At the time of RET measurement, the whole blood sample is also supplied to the third mixing chamber MC3.

  A part of the whole blood sample is also supplied to the fourth mixing chamber MC4 and temporarily stored. Then, the dilution liquid PLD and the staining liquid PLS are supplied to the fourth mixing chamber MC4 only when it is determined that the reliability of the measurement data of the specimen is low by the method described later and re-preparation is instructed.

  The diluent container EPK-V and the hemoglobin hemolyzing agent container SLS-V are connected so that the reagent can be supplied to the first mixing chamber MC1. That is, the dilution liquid can be supplied from the dilution liquid container EPK-V to the first mixing chamber MC1 by the dilution liquid supply (EPK) diaphragm pump DP1, and the EPK diaphragm pump DP1 is used for the dilution liquid. The reagent supply unit is configured. Further, the hemoglobin hemolytic agent can be supplied from the hemoglobin hemolytic agent container SLS-V to the first mixing chamber MC1 by the hemolytic agent supply (SLS) diaphragm pump DP3, and the SLS diaphragm pump DP3 is hemolyzed. The reagent supply part for the agent is configured.

  The hemolytic agent container FFD-V and the staining liquid container FFS-V are connected so that the reagent can be supplied to the second mixing chamber MC2. That is, the hemolytic agent can be supplied from the hemolytic agent container FFD-V to the second mixing chamber MC2 by the hemolytic agent supply (FFD) diaphragm pump DP4, and the FFD diaphragm pump DP4 is a common reagent. A reagent supply unit (a common reagent supply unit) for the hemolytic agent is configured. Further, the staining solution can be supplied from the staining solution container FFS-V to the second mixing chamber MC2 by the staining solution supply (FFS) diaphragm pump DP5, and the FFS diaphragm pump DP5 is used for the staining solution. The reagent supply unit (dedicated reagent supply unit) is configured.

  As shown in FIGS. 4 and 5, the reagent supply path from the diluent container EPK-V to the first mixing chamber MC1 and the reagent supply path from the hemolytic agent container SLS-V to the first mixing chamber MC1 are: The merging point CR1 is joined at an intermediate point, and a reagent supply path T1 common to both reagents is connected to the first mixing chamber MC1. Accordingly, although two types of reagents are supplied to the first mixing chamber MC1, only one reagent supply port is required for the first mixing chamber MC1, and the structure is simplified.

  Further, as shown in FIG. 5, the reagent supply path from the hemolytic agent container FFD-V to the second mixing chamber MC2 and the reagent supply path from the staining solution container FFS-V to the second mixing chamber MC2 are joined together. The reagent is joined at a point CR2, and a reagent supply path T2 common to both reagents is connected to the second mixing chamber MC2. Therefore, although two types of reagents are supplied to the second mixing chamber MC2, only one reagent supply port is required for the second mixing chamber MC2, and the structure is simplified. The reagent supply paths T1 and T2 may be provided for each reagent. That is, two reagent supply ports may be provided in each of the chambers MC1 and MC2.

  The first measurement unit (detection unit, first detection unit) D1 performs measurement related to red blood cells and platelets, and the second measurement unit D2 performs measurement related to hemoglobin. Furthermore, the third measurement unit (other detection unit, second detection unit) D3 performs measurement related to white blood cells. The first mixing chamber MC1 is a part for preparing a sample for analyzing red blood cells, platelets and hemoglobin, and the measurement samples prepared in the first mixing chamber MC1 are the first measurement unit D1 and the second measurement unit D2. Used for measurement in The second mixing chamber MC2 is a part for preparing a sample for analyzing leukocytes, and the measurement sample prepared in the second mixing chamber MC2 is used for measurement in the third measurement unit D3.

  The first measurement unit D1 is configured as an RBC / PLT detection unit that performs RBC measurement (red blood cell count) and PLT measurement (platelet count). The first measurement unit D1 is a so-called electric resistance type measuring instrument that can perform RBC measurement and PLT measurement by a sheath flow DC detection method.

  The second measurement unit D2 is configured as an HGB detection unit that performs HGB measurement (measurement of the amount of hemoglobin in the blood). The second measurement unit D2 can perform HGB measurement by the SLS-hemoglobin method.

  The third measurement unit D3 is configured as an optical detection unit that can perform WBC measurement (white blood cell count), RET measurement (reticulocyte count), and PLT measurement (platelet count). The third measuring unit D3 is a so-called optical measuring instrument that can perform WBC measurement, RET measurement, and PLT measurement by a flow cytometry method using a semiconductor laser.

