Specimen analyzer and specimen analysis method

Abstract

To provide a specimen analyzer and a specimen analysis method capable of providing test results that do not rely solely on a specific measurement principle.SOLUTION: A specimen analyzer for analyzing cells in a specimen collected from a subject comprises: a first measurement unit which measures first light information obtained when the cells pass through at least one beam spot of first illumination light; a second measurement unit which measures second light information obtained when the cells pass through an irradiation area of second illumination light in which multiple diffracted lights, generated by a diffractive optical element on which light is incident, are distributed; and a control unit 31 which generates a cell analysis result on the basis of (1) a first analysis result based on the first light information, (2) a second analysis result based on the second light information, and (3) the first analysis result and the second analysis result.SELECTED DRAWING: Figure 11

Description

[Technical Field]

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

[0002] In hematology testing, a blood cell counter is used to classify and count cells in a specimen. Patent Document 1 discloses a technology for classifying and counting cells by utilizing the principle of irradiating a flow cell with light and measuring optical information obtained when cells flowing through the flow cell pass through the beam spot of the irradiated light. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] U.S. Patent Application Publication No. 2021 / 0164885 Summary of the Invention [Problem to be solved by the invention]

[0004] In the technology disclosed in Patent Document 1, cell classification and counting results are generated by measurements based on a specific measurement principle. The accuracy of the cell classification and counting results is problematic in that it depends solely on the specific measurement principle.

[0005] In view of the above, an object of the present invention is to provide a sample analyzer and a sample analysis method that can provide test results that do not rely solely on a specific measurement principle. [Means for solving the problem]

[0006] The sample analyzer (1) of the present invention relates to a sample analyzer for analyzing cells in a sample collected from a subject. The sample analyzer (1) of the present invention includes a first measurement unit (100, 400) that measures first light information obtained when a cell passes through at least one beam spot (BS) of a first illumination light, a second measurement unit (200, 400) that measures second light information obtained when a cell passes through an irradiation range (R) of a second illumination light in which a plurality of diffracted lights generated by a diffractive optical element (215) on which the light is incident is distributed, and a control unit (31) that generates (1) a first analysis result based on the first light information, (2) a second analysis result based on the second light information, or (3) a cell analysis result based on any of the first analysis result and the second analysis result. [Effects of the Invention]

[0007] According to the present invention, it is possible to provide test results that do not depend solely on a specific measurement principle. [Brief explanation of the drawings]

[0008] [Figure 1] FIG. 1 is a front view schematically showing the configuration of a sample analyzer according to a first embodiment. [Figure 2] FIG. 2 is a block diagram showing the functional configuration of the first measurement unit according to the first embodiment. [Figure 3] FIG. 3 is a block diagram showing the functional configuration of the sample preparation section of the first measurement unit according to the first embodiment. [Figure 4] FIG. 4 is a diagram schematically showing the configuration of the optical measurement section of the first measurement unit according to the first embodiment. [Figure 5] FIG. 5 is a side view schematically showing the configuration of a flow cell of the first measurement unit according to the first embodiment. [Figure 6] FIG. 6 is a block diagram showing the functional configuration of the second measurement unit according to the first embodiment. [Figure 7] FIG. 7 is a block diagram showing the functional configuration of the sample preparation section of the second measurement unit according to the first embodiment. [Figure 8]FIG. 8 is a diagram schematically showing the configuration of the optical measurement section of the second measurement unit according to the first embodiment. [Figure 9] FIG. 9 is a diagram schematically showing a flow cell of the second measurement unit and a second illumination light according to the first embodiment. [Figure 10] FIG. 10 is a diagram schematically showing a distribution pattern of diffracted light contained in the second illumination light according to the first embodiment. [Figure 11] FIG. 11 is a block diagram illustrating a functional configuration of a control unit according to the first embodiment. [Figure 12] FIG. 12 is a diagram showing a scattergram based on the first light information and a diagram showing a schematic diagram of grouping of cell groups according to the first embodiment. [Figure 13] FIG. 13 is a schematic diagram illustrating an AI algorithm before and after training according to the first embodiment. [Figure 14] FIG. 14 is a flowchart showing a control process related to measurement by the control unit according to the first embodiment. [Figure 15] FIG. 15 is a flowchart showing the first measurement process according to the first embodiment. [Figure 16] FIG. 16 is a flowchart showing the second measurement process according to the first embodiment. [Figure 17] FIG. 17 is a diagram schematically showing the configuration of a cell analysis result screen according to the first embodiment. [Figure 18] FIG. 18 is a diagram schematically showing the configuration of the cell analysis result screen when the second measurement process is not performed according to the first embodiment. [Figure 19] FIG. 19 is a diagram schematically showing the configuration of a cell analysis result screen when the second measurement process is performed according to the first embodiment. [Figure 20] FIG. 20 is a diagram showing an example of display of an abnormal cell flag related to a white blood cell on a cell analysis result screen according to the first embodiment. [Figure 21] FIG. 21 is a flowchart showing a process for determining the flow rate per unit time of the measurement sample to be flowed through the flow cell of the second measurement unit in the second measurement process according to the first embodiment. [Figure 22] Figure 22 is a graph showing that the flow rate per unit time in the flow cell of the second measurement unit is switched in two stages depending on the blood cell concentration, and a graph showing that the flow rate per unit time in the flow cell of the second measurement unit is changed linearly depending on the blood cell concentration, according to embodiment 1. [Figure 23] FIG. 23 is a flowchart showing a control process related to measurement by the control unit according to the first modification of the first embodiment. [Figure 24] FIG. 24 is a diagram schematically showing the configuration of a cell analysis result screen when the second measurement process is performed, according to Modification 1 of Embodiment 1. In FIG. [Figure 25] FIG. 25 is a diagram schematically showing the configuration of a cell analysis result screen when the second measurement process is performed, according to Modification 1 of Embodiment 1. In FIG. [Figure 26] FIG. 26 is a flowchart showing a control process related to measurement by the control unit according to the second modification of the first embodiment. [Figure 27] FIG. 27 is a diagram schematically showing the configuration of a cell analysis result screen when the second measurement process is performed, according to Modification 2 of Embodiment 1. In FIG. [Figure 28] FIG. 28 is a front view schematically showing the configuration of a sample analyzer according to the second embodiment. [Figure 29] FIG. 29 is a block diagram showing the functional configuration of the third measurement unit according to the second embodiment. [Figure 30] FIG. 30 is a block diagram showing the functional configuration of the sample preparation section of the third measurement unit according to the second embodiment. [Figure 31] FIG. 31 is a diagram schematically showing the configuration of an optical measurement section of a third measurement unit according to the second embodiment. [Figure 32] FIG. 32 is a flowchart showing a control process related to measurement by the control unit according to the second embodiment. [Figure 33] FIG. 33 is a flowchart showing a control process related to measurement by the control unit according to the first modification of the second embodiment. [Figure 34]FIG. 34 is a block diagram showing the functional configuration of the sample preparation section of the third measurement unit according to the second modification of the second embodiment. [Figure 35] FIG. 35 is a diagram schematically showing a procedure for generating a reconstructed image according to the third embodiment. [Figure 36] FIG. 36 is a diagram schematically showing the configuration of a reconstructed image display screen that displays a reconstructed image according to the third embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0009] The sample analyzer 1 shown in the following embodiment includes a first measurement unit and a second measurement unit that use different measurement principles for measuring samples. Therefore, the sample analyzer 1 can provide test results that do not rely solely on one measurement principle (e.g., test results that provide classification and counting of cells in a sample). For example, cell types that are difficult to classify using the measurement principle of the first measurement unit can be classified using the measurement principle of the second measurement unit, improving the accuracy of the test results provided by the sample analyzer 1.

[0010] <Embodiment 1> FIG. 1 is a front view showing a schematic configuration of a sample analyzer 1. As shown in FIG.

[0011] The sample analyzer 1 includes a first measurement unit 10, a second measurement unit 20, a control unit 30, and a transport unit 40.

[0012] The sample analyzer 1 is an apparatus that automatically analyzes samples. The sample is blood collected from a subject. A sample container 51 containing the sample is transported while being held in a sample rack 50.

[0013] The laboratory technician, who is the operator of the sample analyzer 1, places sample containers 51 containing samples in the sample rack 50 and places the sample rack 50 in the right end area of ​​the transport unit 40. The transport unit 40 transports the sample rack 50 and positions it in front of the first measurement unit 10 and the second measurement unit 20 as appropriate.

