Specimen analyzer

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

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

For example, when cerebrospinal fluid, which is one of the body fluids, is measured, the following estimation can be made from the measurement results. Increase in red blood cells: subarachnoid hemorrhage Increase in neutrophils: meningitis Eosinophilia: infectious diseases (parasites and fungi) Increase in mononuclear cells: tuberculous meningitis, viral meningitis Other cells: tumor meningeal extension As a blood cell analyzer capable of measuring cells in body fluid, there is one disclosed in Patent Document 1. In Patent Document 1, in order to stably store the body fluid for a long period of time, the operator mixes the body fluid sample with a reagent (aldehyde, surfactant and cyclodextrin), prepares a measurement sample in advance, and prepares the measurement sample. Is given to the analyzer to analyze the body fluid.

<patcit num="1"><text>Japanese Unexamined Patent Publication No. 2003-344393</text></patcit>

<p> However, in Patent Document 1 described above, 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. Further, in the analyzer disclosed in Patent Document 1,<u style="single">What about the carryover problem when measuring fluid continuously?</u>Not disclosed.</p><p> The present invention has been made in view of such circumstances, and the operator does not need to perform complicated work such as preparation of a measurement sample.<u style="single">While suppressing the occurrence of carryover when continuously measuring body fluids</u>An object of the present invention is to provide a sample analyzer capable of analyzing body fluids with high accuracy.</p>

<p> The sample analyzer according to the present invention is<u style="single">It is a sample analyzer that can measure and analyze a blood sample and a body fluid sample different from the blood sample as a sample. The sample is aspirated, and a measurement sample is prepared from the sucked sample and the reagent, and the prepared measurement is performed. It is provided with a measuring unit and a display unit that measure the sample by detecting the components in the sample, and when the measurement result of the body fluid sample is equal to or higher than a predetermined value, it is urged to measure the blank sample containing no sample. Display the message on the display</u>It is characterized by that.</p><p> By doing so, the operator simply sucks the sample into the sample analyzer, and the sample analyzer automatically prepares the measurement sample and automatically executes the measurement operation suitable for each of the blood sample and the body fluid sample. Will be done. Therefore, it is possible to analyze the body fluid sample without the need for complicated operations by the operator.<u style="single">Furthermore, since body fluids have a lower cell concentration than blood, even a small amount of residual components (carryover) greatly affects the measurement results. According to the present invention, since the blank sample is measured when the body fluid sample whose measurement result is equal to or higher than a predetermined value is measured, it is possible to suppress the occurrence of carryover due to the high value body fluid sample, and the body fluid sample is analyzed with high accuracy. can do.</u></p><p><u style="single"> In the above invention, it is preferable to display a button instructing the measurement of the blank sample on the display unit together with the message.</u></p><p><u style="single"> In the above invention, it is preferable to display on the display unit a button for transitioning the measurement unit to a state in which the next body fluid sample can be measured without executing the measurement of the blank sample together with the button.</u></p><p><u style="single"> In the above invention, when the next body fluid sample is measured without executing the measurement of the blank sample, information indicating that the reliability is low may be added to the measurement result of the body fluid sample and displayed on the display unit. preferable.</u></p><p><u style="single"> In the above invention, when the measurement result of the blank sample is equal to or less than the reference value, it is preferable to shift the measuring unit to a state in which the next body fluid sample can be measured.</u></p><p><u style="single"> In the above invention, when the measurement result of the blank sample is not equal to or less than the reference value, it is preferable to have the measuring unit measure the blank sample again.</u></p><p><u style="single"> In the above invention, if the measurement result does not fall below the reference value even after the measurement of the blank sample a predetermined number of times, it is preferable to display a button on the display unit instructing the execution of cleaning using the cleaning liquid.</u></p>

<p> According to the sample analyzer according to the present invention, there is no need for complicated operations by the operator.<u style="single">While suppressing the occurrence of carryover when continuously measuring body fluids</u>It is possible to analyze body fluid samples with high accuracy.</p>