  The analyzer main body 1 includes a control unit 11 that controls operations of the sample preparation unit, the first measurement unit D1, the second measurement unit D2, and the third measurement unit D3. Further, the analyzer main body 1 includes electromagnetic valves SV1 to SV33, SV40, SV41, various pumps / motors 68, 69, SP1, SP2, P, V, DP1 to DP5, etc. in the fluid circuit constituting the sample preparation unit and the like. A drive circuit unit 12 for driving is also provided, and the control unit 11 drives an electromagnetic valve or the like via the drive circuit unit 12. The control unit (detection unit control unit) 11 can perform data communication with the calculation display device 2 via the communication interface 13, and can exchange various signals, data, and the like with the calculation display device 2. it can.

  FIG. 8 is a block diagram showing the configuration of the arithmetic display device 2 according to Embodiment 1 of the present invention. As shown in FIG. 8, the arithmetic display device 2 includes a CPU (central processing unit) 21, a RAM 22, a storage device 23, an input device 24, a display device 25, an output device 26, a communication interface 27, a portable disk drive 28, and the above-mentioned. The internal bus 29 is connected to the hardware. The CPU 21 is connected to each hardware unit as described above of the arithmetic display device 2 via the internal bus 29, and controls the operation of each hardware unit described above, and also stores a computer program 90 stored in the storage device 23. Various software functions are executed according to the above. The RAM 22 is composed of a volatile memory such as SRAM or SDRAM, and a load module is expanded when the computer program 90 is executed, and stores temporary data generated when the computer program 90 is executed.

  The storage device 23 includes a built-in fixed storage device (hard disk), a volatile memory such as SRAM, and a nonvolatile memory such as ROM. The computer program 90 stored in the storage device 23 is downloaded by a portable disk drive 28 from a portable recording medium 80 such as a DVD or CD-ROM in which information such as programs and data is recorded. To the RAM 22 for execution. Of course, a computer program downloaded from an external computer connected via the communication interface 27 may be used.

  In addition, the storage device 23 includes a measurement result storage unit 231 that stores measurement results from the first measurement unit D1, the second measurement unit D2, and the third measurement unit D3, and the CPU 21 stores the measurement results stored therein. Based on this, the reliability of the detection result is determined.

  The communication interface 27 is connected to the internal bus 29, and is connected to the analyzer main body 1 via a communication line, so that data can be transmitted and received. That is, instruction information indicating the start of measurement is transmitted to the analyzer main body 1 and measurement data such as measurement results is received.

  The input device 24 is a data input medium such as a keyboard and a mouse. The display device 25 is a display device such as a CRT monitor or LCD, and displays the analysis result graphically. The output device 26 is a printing device such as a laser printer or an inkjet printer.

  The analyzer main body 1 has two measurement modes for measuring platelets in blood, which is a measurement sample. The first measurement mode is a CBC measurement mode, in which RBC measurement and PLT measurement are performed by the first measurement unit D1, and WBC measurement is performed by the third measurement unit D3. The second measurement mode is a CBC + RET measurement mode, in which RBC measurement and PLT measurement are performed by the first measurement unit D1, and WBC measurement, RET measurement, and PLT measurement are performed by the third measurement unit D3. That is, PLT measurement is performed by both an electric resistance type measuring instrument and an optical measuring instrument.

  In the first embodiment, the operation of the sample analyzer when the CBC measurement mode (first measurement mode) is selected will be described. In the analyzer main body 1 according to the first embodiment, when the CBC measurement mode is selected, the RBC measurement and the PLT measurement are performed by a first measurement unit (detection unit, first detection unit) D1 that is an electrical resistance measuring instrument. The WBC measurement is performed by a third measurement unit (another detection unit, second detection unit) D3 that is an optical measuring instrument.

  FIG. 9 is a schematic diagram illustrating a configuration of a main part of the first measuring unit D1 that is an electrical resistance measuring instrument. The first measurement unit D1 includes a reaction unit 111, which sucks blood as a sample with the suction tube 14 and introduces a diluted solution into the reaction unit 111.

  A flow path 112 is extended from the reaction unit 111, and a sheath flow cell 113 is provided at the end of the flow path 112. The measurement sample diluted in the reaction unit 111 is sent to the sheath flow cell 113 through the flow path 112. Further, the first measurement unit D1 is provided with a sheath liquid chamber (not shown), and the sheath liquid stored in the sheath liquid chamber is supplied to the sheath flow cell 113.

In the sheath flow cell 113, the measurement sample flows so as to be surrounded by the sheath liquid. The sheath flow cell 113 is provided with an orifice 114, and the flow of the measurement sample is narrowed by the orifice 114 so that particles (formation) contained in the measurement sample pass through the orifice 114 one by one. A pair of electrodes 115 are attached to the sheath flow cell 113 so as to sandwich the orifice 114. A DC power source 116 is connected to the pair of electrodes 115, and a DC current is supplied between the pair of electrodes 115. The impedance between the pair of electrodes 115 can be detected while a direct current is supplied from the direct current power source 116.