[0014] The first measurement unit 10 removes a sample container 51 from the sample rack 50, transfers it into the first measurement unit 10, and measures the sample in the sample container 51. When measurement of the sample in the sample container 51 is complete, the first measurement unit 10 returns the sample container 51 to its original position in the sample rack 50. Similarly, the second measurement unit 20 removes a sample container 51 from the sample rack 50, transfers it into the second measurement unit 20, and measures the sample in the sample container 51. When measurement of the sample in the sample container 51 is complete, the second measurement unit 20 returns the sample container 51 to its original position in the sample rack 50. When the required measurements for all sample containers 51 on one sample rack 50 have been completed, the transport unit 40 transports the sample rack 50 to the left end area of ​​the transport unit 40. The laboratory technician removes the sample rack 50 that has been transported to the left end area.

[0015] The first measurement unit 10 and the second measurement unit 20 can measure samples transported on the transport unit 40. The transport unit 40 can automatically supply sample racks 50 containing samples to the first measurement unit 10 and the second measurement unit 20. Because samples can be automatically supplied to the first measurement unit 10 and the second measurement unit 20 via the transport unit 40, the labor of a laboratory technician required to transport samples between the first measurement unit 10 and the second measurement unit 20 can be reduced.

[0016] The control unit 30 controls the first measurement unit 10, the second measurement unit 20, and the transport unit 40. The control unit 30 analyzes the measurement information obtained by the first measurement unit 10 and the second measurement unit 20.

[0017] FIG. 2 is a block diagram showing the functional configuration of the first measurement unit 10. As shown in FIG.

[0018] The first measurement unit 10 includes a measurement control unit 11 , a storage unit 12 , a communication unit 13 , a reading unit 14 , a sample preparation unit 15 , and a measurement unit 16 .

[0019] The measurement control unit 11 is configured with, for example, an FPGA or a CPU. The storage unit 12 is configured with, for example, an HDD, an SSD, a RAM, a ROM, etc. The measurement control unit 11 performs various processes based on programs stored in the storage unit 12 and controls each part of the first measurement unit 10. The communication unit 13 is configured with, for example, a connection terminal based on the USB standard, and communicates with the control unit 30.

[0020] The reading unit 14 is configured by, for example, a barcode reader. The reading unit 14 reads the barcode from the barcode label attached to the sample container 51 and acquires the sample ID. The sample preparation unit 15 aspirates the sample from the sample container 51 and mixes the aspirated sample with a reagent to prepare a measurement sample.

[0021] The measurement unit 16 includes an electrical measurement unit 16a, an HGB (hemoglobin) detection unit 16b, and an optical measurement unit 100. The electrical measurement unit 16a measures cells (blood cells) in the specimen using a sheath flow DC detection method. The HGB measurement unit 16b measures hemoglobin in the cells (blood cells) in the specimen using an SLS-hemoglobin method. The optical measurement unit 100 measures cells (blood cells) in the specimen using a flow cytometry method.

[0022] The electrical measurement unit 16a and the HGB measurement unit 16b are equipped with amplifiers and A / D converters, perform signal processing on detection signals acquired by measurement, and output the measurement information after signal processing to the measurement control unit 11. The optical measurement unit 100 is equipped with an amplifier and A / D converter, performs signal processing on detection signals acquired by measurement, and outputs the measurement information after signal processing (hereinafter referred to as "first optical information") to the measurement control unit 11. The measurement control unit 11 stores the measurement information and first optical information output from the measurement unit 16 in the memory unit 12. When the measurement of one sample is completed, the measurement control unit 11 associates the measurement information and first optical information stored in the memory unit 12 with the sample ID read by the reading unit 14 and transmits them to the control unit 30.

[0023] FIG. 3 is a block diagram showing the functional configuration of the sample preparation unit 15 for preparing a measurement sample.

[0024] The sample preparation section 15 includes a stirring section 15a, an aspirating tube 15b, and reaction chambers C11, C12, and C21 to C24.

[0025] The agitator 15a is configured to grip a specimen container 51 and to rock the gripped specimen container 51 to agitate the specimen inside the specimen container 51. The suction tube 15b is a nozzle with a pointed bottom end, and is configured to be able to penetrate a lid of the specimen container 51, which is made of an elastic material. The suction tube 15b aspirates the specimen from the specimen container 51 after stirring, and dispenses the aspirated specimen into reaction chambers C11, C12, C21 to C24 as appropriate.

[0026] In the reaction chamber C11, the specimen and the RBC / PLT diluent are mixed to prepare an RBC / PLT measurement sample. The RBC / PLT diluent is, for example, CellPack (registered trademark) DCL. The RBC / PLT measurement sample prepared in the reaction chamber C11 is measured by the electrical measurement unit 16a. The electrical measurement unit 16a acquires detection signals corresponding to blood cells in the RBC / PLT measurement sample and performs signal processing on the acquired detection signals to obtain measurement information. The control unit 31 of the control unit 30 (see FIG. 11) analyzes the measurement information obtained by measuring the RBC / PLT measurement sample to obtain the red blood cell count, platelet count, etc.

[0027] In reaction chamber C12, the specimen, HGB hemolyzing agent, and HGB diluent are mixed to prepare an HGB measurement sample. The HGB hemolyzing agent is, for example, Sulfolyzer (registered trademark), and the HGB diluent is, for example, CellPack (registered trademark) DCL. The HGB measurement sample prepared in reaction chamber C12 is measured by HGB measurement unit 16b. HGB measurement unit 16b acquires a detection signal corresponding to the hemoglobin concentration and performs signal processing on the acquired detection signal to acquire measurement information. Control unit 31 of control unit 30 analyzes the measurement information acquired by measuring the HGB measurement sample to acquire the hemoglobin concentration, etc.

[0028] In the reaction chamber C21, a specimen, a WDF hemolyzing agent, and a WDF staining solution are mixed to prepare a WDF measurement sample. The WDF hemolyzing agent is, for example, LyserCell (registered trademark) WDF II, and the WDF staining solution is, for example, FluoroCell (registered trademark) WDF. The WDF measurement sample prepared in the reaction chamber C21 is measured by the optical measurement unit 100. The optical measurement unit 100 acquires detection signals corresponding to blood cells in the WDF measurement sample and performs signal processing on the acquired detection signals to acquire first optical information. The control unit 31 of the control unit 30 analyzes the first optical information obtained by measuring the WDF measurement sample and the first optical information obtained by measuring the WNR measurement sample (described later) to classify the blood cells into neutrophils, normal lymphocytes, monocytes, eosinophils, basophils, blasts, abnormal lymphocytes, atypical lymphocytes, immature granulocytes, nucleated red blood cells, etc., and acquires the number of each blood cell.

[0029] In this case, the first light information includes time series data of side scattered light corresponding to each cell, which indicates the change in intensity of side scattered light received by the light receiving unit 133 while each cell in the WDF measurement sample flowing through the flow cell 101 (see FIG. 4) passes through the beam spot BS, and time series data of fluorescence corresponding to each cell, which indicates the change in intensity of fluorescence received by the light receiving unit 143 while each cell in the WDF measurement sample flowing through the flow cell 101 passes through the beam spot BS. The control unit 31 of the control unit 30 obtains the peak values ​​of the side scattered light and fluorescence corresponding to each cell from the time series data of side scattered light and the time series data of fluorescence, and generates a scattergram (see FIG. 12), which will be described later.

[0030] In reaction chamber C22, a specimen, a WNR hemolyzing agent, and a WNR staining solution are mixed to prepare a WNR measurement sample. The WNR hemolyzing agent is, for example, LyserCell (registered trademark) WNR, and the WNR staining solution is, for example, FluoroCell (registered trademark) WNR. The WNR measurement sample prepared in reaction chamber C22 is measured by optical measurement unit 100. Optical measurement unit 100 acquires detection signals corresponding to blood cells in the WNR measurement sample and performs signal processing on the acquired detection signals to acquire first optical information. Control unit 31 of control unit 30 analyzes the first optical information acquired by measurement of the WNR measurement sample, classifies white blood cells, nucleated red blood cells, etc., and acquires the number of each blood cell.

[0031] In this case, the first light information includes time series data of forward scattered light corresponding to each cell, which indicates the change in intensity of forward scattered light received by the light receiving unit 124 while each cell in the WNR measurement sample flowing through the flow cell 101 (see FIG. 4) passes through the beam spot BS, and time series data of fluorescence corresponding to each cell, which indicates the change in intensity of fluorescence received by the light receiving unit 143 while each cell in the WNR measurement sample flowing through the flow cell 101 passes through the beam spot BS. The control unit 31 of the control unit 30 obtains the peak values ​​of the forward scattered light and fluorescence corresponding to each cell from the time series data of forward scattered light and the time series data of fluorescence, and generates a scattergram (see FIG. 12), which will be described later.

