JP4994920B2 - Sample analyzer - Google Patents

Description

  The present invention relates to a sample analyzer that can measure not only blood but also body fluids other than blood, such as cerebrospinal fluid (spinal fluid), pleural effusion (pleural fluid), and ascites.

  It is a common practice in the field of clinical testing to measure blood collected from the body as a test sample with a testing device and to aid in diagnosis and treatment monitoring. In addition, body fluids other than blood are also measured with a testing device as a test sample. Usually, the body fluid is transparent and contains almost no cells, but if there is a tumor or damage in the disease or related organs, cells such as bleeding (blood cells), abnormal cells, bacteria, etc. are observed become.

For example, when cerebrospinal fluid, which is one of body fluids, is measured, the following estimation can be made from the measurement result.
・ Red blood cell increase: subarachnoid hemorrhage ・ neutrophil increase: meningitis ・ eosinophil increase: infectious diseases (parasites and fungi)
-Increase in mononuclear cells: tuberculous meningitis, viral meningitis-Other cells: Meningeal development of tumors Patent Document 1 discloses a blood cell analyzer capable of measuring cells in body fluids There is something. In Patent Document 1, in order to stably store a body fluid for a long period of time, an operator mixes a body fluid sample with a reagent (aldehyde, surfactant and cyclodextrin) to prepare a measurement sample in advance, and this measurement sample Is applied to the analyzer to analyze the body fluid.

JP 2003-344393 A

  However, in the above-mentioned Patent Document 1, it is necessary for an operator who operates the analyzer to prepare the measurement sample, instead of preparing the measurement sample by the analyzer when measuring the body fluid. In addition, the analyzer disclosed in Patent Document 1 does not disclose performing a measurement operation suitable for body fluid when body fluid is measured.

The present invention has been made in view of such circumstances, and it is not necessary for an operator to perform a complicated operation of preparing a measurement sample by mixing a body fluid sample and a reagent, and automatically analyzes body fluid with high accuracy. It is an object of the present invention to provide a sample analyzer that can perform the above-described process.

The sample analyzer according to the present invention prepares a measurement sample by mixing a suction part for sucking a specimen, the specimen sucked by the suction part and a reagent, measures the prepared measurement sample, and measures the measurement sample. One of a measurement unit that acquires characteristic information representing the characteristics of the components in the blood, a blood measurement mode for measuring a blood sample, and a body fluid measurement mode for measuring a body fluid sample different from the blood sample is set as an operation mode. comprising a mode setting means for, and a motion control means for controlling the operation of the measuring unit, the operation control means, when the blood measurement mode is set by said mode setting means, is sucked by the suction unit was by mixing a blood sample and a reagent to prepare a measurement sample, and the operation control of the measuring unit to measure a measurement sample of a first amount at a predetermined first measuring time, the body fluid measured by said mode setting means Mo If the de is set, the by suction unit mixing a suction body fluid sample and a reagent to prepare a measurement sample, the first amount in the second measurement time longer given than the first measuring time characterized in that that runs controls the measurement unit to measure a measurement sample of greater second amount.

By doing so, the operator simply sucks the body fluid sample into the sample analyzer, and the sample analyzer automatically mixes the body fluid and the reagent to prepare the measurement sample, and prepares the measurement sample prepared from the body fluid sample. Therefore, it takes a longer time than the blood sample and measures a larger amount than the blood sample . Therefore, the operator is not required is complicated labor for preparing a measurement sample from a bodily fluid analyte, and typically can measure bodily fluid low cell concentration as compared to the blood, to automatically high accuracy.

  In the above-mentioned invention, it is preferable to further include a blank measurement operation control means for controlling the operation of the measurement unit so as to measure a blank sample not containing the sample before measuring the body fluid sample. Thereby, when measuring a bodily fluid whose cell concentration is usually lower than that of blood, it is possible to confirm the degree of influence due to the previously measured specimen remaining in the measurement unit (carry over).

  In the above invention, the measurement unit compares the measurement result obtained by measuring the body fluid sample with a predetermined reference value, and the comparison result by the comparison unit indicates that the measurement result is greater than the reference value. It is preferable to further include a cleaning control unit that controls the operation of the measurement unit so as to execute the operation. As a result, when the measured concentration of the body fluid sample is high, the measurement unit can be washed to suppress carryover.

The sample analyzer according to the second aspect of the present invention prepares a measurement sample by mixing a suction unit for sucking a sample, the sample sucked by the suction unit and the reagent, and measures the prepared measurement sample A measurement unit that acquires characteristic information representing characteristics of the components in the measurement sample, a blood measurement mode for measuring a blood sample, and a body fluid measurement mode for measuring a body fluid sample different from the blood sample. Mode setting means for setting the operation mode, and analysis means for analyzing the characteristic information obtained by the measurement unit measuring the measurement sample, wherein the analysis means uses the mode setting means to measure the blood measurement mode. There when set, for the feature information obtained the measurement unit measures the measurement sample first amount over a first measurement time predetermined, executes a predetermined first analysis processing, Body fluid by the mode selection means If the constant mode is set, the measuring unit is obtained by measuring a measurement sample of the first over the second measurement time longer given than the measurement time said first amount more than the second amount relative feature information, and wherein the that perform different second analysis processing from the first analysis process.

By doing so, the operator simply sucks the body fluid sample into the sample analyzer, and the sample analyzer automatically mixes the body fluid and the reagent to prepare the measurement sample, and prepares the measurement sample prepared from the body fluid sample. Therefore, it takes a longer time than the blood sample and measures a larger amount than the blood sample. Therefore, it is not necessary for the operator to prepare a measurement sample from the body fluid specimen, and a body fluid having a cell concentration lower than that of blood can be measured automatically with high accuracy.

In the above invention, the first analysis process includes a process of classifying white blood cells into at least four types, and the second analysis process includes a process of classifying white blood cells into fewer types than the first analysis process. preferable.

  According to the sample analyzer according to the present invention, the present invention has an excellent effect, for example, it is possible to analyze each of a blood sample and a body fluid sample with high accuracy without requiring complicated labor of an operator.