<figref num="1"><u style="single">It is an external view of the blood cell analyzer of this invention.</u></figref><figref num="2"><u style="single">It is a block diagram of the measurement part of an analyzer.</u></figref><figref num="3"><u style="single">It is a block diagram of a fluid mechanism part.</u></figref><figref num="4"><u style="single">It is a figure which shows the optical system of the leukocyte detection part.</u></figref><figref num="5"><u style="single">It is a figure which shows the RBC / PLT detection part.</u></figref><figref num="6"><u style="single">It is a figure which shows the HGB detection part.</u></figref><figref num="7"><u style="single">It is a flowchart which shows the measurement process of a sample.</u></figref><figref num="8"><u style="single">It is a figure which shows the display screen for setting a measurement mode.</u></figref><figref num="9"><u style="single">It is a flow chart which shows the processing of a pre-sequence.</u></figref><figref num="10"><u style="single">It is a schematic diagram of the scattergram which measured the measurement sample for DIFF prepared from the body fluid.</u></figref><figref num="11"><u style="single">It is the figure which compared the measurement result by the blood cell analyzer of embodiment and the measurement result by a reference method.</u></figref><figref num="12"><u style="single">It is a schematic diagram of the scattergram which measured the measurement sample for DIFF prepared from the blood.</u></figref><figref num="13"><u style="single">It is a display screen which shows the measurement result in a blood measurement mode.</u></figref><figref num="14"><u style="single">It is a display screen which shows the measurement result in the body fluid measurement mode.</u></figref><figref num="15"><u style="single">It is a display screen which shows the measurement result in the body fluid measurement mode.</u></figref><figref num="16"><u style="single">It is a display screen which shows the measurement result in the body fluid measurement mode.</u></figref>

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

FIG. 1 shows the 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. The feature information is acquired, and the feature information is analyzed. In addition, this 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 a body cavity fluid existing in the body cavity other than blood. Specifically, cerebrospinal fluid (cerebrospinal fluid, CSF: fluid that fills the ventricles and subsynovial space), pleural effusion (pleural effusion, PE: fluid that collects in the pleural space), peritoneal fluid (collected in the peritoneal cavity). Fluid), cerebrospinal fluid (fluid accumulated in the peritoneal cavity), joint fluid (synovial fluid: fluid present in joints, synovial sac, and tendon sheath), etc. In addition, peritoneal dialysis (CAPD) dialysate and intraperitoneal lavage fluid can also be analyzed as a type of body fluid. Normally, almost no cells are found in these body fluids, but cells such as blood cells, abnormal cells, and bacteria may be contained when there is a tumor or damage to a disease or related organs. For example, in the case of cerebrospinal fluid, the following clinical estimation is possible from the analysis results. For example, subarachnoid hemorrhage when red blood cells are increasing, meningitis when neutrophils are increasing, and infectious diseases (parasites and parasites) when eosinophils are increasing. Fungal), meningitis or viral meningitis can be suspected when mononuclear cells are increased, and meningeal progression of the tumor can be suspected when other cells are increased. In addition, when ascites, pleural effusion, etc. contain nucleated cells such as mesothelial cells, macrophages, and tumor cells in addition to blood cells, by analyzing such nucleated cells other than blood cells, cancer and the like can be detected. It can be an indicator of suspicion of a disease.

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

FIG. 2 shows a block diagram of the measuring unit 2 of the analyzer 1. As shown in FIG. 2, the measuring unit 2 includes a blood cell detection unit 4, an analog processing unit 5 that processes the output (analog signal) of the detection unit 4, a microcomputer unit 6, a display / operation unit 7, and blood. It also includes a device mechanism 8 for measuring body fluids. Further, the device mechanism unit 8 includes the following fluid mechanism unit 81.

FIG. 3 is a block diagram showing the configuration of the fluid mechanism unit 81. As shown in FIG. 3, the fluid mechanism unit 81 includes a sample suction nozzle 18, a plurality of reagent containers, a sampling valve 12, and reaction chambers 13 to 17. The sample suction nozzle 18 sucks the 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), and 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 above CBC measurement items, in the CBC + DIFF mode, which classifies leukocytes into five, the sample is divided into four aliquots. In addition to the CBC + DIFF mode measurement items, the CBC + DIFF + RET mode, which measures reticulocytes, is divided into five aliquots. Similarly, in addition to the measurement items in CBC + DIFF mode, in CBC + DIFF + NRBC mode for measuring nucleated red blood cells, the sample is divided into five aliquots. In addition to the CBC + DIFF mode + RET measurement items, the CBC + DIFF + RET + NRBC mode for measuring nucleated red blood cells is divided into 6 aliquots. The above measurement modes are all blood measurement modes for measuring blood. Finally, in fluid measurement mode, where fluid is measured, the specimen is divided into two aliquots.