[0032] In reaction chamber C23, the specimen, RET diluent, and RET staining solution are mixed to prepare a RET measurement sample. The RET diluent is, for example, CellPack (registered trademark) DFL, and the RET staining solution is, for example, FluoroCel (registered trademark) RET. The RET measurement sample prepared in reaction chamber C23 is measured by optical measurement unit 100. Optical measurement unit 100 acquires detection signals corresponding to blood cells in the RET measurement sample and performs signal processing on the acquired detection signals to acquire first optical information. Control unit 31 of control unit 30 analyzes the first optical information acquired by measurement of the RET measurement sample, classifies reticulocytes and the like, and acquires the number of each blood cell.

[0033] In this case, the first light information includes time series data of forward scattered light corresponding to each cell, which indicates changes in the intensity of forward scattered light received by the light receiving unit 124 while each cell in the RET measurement sample flowing through the flow cell 101 (see FIG. 4) passes through the beam spot BS, and time series data of fluorescence corresponding to each cell, which indicates changes in the intensity of fluorescence received by the light receiving unit 143 while each cell in the RET measurement sample flowing through the flow cell 101 passes through the beam spot BS. The control unit 31 of the control unit 30 obtains peak values ​​of the forward scattered light and fluorescence corresponding to each cell from the time series data of forward scattered light and the time series data of fluorescence, and generates a scattergram (see FIG. 12), which will be described later.

[0034] In reaction chamber C24, the specimen, PLT-F dilution solution, and PLT-F staining solution are mixed to prepare a PLT-F measurement sample. The PLT-F dilution solution is, for example, CellPack (registered trademark) DFL, and the PLT-F staining solution is, for example, FluoroCel (registered trademark) PLT. The PLT-F measurement sample prepared in reaction chamber C24 is measured by optical measurement unit 100. Optical measurement unit 100 acquires detection signals corresponding to blood cells in the PLT-F measurement sample and performs signal processing on the acquired detection signals to acquire first optical information. Control unit 31 of control unit 30 analyzes the first optical information obtained by measurement of the PLT-F measurement sample, classifies blood cells, etc., and acquires the number of each blood cell.

[0035] In this case, the first light information includes time series data of forward scattered light corresponding to each cell, which indicates changes in the intensity of forward scattered light received by light receiving unit 124 while each cell in the PLT-F measurement sample flowing through flow cell 101 (see FIG. 4) passes through beam spot BS, and time series data of fluorescence corresponding to each cell, which indicates changes in the intensity of fluorescence received by light receiving unit 143 while each cell in the PLT-F measurement sample flowing through flow cell 101 passes through beam spot BS. Control unit 31 of control unit 30 obtains peak values ​​of forward scattered light and fluorescence corresponding to each cell from the time series data of forward scattered light and the time series data of fluorescence, and generates a scattergram (see FIG. 12), which will be described later.

[0036] The first light information is not limited to the peak value, and may be any information reflecting the size, shape, internal structure, or nucleic acid content of each cell obtained by irradiating each cell in the measurement sample with at least one light having a single beam spot. Furthermore, the diluent, hemolytic agent, and staining solution mixed in the reaction chambers C11, C12, and C21 to C24 are not limited to the reagents described above.

[0037] Fig. 4 is a diagram schematically showing the configuration of the optical measurement unit 100. For convenience, mutually orthogonal X, Y, and Z axes are indicated in Fig. 4. The Z axis direction is the flow direction of the measurement sample in the flow cell 101.

[0038] The optical measurement unit 100 includes a flow cell 101, a light source 111, a collimator lens 112, a cylindrical lens 113, a condenser lens 114, condenser lenses 121 and 131, a beam stopper 122, optical filters 123, 132 and 142, light receiving units 124, 133 and 143, and a dichroic mirror 141.

[0039] The light source 111 is, for example, a semiconductor laser light source. The light source 111 emits light of a predetermined wavelength λ10 in the X-axis direction. The wavelength λ10 is, for example, 488 nm or 642 nm. The collimator lens 112 converts the light emitted from the light source 111 into parallel light. The cylindrical lens 113 converges the light from the light source 111 in the Y-axis direction. The condenser lens 114 converges the light from the light source 111 in the Y-axis and Z-axis directions, flattens the light at the position of the flow cell 101, and condenses the light into the flow channel 101a of the flow cell 101.

[0040] FIG. 5 is a side view schematically showing the configuration of the flow cell 101. As shown in FIG.

[0041] Light from the light source 111 is irradiated onto the irradiation position of the flow channel 101a of the flow cell 101 as a single beam spot BS with a flat shape having a small width in the Z-axis direction by the action of the cylindrical lens 113 and the condenser lens 114. Hereinafter, the light emitted from the light source 111 and irradiated onto the irradiation position of the flow channel 101a will be referred to as "first illumination light." When the first illumination light is irradiated onto cells flowing through the flow channel 101a, forward scattered light, side scattered light, and fluorescence are generated from the site of the cells irradiated with the light. Here, it is assumed that when the first illumination light with wavelength λ10 is irradiated onto a fluorescent dye that stains cells, light with wavelength λ11 is generated from the fluorescent dye.

[0042] Returning to FIG. 4, the condenser lens 121 condenses the forward scattered light of wavelength λ10 generated from the cells onto the light receiving unit 124. The beam stopper 122 blocks the light of wavelength λ10 that has passed through the flow cell 101 without irradiating the cells, and passes the forward scattered light of wavelength λ10 generated from the cells. The optical filter 123 is configured to transmit only the light of wavelength λ10. The light receiving unit 124 receives the forward scattered light of wavelength λ10 that has passed through the optical filter 123, and outputs a detection signal according to the intensity of the received light. The light receiving unit 124 is, for example, a photodiode (PD).

[0043] The condenser lens 131 condenses side scattered light of wavelength λ10 generated from the cells onto the light receiving unit 133, and condenses fluorescence of wavelength λ11 generated from the cells onto the light receiving unit 143. The dichroic mirror 141 transmits light of wavelength λ10 and reflects light of wavelength λ11. The optical filter 132 is configured to transmit only light of wavelength λ10 from the dichroic mirror 141. The light receiving unit 133 receives the side scattered light of wavelength λ10 that has transmitted through the optical filter 132, and outputs a detection signal according to the intensity of the received light. The light receiving unit 133 is, for example, a photodiode (PD).

[0044] The optical filter 142 is configured to transmit only the light of wavelength λ11 from the dichroic mirror 141. The light receiving unit 143 receives the fluorescence of wavelength λ11 that has transmitted through the optical filter 142, and outputs a detection signal according to the intensity of the received light. The light receiving unit 143 is, for example, a photomultiplier tube (PMT), an avalanche photodiode (APD), or a photodiode (PD).

[0045] FIG. 6 is a block diagram showing the functional configuration of the second measurement unit 20. As shown in FIG.

[0046] The second measurement unit 20 includes a measurement control section 21, a storage section 22, a communication section 23, a reading section 24, a sample preparation section 25, and a measurement section 26.

[0047] The measurement control unit 21 is configured, for example, by an FPGA or a CPU. The storage unit 22 is configured, for example, by an HDD, SSD, RAM, ROM, etc. The measurement control unit 21 performs various processes based on programs stored in the storage unit 22 and controls each part of the second measurement unit 20. The communication unit 23 is configured, for example, by a connection terminal based on the USB standard, and communicates with the control unit 30.

[0048] The reading unit 24 is configured by, for example, a barcode reader. The reading unit 24 reads the barcode from the barcode label attached to the sample container 51 and acquires the sample ID. The sample preparation unit 25 aspirates the sample from the sample container 51 and mixes the aspirated sample with a reagent to prepare a measurement sample.

[0049] The measurement unit 26 includes an optical measurement unit 200, and the optical measurement unit 200 includes a fluid adjustment unit 2200a.

[0050] The fluid adjusting unit 200a includes a container for storing sheath liquid, a syringe for transferring the measurement sample, and an air pressure source (pump) for transferring the sheath liquid. The fluid adjusting unit 200a supplies the sheath liquid together with the measurement sample prepared in the sample preparing unit 25 to a flow cell 201 (see FIG. 8) of the optical measurement unit 200, and adjusts the flow rate of the measurement sample flowing through the flow cell 201 per unit time (hereinafter referred to as the flow rate per unit time). The optical measurement unit 200 measures the measurement sample supplied to the flow cell 201.

[0051] The optical measurement section 200 includes an amplifier and an A / D converter, performs signal processing on the detection signal acquired by measurement, and outputs the measurement information after signal processing (hereinafter referred to as "second optical information") to the measurement control section 21. The measurement control section 21 stores the second optical information output from the measurement section 26 in the memory section 22. When the measurement of one sample is completed, the measurement control section 21 transmits the second optical information stored in the memory section 22 to the control unit 30 in association with the sample ID read by the reading section 24.

[0052] FIG. 7 is a block diagram showing the functional configuration of the sample preparation unit 25 for preparing a measurement sample.