  A sample analyzer according to an embodiment of the present invention will be described with reference to the drawings.

  FIG. 1 shows a sample analyzer 1. This analyzer 1 is configured as a multi-item automatic blood cell analyzer for performing a blood test, measures a blood sample contained in a sample container (collecting blood vessel), and represents the characteristics of blood cells contained in the sample. Feature information is acquired, and analysis processing is performed on the feature information. The sample analyzer 1 can also analyze body fluids. In the blood cell analyzer of the present embodiment, the body fluid to be analyzed refers to body cavity fluid that exists in the body cavity other than blood. Specifically, cerebrospinal fluid (CSF, CSF: fluid filled in ventricles and subarachnoid space), pleural effusion (pleural fluid, PE: fluid collected in pleural space), ascites (peritoneal fluid) Fluid), pericardial fluid (fluid accumulated in the pericardial cavity), joint fluid (synovial fluid: fluid present in joints, synovial sac, and tendon sheath). Further, peritoneal dialysis (CAPD) dialysis fluid, intraperitoneal washing fluid, and the like can be analyzed as a kind of body fluid. Usually, cells are hardly found in these body fluids, but cells such as blood cells, abnormal cells, and bacteria may be contained when a disease or related organ has a tumor or damage. For example, in the case of cerebrospinal fluid, the following clinical estimation is possible from the analysis result. For example, when red blood cells are increasing, subarachnoid hemorrhage, when neutrophils are increasing, meningitis, when eosinophils are increasing, infectious diseases (parasites and Fungi), if mononuclear cells are increasing, tuberculosis meningitis and viral meningitis, and if other cells are increasing, tumor meninges can be suspected. In addition, in ascites, pleural effusion, etc., when nucleated cells such as mesothelial cells, macrophages and tumor cells are included in addition to blood cells, by analyzing such nucleated cells other than blood cells, It can be an indicator of suspicion of disease.

  The analyzer 1 includes a measuring unit 2 having a function of measuring blood and body fluid as samples, and a data processing unit 3 that processes the measurement result output from the measuring unit 2 and obtains an analysis result. Has been. The data processing unit 3 includes a control unit 301, a display unit 302, and an input unit 303. In FIG. 1, the measurement unit 2 and the data processing unit 3 are configured as separate devices, but may be configured as an integrated device.

  FIG. 2 shows a block diagram of the measurement unit 2 of the analyzer 1. As shown in FIG. 2, the measurement unit 2 includes a blood cell detection unit 4, an analog processing unit 5 that performs processing on the output (analog signal) of the detection unit 4, a microcomputer unit 6, a display / operation unit 7, blood And a device mechanism unit 8 for measuring body fluid. Further, the device mechanism unit 8 includes a fluid mechanism unit 81 as follows.

  FIG. 3 is a block diagram showing the configuration of the fluid mechanism 81. As shown in FIG. As shown in FIG. 3, the fluid mechanism 81 includes a specimen aspirating nozzle 18, a plurality of reagent containers, a sampling valve 12, and reaction chambers 13 to 17. The sample suction nozzle 18 sucks a sample from the sample container and sends the sample to the sampling valve 12. The sampling valve 12 divides the introduced sample into a plurality of aliquots of a predetermined amount. The number of divisions differs depending on the measurement mode (discrete mode). In the CBC mode for measuring the red blood cell count, white blood cell count, platelet count, and hemoglobin concentration, the sample is divided into three aliquots. In addition to the CBC measurement items described above, in the CBC + DIFF mode in which white blood cells are classified into five, the specimen is divided into four aliquots. In addition to the measurement items in the CBC + DIFF mode, the CBC + DIFF + RET mode for measuring reticulocytes is divided into five aliquots. Similarly, in addition to the measurement items in the CBC + DIFF mode, in the CBC + DIFF + NRBC mode in which nucleated red blood cells are measured, the specimen is divided into five aliquots. In addition to the measurement item of CBC + DIFF mode + RET, in the CBC + DIFF + RET + NRBC mode for measuring nucleated red blood cells, the aliquot is divided into six aliquots. The above measurement modes are all blood measurement modes for measuring blood. Finally, in the body fluid measurement mode for measuring body fluid, the specimen is divided into two aliquots.

  In addition, a reagent (diluent) is introduced into the sampling valve 12 from the reagent container, and an aliquot of the divided specimen is sent to the reaction chambers 13 to 17 and an HGB detection unit 43 described later together with the reagent. It has become. A predetermined amount of sample (aliquot) collected by the sampling valve 12, a predetermined amount of diluent, and a predetermined amount of staining solution are supplied to the reaction chamber 13 by a metering pump (not shown). Are mixed to prepare a measurement sample for white blood cell 4 classification (DIFF).

  As this diluting solution, a reagent “Stomatolizer-4DL” provided by Sysmex Corporation can be preferably used. This reagent contains a surfactant and hemolyzes red blood cells. As the staining solution, the reagent “Stomatolizer-4DS” similarly provided by Sysmex Corporation can be preferably used. This staining solution contains ethylene glycol, a lower alcohol, and a polymethine dye. After hemolysis with the above-described diluent, the blood cell component is stained, and finally a 50-fold diluted sample is prepared.

  In addition, when the body fluid measurement mode is selected, the measurement sample for leukocyte classification under the condition that the amount of the specimen is the same as that of the measurement sample for classification of the white blood cells, the reagent is the same, and the amount of the reagent is the same for the body fluid specimen Is created. However, as will be described later, in the white blood cell classification in the body fluid measurement mode, the white blood cells are classified into two types instead of four types.

  A predetermined amount of sample collected by the sampling valve 12, a predetermined amount of diluted hemolyzing agent, and a predetermined amount of staining solution are supplied to the reaction chamber 14 by a metering pump (not shown), and these sample and reagent are mixed. A measurement sample for measuring nucleated red blood cells (NRBC) is prepared.

  A predetermined amount of sample collected by the sampling valve 12, a predetermined amount of diluent, and a predetermined amount of staining solution are supplied to the reaction chamber 15 by a metering pump (not shown), and these sample and reagent are mixed, A measurement sample for reticulocyte (RET) measurement is prepared.