  An electric resistance signal indicating a change in impedance is amplified by the amplifier 117 and transmitted to the control unit 11. The magnitude of the electric resistance signal corresponds to the volume (size) of the particle, and the volume of the particle can be obtained by the signal processing of the electric resistance signal by the control unit 11.

  FIG. 10 is a schematic diagram showing the configuration of the third measuring unit D3 that is an optical measuring instrument. The third measurement unit D3 sends a measurement sample to the flow cell 301, generates a liquid flow in the flow cell 301, and irradiates a blood cell included in the liquid flow passing through the flow cell 301 with a semiconductor laser beam for measurement. The third measurement unit D3 includes a sheath flow system 300, a beam spot system 310, a forward scattered light receiving system 320, a side scattered light receiving system 330, and a side fluorescent light receiving system 340.

  The sheath flow system 300 flows through the flow cell 301 in a state where blood cells included in the measurement sample are arranged in a line, and improves the accuracy and reproducibility of the blood cell count. The beam spot system 310 is configured such that light emitted from the semiconductor laser 311 is irradiated to the flow cell 301 through the collimator lens 312 and the condenser lens 313. The beam spot system 310 also includes a beam stopper 314.

  The forward scattered light receiving system 320 is configured to collect forward scattered light by the forward condenser lens 321 and receive light passing through the pinhole 322 by the forward scattered light receiving unit (photodiode) 323. Yes.

  The side scattered light receiving system 330 condenses side scattered light by the side condensing lens 331 and reflects a part of the light by the dichroic mirror 332, and the side scattered light receiving unit (photodiode) 333. Is configured to receive light.

  Light scattering is a phenomenon that occurs when particles such as blood cells exist as obstacles in the traveling direction of light and the light changes its traveling direction. By detecting the scattered light, information on the size, material, etc. of the particles can be obtained. In particular, information on the size of the particles (blood cells) can be obtained from the forward scattered light. Further, from the side scattered light, information on the inside of the particle such as information on the material of the particle can be obtained.

  The side fluorescent light receiving system 340 is configured so that the light transmitted through the dichroic mirror 332 is further passed through the spectral filter 341 and received by the fluorescent light receiving unit (photomultiplier) 342.

  When a fluorescent material such as a stained blood cell is irradiated with light, the fluorescent material emits light having a wavelength longer than the wavelength of the irradiated light. If the fluorescence intensity is well-stained, it becomes stronger, and information on the degree of staining of blood cells can be obtained by measuring the fluorescence intensity. Therefore, blood cell classification and other measurements can be performed based on the difference in the side fluorescence intensity.

  When the light receiving units 323, 333, and 342 receive light, the light receiving units 323, 333, and 342 output electrical pulse signals, and measurement data is created based on the output electrical pulse signals. The measurement data is transmitted from the analyzer main body 1 to the calculation display device 2, and processing, analysis, etc. are performed in the calculation display device 2.

  When the CBC measurement mode is selected, the calculation display device 2 counts the number of platelets by performing platelet particle size analysis based on the measurement data in the first measurement unit D1. More specifically, the number of platelets is analyzed by a histogram in which the horizontal axis represents the platelet volume (unit: fL (hemtritta)) and the vertical axis represents the PLT frequency, which is the number of platelets.

  In the sample analyzer configured as described above, PLT measurement is performed by the first measurement unit D1. Since the first measurement unit D1 measures the size of the sample, for example, when broken red blood cells are mixed, the platelet size and the number of adjacent red blood cells are also non-negligible values, and the platelet count is accurately counted. It can also be difficult to do. Therefore, in the sample analyzer according to Embodiment 1 of the present invention, when the measurement data of the first PLT measurement is analyzed and it is determined that the measurement data is not reliable, the second PLT measurement is performed. Is performed by the third measuring unit D3.

  FIG. 11 is a flowchart showing a processing procedure of the CPU 21 of the calculation display device 2 of the sample analyzer according to Embodiment 1 of the present invention. CPU21 of the calculation display apparatus 2 acquires measurement data as a result of PLT measurement from the control part 11 of the analyzer main body 1 (step S1101).

  The CPU 21 generates a histogram based on the acquired measurement data (step S1102) and displays it on the display device 25. In the generated histogram, the horizontal axis is the platelet volume, and the vertical axis is the PLT frequency.

  The CPU 21 determines whether or not the measurement data has reliability (step S1103). The process for determining whether the measurement data of the PLT measurement has reliability is not particularly limited. In the first embodiment, it is determined that there is no reliability when the PLT frequency, which is a count value of platelets, is equal to or less than a predetermined number, or when abnormal distribution of platelets occurs.