[0053] The sample preparation section 25 includes a stirring section 25a, a suction tube 25b, and a reaction chamber C30.

[0054] The stirring unit 25a is configured to grip the specimen container 51 and to rock the gripped specimen container 51 to stir the specimen inside the specimen container 51. The suction tube 25b is a nozzle with a pointed bottom end, and is configured to be able to penetrate the lid of the specimen container 51, which is made of an elastic material. The suction tube 25b aspirates the specimen from the specimen container 51 after stirring, and dispenses the aspirated specimen into the reaction chamber C30.

[0055] In the reaction chamber C30, a specimen, a hemolyzing agent for hemolyzing red blood cells, and a staining solution containing a fluorescent dye for staining a specific portion of the cells are mixed to prepare a measurement sample. The hemolyzing agent mixed in the reaction chamber C30 is, for example, a WDF hemolyzing agent. The staining solution mixed in the reaction chamber C30 is, for example, a WDF staining solution. The measurement sample prepared in the reaction chamber C30 is measured by the optical measurement unit 200. The optical measurement unit 200 acquires detection signals corresponding to the blood cells in the measurement sample and performs signal processing on the acquired detection signals to acquire second optical information. The control unit 31 and calculation unit 32 of the control unit 30 analyze the second optical information obtained by measuring the measurement sample and classify the blood cells into neutrophils, normal lymphocytes, monocytes, eosinophils, basophils, blasts, abnormal lymphocytes, atypical lymphocytes, immature granulocytes, nucleated red blood cells, etc., to acquire the number of each blood cell.

[0056] In this case, the second light information includes time series data of forward scattered light corresponding to each cell, which indicates the change in intensity of forward scattered light received by light receiving unit 225 while each cell in the measurement sample flowing through flow cell 201 (see FIGS. 8 and 9) passes through irradiation range R of the second illumination light, time series data of side scattered light corresponding to each cell, which indicates the change in intensity of side scattered light received by light receiving unit 233 while each cell in the measurement sample flowing through flow cell 201 passes through irradiation range R of the second illumination light, and time series data of fluorescence corresponding to each cell, which indicates the change in intensity of fluorescence received by light receiving unit 243 while each cell in the measurement sample flowing through flow cell 201 passes through irradiation range R of the second illumination light. As will be described later, control unit 31 and calculation unit 32 of control unit 30 input the time series data of forward scattered light, side scattered light, and fluorescence to trained AI algorithm 62 (see FIG. 13) for analysis.

[0057] The second optical information may be information reflecting the size, shape, internal structure, or nucleic acid content of each cell, obtained by irradiating each cell in the measurement sample with light in which multiple diffracted light beams generated by the diffractive optical element 215 incident on the light, and is not limited to the time-series data. The hemolytic agent and staining solution mixed in the reaction chamber C30 are not limited to the reagents. The staining solution may not be mixed in the reaction chamber C30, or a diluting solution may be mixed instead of the staining solution. In this case, the fluorescence collecting optical system 205 and the light receiving unit 243, which will be described later with reference to FIG. 8, are omitted.

[0058] Fig. 8 is a diagram schematically showing the configuration of the optical measurement unit 200. For convenience, mutually orthogonal X, Y, and Z axes are indicated in Fig. 8. The Z axis direction is the flow direction of the measurement sample in the flow cell 201.

[0059] The optical measurement unit 200 includes a flow cell 201, a light source 211, an irradiation optical system 202, a forward light collecting optical system 203, a side light collecting optical system 204, a fluorescence collecting optical system 205, and light receiving units 225, 233, and 243.

[0060] The illumination optical system 202 includes a collimator lens 212, cylindrical lenses 213 and 214, a diffractive optical element (DOE) 215, and a condenser lens 216. The illumination optical system 202 irradiates the flow path 201a of the flow cell 201 with light from a light source 211. Hereinafter, the light emitted from the light source 211 and irradiated onto the flow path 201a will be referred to as "second illumination light." The second illumination light is light in which a plurality of diffracted lights generated by the diffractive optical element 215 are distributed. More specifically, the second illumination light is light having a structured illumination pattern.

[0061] The forward light collecting optical system 203 includes a collecting lens 221, a beam stopper 222, a collecting lens 223, and an optical filter 224. The forward light collecting optical system 203 collects forward scattered light generated from blood cells onto a light receiving unit 225, and blocks the second illumination light that passed through the flow cell 201 without being irradiated onto the blood cells. The side light collecting optical system 204 includes a collecting lens 231 and an optical filter 232. The side light collecting optical system 204 collects side scattered light generated from blood cells onto a light receiving unit 233. The fluorescence collecting optical system 205 includes a collecting lens 241 and an optical filter 242. The fluorescence collecting optical system 205 collects fluorescence generated from blood cells onto a light receiving unit 243.

[0062] Light source 211 is, for example, a semiconductor laser light source. Light source 211 emits light of a predetermined wavelength λ20 in the X-axis direction. Wavelength λ20 is, for example, 405 nm. The fast axis direction and slow axis direction of light source 211 are parallel to the Y-axis direction and the Z-axis direction, respectively. Collimator lens 212 converts the light emitted from light source 211 into parallel light.

[0063] Cylindrical lens 213 is a concave cylindrical lens, and cylindrical lens 214 is a convex cylindrical lens. Cylindrical lens 213 increases the width in the Z-axis direction without changing the width in the Y-axis direction of the light emitted from light source 211, forming a substantially perfect circle, which is then incident on cylindrical lens 214. Cylindrical lens 214 converts the light emitted from light source 211 into parallel light.

[0064] The collimator lens 212 and the cylindrical lenses 213 and 214 are arranged so that the light emitted from the light source 211 and transmitted through the collimator lens 212 and the cylindrical lenses 213 and 214 has an approximately perfect circle shape when viewed in the X-axis direction. As a result, the light incident on the diffractive optical element 215 has an approximately perfect circle shape.

[0065] The light source 211, the collimator lens 212, and the cylindrical lenses 213 and 214 may have any other configuration as long as the light incident on the diffractive optical element 215 has a substantially circular shape. For example, the light source 211, the collimator lens 212, and the cylindrical lenses 213 and 214 may each be rotated 90 degrees about the X-axis direction. In this case, the fast axis direction and the slow axis direction of the light source 211 are parallel to the Z-axis direction and the Y-axis direction, respectively. Alternatively, a light source that irradiates light with a substantially circular shape may be used as the light source 211, and the collimator lens 212 and the cylindrical lenses 213 and 214 may be omitted.

[0066] The diffractive optical element 215 has a complex uneven diffraction pattern formed by grooves, inclinations, and the like to diffract incident light. The diffractive optical element 215 can be manufactured, for example, based on the description in U.S. Pat. No. 9,477,018, which is incorporated herein by reference. The diffractive optical element 215 diffracts light incident in the X-axis direction from the cylindrical lens 214 along the X-axis, generating multiple diffracted beams traveling in different directions. The multiple diffracted beams are obtained by splitting the incident light. The multiple diffracted beams have different diffraction orders. The condenser lens 216 condenses the multiple diffracted beams generated by the diffractive optical element 215 onto the flow cell 201. The multiple diffracted beams traveling in different directions generated by the diffractive optical element 215 are condensed onto the flow cell 201 to form the second illumination light.

[0067] A measurement sample prepared in reaction chamber C30 of Fig. 7 is passed through flow cell 201. Cells in the measurement sample flowing through flow cell 201 are irradiated with the second illumination light, and forward scattered light, side scattered light, and fluorescence are generated from the portions of the cells irradiated with the respective diffracted lights in the second illumination light. Forward scattered light is generated in the X-axis direction, and side scattered light and fluorescence are generated in a direction intersecting the X-axis direction (for example, the Y-axis direction).

[0068] The condenser lens 221 converges the forward scattered light generated from the cells and the second illumination light that has passed through the flow cell 201 without being irradiated onto the cells. The beam stopper 222 passes the forward scattered light generated from the cells and blocks the second illumination light that has passed through the flow cell 201. The condenser lens 223 collects the forward scattered light that has passed through the beam stopper 222 onto the light receiving unit 225. The optical filter 224 is configured to transmit only light of wavelength λ20. The light receiving unit 225 receives the forward scattered light that has passed through the optical filter 224 and outputs a detection signal according to the intensity of the received light. The light receiving unit 225 is a photomultiplier tube (PMT).

[0069] The condenser lens 231 condenses the side scattered light generated from the cells onto the light receiving unit 233. The optical filter 232 is configured to transmit only light of wavelength λ20. The light receiving unit 233 receives the side scattered light that has passed through the optical filter 232 and outputs a detection signal according to the intensity of the received light. The light receiving unit 233 is a photomultiplier tube (PMT).