  A predetermined amount of sample collected by the sampling valve 12 and a predetermined amount of diluted hemolytic agent are supplied to the reaction chamber 16 by a metering pump (not shown), and these sample and reagent are mixed to obtain white blood cells / basophils ( A measurement sample for WBC / BASO) is prepared.

  A predetermined amount of sample collected by the sampling valve 12 and a predetermined amount of diluent are supplied to the reaction chamber 17 by a metering pump (not shown), and these sample and reagent are mixed to obtain red blood cells / platelets (RBC / PLT). ) Measurement sample is prepared.

  In addition, a predetermined amount of sample collected by the sampling valve 12 and a predetermined amount of diluted hemolytic agent are supplied to the HGB detection unit 43 described later.

  Next, the detection unit 4 includes a white blood cell detection unit 41 for detecting white blood cells. The leukocyte detection unit 41 is also used for detecting nucleated red blood cells and reticulocytes. In addition to the white blood cell detection unit, the detection unit 4 also includes an RBC / PLT detection unit 42 that measures the number of red blood cells and platelets, and an HGB detection unit 43 that measures the amount of hemoglobin in the blood.

  The white blood cell detection unit 41 is configured as an optical detection unit, and specifically, is configured as a detection unit using a flow cytometry method. Here, cytometry is the measurement of the physical and chemical properties of cells and other biological particles, and flow cytometry passes through these particles in a narrow stream. This is a method of measuring. FIG. 4 shows the optical system of the white blood cell detection unit 41. In the figure, a beam emitted from a laser diode 401 is irradiated on a blood cell passing through a sheath flow cell 403 via a collimator lens 402. In the leukocyte detection unit 41, the intensity of forward scattered light, the intensity of side scattered light, and the intensity of side fluorescence emitted from the blood cells in the sheath flow cell irradiated with light are detected as characteristic parameters of the blood cells.

  Here, light scattering is a phenomenon that occurs when particles such as blood cells are present as obstacles in the traveling direction of light and light changes its traveling direction. By detecting this scattered light, it is possible to obtain particle characteristic information relating to the size and composition of the particles. Note that forward scattered light is scattered light emitted from particles in substantially the same direction as the traveling direction of irradiated light. Characteristic information relating to the size of the particles (blood cells) can be obtained from the forward scattered light. Side scattered light refers to scattered light emitted from particles in a direction substantially perpendicular to the traveling direction of irradiated light. Characteristic information about the inside of the particle can be obtained from the side scattered light. When blood cells are irradiated with laser light, the side scattered light intensity depends on the complexity of the cell (the shape, size, density, and amount of granules). Therefore, by utilizing this characteristic of the side scattered light intensity, the number of blood cells can be measured after the blood cells are classified (discriminated). In the present embodiment, the configuration using forward scattered light and side scattered light as scattered light has been described. However, the present invention is not limited to this, and a scattered light signal that expresses the characteristics of particles necessary for analysis is used. As long as it can be obtained, scattered light of any angle with respect to the optical axis of the light passing through the sheath flow cell from the light source may be used.

  Further, when a fluorescent material such as a stained blood cell is irradiated with light, light having a wavelength longer than the wavelength of the irradiated light is emitted. The intensity of fluorescence becomes stronger if it is well stained, and characteristic information relating to the degree of staining of blood cells can be obtained by measuring this fluorescence intensity. Therefore, leukocyte classification and other measurements can be performed based on the difference in (side) fluorescence intensity.

  As shown in FIG. 4, forward scattered light emitted from blood cells (white blood cells or nucleated red blood cells) that pass through the sheath flow cell 403 passes through a condenser lens 404 and a pinhole portion 405, and a photodiode (forward scattered light receiving portion). The light is received by 406. Side scattered light is received by a photomultiplier (side scattered light receiving unit) 411 through a condenser lens 407, a dichroic mirror 408, an optical filter 409, and a pinhole unit 410. The side fluorescence is received by the photomultiplier (side fluorescence light receiving unit) 412 via the condenser lens 407 and the dichroic mirror 408. The received light signals output from the light receiving units 406, 411, and 412 are subjected to analog processing such as amplification and waveform processing by the analog processing unit 5 including amplifiers 51, 52, and 53, and are given to the microcomputer unit 6. It is done.

  Next, the configuration of the RBC / PLT detector 42 will be described. FIG. 5 is a schematic diagram showing a schematic configuration of the RBC / PLT detection unit 42. The RBC / PLT detector 42 can measure the red blood cell count and the platelet count by the sheath flow DC detection method. The RBC / PLT detector 42 includes a sheath flow cell 42a as shown in FIG. The sheath flow cell 42a is provided with a sample nozzle 42b opened upward, and a sample is supplied from the reaction chamber 17 to the sample nozzle 42b. The sheath flow cell 42a has a tapered chamber 42c that becomes thinner as it goes upward, and the above-described sample nozzle 42b is arranged at the center of the inside of the chamber 42c. An aperture 42d is provided at the upper end of the chamber 42c, and the center position of the aperture 42d is aligned with the sample nozzle 42b. The measurement sample supplied from the sample supply unit is sent upward from the tip of the sample nozzle 42b. At the same time, the front sheath liquid is supplied to the chamber 42c, and the front sheath liquid flows upward toward the aperture 42d. . Here, the measurement sample flows so as to be surrounded by the front sheath liquid, and the flow of the measurement sample is narrowed down by the tapered chamber 42c, so that blood cells in the measurement sample pass through the aperture 42d one by one. The aperture 42d is provided with electrodes, and a direct current is supplied between the electrodes. Then, a change in DC resistance in the aperture 42 d when the measurement sample flows through the aperture 42 d is detected, and this electric signal is output to the control unit 25. Since the DC resistance increases when a blood cell passes through the aperture 42d, the electrical signal reflects the passage information of the blood cell in the aperture 42d. By processing the electrical signal, red blood cells and platelets are counted. It is supposed to be.