Further, a reagent (diluted solution) is introduced into the sampling valve 12, and the aliquot of the divided sample is sent together with the reagent to the reaction chambers 13 to 17 and the HGB detection unit 43 described later. It has become. A predetermined amount of sample (alicoat) collected by the sampling valve 12, a predetermined amount of diluted solution, and a predetermined amount of staining solution are supplied to the reaction chamber 13 by a metering pump (not shown), and these samples and reagents are used. Are mixed to prepare a measurement sample for leukocyte 4 classification (DIFF).

As this diluent, the reagent "Stomach Riser-4DL" provided by Sysmex Corporation can be preferably used. This reagent contains a surfactant to hemolyze red blood cells. As the staining solution, the reagent "Stomach Riser-4DS" also provided by Sysmex Corporation can be preferably used. This staining solution contains ethylene glycol, a lower alcohol, and a polymethine-based pigment, and after hemolysis with the above-mentioned diluted solution, the blood cell components are stained, and finally a 50-fold diluted sample is prepared.

When the body fluid measurement mode is selected, the measurement sample for white blood cell classification is the same as the measurement sample for white blood cell 4 classification, the same reagent, and the same amount of reagent depending on the body fluid sample. Is created. However, as will be described later, in the leukocyte classification in the body fluid measurement mode, leukocytes 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 hemolytic agent, and a predetermined amount of staining solution are supplied to the reaction chamber 14 by a metering pump (not shown), and these samples and reagents are mixed. , A measurement sample for the measurement of nucleated red blood cells (NRBC) is prepared.

A predetermined amount of sample collected by the sampling valve 12, a predetermined amount of diluted solution, and a predetermined amount of staining solution are supplied to the reaction chamber 15 by a metering pump (not shown), and these samples and reagents 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 samples and reagents are mixed to form leukocytes / basophils (leukocytes / 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 diluted solution are supplied to the reaction chamber 17 by a metering pump (not shown), and these samples and reagents are mixed and red blood cells / platelets (RBC / PLT). ) Is prepared.

Further, a predetermined amount of the sample collected by the sampling valve 12 and a predetermined amount of the diluted hemolytic agent are supplied to the HGB detection unit 43, which will be 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 for measuring the number of red blood cells and platelets, and an HGB detection unit 43 for measuring the amount of hemoglobin in blood.

The leukocyte detection unit 41 is configured as an optical detection unit, and specifically, is configured as a detection unit by a flow cytometry method. Here, cytometry is the measurement of the physical and chemical properties of cells and other biological particles, and flow cytometry is the passage of these particles through a narrow stream. It refers to the method of making measurements. FIG. 4 shows the optical system of the white blood cell detection unit 41. In the figure, the beam emitted from the laser diode 401 irradiates blood cells passing through the sheath flow cell 403 via the collimating lens 402. The leukocyte detection unit 41 detects the intensity of forward scattered light, the intensity of laterally scattered light, and the intensity of lateral fluorescence emitted from blood cells in the sheath flow cell irradiated with light as characteristic parameters of blood cells.

Here, 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 the traveling direction. By detecting this scattered light, it is possible to obtain characteristic information of the particles regarding the size and components of the particles. The forward scattered light is scattered light emitted from particles in a direction substantially the same as the traveling direction of the irradiated light. From the forward scattered light, characteristic information regarding the size of particles (blood cells) can be obtained. Further, the laterally scattered light is scattered light emitted from the particles in a direction substantially perpendicular to the traveling direction of the irradiated light. From the laterally scattered light, characteristic information about the inside of the particle can be obtained. When blood cell particles are irradiated with laser light, the intensity of laterally scattered light depends on the internal complexity of the cell (nucleus shape, size, density and amount of granules). Therefore, by utilizing this characteristic of the lateral scattered light intensity, the number of blood cells can be measured after classifying (discriminating) the blood cells. In the present embodiment, the configuration in which the forward scattered light and the side scattered light are used as the scattered light has been described, but the present invention is not limited to this, and the scattered light signal showing the characteristics of the particles necessary for the analysis is used. If it can be obtained, scattered light at any angle with respect to the optical axis of the light transmitted from the light source through the sheath flow cell may be used.

Further, when a fluorescent substance 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 fluorescence intensity becomes stronger if it is well stained, and by measuring this fluorescence intensity, characteristic information regarding the degree of staining of blood cells can be obtained. Therefore, leukocyte classification and other measurements can be made based on the difference in (lateral) fluorescence intensity.