[0070] The condensing lens 241 condenses the fluorescence emitted from the cells onto the light receiving unit 243. The optical filter 242 is configured to transmit only light of wavelength λ21. The light receiving unit 243 receives the fluorescence that has passed through the optical filter 242 and outputs a detection signal according to the intensity of the received light. The light receiving unit 243 is a photomultiplier tube (PMT). The light receiving units 225, 233, and 243 are not limited to photomultiplier tubes (PMT) and may be, for example, photodiodes (PD).

[0071] 9 is a diagram schematically showing the flow cell 201 and the second illumination light, and in FIG. 9, the X, Y, and Z axes are indicated in the same manner as in FIG.

[0072] A flow channel 201a, through which the measurement sample flows, is formed parallel to the Z axis inside the flow cell 201. By flowing a sheath fluid together with the measurement sample through the flow channel 201a, cells contained in the measurement sample are enveloped in the sheath fluid and pass through a central region CE of the flow channel 201a. The second illumination light condensed by the condenser lens 216 is irradiated onto a predetermined irradiation range R located in the central region CE of the flow channel 201a. The flow rate of the measurement sample per unit time is adjusted so that only one cell is positioned in the irradiation range R at a time, in other words, so that two or more cells do not pass through the irradiation range R simultaneously.

[0073] Because the flow rate is adjusted in this manner, the throughput of measurement by the second measurement unit 20 may be lower than the throughput of measurement by the first measurement unit 10. Furthermore, the control unit 31 can control the operation of the second measurement unit 20 in accordance with the above-mentioned flow rate adjustment so that the number of cells measured by the second measurement unit 20 is smaller than the number of cells measured by the first measurement unit 10.

[0074] The bottom part of FIG. 9 illustrates an image obtained by irradiating a darkroom with the second illumination light generated by the diffractive optical element 215 and capturing an image with a camera. In the image of the second illumination light in FIG. 9, black areas indicate areas that do not contain light, and white dots indicate areas that contain light. The white dots in the image of the second illumination light represent diffracted light generated by the diffractive optical element 215. In the example shown in FIG. 9, the diffracted light includes 0th-order diffracted light, +1st to +300th-order diffracted light, and −1st to −300th-order diffracted light, and are displayed as a total of 601 white dots in the image of the second illumination light. A diffraction pattern (steps or grooves) or the like is formed on the diffractive optical element 215 so that the diffracted light is distributed as shown in the image of the second illumination light.

[0075] FIG. 10 is a diagram schematically showing a distribution pattern of the diffracted light contained in the second illumination light.

[0076] FIG. 10 shows an image in which the illumination range R (see FIG. 9) is divided into a grid pattern using multiple squares with sides the same length as the diameter of the diffracted light spot. The black squares indicate areas that contain the diffracted light spot. The white squares indicate areas that do not contain the diffracted light spot. In FIG. 10, cells passing through the illumination range R are shown as dashed circles. The diameter of the diffracted light spot contained in the image of the second illumination light shown in FIG. 10 is approximately 1 μm, so in this case, the size of each square is 1 μm × 1 μm. The size of a cell is approximately 10 μm.

[0077] The size of the second illumination light in the illumination range R and its length in the Y-axis direction or Z-axis direction can be expressed in terms of the number of pixels, assuming that each grid-like region is one pixel. In the example shown in Fig. 10, the length of the second illumination light in the flow direction (Z-axis direction) of the measurement sample is px1 (pixels), the length of the second illumination light in the short direction (Y-axis direction) is px2 (pixels), and the size of the second illumination light is px1 × px2 (pixels).

[0078] The diffractive optical element 215 is designed so that the multiple diffracted light beams constituting the second illumination light are distributed in a predetermined pattern. Here, the predetermined pattern is a random pattern. Note that the pattern may not have any specific pattern repetition at all, or may have a periodic pattern where a specific pattern repeats. However, it is preferable that at least one diffracted light beam is arranged in an area extending in the Z-axis direction and having a length of one pixel in the Y-axis direction, so that the entire cell site is exposed to the second illumination light at least once.

[0079] During measurement, when a measurement sample is flowed through flow path 201a of flow cell 201, cells in the measurement sample move in the Z-axis direction within the illumination range R of the second illumination light. At this time, the flow rate per unit time is adjusted by fluid adjustment unit 200a (see FIG. 6) to be approximately constant. When diffracted light contained in the second illumination light is irradiated onto cells flowing in the Z-axis direction, forward scattered light and side scattered light are generated from the portion of the cells irradiated with the diffracted light. Furthermore, when diffracted light is irradiated onto cells stained with a fluorescent dye, fluorescence is generated from the fluorescent dye irradiated with the diffracted light. Light receiving unit 225 (see FIG. 8) receives forward scattered light generated by the multiple diffracted light beams irradiated onto the cells. Light receiving unit 233 (see FIG. 8) receives side scattered light generated by the multiple diffracted light beams irradiated onto the position of the cells. Light receiving unit 243 (see FIG. 8) receives fluorescence generated by the multiple diffracted light beams irradiated onto a predetermined position of the stained cells.

[0080] As the cells flow in the Z-axis direction, the number of diffracted light beams irradiating the cells changes, and the parts of the cells that are hit by each diffracted light beam change, causing the intensities of forward scattered light, side scattered light, and fluorescence emitted from the cells to change over time. Therefore, the detection signals of the light-receiving units 225, 233, and 243 also change over time. As will be described later, the calculation unit 32 (see FIG. 11) classifies the cells using an AI algorithm 62 (see FIG. 13) based on the second light information acquired from these detection signals.

[0081] FIG. 11 is a block diagram showing the functional configuration of the control unit 30. As shown in FIG.

[0082] The control unit 30 includes a control unit 31, a calculation unit 32, a storage unit 33, a display unit , an input unit 35, and a communication unit .

[0083] The control unit 31 is configured by, for example, a CPU. The calculation unit 32 is configured by, for example, a GPU. The storage unit 33 is configured by, for example, an HDD, an SSD, a RAM, a ROM, etc. The control unit 31 executes programs stored in the storage unit 33 to control each part of the control unit 30 and analyzes cells based on the measurement information acquired by the first measurement unit 10 and the second measurement unit 20.

[0084] The control unit 31 analyzes the measurement information acquired by the electrical measurement unit 16a and the HGB measurement unit 16b of the first measurement unit 10 and the first optical information acquired by the optical measurement unit 100 of the first measurement unit 10 to acquire a first analysis result. At this time, the control unit 31 generates a scattergram for each sample based on the first optical information, and classifies the cells based on the generated scattergram.

[0085] 12 based on the first light information obtained by measuring the WDF measurement sample, and groups a plurality of cell groups corresponding to the plots on the generated scattergram. In grouping the cell groups, for example, the control unit 31 calculates the center of gravity of the plots in a predetermined region on the scattergram, and performs cluster analysis on the cell groups based on the distance from each plot to the center of gravity, thereby classifying each cell.

[0086] By grouping the cell populations, as illustrated in the lower part of Figure 12, a region A11 corresponding to normal lymphocytes, a region A12 corresponding to monocytes, a region A13 corresponding to neutrophils and basophils, and a region A14 corresponding to eosinophils are set. In addition, if the measurement sample contains blast cells, abnormal lymphocytes, atypical lymphocytes, immature granulocytes, or nucleated red blood cells, regions corresponding to these blood cells are also set. The control unit 31 counts the plots within the regions set in the scattergram to obtain the number of blood cells for each classification.

[0087] It should be noted that the control unit 31 does not necessarily have to actually generate a scattergram and perform grouping of cell groups, but may instead perform grouping based on cell groups by processing data corresponding to a scattergram, for example.

[0088] Furthermore, the control unit 31 causes the calculation unit 32 to perform analysis using an AI algorithm 62 (see FIG. 13), analyzes the second optical information acquired by the optical measurement unit 200 of the second measurement unit 20, and acquires a second analysis result. The AI ​​algorithm 62 in this case is, for example, a deep learning algorithm.

[0089] The display unit 34 is configured, for example, by a liquid crystal display. The input unit 35 is configured by a pointing device including a keyboard, a mouse, and a touch panel. The liquid crystal display of the display unit 34 and the touch panel of the input unit 35 may be configured integrally. The communication unit 36 ​​is configured, for example, by a connection terminal based on the USB standard, and communicates with the first measurement unit 10, the second measurement unit 20, and the transport unit 40.

[0090] FIG. 13 is a schematic diagram showing an AI algorithm 61 before training and an AI algorithm 62 after training.