  A recovery pipe 42e extending vertically is provided above the aperture 42d. Further, the recovery pipe 42e is arranged inside a chamber 42f connected to the chamber 42c through an aperture 42d. The lower end portion of the recovery pipe 42e is separated from the inner wall of the chamber 42f. A back sheath liquid is supplied to the chamber 42f, and this back sheath liquid flows downward in the outer region of the recovery pipe 42e of the chamber 42f. The back sheath liquid flowing outside the recovery pipe 42e reaches the lower end of the chamber 42f, then passes between the lower end of the recovery pipe 42e and the inner wall of the chamber 42f, and flows into the recovery pipe 42e. For this reason, it is possible to prevent the blood cells that have passed through the aperture 42d from returning, thereby preventing erroneous detection of the blood cells.

  Next, the configuration of the HGB detection unit 43 will be described. The HGB detection unit 43 can measure the amount of hemoglobin (HGB) by the SLS hemoglobin method. FIG. 6 is a perspective view showing a configuration of the HGB detection unit 43. The HGB detection unit 43 includes a cell 43a that houses a diluted sample, a light emitting diode 43b that emits light toward the cell 43a, and a light receiving element 43c that receives transmitted light that has passed through the cell 43a. The blood quantified by the sampling valve 12 is diluted with a diluent and a predetermined hemolytic agent at a predetermined dilution rate, and a diluted sample is created. This hemolytic agent has the property of converting hemoglobin in blood into SLS-hemoglobin. The diluted sample is supplied to the cell 43a and stored in the cell 43a. In this state, the light emitting diode 43b emits light, and the transmitted light is received by the light receiving element 43c disposed opposite to the light emitting diode 43b with the cell 43a interposed therebetween. The light-emitting diode 43b emits light having a wavelength with a high absorbance by SLS-hemoglobin, and the cell 43a is made of a highly transparent plastic material. The transmitted light in which the light emission of 43b is absorbed only by the substantially diluted sample is received. The light receiving element 43c outputs an electrical signal corresponding to the amount of received light (absorbance) to the microcomputer unit 6, and the microcomputer unit 6 uses this absorbance and the absorbance of only the diluted solution measured in advance. In comparison, the hemoglobin value is calculated.

  The microcomputer unit 6 includes an A / D conversion unit 61 that converts an analog signal supplied from the analog processing unit 5 into a digital signal. The output of the A / D conversion unit 61 is given to the calculation unit 62 of the microcomputer unit 6, and the calculation unit 62 performs a calculation for performing a predetermined process on the received light signal. The computing unit 62 creates distribution data (a two-dimensional scattergram (unclassified) and a one-dimensional histogram) based on the output of the detection unit 4.

  Further, the microcomputer unit 6 includes a control unit 63 including a control processor and a memory for operating the control processor, and a data analysis unit 64 including an analysis processor and a memory for operating the analysis processor. ing. The control unit 63 controls the device mechanism unit 8 including a sampler (not shown) that automatically supplies a blood collection tube, a fluid system for sample preparation / measurement, and the like. The data analysis unit 64 performs analysis processing such as clustering on each distribution data. The analysis result is sent to the external data processing unit 3 via the interface 65, and processing such as data screen display and storage is performed.

  Further, the microcomputer section 6 includes an interface section 66 interposed between the display / operation section 7 and an interface section 67 interposed between the apparatus mechanism section 8. The calculation unit 62, the control unit 63, and the interface units 66 and 67 are connected via a bus 68, and the control unit 63 and the data analysis unit 64 are connected via a bus 69. The display / operation unit 7 includes a start switch for an operator to instruct the start of measurement, a touch panel type for displaying the state of the apparatus, various setting values, and analysis results, and receiving input from the operator. And a liquid crystal display.

  Next, the operation of the sample analyzer 1 according to this embodiment will be described. FIG. 7 is a flowchart showing an operation flow of the sample analyzer according to the present embodiment. When the user (operator) turns on the sample analyzer 1 (step S1), the sample analyzer 1 is activated. The sample analyzer 1 first performs a self-check at the time of activation (step S2). In this self-check, in addition to the test of the microcomputer unit 6 and the operation check of each operation mechanism unit of the sample analyzer 1, a blank check operation for measuring a blank sample containing no sample is performed. Next, the microcomputer unit 6 initializes the measurement mode (step S3). This initial set value is set to CBC + DIFF mode. Specifically, in the process of step S3, parameters (operating conditions) for performing blood measurement, for example, a reaction chamber to be used, a measurement time setting, and the like are set. Thus, in the sample analyzer according to the present embodiment, the blood measurement mode is set as the initial operation mode. As a result, the sample analyzer 1 enters a standby state in which the start of measurement can be accepted. The microcomputer unit 6 displays a screen for notifying the standby state on the liquid crystal display unit (step S4).

  In this standby state, the operator can change the measurement mode by operating the display / operation unit 7. FIG. 8 is a schematic diagram showing an input screen for setting the measurement mode. This screen includes a nuclear display area of a specimen number 120, a specimen capture mode type 121, a discrete test (measurement mode) type 122, and a specimen type 123. The sample uptake mode includes a manual mode in which the operator manually inserts the sample container into the sample suction nozzle 18 and performs sample suction, and the operator prepares a measurement sample by mixing the sample with the reagent in advance. Three modes are provided: a capillary mode for aspiration by the specimen aspirating nozzle 18 and a closed mode for supplying a specimen by a transport device that automatically transports the specimen container. As the types of specimens, Normal, which is a normal blood specimen, HPC, which is an HPC (hematopoietic progenitor cell), and Body Fluid, which is a body fluid, are provided. The operator can designate the sample uptake mode, the measurement mode, and the type of sample. Then, when designating the blood measurement mode, the operator designates the specimen type as Normal, and designates an arbitrary specimen uptake mode and measurement mode. When the body fluid measurement mode is designated, the operator selects “Manual mode” for the capture mode, and “CBC + DIFF”, “CBC + DIFF + RET”, “CBC + DIFF + NRBC”, and “CBC + DIFF + NRBC + RET” for the discrete test. “Body Fluid” is designated as the type of each. In step S4, the operator thus designates a desired measurement mode. When blood measurement is performed without changing the default measurement mode (N in step S5), the operator instructs the start of measurement by pressing the start switch. The microcomputer unit 6 receives an instruction to start measurement (step S6), and sucks the blood sample from the sample suction nozzle (step S7).