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

Next, the configuration of the RBC / PLT detection unit 42 will be described. FIG. 5 is a schematic diagram showing a schematic configuration of the RBC / PLT detection unit 42. The RBC / PLT detection unit 42 can measure the red blood cell count and the platelet count by the sheath flow DC detection method. The RBC / PLT detection unit 42 has a sheath flow cell 42a as shown in FIG. The sheath flow cell 42a is provided with a sample nozzle 42b that opens upward, and a sample is supplied from the reaction chamber 17 to the sample nozzle 42b. Further, the sheath flow cell 42a has a tapered chamber 42c that becomes thinner toward the upper side, and the sample nozzle 42b described above is arranged in the center of the inside of the chamber 42c. Further, an aperture 42d is provided at the upper end of the chamber 42c, and the aperture 42d is centered 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, and 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, the flow of the measurement sample is narrowed down by the tapered chamber 42c, and the blood cells in the measurement sample pass through the aperture 42d one by one. An electrode is provided on the aperture 42d, and a direct current is supplied between the electrodes. Then, when the measurement sample passes through the aperture 42d, the change in the DC resistance in the aperture 42d is detected, and this electric signal is output to the control unit 25. Since the DC resistance increases when blood cells pass through the aperture 42d, this electrical signal reflects the passage information of the blood cells in the aperture 42d, and the red blood cells and platelets are counted by processing this electrical signal. It is designed to do.

Further, above the aperture 42d, a recovery pipe 42e extending vertically is provided. Further, the recovery pipe 42e is arranged inside the chamber 42f which is connected to the chamber 42c via the aperture 42d. The lower end of the recovery tube 42e is separated from the inner wall of the chamber 42f. The back sheath liquid is supplied to the chamber 42f, and the back sheath liquid flows downward through the outer region of the recovery pipe 42e of the chamber 42f. The backsheath liquid flowing outside the recovery pipe 42e reaches the lower end of the chamber 42f, passes between the lower end of the recovery pipe 42e and the inner wall of the chamber 42f, and flows into the inside of the recovery pipe 42e. Therefore, the return of blood cells that have passed through the aperture 42d is prevented, which prevents erroneous detection of 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 the configuration of the HGB detection unit 43. The HGB detection unit 43 includes a cell 43a for accommodating the diluted sample, a light emitting diode 43b that emits light toward the cell 43a, and a light receiving element 43c that receives the transmitted light transmitted 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 ratio to prepare a diluted sample. This hemolytic agent has the property of converting hemoglobin in blood to SLS-hemoglobin. Such diluted samples are fed into cell 43a and housed in cell 43a. In this state, the light emitting diode 43b is made to emit light, and the transmitted light is received by the light receiving element 43c arranged to face the light emitting diode 43b with the cell 43a interposed therebetween. The light emitting diode 43b emits light having a wavelength having a high absorbance due to SLS-hemoglobin, and since the cell 43a is made of a highly translucent plastic material, the light emitting device 43c is a light emitting diode. The transmitted light whose light emission of 43b is absorbed only by the substantially diluted sample will be received. The light receiving element 43c outputs an electric signal according to the amount of light received (absorbance) to the microcomputer unit 6, and the microcomputer unit 6 calculates this absorbance and the absorbance of only the diluted solution measured in advance. The hemoglobin value is calculated by comparison.

The microcomputer unit 6 includes an A / D conversion unit 61 that converts an analog signal given by 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 an operation to perform a predetermined process on the received signal. The calculation unit 62 creates distribution data (two-dimensional scattergram (unclassified) and 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 the analysis processor and the 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 preparing and measuring a sample, and other controls. The data analysis unit 64 executes 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 screen display and storage of data is performed.