[0091] To train the AI ​​algorithm 61, a light source is added to the optical measurement unit 200 shown in Figure 8, which irradiates the measurement sample flowing through the flow cell 201 with light that excites fluorescence. In addition, each cell contained in the measurement sample is labeled with a fluorescent dye (e.g., an antibody to which a fluorescent dye has been attached) that binds to a cell surface marker (e.g., an antigen) and whose fluorescence is excited by the light from the light source. The fluorescence excited by the light from the light source is received by the light receiving unit 243.

[0092] As shown in the upper part of Fig. 13, the second training optical information used to train the pre-training AI algorithm 61 is, for example, information obtained by measuring specific cells using the second measurement unit 20. In addition, the type of each cell flowing through the flow cell 201 is determined based on the fluorescence received by the light receiving unit 243, and the determined cell type ("cell A" in the example in the upper part of Fig. 13) is associated with the second training optical information. Note that when multiple types of cell surface markers need to be detected, the optical measurement unit 200 may be provided with multiple light receiving units corresponding to each of the multiple types of cell surface markers.

[0093] The AI ​​algorithm 61 is configured by a neural network including multiple intermediate layers. In this case, the neural network is, for example, a convolutional neural network having a convolutional layer. The AI ​​algorithm 61 has an input layer 61a, an output layer 61b, and an intermediate layer 61c. A data group of the second optical information obtained by sampling an analog detection signal obtained from one cell at a predetermined sampling period is input to the input layer 61a, and a label value corresponding to the type of cell is input to the output layer 61b, thereby training the AI ​​algorithm 61. By repeatedly performing such training in advance, a trained AI algorithm 62 is generated.

[0094] As shown in the lower part of FIG. 13, the trained AI algorithm 62 also has an input layer 62a, an output layer 62b, and an intermediate layer 62c. Second optical information acquired based on a sample from a subject is input to the input layer 62a. As a result, classification information 63 regarding the type of cell corresponding to the second optical information is output from the output layer 62b. The classification information 63 includes the probability that the target cell belongs to each of multiple types. Furthermore, based on the calculation results including these probabilities calculated by the calculation unit 32, the control unit 31 determines the type with the highest probability ("cell A" in the example of the lower part of FIG. 13) as the type of the target cell.

[0095] Training of AI algorithm 61 and classification using AI algorithm 62 are performed by inputting data groups of second optical information obtained for each cell by one or more of the three light receiving units 225, 233, and 243 (see FIG. 8) to the input layer as input data. Specifically, when n data groups are obtained from detection signals obtained for each cell using the second optical information obtained from any one of light receiving units 225, 233, and 243, the number of detection signal data input to AI algorithms 61 and 62 corresponding to one cell is n, and the number of nodes in input layers 61a and 62a is also n. Furthermore, for example, when data groups of three detection signals obtained from each of the three light receiving units 225, 233, and 243 are input to input layers 61a and 62a as input data, 3n data groups are obtained from the three detection signals, and the number of nodes in input layers 61a and 62a is also 3n.

[0096] In the first embodiment, the calculation unit 32 classifies the cells using the AI ​​algorithm 62, but the control unit 31 may classify the cells using the AI ​​algorithm 62. However, the calculation unit 32 made up of a GPU can classify the cells using the AI ​​algorithm 62 more quickly.

[0097] Next, the measurement process of the sample analyzer 1 will be described with reference to FIGS.

[0098] FIG. 14 is a flowchart showing the control process regarding measurement by the control unit 30.

[0099] In step S11, the control unit 31 of the control unit 30 controls the first measurement unit 10 to perform a first measurement process. As a result, the control unit 31 analyzes the measurement information and first light information acquired by the first measurement unit 10 and acquires a first analysis result.

[0100] The first analysis result includes a count value of cells in the specimen (e.g., the number per unit volume), an abnormal cell flag indicating the presence of abnormal cells, and a scattergram and a histogram. In the first embodiment, the count values ​​of the first analysis result include count values ​​of red blood cells, white blood cells, neutrophils, normal lymphocytes, monocytes, eosinophils, basophils, platelets, abnormal cells, etc. The abnormal cell flags of the first analysis result include flags indicating that the number per unit volume of abnormal cells, such as blast cells, abnormal lymphocytes, atypical lymphocytes, immature granulocytes, and nucleated red blood cells, in the specimen is equal to or greater than a predetermined threshold, and a flag indicating that the classification state of white blood cells is abnormal. When the specimen is blood, abnormal cells are cells that are not present or present in small numbers in the peripheral blood of healthy individuals. The first measurement process will be described later with reference to FIG. 15.

[0101] In step S12, the control unit 31 determines whether the first analysis result acquired in step S11 includes an abnormal cell flag. If the first analysis result includes an abnormal cell flag (step S12: YES), in step S13, the control unit 31 controls the second measurement unit 20 to perform a second measurement process. As a result, the control unit 31 analyzes the second optical information acquired by the second measurement unit 20 and acquires a second analysis result. In step S12, the control unit 31 selectively determines whether to generate a cell analysis result based on the first analysis result or based on the first analysis result and the second analysis result.

[0102] The second analysis result includes a count value (number per unit volume) of cells in the specimen and an abnormal cell flag indicating the presence of abnormal cells. In the first embodiment, the count values ​​of the second analysis result are count values ​​of red blood cells, white blood cells, neutrophils, normal lymphocytes, monocytes, eosinophils, basophils, blasts, abnormal lymphocytes, atypical lymphocytes, immature granulocytes, nucleated red blood cells, etc. The abnormal cell flag of the second analysis result is a flag indicating that the number of abnormal cells per unit volume, such as blasts, abnormal lymphocytes, atypical lymphocytes, immature granulocytes, and nucleated red blood cells, in the specimen is equal to or greater than a threshold value set for each abnormal cell. The second measurement process will be described later with reference to FIG. 16.

[0103] Next, in step S14, the control unit 31 generates an analysis result (cell analysis result) of the cells in the target specimen based on the first analysis result obtained in step S11 and the abnormality flag of the second analysis result obtained in step S13.

[0104] On the other hand, if the first analysis result does not include an abnormal cell flag (step S12: NO), in step S15, the control unit 31 generates an analysis result (cell analysis result) of the cells in the target specimen based on the first analysis result obtained in step S11.

[0105] When the laboratory technician inputs a display instruction via the input unit 35 (see FIG. 11), in step S16, the control unit 31 displays a cell analysis result screen 300 including the cell analysis results generated in step S14 or step S15 on the display unit 34 (see FIG. 11). The cell analysis result screen 300 will be described later with reference to FIGS. 17 to 20.

[0106] As described above, in the example of FIG. 14 , the second measurement process is performed when the first analysis result includes an abnormal cell flag. Therefore, the measurement frequency by the second measurement unit 20 is lower than the measurement frequency by the first measurement unit 10. That is, the control unit 31 can control each measurement unit so that the measurement frequency by the second measurement unit 20 is lower than the measurement frequency by the first measurement unit 10. As described with reference to FIG. 9 , in the second measurement unit 20, the flow rate of the measurement sample is adjusted so that only one cell is positioned in the irradiation range R of the second illumination light at a time. Therefore, the throughput of the measurement by the second measurement unit 20 may be lower than the throughput of the measurement by the first measurement unit 10. Therefore, if the measurement frequency by the second measurement unit 20 is approximately the same as the measurement frequency by the first measurement unit 10, the throughput of the entire laboratory may decrease. By making the measurement frequency by the second measurement unit 20 lower than the measurement frequency by the first measurement unit 10, it is possible to prevent a decrease in the throughput of the entire laboratory while taking advantage of the advantages of the second measurement unit 20.

[0107] FIG. 15 is a flowchart showing the first measurement process.

[0108] In step S101, the control section 31 of the control unit 30 controls the first measurement unit 10 so that sample preparation is performed by the sample preparation section 15 (see FIGS. 2 and 3) of the first measurement unit 10. As a result, measurement samples are prepared in the reaction chambers C11, C12, and C21 to C24.

[0109] For convenience, the following description will be given assuming that measurement samples are prepared in all reaction chambers C11, C12, C21 to C24, but in reality, the required measurement samples are prepared according to the measurement items specified for the target specimen, and in subsequent steps S102 and S103, the measurement samples are measured in the electrical measurement unit 16a, HGB measurement unit 16b and optical measurement unit 100 according to the prepared measurement samples.

[0110] In step S102, the control unit 31 controls the first measurement unit 10 to perform measurements using the electrical measurement unit 16a and the HGB measurement unit 16b, and acquires measurement information based on these measurements from the first measurement unit 10. In step S103, the control unit 31 controls the first measurement unit 10 to perform measurements using the optical measurement unit 100. As a result, the optical measurement unit 100 irradiates cells in a specimen contained in the measurement sample flowing through the flow cell 101 with first illumination light having a single beam spot BS, as shown in FIG. 5, and acquires first light information. Then, the control unit 31 acquires the first light information acquired by the measurement unit 16 from the first measurement unit 10.