  After the blood sample is aspirated, the sample is introduced into the sampling valve 18 as described above, and sample adjustment necessary for measurement is performed according to the type of discrete test in the measurement mode (step S14). Then, the measurement operation of the measurement sample is executed (step S16). For example, when the type of the discrete test is set to “7”, measurement samples for HGB, WBC / BASO, DIFF, RET, NRBC, and RBC / PLT are produced. Thereafter, the WBC / BASO, DIFF, RET, and NRBC measurement samples are measured by the leukocyte detection unit 41, the RBC / PLT measurement sample is measured by the RBC / PLT detection unit 42, and the HGB measurement sample is the HGB detection unit. Measured at 43. At this time, since only one leukocyte detection unit 41 is provided, the NRBC, WBC / BASO, DIFF, and RET measurement samples are introduced into the leukocyte detection unit 41 in the order of NRBC, WBC / BASO, DIFF, and RET. And are measured in order. In this measurement operation, the calculation unit 62 creates a particle distribution map (scattergram, histogram). Here, a case where a scattergram is created from optical information obtained by DIFF measurement will be described. The calculation unit 62 generates a two-dimensional scattergram (particle distribution map) using the side scattered light and side fluorescence signals of the received light signal output from the leukocyte detection unit 41 in the DIFF measurement as characteristic parameters. This scattergram (hereinafter referred to as the DIFF scattergram) is drawn with the side scattered light intensity on the X-axis and the side fluorescence intensity on the Y-axis. “Spherical particle population”, “Monocyte particle population”, “Neophilic + basophil particle population” and “Eosinophil particle population” appear. These particle populations are recognized by the data analysis unit 64 processing the DIFF scattergram.

  Then, an analysis process is performed based on the particle distribution map obtained by the measurement (step S18). In this analysis processing, the data analysis unit 64 of the microcomputer unit 6 performs the DIFF scattergram created by the calculation unit 62 when the DIFF measurement sample is measured by the leukocyte detection unit 41 as shown in FIG. The four white blood cell clusters (lymphocyte cluster, monocyte cluster, neutrophil + basophil cluster, and eosinophil cluster) and erythrocyte ghost cluster are classified. In the analysis processing of this embodiment, the degree of attribution of each particle to each cluster is obtained from the distance between each particle plotted on the scattergram and the center of gravity of each cluster. Each particle is assigned to each cluster according to the degree of attribution. This particle classification method is described in detail in JP-A-5-149863. In addition, basophil clusters, leukocyte clusters other than basophils, and erythrocyte ghost clusters are classified on the scattergram obtained by WBC / BASO measurement. Further, based on the result of classifying and counting leukocytes into four by the analysis process of the DIFF scattergram (see FIG. 12) and the result of classifying and counting leukocytes in two by the analysis process of the WBC / BASO scattergram, The white blood cells contained in the blood sample are classified into five. Specifically, the data analysis unit 64 calculates the “basophil base” obtained by the WBC / BASO scattergram analysis process from the “neutrophil + basophil blood count” obtained by the DIFF scattergram analysis process. The blood cell count of the neutrophil and the blood cell count of the basophil are obtained by subtracting the “blood cell count of sphere”. Thereby, leukocytes are classified into 5 categories (lymphocytes, monocytes, neutrophils, basophils, eosinophils), and the blood cell count of each category item is acquired. In addition, in the RBC / PLT measurement, a valley of a one-dimensional histogram curve created based on the feature information of the detection unit 42 is detected, and red blood cells and platelets are classified. The analysis result obtained in this way is output to the display unit 302 of the data processing unit 3 (step S21).

  On the other hand, when the microcomputer unit 6 receives an input designating the measurement mode as the body fluid measurement mode as described above in step S5, the microcomputer unit 6 uses parameters (operating conditions) for performing body fluid measurement, for example, The reaction chamber, measurement time setting, etc. are set (step S8). In the present embodiment, the measurement time is three times as long as blood measurement, as will be described later.

  When the measurement mode is switched from another measurement mode (here, blood measurement mode) to the body fluid measurement mode (step S9), the measurement unit 2 starts a pre-sequence (step S10). This pre-sequence is a process for preparing for body fluid measurement. In the body fluid measurement mode, a specimen having a low concentration of blood cell components is measured. Therefore, when the setting is switched from the blood measurement mode (displayed as “1: Normal” in FIG. 8) to the body fluid measurement mode, a pre-sequence is performed. To confirm that the body fluid measurement results are not affected by the background.

  The pre-sequence includes a blank check operation. The criterion for blank check in this pre-sequence is set to a value that is less than a fraction of the stricter criteria for blank checks performed in the blood cell measurement mode (for example, after power-on or after automatic cleaning). ing. Note that when the setting is changed from the body fluid measurement mode to the blood measurement mode, the normal blood measurement result is not affected by the background (carryover effect), and thus this pre-sequence is not performed. In addition, when a body fluid sample is repeatedly measured in the body fluid measurement mode, the pre-sequence is not performed because the influence of the background is usually not exerted. However, since some body fluid samples have a very large number of particles, if the analysis result of the body fluid sample is greater than or equal to a predetermined value, the operator may be notified that the analysis result of the next sample may be affected. , "Since the measurement result is high, it may affect the measurement of the next sample. Blank check measurement is performed. Press" Confirm "" on the screen and the operator "Confirm" It is preferable that a blank check is performed by pressing a button. In this case, a “cancel” button may be provided on the screen, and when the operator presses the “cancel” button, a blank check is not performed and a transition to the standby screen can be made. Furthermore, when a blank check is not performed, it is preferable to provide a flag indicating that the reliability of the measurement result is low. As described above, the blank check is additionally performed only when necessary, so that consumption of time and reagents can be suppressed.