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

Next, the operation of the sample analyzer 1 according to the present embodiment will be described. FIG. 7 is a flowchart showing the operation flow of the sample analyzer according to the present embodiment. When the user (operator) turns on the power of the sample analyzer 1 (step S1), the sample analyzer 1 is activated. At startup, the sample analyzer 1 first executes a self-check (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 initially sets the measurement mode (step S3). This default value is 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, measurement time setting, and the like are set. As described above, 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 is in a standby state capable of accepting the start of measurement. The microprocessor unit 6 displays a screen 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 region of sample number 120, sample uptake mode type 121, discrete test (measurement mode) type 122, and sample type 123. The sample uptake mode is a manual mode in which the operator manually inserts the sample container into the sample suction nozzle 18 to suck the sample, and the operator mixes the sample with the reagent in advance to prepare a measurement sample and prepares the measurement sample. Three modes are provided: a capillary mode in which the sample is sucked by the sample suction nozzle 18, and a closed mode in which the sample is supplied by a transport device that automatically transports the sample container. The types of samples include Normal, which is a normal blood sample, HPC, which is HPC (hematopoietic progenitor cell), and Body, which is a body fluid. Fluid is provided. The operator can specify the sample uptake mode, the measurement mode, and the sample type, respectively. Then, when the operator specifies the blood measurement mode, the type of the sample is specified as Normal, and the uptake mode and the measurement mode of any sample are specified. When specifying the body fluid measurement mode, the operator sets "manual mode" for the uptake mode and "CBC + DIFF", "CBC + DIFF + RET", "CBC + DIFF + NRBC" and "CBC + DIFF + NRBC" for the discrete test. Specify one of "CBC + DIFF + NRBC + RET" and "Body Fluid" as the sample type. In step S4, the operator thus specifies the desired measurement mode. When the blood measurement is performed without changing the default measurement mode (N in step S5), the operator presses the start switch to instruct the measurement to start. The microcomputer unit 6 receives the instruction to start the 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 the sample required for measurement is adjusted 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 discrete test type is set to "7", each measurement sample for HGB, WBC / BASO, DIFF, RET, NRBC, and RBC / PLT is prepared. After that, the measurement sample for WBC / BASO, DIFF, RET, and NRBC is measured by the leukocyte detection unit 41, the measurement sample for RBC / PLT is measured by the RBC / PLT detection unit 42, and the measurement sample for HGB is the HGB detection unit. Measured at 43. At this time, since only one leukocyte detection unit 41 is provided, each measurement sample of NRBC, WBC / BASO, DIFF, and RET is introduced into the leukocyte detection unit 41 in the order of NRBC, WBC / BASO, DIFF, and RET. And are measured in sequence. In this measurement operation, the calculation unit 62 creates a particle distribution map (scattergram, histogram). Here, a case where a scattergram is created from the optical information obtained by the DIFF measurement will be described. The calculation unit 62 generates a two-dimensional scattergram (particle distribution map) using the laterally scattered light and the lateral fluorescence signals among the received signals output from the leukocyte detection unit 41 in the DIFF measurement as characteristic parameters. This scattergram (hereinafter referred to as DIFF scattergram) is drawn with the lateral scattered light intensity on the X-axis and the lateral fluorescence intensity on the Y-axis, and is usually drawn as "red blood cell ghost particle population" or "lymph". "Spherical particle population", "monocyte particle population", "neutrophil + basophil particle population" and "eosinophil particle population" appear. These particle populations are recognized by processing the DIFF scattergram by the data analyzer 64.

Then, the analysis process is performed based on the particle distribution map obtained by the measurement (step S18). In this analysis process, the data analysis unit 64 of the microcomputer unit 6 is shown in FIG. 12 with respect to the DIFF scattergram created by the calculation unit 62 when the sample for DIFF measurement is measured by the leukocyte detection unit 41. We classify four white blood cell clusters (lymphocyte cluster, monocyte cluster, neutrophil + basophil cluster, and eosinophil cluster) and erythrocyte ghost cluster. In the analysis process of the present embodiment, the degree of attribution of each particle to each cluster can be obtained from the distance between each particle plotted on the scattergram and the position of the center of gravity of each cluster. Then, each particle is assigned to each cluster according to the degree of these attributions. This particle classification method is described in detail in Japanese Patent Application Laid-Open No. 5-149863. In addition, basophil clusters, non-basophil leukocyte clusters, and erythrocyte ghost clusters are classified on the scattergram obtained by WBC / BASO measurement. In addition, based on the result of classifying and counting leukocytes into 4 by the analysis process of DIFF scattergram (see Fig. 12) and the result of classifying and counting leukocytes into 2 by the analysis process of WBC / BASO scattergram. The white blood cells contained in the blood sample are classified into 5 categories. Specifically, the data analysis unit 64 uses the "neutrophil + basophil blood cell count" obtained by the DIFF scattergram analysis process to obtain the "basophil" obtained by the WBC / BASO scattergram analysis process. Subtract the "blood cell count of spheres" to obtain the blood cell count of neutrophils and the blood cell count of basophils, respectively. As a result, white blood cells are classified into 5 categories (lymphocytes, monocytes, neutrophils, basophils, and eosinophils), and the blood cell count of each category is obtained. In addition to this, in the RBC / PLT measurement, the valley of the curve of the one-dimensional histogram created based on the feature information of the detection unit 42 is detected, and erythrocytes and platelets are classified. The analysis result obtained in this way is obtained by the data processing unit 3.