  FIG. 12 is an exemplary diagram of reliability determination based on a histogram. In the histogram of FIG. 12, the vertical axis represents the PLT frequency (count value) and the horizontal axis represents the platelet size. LD is a platelet size for which a reference frequency is set for a predetermined small size, and UD is a platelet size for which a reference frequency is set for a predetermined large size. That is, when the PLT frequency exceeds the reference frequency in the LD, there is a high possibility of the presence of impurities that are not originally counted, so it can be determined that there is no reliability. In addition, when the PLT frequency exceeds the reference frequency in UD, the count value should converge to the lower right, but it is not sufficiently converged, that is, there is a high possibility of the presence of impurities. It can be determined that there is no reliability.

  Further, the distribution width PDW of the 20% frequency level when the peak height of the PLT frequency is set to 100% is calculated, and if the PDW is larger than the predetermined reference width, it is determined that the distribution abnormality has occurred.

  FIG. 13 is an exemplary diagram of a histogram based on measurement data of PLT measurement. FIG. 13A shows a typical example of a histogram of measurement data. As shown in FIG. 13A, if the measurement data has reliability, the PLT frequency in LD and UD is sufficiently smaller than the reference frequency, and the distribution width PDW is also smaller than the predetermined reference width.

  FIG.13 (b) is an illustration figure of a histogram in case the count value of platelets exceeds reference frequency in UD. In this case, not only the PLT frequency in the UD greatly exceeds the reference frequency, but also the distribution width PDW exceeds the predetermined reference width, so that it can be determined that a platelet distribution abnormality has occurred.

  FIG.13 (c) is an illustration figure of a histogram in case there exist two or more peaks of PLT frequency. In this case, even if the PLT frequency in the LD and UD is sufficiently smaller than the reference frequency, the distribution width PDW exceeds the predetermined reference width, and it can be determined that an abnormal platelet distribution has occurred. Even if the distribution width PDW does not exceed the predetermined reference width, it may be determined that a distribution abnormality has occurred if there are two or more distribution peaks.

  FIG. 14 is a flowchart showing a procedure of reliability determination processing of the CPU 21 of the calculation display device 2 of the sample analyzer according to Embodiment 1 of the present invention. The CPU 21 of the calculation display device 2 generates a histogram based on the acquired measurement data (step S1102), and determines whether or not a platelet distribution abnormality has occurred (step S1401).

  If the CPU 21 determines that there is an abnormal platelet distribution (step S1401: YES), the CPU 21 determines that the platelet is not reliable (step S1404) and advances the process to step S1104. When the CPU 21 determines that no abnormal platelet distribution has occurred (step S1401: NO), the CPU 21 determines whether or not the platelet count value is equal to or less than a predetermined value (step S1402).

  When the CPU 21 determines that the platelet count value is equal to or smaller than the predetermined value (step S1402: YES), the CPU 21 determines that the platelet count is not reliable (step S1404), and advances the processing to step S1104. This is because it is considered that small platelets increase and platelets leaked from the counting target exist. When the CPU 21 determines that the platelet count value exceeds the predetermined value (step S1402: NO), the CPU 21 determines that the platelet count is reliable (step S1403) and ends the process.

  Returning to FIG. 11, when the CPU 21 of the calculation display device 2 determines that the calculation display device 2 is not reliable (step S <b> 1103: NO), the CPU 21 instructs the analyzer main body 1 to instruct to reprepare the measurement sample from the same sample. Transmit (step S1104). The control unit 11 of the analyzer main body 1 that has received the re-preparation instruction instructs the drive circuit unit 12 to operate the sample preparation unit.

  The CPU 21 transmits an instruction to re-suck the re-prepared measurement sample to the analyzer main body 1 (step S1105). The control unit 11 of the analyzer main body 1 that has received the re-suction instruction instructs the drive circuit unit 12 to operate the suction tube 14.

  The CPU 21 transmits a measurement instruction to the analyzer main body 1 to measure the re-aspirated measurement sample with the third measurement unit D3, that is, the optical measurement instrument (step S1106). Upon receiving the measurement instruction, the control unit 11 of the analyzer main body 1 transmits a measurement start signal to the third measurement unit D3. When the CPU 21 determines that the CPU 21 has reliability (step S1103: YES), the CPU 21 ends the process.