  FIG. 9 is a flowchart illustrating a pre-sequence process performed when the measurement mode is changed from the blood measurement mode to the body fluid measurement mode. The sample analyzer 1 performs a blank check by measuring the blank sample in the measurement unit 2 (step S31), and the microcomputer unit 6 compares the measurement result with a predetermined allowable value, and the measurement result is the allowable value. It is determined whether it is below (step S32). If the measurement result is less than the allowable value, the microcomputer unit 6 ends the pre-sequence and returns the process. If the measured value is not less than or equal to the allowable value, the microcomputer unit 6 determines whether or not a blank check has been performed a predetermined number of times (for example, three times) (step S33), and the number of times the blank check has been performed is a predetermined number of times. If not, the process returns to step S31, and a blank check is performed again within the predetermined number of times. If the measurement result of the blank check does not fall below the allowable value within the specified number of times, the measurement result of the blank check and the “Confirm” button, “Blank check” button, and “Automatic cleaning” button are displayed on the display / operation unit 7. A screen including this is displayed (step S34). If the “confirm” button is pressed by the operator (step S35), the microcomputer unit 6 ends the pre-sequence and returns the process. If the “blank check” button is pressed (step S36), the process returns to step S31 to perform a blank check again. If the “automatic cleaning” button is pressed (step S37), a dedicated check is performed. After performing the automatic cleaning with the cleaning liquid (step S38), the process returns to step S31 and the plank check is performed again.

  When the pre-sequence as described above is completed, the sample analyzer 1 is in a standby state (step S11). When starting the body fluid measurement, the operator immerses the sample suction nozzle 18 of the measurement unit 2 in the body fluid sample in the sample container, and presses the start switch, as in the case of manual measurement of the blood sample. When the microcomputer unit 6 receives the measurement start instruction as described above (step S12), the microcomputer unit 6 starts aspiration of the body fluid sample (step S13).

  After the body fluid sample is aspirated, the body fluid sample is introduced into the sampling valve 91 as in the case of the blood sample. Then, an RBC / PLT measurement sample is prepared by the reaction chamber 13 (step S15). Thereafter, the DIFF measurement sample is measured by the leukocyte detection unit 41, and the RBC / PLT measurement sample is measured by the RBC / PLT detection unit 42 (step S17). In the body fluid measurement mode, only the measurement sample for DIFF is measured by the leukocyte detection unit 41. Therefore, even if the measurement is performed longer than the measurement time in the blood measurement mode, the measurement is performed in a shorter time than in the blood measurement. Is possible to complete. As described above, it is possible to improve the analysis accuracy of a body fluid sample having a low particle concentration by extending the body fluid measurement time compared to the blood measurement time. If the measurement time is lengthened, the number of particles to be counted increases, so that the measurement accuracy is improved. However, if the measurement time is excessively long, the specimen processing ability is lowered, and the ability of the syringe pump to send the measurement sample to the leukocyte detection unit 41 2 to 6 times is appropriate. In the present embodiment, the measurement time in the body fluid measurement mode is three times that in the blood measurement mode.

  On the other hand, the measurement sample for RBC / PLT is similarly introduced into the electric resistance detection unit 41 in any measurement mode, and measurement is performed under a constant flow rate condition. Thereafter, an analysis process is performed based on the characteristic information obtained by the measurement (step S19), and the analysis result is output to the display unit 302 of the data processing unit 3 (step S21). In the analysis process in the blood measurement mode, the DIFF scattergram and the like are analyzed, and five types of leukocyte subclasses (neutrophil: NEUT, lymphocyte: LYMPH, monocyte: MONO, eosinophil: EO, basophil) : BASO) information (number and ratio) is calculated, but in the analysis process in the body fluid measurement mode, there are cases in which the number of blood cells is small or damage may occur, so there are two types in a partially integrated form Are classified into the following subclasses (mononuclear cell: MN, polynuclear cell: PMN). Lymphocytes and monocytes belong to mononuclear cells, and neutrophils, eosinophils and basophils belong to polynuclear cells. Since this classification algorithm is the same as the algorithm described in the analysis processing in the blood measurement mode, description thereof is omitted.

  By the way, foreign particles (macrophages, mesothelial cells, tumor cells, etc.) other than blood cells may be present in the body fluid sample. Although these foreign particles are rarely present in cerebrospinal fluid, they appear relatively frequently in other body fluids such as pleural effusion and ascites. Therefore, in order to classify and count blood cells in a body fluid with high accuracy regardless of the type of body fluid, it is necessary to eliminate the influence of these different particles. Therefore, according to the present invention, leukocytes in a target body fluid sample can be measured with higher accuracy based on the novel finding that different particles appear in the upper part of the DIFF scattergram of the present blood cell analyzer. Note that this point is not taken into consideration in the prior art.

  FIG. 10 is a schematic diagram of a scattergram obtained by measuring and analyzing a DIFF measurement sample prepared from a body fluid and a leukocyte measurement reagent in the body fluid measurement mode of the blood cell analyzer 1 of the present embodiment. The vertical axis of the scattergram represents the side fluorescence intensity (the fluorescence intensity is higher toward the upper side), and the horizontal axis is the side scattered light intensity (the scattered light intensity is greater toward the right side). Red blood cell ghosts Gc generated by hemolysis are distributed in the region LF where the fluorescence intensity of the scattergram is low, different particles such as mesothelial cells are distributed in the region HF where the fluorescence intensity is high, and mononuclear leukocytes Mc are distributed in the intermediate region MF. , Multinucleated leukocytes Pc are distributed. Therefore, in the analysis of the scattergram, the particle components distributed in the region MF excluding the regions LF and HF are analyzed as white blood cells, and are classified into the above two groups and counted. The mononuclear leukocytes Mc include lymphocytes and monocytes, and the polynuclear leukocytes Pc include neutrophils, eosinophils, and basophils.

  When analyzing leukocytes in body fluids in this way, the number of blood cells contained in body fluids may be small or damaged, so as clinically significant information, leukocytes are classified into mononuclear leukocytes and multinucleated leukocytes. They are classified into white blood cells and counted.