On the other hand, when the microcomputer unit 6 receives the input for designating the measurement mode to the body fluid measurement mode as described above in step S5, the microcomputer unit 6 uses a parameter (operating condition) for performing the body fluid measurement, for example. Set the reaction chamber, measurement time setting, etc. (step S8). In the present embodiment, the measurement time is three times as long as that in the case of 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 the presequence (step S10). This presequence is a process in preparation for fluid measurement. Since the body fluid measurement mode measures a sample with a low concentration of blood cell components, presequence is performed when the setting is switched from the blood measurement mode (displayed as "1: Normal" in Fig. 8) to the body fluid measurement mode. To confirm that the body fluid measurement results are not affected by the background.

The presequence includes a blank check operation. The criteria for the blank check in this presequence are stricter than the criteria for the blank check performed in the blood cell measurement mode (for example, after the power is turned on or after automatic washing), and are set to a value of a fraction or less. ing. When the setting is changed from the body fluid measurement mode to the blood measurement mode, the background effect (the effect of carryover) does not usually affect the blood measurement result, so this presequence is not performed. Also, when the body fluid sample is repeatedly measured in the body fluid measurement mode, the presequence is not usually performed because the influence of the background does not affect. However, since some body fluid samples have an extremely large number of particles, if the analysis result of the body fluid sample is equal to or higher than a predetermined value, the operator may be notified that the analysis result of the next sample may be affected. , "Because the measurement result is high, it may affect the measurement of the next sample. Perform blank check measurement. Please press" Confirm "" is output on the screen, and the operator "Confirms". It is preferable to configure the blank check by pressing a button. Further, in this case, a "stop" button may be provided on the screen, and when the operator presses the "stop" button, the blank check may not be performed and the screen may transition to the standby screen. Furthermore, it is preferable to add a flag indicating that the measurement result is unreliable when the blank check is not performed. By additionally performing a blank check only when necessary in this way, time and consumption of reagents can be suppressed.

FIG. 9 is a flowchart showing a pre-sequence processing procedure 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 a blank sample in the measuring 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 or not the following (step S32). If the measurement result is equal to or less than the permissible value, the microprocessor unit 6 ends the presequence and returns the process. If the measured value is not less than the permissible value, the microprocessor unit 6 determines whether or not the blank check has been executed a predetermined number of times (for example, three times) (step S33), and the number of times the blank check is performed is a predetermined number of times. If the above is not reached, the process is returned to step S31, and the blank check is performed again within the predetermined number of times. If the blank check measurement result does not fall below the permissible value within the specified number of times, the blank check measurement result and the "confirm" button, "blank check" button, and "automatic cleaning" button are displayed on the display / operation unit 7. Display the including screen (step S34). When the "confirm" button is pressed by the operator (step S35), the microprocessor unit 6 ends the presequence and returns the process. When the "blank check" button is pressed (step S36), the process is returned to step S31 and the blank check is performed again, and when the "automatic cleaning" button is pressed (step S37), the dedicated process is performed. After performing automatic cleaning with the cleaning liquid (step S38), the process is returned to step S31 and the plank check is performed again.

When the presequence as described above is completed, the sample analyzer 1 is put into the 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 in the same manner as in the manual measurement of the blood sample. When the microprocessor unit 6 receives the instruction to start the measurement in this way (step S12), it starts sucking 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, the reaction chamber 13 prepares a sample for RBC / PLT measurement (step S15). After that, 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 DIFF measurement sample is measured by the leukocyte detection unit 41, so 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, by lengthening the measurement time of the body fluid measurement longer than the measurement time of the blood measurement, it is possible to improve the analysis accuracy of the body fluid sample having a low particle concentration. If the measurement time is lengthened, the number of particles counted increases, so the measurement accuracy improves, but if the measurement is performed for an excessively long time, the sample processing capacity decreases, and the capacity of the syringe pump that sends the measurement sample to the leukocyte detection unit 41. 2 to 6 times is appropriate because there is a limit to. In the present embodiment, the measurement time in the body fluid measurement mode is three times as long as in the blood measurement mode.