  FIG. 15 is an exemplary scattergram showing the PLT remeasurement results in the sample analyzer according to Embodiment 1 of the present invention. In the scattergram of FIG. 15, the vertical scattered light intensity is plotted on the vertical axis and the side fluorescent light intensity is plotted on the horizontal axis, and the staining solution is changed (for example, Nile Blue) to increase the degree of platelet staining. As is clear from FIG. 15, the count values of platelets are concentrated in the region 1501, and there is no region that intersects with red blood cells, contaminants, and the like. Therefore, the blood can be analyzed with high accuracy by changing the detection conditions in the second detection, that is, the detection method in the first embodiment, depending on whether or not the first measurement data is reliable.

  In addition, only when it is determined that the detection result of the predetermined component is not reliable, the measurement sample is prepared again based on the same specimen, and the sample preparation unit and the suction unit are aspirated again to aspirate the prepared measurement sample. Since the operation of the tube 14 is controlled, the reagent for preparation can be saved and the increase in the number of measurement steps can be minimized.

(Embodiment 2)
Since the configuration of the sample analyzer according to the second embodiment of the present invention is the same as that of the first embodiment, detailed description thereof will be omitted by attaching the same reference numerals. The second embodiment is different from the first embodiment in that the CBC + RET measurement mode (second measurement mode) is selected instead of the CBC measurement mode (first measurement mode).

  In the second embodiment, the operation of the sample analyzer when the CBC + RET measurement mode (second measurement mode) is selected will be described. In the analyzer main body 1 according to the second embodiment, when the CBC + RET measurement mode is selected, the RBC measurement and the PLT measurement are performed by the first measurement unit D1, and the WBC measurement, the RET measurement, and the PLT measurement are performed by the third measurement unit ( Detection unit) D3.

  The configuration of the main part of the first measuring unit D1 that is an electrical resistance measuring instrument and the configuration of the third measuring unit D3 that is an optical measuring instrument are also the same as those in the first embodiment, and thus are denoted by the same reference numerals. Thus, detailed description is omitted.

  When the CBC + RET measurement mode (second measurement mode) is selected, the calculation display device 2 performs platelet particle size analysis based on the measurement data in the first measurement unit D1 and the measurement data in the third measurement unit D3. Thus, the number of platelets is counted. More specifically, in the case of measurement data in the first measurement unit D1, the platelet count is analyzed by a histogram in which the horizontal axis is the volume of platelets and the vertical axis is the PLT frequency. In the case of the measurement data at the third measurement unit D3, the number of platelets is analyzed by a histogram in which the horizontal axis is the forward scattered light intensity and the vertical axis is the PLT frequency which is the number of platelets.

  In the sample analyzer configured as described above, PLT measurement is performed by both the first measurement unit D1 and the third measurement unit D3. The first measuring unit D1 uses an electrical resistance measuring device, and the third measuring unit D3 uses an optical measuring device to measure the size of a predetermined component of the specimen. In this case, the size of platelets and the number of adjacent red blood cells are also non-negligible values, and it may be difficult to accurately count the number of platelets. Therefore, in the sample analyzer according to Embodiment 2 of the present invention, the reliability of the measurement data of the first PLT measurement is analyzed in each of the first measurement unit D1 and the third measurement unit D3, and the reliability of the measurement data is measured. Use more reliable measurement data for analysis. When both are reliable, the measurement data at the third measurement unit D3 is adopted, and when both are not reliable, the second PLT measurement is performed at the third measurement unit D3.

  FIG. 16 is a flowchart showing a processing procedure of the CPU 21 of the calculation display device 2 of the sample analyzer according to Embodiment 2 of the present invention. The CPU 21 of the calculation display device 2 acquires the measurement data in the first measurement unit D1 and the third measurement unit D3 from the control unit 11 of the analyzer main body 1 (step S1601).

  CPU21 produces | generates a histogram based on the measurement data in the acquired 1st measurement part D1 (step S1602), and displays it on the display apparatus 25. FIG. In the generated histogram, the horizontal axis represents the platelet particle size, and the vertical axis represents the PLT frequency.

  The CPU 21 generates a scattergram based on the acquired measurement data at the third measurement unit D3 (step S1603) and displays it on the display device 25. In the generated scattergram, the horizontal axis represents the side fluorescence intensity, and the vertical axis represents the forward scattered light intensity.

  CPU21 judges whether the measurement data in the 3rd measurement part D3 have reliability (step S1604). The process for determining whether the measurement data of the PLT measurement has reliability is not particularly limited. In the second embodiment, as in the first embodiment, when the PLT frequency, which is the platelet count value, is equal to or less than a predetermined number, or when abnormal distribution of platelets occurs, it is determined that there is no reliability. .