  Further, foreign particles other than blood cells (nucleated cells such as macrophages, mesothelial cells, and tumor cells) may exist in the body fluid. Although these foreign particles are rarely present in cerebrospinal fluid, they appear relatively frequently in other body fluids such as pleural effusion and ascites. In the scattergram of FIG. 10, such nucleated cells other than leukocytes are distributed in the region HF. Thus, in this embodiment, since nucleated cells other than leukocytes can be separated from leukocytes, it is possible to obtain an accurate leukocyte count even in a body fluid containing such nucleated cells other than leukocytes. become. In addition, by counting the cells that appear in the region HF, it is possible to provide the degree of appearance of abnormal cells. In the present embodiment, each cell is fractionated into regions LF, MF, and HF based on a threshold value for fractionating each region. However, this threshold value may be manually changed.

  FIG. 11 is a diagram comparing the analysis result by the blood cell analyzer 1 of the present embodiment and the count result by the reference method in order to show the validity of the above-described scattergram analysis method. The test sample is pleural effusion, and “this method” in the figure represents the number of white blood cells (WBC) and the number of other foreign particles (Others) calculated by the blood cell analyzer 1 of the present embodiment, and “Ref”. Represents a calculation result by a reference method (Fuchs-Rozental calculation board method and cytospin method). Examples 1, 2, and 3 are the results of analyzing pleural effusion in which many different particles appear, and it can be seen that there is a correlation between the analysis result by the blood cell analyzer 1 of the present embodiment and the reference method.

  FIG. 13 shows a screen 100 displayed on the display unit 302 of the data processing unit 3 as an analysis result of the DIFF measurement sample prepared from blood. A sample number display area for displaying the sample number 101 is provided at the top of the screen 100, and an attribute display area for displaying patient attributes is provided in the vicinity thereof. Specifically, a specimen number, patient ID, patient name, sex date, sex, ward, doctor in charge, measurement date, measurement time, comment, and the like are displayed in the attribute display area. A measurement result display area for displaying the measurement result is provided below the attribute display area. The measurement result display area includes a plurality of pages, and these pages are displayed on the screen when selected by a plurality of tabs 102. There are multiple tabs available for the main screen, graph screen, and other measurement items. FIG. 12 shows a display screen when a tab on the graph screen is selected. A measurement value display area 103 for displaying a measurement value as a measurement result and a flag display area 104 for displaying a flag are provided in the left half of the measurement value display area, and a distribution chart 105 as a measurement result is provided in the right half. A distribution map display area to be displayed is provided. The measured value display area displays items such as WBC, RBC,..., NEUT #,..., BASO #, NEUT%,. A flagging result indicating a specimen abnormality or a suspicion of a disease that can be useful information in clinical examination regarding WBC, PLT, RBC, or RET is displayed.

  Six distribution charts are displayed in the distribution chart display area 105. The upper left scattergram is a scattergram for DIFF. The upper right side is a scattergram for WBC / BASO, the middle left side is for immature sphere (IMI), and the middle right side is for RET. The lower left is the RBC histogram, and the lower right is the PLT histogram.

  FIG. 14 shows a screen 110 displayed on the display unit 302 of the data processing unit 3 as a measurement result of the DIFF measurement sample prepared from the body fluid. A sample number display area 111 for displaying a sample number is provided at the top of the screen 110, and a patient attribute display area is provided in the vicinity thereof. At the left end of the sample number display area 111, “F” indicating that measurement has been performed in the body fluid measurement mode is displayed. This makes it possible to clearly recognize that this analysis result is a result of body fluid measurement. The measurement result display area includes a plurality of pages that can be selected on the tab 112. In this example, the “Body Fluid Measurement” tab is selected.

  In the measurement value display area 113, the measurement item names for body fluids, which are different from the measurement results in the blood measurement mode, are WBC-BF (WBC number), RBC-BF (RBC number), MN # (monocyte) Number (lymphocytes + monocytes)), PMN # (number of polynuclear cells (neutrophils + basophils + eosinophils)), MN% (monocyte ratio in leukocytes), PMN% (polynuclear in leukocytes) Sphere ratio), measured values, and units are displayed in association with each other. In the body fluid measurement, a flag display area 114 is provided as in the blood measurement. Two distribution maps 115 are displayed in the distribution map display area, and the upper scattergram is a scattergram for DIFF. The lower row is an RBC histogram.

  FIG. 15 shows an example in which the tab “Research BF” is selected on the tab 112 in the screen 110 of FIG. 14. This screen displays the same items as the screen 110 except that the research parameter display area 116 is displayed. In the research parameter display area 116, in FIG. 10, “HF-BF #” which is the number of particles existing in the region HF, the number of particles existing in the region HF with respect to the number of particles existing in the region including the region HF and the region MF The ratio “HF-BF%” and the number of particles existing in the region including the region HF and the region MF “TC-BF #” are displayed. “HF-BF%” is the ratio of HF-BF to TC-BF.

  FIG. 16 shows a list display screen 120 of stored samples displayed on the display unit 302 of the data processing unit 3. Reference numeral 130 denotes a patient attribute display area. Above that, a measurement result display area for displaying a measurement result by tab selection is provided. A column 131 at the left end of the measurement result display area is used to indicate whether or not the measurement result is validated. The symbol V indicates that the validation has been completed. The right column 132 is for indicating the measurement mode. What is indicated by “F” is the measurement result in the body fluid measurement mode. In the body fluid measurement mode, a high-value sample requiring a blank check is used, but when the blank check is not performed, F can be written in reverse notation to indicate that.

  As described above, the configuration and function of the blood cell analyzer of the present invention have been described as being provided in advance in the blood cell analyzer, but the function is realized by a computer program and the computer program is installed in the conventional blood cell analyzer. Thus, the conventional blood cell analyzer can be configured to exhibit the function according to the present invention.