On the other hand, the measurement sample for RBC / PLT is similarly introduced into the electric resistance type detection unit 41 in any measurement mode, and the measurement is performed under a constant flow velocity condition. After that, an analysis process is performed based on the feature 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, DIFF scattergrams are analyzed to analyze 5 types of white blood cell subclasses (neutrophils: NEUT, lymphocytes: LYMPH, monocytes: MONO, eosinophils: EO, basophils. : BASO) information (number and ratio) is calculated, but in the analysis process in the body fluid measurement mode, there are cases where the blood cell count is low or damaged, so there are two types in a partially integrated form. It is classified into subclasses (monocytes: MN, polynuclear cells: 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 process in the blood measurement mode, the description thereof will be omitted.

By the way, foreign particles other than blood cells (macrophages, mesothelial cells, tumor cells, etc.) may be present in the body fluid sample. These foreign particles are rarely present in cerebrospinal fluid, but are relatively common in other body fluids, pleural effusion and ascites. Therefore, in order to accurately classify and count blood cells in body fluid regardless of the type of body fluid, it is necessary to eliminate the influence of these different particles. Therefore, in the present invention, based on the novel finding that different particles appear in the upper part of the DIFF scattergram of the blood cell analyzer, the leukocytes in the target body fluid sample can be measured more accurately. It should be noted that this point is not taken into consideration in the above-mentioned 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 white blood cell 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 lateral fluorescence intensity (the higher the fluorescence intensity, the higher the fluorescence intensity), and the horizontal axis represents the lateral scattered light intensity (the right side, the higher the scattered light intensity). Erythrocyte ghost Gc generated by hemolysis is distributed in the region LF where the fluorescence intensity is low in the scattergram, foreign particles such as mesenteric cells are distributed in the region HF where the fluorescence intensity is high, and mononuclear leukocyte Mc in the intermediate region MF. , Polymorphonuclear leukocyte Pc is 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 leukocytes, and classified and counted into the above two groups. The mononuclear leukocyte Mc includes lymphocytes and monocytes, and the polynuclear leukocyte Pc includes neutrophils, eosinophils and basophils.

When analyzing leukocytes in body fluids in this way, the number of blood cells contained in the body fluids may be low or damaged, so clinically significant information is that leukocytes are mononuclear leukocytes and polynuclear. It is classified into white blood cells and counted.

In addition, foreign particles other than blood cells (nucleated cells such as macrophages, mesothelial cells, and tumor cells) may be present in body fluids. These foreign particles are rarely present in cerebrospinal fluid, but are relatively common in other body fluids, pleural effusion and ascites. In the scattergram of FIG. 10, such nucleated cells other than leukocytes are distributed in region HF. As described above, in the present 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. Further, by counting the cells appearing in the region HF, it becomes possible to provide the degree of appearance of abnormal cells. In the present embodiment, each cell is divided into regions LF, MF and HF by a threshold value for fractionating each region, but 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 counting result by the reference method in order to show the validity of the above-mentioned 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 this embodiment, and is "Ref". Represents the calculation result by the reference method (Fuchs-Rosenthal calculation board method and cytospin method). Examples 1, 2 and 3 are the results of analysis of 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 the screen 100 displayed on the display unit 302 of the data processing unit 3 as the analysis result of the measurement sample for DIFF prepared from blood. A sample number display area for displaying the sample number 101 is provided at the upper part of the screen 100, and an attribute display area for displaying the patient attribute is provided in the vicinity thereof. Specifically, the sample number, patient ID, patient name, sex date, gender, ward, doctor in charge, measurement date, measurement time, comment, etc. are displayed in the attribute display area. A measurement result display area for displaying the measurement result is provided at the bottom of the attribute display area. The measurement result display area consists of a plurality of pages, and these pages are displayed on the screen by being selected by the plurality of tabs 102. There are multiple tabs for the main screen, graph screen, and other measurement items. FIG. 12 is a display screen when the tab of the graph screen is selected. The left half of the measured value display area is provided with a measured value display area 103 for displaying the measured value which is the measurement result and a flag display area 104 for displaying the flag, and the distribution map 105 which is the measurement result is provided in the right half. A distribution map display area to be displayed is provided. Items such as WBC, RBC, ..., NEUT #, ..., BASO #, NEUT%, ..., BASO% are displayed in the measured value display area, and data and units are displayed in the flag display area 104. Flagging results indicating suspicion of sample abnormalities or diseases that may be useful laboratory information regarding WBC, PLT, RBC or RET are displayed.