  FIG. 17 is a flowchart showing a procedure of reliability determination processing of the CPU 21 of the calculation display device 2 of the sample analyzer according to Embodiment 2 of the present invention. The CPU 21 of the calculation display device 2 generates a histogram based on the acquired measurement data at the first measurement unit D1 (step S1602), and generates a scattergram based on the acquired measurement data at the third measurement unit D3. It is generated (step S1603), and based on the measurement data at the third measurement unit D3, it is determined whether or not platelet distribution abnormality has occurred (step S1701).

  FIG. 18 is an exemplary scattergram showing a result of the first PLT measurement in the third measurement unit D3 in the sample analyzer according to Embodiment 2 of the present invention. In the scattergram of FIG. 18, the vertical axis represents the forward scattered light intensity, and the horizontal axis represents the side fluorescence intensity. In the example of FIG. 18, there is a region where the PLT display region 181 and the foreign matter display region 182 intersect, and it is difficult to clearly distinguish the two.

  FIG. 19 is another example of a scattergram showing the result of the first PLT measurement in the third measurement unit D3 in the sample analyzer according to Embodiment 2 of the present invention. Also in the scattergram of FIG. 19, the vertical axis represents the forward scattered light intensity, and the horizontal axis represents the side fluorescence intensity. In the example of FIG. 19, there is an area where the PLT display area 191 and the red blood cell display area 192 intersect, and it is difficult to clearly distinguish the two. Accordingly, the number of appearances of particles in a predetermined region where it is difficult to distinguish particles on the scattergram as shown in FIGS. 18 and 19 is counted, and whether or not the counted number of appearances is equal to or greater than a predetermined number is counted. Thus, it may be determined whether or not an abnormal distribution of platelets has occurred.

  Returning to FIG. 17, when the CPU 21 of the calculation display device 2 determines that platelet distribution abnormality has occurred (step S <b> 1701: YES), the CPU 21 determines that the measurement data at the third measurement unit D <b> 3 has reliability. It is determined not to do so (step S1704), and the process proceeds to step S1705. When the CPU 21 determines that no abnormal platelet distribution has occurred (step S1701: NO), the CPU 21 determines whether or not the platelet count value is less than or equal to a predetermined value based on the measurement data at the third measurement unit D3. Is determined (step S1702).

  When the CPU 21 determines that the platelet count value is equal to or less than the predetermined value (step S1702: YES), the CPU 21 determines that the measurement data at the third measurement unit D3 is not reliable (step S1704). ), The process proceeds to step S1705. This is because it is considered that small platelets increase and platelets leaked from the counting target exist. When the CPU 21 determines that the platelet count value exceeds the predetermined value (step S1702: NO), the CPU 21 determines that the measurement data in the third measurement unit D3 has reliability (step S1703). The process proceeds to step S1606.

  The CPU 21 determines whether or not a platelet distribution abnormality has occurred based on the measurement data obtained by the first measurement unit D1 (step S1705). When the CPU 21 determines that platelet distribution abnormality has occurred (step S1705: YES), the CPU 21 determines that the measurement data obtained by the first measurement unit D1 is not reliable (step S1708). The process advances to step S1608. When the CPU 21 determines that no abnormal platelet distribution has occurred (step S1705: NO), the CPU 21 determines whether or not the platelet count value is equal to or less than a predetermined value based on the measurement data in the first measurement unit D1. Is determined (step S1706).

  When the CPU 21 determines that the platelet count value is equal to or less than the predetermined value (step S1706: YES), the CPU 21 determines that the measurement data in the first measurement unit D1 is not reliable (step S1708). ), The process proceeds to step S1608. This is because it is considered that small platelets increase and platelets leaked from the counting target exist. When the CPU 21 determines that the platelet count value exceeds the predetermined value (step S1706: NO), the CPU 21 determines that the measurement data in the first measurement unit D1 is reliable (step S1707). , The process proceeds to step S1607.

  Returning to FIG. 16, when the CPU 21 of the calculation display device 2 determines that the measurement data in the third measurement unit D3 is not reliable (step S1604: NO), the CPU 21 determines that the first measurement unit D1. It is determined whether or not the measurement data at is reliable (step S1605). The method for determining whether or not there is reliability is the same as in the first embodiment.

  When the CPU 21 determines that the measurement data obtained by the first measurement unit D1 is not reliable (step S1605: NO), the CPU 21 instructs the analyzer main body 1 to prepare the measurement sample again from the same sample. Transmit (step S1608). The control unit 11 of the analyzer main body 1 that has received the re-preparation instruction instructs the drive circuit unit 12 to operate the sample preparation unit.

  The CPU 21 transmits an instruction to re-suction the reconstituted measurement sample to the analyzer main body 1 (step S1609). The control unit 11 of the analyzer main body 1 that has received the re-suction instruction instructs the drive circuit unit 12 to operate the suction tube 14.