  In the present embodiment, the specimen amount, the reagent type, and the reagent amount are the same when preparing the measurement sample in the white blood cell classification measurement in the blood measurement mode and in the white blood cell classification measurement in the body fluid measurement mode. Although the configuration has been described, the present invention is not limited to this, and the amount of specimen and reagent for preparing a measurement sample for white blood cell classification measurement in the body fluid measurement mode are the same as the measurement sample for white blood cell classification measurement in the blood measurement mode. It is also possible to increase the amount of the specimen and the amount of the reagent for preparing each. In the leukocyte classification measurement in the body fluid measurement mode, the measurement time is longer than in the blood measurement mode, and the amount of the measurement sample required for the measurement is large. By doing so, the white blood cell classification measurement and the body fluid measurement in the blood measurement mode are performed. In each of the mode leukocyte classification measurements, an appropriate amount of measurement sample can be created.

  In the present embodiment, the configuration for performing white blood cell classification in the body fluid measurement mode using scattered light and fluorescence has been described. However, the present invention is not limited to this, and for example, using scattered light and absorbed light. It may be configured to perform white blood cell classification in the body fluid measurement mode. In the measurement of absorbed light, a staining reagent for staining white blood cells is mixed with a sample together with a sample to prepare a measurement sample, and the measurement sample is supplied to the flow cell to form a sample flow in the flow cell. This is possible by irradiating light and receiving light emitted from the sample stream by a light receiving element such as a photodiode. When white blood cells pass through the flow cell, light is absorbed by the white blood cells, and the degree of absorption is captured as the amount of light received by the light receiving element. Such measurement of absorbed light is disclosed in US Pat. No. 5,122,453 and US Pat. No. 5,138,181. Further, it is also possible to measure the electrical resistance instead of the scattered light, and perform the white blood cell classification measurement based on the electrical resistance value and the absorbed light.

It is an external view of the blood cell analyzer of the present invention. It is a block diagram of the measurement part of an analyzer. It is a block diagram of a fluid mechanism part. It is a figure which shows the optical system of a leukocyte detection part. It is a figure which shows a RBC / PLT detection part. It is a figure which shows an HGB detection part. It is a flowchart which shows the measurement process of a sample. It is a figure which shows the display screen for setting a measurement mode. It is a flowchart showing the process of a pre sequence. It is the schematic diagram of the scattergram which measured the measurement sample for DIFF prepared from the body fluid. It is the figure which contrasted the measurement result by the blood cell analyzer of embodiment, and the measurement result by a reference method. It is the schematic diagram of the scattergram which measured the measurement sample for DIFF prepared from the blood. It is a display screen showing the measurement result in the blood measurement mode. It is a display screen showing the measurement result in body fluid measurement mode. It is a display screen showing the measurement result in body fluid measurement mode. It is a display screen showing the measurement result in body fluid measurement mode.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Blood cell analyzer 2 Measuring part 3 Data processing part 4 Detection part 5 Analog signal processing part 6 Microcomputer part 7 Display operation part 8 Fluid processing part

Claims (7)

A suction section for sucking a specimen;
A measurement unit that mixes the specimen aspirated by the aspiration unit and a reagent to prepare a measurement sample, measures the prepared measurement sample, and obtains characteristic information representing the characteristics of the components in the measurement sample;
Mode setting means for setting one of a blood measurement mode for measuring a blood sample and a body fluid measurement mode for measuring a body fluid sample different from the blood sample as an operation mode;
An operation control means for controlling the operation of the measurement unit,
The operation control means includes
When the blood measurement mode is set by said mode setting means, said mixing a suction blood sample and reagent by suction unit to prepare the measurement sample, the measurement of the first amount at a predetermined first measuring time Control the operation of the measurement unit to measure the sample ,
When the body fluid measurement mode is set by said mode setting means, the suction unit by mixing a suction body fluid sample and a reagent to prepare a measurement sample, a second measurement of the longer given than the first measuring time Controlling the measurement unit to measure a second amount of the measurement sample that is greater than the first amount over time ;
Sample analyzer. The measurement unit includes a detection unit that detects a component in the measurement sample that passes through the flow cell, and a pump that sends the measurement sample to the detection unit at a constant flow rate.
The operation control means includes
When the blood measurement mode is set , the measurement unit is controlled to detect components in the measurement sample while sending the measurement sample to the detection unit at a constant flow rate over the first measurement time.
When the body fluid measurement mode is set , the measurement unit is controlled to detect components in the measurement sample while sending the measurement sample to the detection unit at a constant flow rate over the second measurement time.
The sample analyzer according to claim 1.   The sample analyzer according to claim 1 or 2, wherein the measurement unit uses the same reagent as the reagent mixed with the blood sample as the reagent mixed with the body fluid sample. The operation control means, prior to measuring the body fluid sample, controls the operation of the measurement unit to measure a blank sample containing no analyte, the sample analyzer according to any one of claims 1 to 3. If the measurement results of body fluid sample by the measurement unit is large Ri by a predetermined reference value, the operation control means, that runs controlling the measurement unit so as to perform the cleaning operation
The sample analyzer according to any one of claims 1 to 4 . A suction section for sucking a specimen;
A measurement unit that mixes the specimen aspirated by the aspiration unit and a reagent to prepare a measurement sample, measures the prepared measurement sample, and obtains characteristic information representing the characteristics of the components in the measurement sample;
Mode setting means for setting one of a blood measurement mode for measuring a blood sample and a body fluid measurement mode for measuring a body fluid sample different from the blood sample as an operation mode;
Analyzing means for analyzing feature information obtained by the measurement unit measuring a measurement sample,
The analysis means includes
When the blood measurement mode is set by the mode setting means, the measurement unit takes a predetermined first measurement time and measures a first amount of measurement sample with respect to feature information obtained performing a first analysis processing,
When the body fluid measurement mode is set by said mode selecting means, the measurement sample in the measuring portion is the greater than the first amount first over a long second predetermined measurement time than the measurement time second amount on the feature information obtained by measuring the perform different second analysis processing from the first analysis processing,
Sample analyzer. The first analysis process includes a process of classifying white blood cells into at least four types,
The second analysis process includes a process of classifying white blood cells into fewer types than the first analysis process.
The sample analyzer according to claim 6 .

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