[0111] In step S104, the control unit 31 analyzes the measurement information acquired in step S102 and the first optical information acquired in step S103. In step S105, the control unit 31 generates first analysis information based on the analysis in step S104. The first analysis information includes a blood cell count value obtained by analyzing the measurement information based on measurements by the electrical measurement unit 16a and the HGB measurement unit 16b, and a blood cell count value and an abnormal cell flag obtained by analyzing the first optical information based on measurements by the optical measurement unit 100.

[0112] FIG. 16 is a flowchart showing the second measurement process.

[0113] In step S201, the control section 31 of the control unit 30 controls the second measurement unit 20 so that sample preparation is performed by the sample preparation section 25 (see FIGS. 6 and 7) of the second measurement unit 20. As a result, a measurement sample is prepared in the reaction chamber C30.

[0114] In step S202, the control unit 31 controls the second measurement unit 20 to perform measurement in the optical measurement unit 200. As a result, the optical measurement unit 200 irradiates cells in the specimen contained in the measurement sample flowing through the flow cell 201 with the second illumination light, as shown in Fig. 9, and acquires second light information. Then, the control unit 31 acquires the second light information acquired by the measurement unit 26 from the second measurement unit 20.

[0115] In step S203, the control unit 31 and the calculation unit 32 input the second optical information acquired in step S202 into the post-training AI algorithm 62 (see FIG. 13) for analysis. In step S204, the control unit 31 and the calculation unit 32 generate second analysis information through the analysis in step S203. The second analysis information includes a blood cell count value and an abnormal cell flag obtained by analyzing the second optical information based on the measurement by the optical measurement unit 200.

[0116] Next, the cell analysis result screen 300 displayed in step S16 of FIG. 14 will be described with reference to FIGS.

[0117] FIG. 17 is a diagram showing a schematic configuration of the cell analysis result screen 300. As shown in FIG.

[0118] The cell analysis result screen 300 includes a count value display area 310 and an abnormal cell flag display area 320.

[0119] The count value display area 310 includes display areas 311 to 314 corresponding to the CBC, DIFF, RET, and PLT-F analysis modes, respectively. Display area 311 displays count values ​​corresponding to the CBC mode, such as the white blood cell count, red blood cell count, hemoglobin content, hematocrit value, and mean corpuscular volume. Display area 312 displays count values ​​corresponding to the DIFF mode, such as the neutrophil count, lymphocyte count, monocyte count, eosinophil count, and basophil count. Display area 313 displays count values ​​corresponding to the RET mode, such as the reticulocyte ratio, reticulocyte count, reticulocyte immature index, and reticulocyte hemoglobin equivalent. Display area 314 displays count values ​​corresponding to the PLT-F mode, such as the immature platelet ratio.

[0120] The cell analysis result screen 300 may also display a scattergram or a histogram included in the first analysis result.

[0121] The abnormal cell flag display area 320 includes display areas 321 to 323 that respectively display an abnormal cell flag related to white blood cells, an abnormal cell flag related to red blood cells, and an abnormal cell flag related to platelets. A label 321a is attached to the display area 321, and the number 1 or 2 is displayed in the label 321a. The label 321a with "1" displayed indicates that the abnormal cell flag related to white blood cells displayed in the display area 321 is based on the first analysis result, and the label 321a with "2" displayed indicates that the abnormal cell flag related to white blood cells displayed in the display area 321 is based on the second analysis result.

[0122] When step S15 in Fig. 14 is executed, the second analysis result is not acquired because the second measurement process has not been executed, and the cellular analysis result is generated based on the first analysis result based on the first measurement process. Therefore, in this case, as shown in Fig. 18, the cellular analysis result screen 300 displays the cellular analysis result based only on the first analysis result, and in the display area 321 displaying the abnormal cell flag for white blood cells, a "1" is displayed in the label 321a to indicate that the abnormal cell flag based on the first analysis result is displayed. Note that in the example shown in Fig. 18, since there was no abnormal cell flag based on the first analysis result, the abnormal cell flag is not displayed in the display areas 321 to 323.

[0123] When step S14 in FIG. 14 is executed, the second measurement process is executed, and the cell analysis result is generated based on the first analysis result based on the first measurement process and the abnormal cell flag of the second analysis result. In this case, as shown in FIG. 19, on the cell analysis result screen 300, the count value display area 310 and display areas 322 and 323 display the count value and abnormal cell flag based on the first analysis result, and the display area 321 displaying the abnormal cell flag related to white blood cells displays the abnormal cell flag based on the second analysis result instead of the abnormal cell flag based on the first analysis result. To indicate that the abnormal cell flag based on the second analysis result is displayed in the display area 321, a "2" is displayed in the label 321a. Note that in the example shown in FIG. 19, since the second analysis result includes an abnormal cell flag related to blasts, "Blasts?" is displayed in the display area 321. In other words, in this example, at least a portion of the result based on the first analysis result (the abnormal cell flag) is complemented based on the second analysis result.

[0124] FIG. 20 is a diagram showing an example of display of an abnormal cell flag related to white blood cells on the cell analysis result screen 300.

[0125] The top, middle, and bottom left sections of Figure 20 show, as a comparative example, an example in which, when the first analysis results include an abnormal cell flag for blast cells, "Blasts?" is displayed in the display area 321 and "1" is displayed in the label 321a.

[0126] In contrast, in the first embodiment, when a second measurement process is performed and the second analysis result also includes an abnormal cell flag for blasts, a "2" is displayed in label 321a to indicate that an abnormal cell flag based on the second analysis result is displayed instead of an abnormal cell flag based on the first analysis result, as shown in the upper right of FIG. 20. Also, in the first embodiment, when a second measurement process is performed and the second analysis result includes an abnormal cell flag for abnormal lymphocytes, "Abn Lympho?" is displayed in display area 321 instead of "Blasts?" in the comparative example, as shown in the middle right of FIG. 20, and a "2" is displayed in label 321a. Also, in the first embodiment, when a second measurement process is performed and the second analysis result does not include an abnormal cell flag, "Blasts?" in the comparative example is not displayed in display area 321, and a "2" is displayed in label 321a, as shown in the lower right of FIG.

[0127] Thus, in embodiment 1, when the second measurement process is performed, only the abnormal cell flag based on the second analysis result is displayed, regardless of the presence or type of abnormal flag in the first analysis result. This allows the laboratory technician to accurately determine the presence of abnormal cells in the target sample, allowing them to accurately determine whether or not a smear sample needs to be prepared at a later stage of the sample analyzer 1. Even if a smear sample is prepared, the smear sample can be smoothly confirmed based on the accurate abnormal cell flag based on the second analysis result.

[0128] Next, with reference to FIG. 21, the control of the fluid adjusting section 200a (see FIG. 6) of the second measurement unit 20 will be described.

[0129] 21 is a flowchart showing the process of determining the flow rate per unit time of the measurement sample to be flowed through the flow cell 201 in the second measurement process. This process is executed after the determination in step S12 of FIG. 14 is YES, and before the second measurement process in step S13 is started.

[0130] In step S301, the control unit 31 of the control unit 30 determines whether a predetermined blood cell concentration based on the first analysis result acquired in the first measurement process is smaller than a threshold value Tc. In the first embodiment, the blood cells to be determined in step S301 are white blood cells, and the blood cell concentration is the number of blood cells per unit volume in the sample. The white blood cell concentration is, for example, the number of white blood cells included in the count value in CBC mode of the first analysis result.

[0131] If the blood cell concentration is lower than the predetermined threshold Tc (step S301: YES), in step S302, the control unit 31 determines the flow rate per unit time of the flow cell 201 in the second measurement process to be the first flow rate. In this case, the control unit 31 controls the fluid adjustment unit 200a so that the flow rate per unit time of the measurement sample flowing through the flow cell 201 becomes the first flow rate in the second measurement process in step S13 of FIG.

[0132] On the other hand, if the blood cell concentration is equal to or higher than the predetermined threshold Tc (step S301: NO), in step S303, the control unit 31 determines the flow rate per unit time of the flow cell 201 in the second measurement process to be a second flow rate that is smaller than the first flow rate. In this case, in the second measurement process in step S13 of FIG. 14, the control unit 31 controls the fluid adjustment unit 200a so that the flow rate per unit time of the measurement sample flowing through the flow cell 201 becomes the second flow rate.

[0133] When the control unit 31 controls the flow rate as described above, the measurement time by the second measurement unit 20 may become longer than the measurement time by the first measurement unit 10. When the measurement time by the second measurement unit 20 becomes longer than the measurement time by the first measurement unit 10, the throughput of the measurement by the second measurement unit 20 becomes lower than the throughput of the measurement by the first measurement unit 10.