  The CPU 21 issues a setting change instruction to the analyzer main body 1 to change the optical sensitivity when the re-aspirated measurement sample is measured by the third measurement unit D3, that is, the optical measurement device, to be higher than that at the first measurement. Transmit (step S1610). The control unit 11 of the analyzer main body 1 that has received the setting change instruction transmits an optical sensitivity (detection sensitivity) setting change instruction signal to the third measurement unit D3.

  CPU21 transmits the measurement instruction | indication which measures the re-aspirated measurement sample with 3rd measurement part D3, ie, an optical measuring device, to the analyzer main body 1 (step S1611). The control unit 11 of the analyzer main body 1 that has received the measurement instruction transmits a measurement start signal to the third measurement unit D3.

  When the CPU 21 determines that the measurement data at the third measurement unit D3 is reliable (step S1604: YES), the CPU 21 adopts the measurement data at the third measurement unit D3 as PLT measurement data (step S1604). S1606), the process is terminated. When the CPU 21 determines that the measurement data at the first measurement unit D1 is reliable (step S1605: YES), the CPU 21 adopts the measurement data at the first measurement unit D1 as PLT measurement data (step S1605). S1607), the process is terminated.

  FIG. 20 is an exemplary scattergram showing a result of the second PLT measurement in the third measurement unit D3 in the sample analyzer according to Embodiment 2 of the present invention. Also in the scattergram of FIG. 20, the vertical axis represents the forward scattered light intensity, and the horizontal axis represents the side fluorescence intensity. In the example of FIG. 20, platelets having a relatively small size are clearly measured by increasing the optical sensitivity, and the staining solution is changed (for example, Nile Blue) to increase the degree of staining of the platelets. In this case, the PLT display area 201 is further clearly distinguished and displayed. Therefore, it is possible to analyze blood with higher accuracy by performing the second measurement by the third measurement unit D3 only when the first detection result is not reliable.

  In addition, only when it is determined that reliable measurement data cannot be acquired as a detection result of a predetermined component, a measurement sample is prepared again based on the same specimen, and the prepared measurement sample is aspirated again. Since the operations of the sample preparation section and the suction tube 14 are controlled, it is possible to save preparation reagents and minimize the increase in the number of measurement steps.

  In the first and second embodiments described above, the remeasurement by the third measurement unit D3 and the change of the optical sensitivity by the third measurement unit D3 are described as detection conditions. However, the detection condition to be changed is this. It is not limited to. For example, an amplification factor in an amplifier that amplifies an electric signal obtained by photoelectrically converting a received optical signal may be changed, or an irradiation intensity of light may be changed.

  In the first and second embodiments described above, blood is used as a sample and a blood analyzer that analyzes blood cells contained in the blood is described as an example. However, the present invention is limited to this. The same effect can be expected even when applied to a sample analyzer that analyzes a sample containing biological particles in urine. Furthermore, in the first and second embodiments described above, the analysis result is displayed on the display device 25 of the calculation display device 2, but there is no particular limitation, and other computers connected via a network can be used. You may display on the display apparatus which has.

  Further, in the first and second embodiments described above, the blood sample analyzer that sets the blood in one blood collection tube 3 to a predetermined position in the analyzer main body 1 has been described. Needless to say, the same effect can be obtained even in a sample analyzer in which a desired blood is measured by housing 3,... In a rack or the like and moving the rack by a transport mechanism. In this case, when the blood determined to be unreliable is measured again, a corresponding movement instruction of the blood collection tube 3 is transmitted to the control unit of the transport mechanism and transported again to the position of the suction tube 14. There is a need. Of course, the movement direction may be transmitted so that the suction tube 14 side is movable and the position of the suction tube 14 is moved to the position of the corresponding blood collection tube 3.

  In addition, the present invention is not limited to the above-described embodiments, and it goes without saying that various modifications and substitutions are possible within the scope of the gist of the present invention.

DESCRIPTION OF SYMBOLS 1 Analysis apparatus main body 2 Computation display apparatus 11 Control part 21 CPU
22 RAM
23 storage device 24 input device 25 display device 26 output device 27 communication interface 28 portable disk drive 29 internal bus 90 computer program 231 measurement result storage unit

Claims (16)