Six distribution maps are displayed in the distribution map display area 105. The scattergram on the upper left is a scattergram for DIFF. The upper right side is for WBC / BASO, the middle left side is for youth ball (IMI), and the middle right side is for RET. The lower left side is the RBC histogram, and the lower right side is the PLT histogram.

FIG. 14 shows the screen 110 displayed on the display unit 302 of the data processing unit 3 as the measurement result of the above-mentioned measurement sample for DIFF prepared from the body fluid. A sample number display area 111 for displaying the sample number is provided at the upper part 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 the measurement was performed in the body fluid measurement mode is displayed. From this, it is possible to clearly recognize that this analysis result is the result of body fluid measurement. The measurement result display area consists of multiple pages that can be selected on tab 112. In this example, the "Body Fluid" tab is selected.

In the measurement value display area 113, WBC-BF (WBC number), RBC-BF (RBC number), MN # (monocyte number), which are measurement item names for body fluids, which are different from the measurement results in the blood measurement mode, are displayed. Number (lymphocytes + monocytes)), PMN # (multinuclear cells (neutrophils + neutrophils + eosinophils)), MN% (mononuclear cell ratio in white blood cells), PMN% (polynuclear cells in white blood cells) The sphere ratio), the measured value, and the unit are displayed in association with each other. In the body fluid measurement, the 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 the histogram for RBC.

FIG. 15 shows an example in which the Research BF (Research (BF)) tab is selected on the tab 112 on the screen 110 of FIG. This screen displays the same items as screen 110 except that the research parameter display area 116 is displayed. In the research parameter display region 116, in FIG. 10, the number of particles existing in the region HF is HF-BF #, and the number of particles existing in the region HF is relative 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 is a list display screen 120 of stored samples displayed on the display unit 302 of the data processing unit 3. 130 is the patient attribute display area. Above that, a measurement result display area for displaying the measurement result by tab selection is provided. The leftmost column 131 of the measurement result display area is for indicating that the measurement result has not been validated or completed. The value indicated by V indicates that it has been validated. The right column 132 is for indicating the measurement mode. The "F" indicates the measurement result in the body fluid measurement mode. It was a high-value sample that required a blank check in the body fluid measurement mode, but when the blank check was not performed, it can be expressed as F in reverse notation to indicate that.

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

In the present embodiment, the sample amount, the type of the reagent, and the amount of the reagent when preparing the measurement sample in the leukocyte classification measurement in the blood measurement mode and the leukocyte classification measurement in the body fluid measurement mode are the same. The configuration is described, but the present invention is not limited to this, and the amount of the sample and the amount of the reagent for preparing the measurement sample for the leukocyte classification measurement in the body fluid measurement mode are the measurement sample for the leukocyte classification measurement in the blood measurement mode. It is also possible to increase the amount of the sample and the amount of the reagent for preparing the above. 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 measurement sample required for the measurement is large. Therefore, by doing so, the leukocyte classification measurement and the body fluid measurement in the blood measurement mode are performed. It is possible to prepare an appropriate amount of measurement sample for each of the leukocyte classification measurements of the mode.

Further, in the present embodiment, the configuration for classifying leukocytes in the body fluid measurement mode using scattered light and fluorescence has been described, but the present invention is not limited to this, and for example, scattered light and absorbed light are used. It may be configured to classify leukocytes in the body fluid measurement mode. In the measurement of absorbed light, a staining reagent that stains leukocytes is mixed with other reagents to prepare a measurement sample, and the measurement sample is supplied to the flow cell to form a sample flow in the flow cell, and the sample flow is used. This is possible by irradiating light and receiving the light emitted from the sample stream with 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 measurements of absorbed light are disclosed in US Pat. No. 5122453 and US Pat. No. 5,138181. It is also possible to measure the electric resistance instead of the scattered light, and to classify and measure the leukocytes based on the electric resistance value and the absorbed light.

1 Blood cell analyzer 2 Measuring unit 3 Data processing unit 4 Detector 5 Analog signal processing unit 6 Microcomputer section 7 Display operation unit 8 Fluid processing unit