Second measurement sample containing the first measurement sample containing a sample and a first reagent, a sample and a second reagent, and a sample preparation section for preparing a third measurement sample containing the analyte and a third reagent,
In order to detect a predetermined component contained in the first measurement sample, a first flow cell and a first voltage measurement unit that measures a voltage change at the time when the first measurement sample passes through the first flow cell are provided. A detection unit;
In order to detect a predetermined component contained in the second measurement sample or the third measurement sample, the second flow cell, a light emitting unit that emits light to the second measurement sample or the third measurement sample that passes through the second flow cell And a second detection unit including a light receiving unit that receives light from the second measurement sample or the third measurement sample irradiated with light, and
And a control unit that performs the judgment whether the result of detecting the predetermined component in the first measurement sample is reliable,
The control unit prepares the sample preparation so as to prepare the third measurement sample based on the same specimen when the result of detection of the predetermined component in the first measurement sample by the first detection unit is unreliable. controls the operation of the parts, a certain component of the tone made by said third measurement sample, a sample analyzer and detecting by using the second detector. 2. The second reagent is a reagent for detecting at least two kinds of components including the predetermined component, and the third reagent is a reagent for detecting the predetermined component. the sample analyzer according to. The sample analyzer according to claim 1, wherein the third reagent includes a staining solution different from the second reagent . The second detection unit is capable of detecting a predetermined component under a first detection condition and a second detection condition in which the optical sensitivity of the light receiving unit is changed.
The said control part detects the predetermined component in the said 3rd measurement sample on the said 2nd detection conditions using the said 2nd detection part, The any one of Claims 1-3 characterized by the above-mentioned. Sample analyzer. The second detection unit is capable of detecting a predetermined component under a second detection condition in which the first detection condition and the first detection condition are obtained by changing an amplification factor of an electric signal output from the light receiving unit,
The said control part detects the predetermined component in the said 3rd measurement sample on the said 2nd detection conditions using the said 2nd detection part, The any one of Claims 1-3 characterized by the above-mentioned. Sample analyzer. The second detection unit is capable of detecting a predetermined component under a first detection condition and a second detection condition in which the light detection intensity of the light emitting unit is changed.
The said control part detects the predetermined component in the said 3rd measurement sample on the said 2nd detection conditions using the said 2nd detection part, The any one of Claims 1-3 characterized by the above-mentioned. Sample analyzer. The control unit detects a predetermined component in the first measurement sample by the first detection unit, detects a predetermined component in the second measurement sample by the second detection unit, and detects these If the result is unreliable, the operation of the sample preparation unit is controlled to prepare the third measurement sample based on the same specimen, and the predetermined component in the prepared third measurement sample is changed to the second component. The sample analyzer according to claim 1, wherein detection is performed using a detection unit. The second detection unit, as the light receiving unit, is a scattered light receiving unit that receives scattered light from the second measurement sample or the third measurement sample irradiated with light, and a second measurement sample that is irradiated with light or the second measurement sample. The sample analyzer according to any one of claims 1 to 7, further comprising a fluorescence light receiving unit that receives fluorescence from the three measurement samples . The sample analyzer according to any one of claims 1 to 8, wherein the sample is blood, and the predetermined component is blood platelets . The control unit is configured to prepare the third measurement sample based on the same specimen when the platelet count is equal to or less than a predetermined value or when an abnormal distribution of platelets occurs. The sample analyzer according to claim 9, wherein a predetermined component in the prepared third measurement sample is detected using the second detection unit . The first reagent contains a diluent, the second reagent contains a staining liquid for reticulocyte staining, and the third reagent contains a staining liquid for platelet staining. The sample analyzer described in 1 . Detection of a predetermined component in the first measurement sample containing the sample and the first reagent by the electric detection unit, detection of a predetermined component in the second measurement sample containing the sample and the second reagent by the optical detection unit, And a sample analysis method capable of detecting, with an optical detection unit, a predetermined component in a third measurement sample including a third reagent different from the sample and the second reagent,
When the result of detecting the predetermined component in the first measurement sample by the electrical detection unit is not reliable, the third measurement sample is prepared based on the same specimen as the first measurement sample, and the prepared A sample analysis method, wherein a predetermined component in a third measurement sample is detected using the optical detection unit . 13. The second reagent is a reagent for detecting at least two types of components including the predetermined component, and the third reagent is a reagent for detecting the predetermined component. 2. The sample analysis method according to 1 . The sample analysis method according to claim 12 or 13, wherein the sample is blood, and the predetermined component is blood platelets . When the platelet count is less than or equal to a predetermined value, or when abnormal platelet distribution occurs, the third measurement sample is prepared based on the same specimen, and the prepared third measurement sample The sample analysis method according to claim 14, wherein the predetermined component is detected using the optical detection unit . The electrical detection unit includes a first flow cell and a voltage measurement unit that measures a voltage change at the time when the first measurement sample passes through the first flow cell, and the optical detection unit includes the second flow cell, the second flow cell, and the second flow cell. A light emitting unit that irradiates light to the second measurement sample or the third measurement sample that passes through the two flow cells, and a light receiving unit that receives light from the second measurement sample or the third measurement sample irradiated with light The sample analysis method according to any one of claims 12 to 15, further comprising:

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