[0134] The upper part of FIG. 22 is a graph showing that the flow rate per unit time in the flow cell 201 is switched in two stages depending on the blood cell concentration.

[0135] In the first embodiment, as described in Fig. 21, the flow rate per unit time in the flow cell 201 is set to either a first flow rate or a second flow rate depending on whether the blood cell concentration is greater than the threshold Tc. The threshold Tc and the drive signals for the fluid adjuster 200a to respectively achieve the first flow rate and the second flow rate are stored in advance in the storage unit 33 of the control unit 30 (see Fig. 11).

[0136] In this way, when the flow rate per unit time in the flow cell 201 is set small when the blood cell concentration of the specimen is high, only one cell is positioned in the irradiation range R (see FIG. 9), and the accuracy of the second analysis result is improved. When the flow rate per unit time is set small in this way, the diameter of the central region CE (see FIG. 9) of the flow channel 201a through which the measurement sample and sheath fluid flow also becomes small, making it even easier to position only one cell in the irradiation range R.

[0137] The flow rate per unit time in flow cell 201 is not limited to being switched between two stages, and may be changed linearly according to the blood cell concentration, for example, as shown in the lower part of Fig. 22. In this case, control unit 31 of control unit 30 determines the flow rate per unit time from the blood cell concentration using, for example, a mathematical formula showing the relationship between the blood cell concentration and the flow rate per unit time, and determines the drive signal for fluid adjustment unit 200a based on a table that associates the flow rate per unit time with the drive signal.

[0138] <Effects of the sample analyzer and sample analysis method according to embodiment 1> A sample analyzer 1 for analyzing cells in a sample collected from a subject includes an optical measurement unit 100 (first measurement unit), an optical measurement unit 200 (second measurement unit), and a control unit 31. As shown in FIG. 5, the optical measurement unit 100 (first measurement unit) measures first light information obtained when a cell passes through at least one beam spot BS of a first illumination light (step S103 in FIG. 15). As shown in FIG. 9, the optical measurement unit 200 (second measurement unit) measures second light information obtained when a cell passes through an irradiation range R of a second illumination light in which a plurality of diffracted lights generated by a diffractive optical element 215 upon which light is incident are distributed (step S202 in FIG. 16). The control unit 31 generates a cell analysis result based on the first analysis result, or on either the first analysis result or the second analysis result (steps S14 and S15 in FIG. 14).

[0139] According to this configuration, the measurement principles of optical measurement unit 100 and optical measurement unit 200 are different from each other. This allows sample analyzer 1 to provide test results that do not rely solely on a specific measurement principle (for example, test results that provide classification and counting of cells in a sample). For example, cell types that were difficult to classify using the measurement principle of first measurement unit 10 can be classified using the measurement principle of second measurement unit 20, improving the accuracy of test results provided by sample analyzer 1.

[0140] The optical measurement unit 200 (second measurement unit) measures the second optical information, which contains more information corresponding to each cell than the first optical information. Also, the optical measurement unit 200 (second measurement unit) measures the second optical information, which contains more information about the morphology of each cell than the first optical information.

[0141] According to this configuration, the laboratory technician can refer to the analysis results of the second optical information and, for example, reduce the number of false positive specimens, thereby reducing the number of times smear samples and other samples need to be prepared and checked, and can check smear samples and other samples with reference to more accurate cell analysis results, thereby eliminating the need to prepare and check smear samples. This reduces the burden on the laboratory technician.

[0142] The control unit 31 generates the first analysis result by a first analysis method and generates the second analysis result by a second analysis method, the first analysis method and the second analysis method being different from each other.

[0143] The first analysis result is obtained by grouping cells on a scattergram based on the first optical information, as explained with reference to FIG. 12. The second analysis result is obtained by inputting the second optical information into the AI ​​algorithm 62, as explained with reference to FIG. 13. In this way, the first analysis result and the second analysis result are generated based on different analysis methods, so that cell types that would be difficult to classify using only one of the analysis results can be easily identified. It becomes possible to classify based on the results of the other analysis.

[0144] The control unit 31 selectively determines whether to generate a cell analysis result based on the first analysis result, and on either the first analysis result or the second analysis result.

[0145] According to this configuration, how to generate cell analysis results is selectively and automatically determined, eliminating the need for laboratory technicians to select analysis results and enabling cell analysis results to be generated quickly.

[0146] The control unit 31 generates a cell analysis result based on the first analysis result and the second analysis result such that the first analysis result is complemented by the second analysis result.

[0147] According to this configuration, a part of the first analysis result (abnormal cell flag) is complemented based on the second analysis result, as shown in Fig. 19. This allows the laboratory technician to refer to a cell analysis result with higher accuracy than a cell analysis result based only on one of the analysis results.

[0148] Optical measurement section 100 (first measurement section) and optical measurement section 200 (second measurement section) measure the sample transported to sample analyzer 1 by transport unit 40.

[0149] According to this configuration, the labor required by the laboratory technician to transfer the sample between the first measurement unit 10 including the optical measurement section 100 and the second measurement unit 20 including the optical measurement section 200 can be reduced.

[0150] The control unit 31 can control the operation of the optical measurement unit 100 (first measurement unit) and the optical measurement unit 200 (second measurement unit) so that the measurement frequency by the optical measurement unit 200 (second measurement unit) is lower than the measurement frequency by the optical measurement unit 100 (first measurement unit).

[0151] The flow rate of the measurement sample is adjusted so that only one cell is positioned in the irradiation range R of the optical measurement unit 200 at a time. Therefore, the throughput of measurements by the optical measurement unit 200 may be lower than the throughput of measurements by the optical measurement unit 100. In contrast, with the above configuration, the frequency of measurements by the optical measurement unit 200 can be set lower than the frequency of measurements by the optical measurement unit 100. This makes it possible to prevent a decrease in the throughput of the sample analyzer 1 while taking advantage of the advantages of the optical measurement unit 200.

[0152] The control unit 31 controls the operation of the optical measurement unit 100 (first measurement unit) and the optical measurement unit 200 (second measurement unit) so that the measurement frequency by the optical measurement unit 200 (second measurement unit) is lower than the measurement frequency by the optical measurement unit 100 (first measurement unit), and generates a cell analysis result based on the first analysis result and the second analysis result so that the first analysis result is complemented by the second analysis result.

[0153] Even in this configuration, it is possible to prevent a decrease in throughput of the sample analyzer 1 while taking advantage of the advantages of the optical measurement unit 200, and laboratory technicians can refer to cell analysis results with higher accuracy than cell analysis results based on only one analysis result.

[0154] The calculation unit 32 (control unit) generates the second analysis result using the AI ​​algorithm 62 (artificial intelligence algorithm) shown in FIG.

[0155] According to this configuration, the second analysis result can be generated quickly and accurately.

[0156] The control unit 31 selectively determines the first analysis result and whether the cell analysis result is to be generated based on the first analysis result or the second analysis result, so that the measurement frequency by the optical measurement unit 200 (second measurement unit) is lower than the measurement frequency by the optical measurement unit 100 (first measurement unit).

[0157] Even in this configuration, it is possible to take advantage of the advantages of the optical measurement section 200 while preventing a decrease in the throughput of the sample analyzer 1, eliminating the need for a laboratory technician to select analysis results, and enabling cellular analysis results to be generated quickly.

[0158] The acquisition of second optical information by the optical measurement unit 200 (second measurement unit) and the generation of second optical analysis results by the control unit 31 (step S13 in FIG. 14) are executed when the first analysis result includes an abnormal cell flag (when the first analysis result meets a predetermined condition) (step S12: YES). When the first analysis result meets the predetermined condition, the control unit 31 generates the cell analysis result exemplified in FIG. 19 based on at least the abnormal cell flag (second analysis result) included in the second analysis result (step S14 in FIG. 14).

[0159] According to this configuration, if the first analysis result does not meet the predetermined conditions, the process of acquiring and analyzing the second optical information is omitted, thereby, for example, shortening the time required to test the sample and reducing the amount of reagent used.

[0160] The above-mentioned predetermined conditions are conditions that suggest the presence of abnormal cells in the specimen.

[0161] According to this configuration, if the first analysis result suggests the presence of abnormal cells in the specimen, a cellular analysis result is generated based on at least the second analysis result, thereby enabling the presence or absence of abnormal cells in the specimen to be determined with high accuracy based on the cellular analysis result.

[0162] The conditions suggesting the presence of the above-mentioned abnormal cells include at least one of the following: a condition suggesting the presence of blast cells, a condition suggesting the presence of abnormal lymphocytes, a condition suggesting the presence of atypical lymphocytes, a condition suggesting the presence of immature granulocytes, a condition suggesting that the classification state of white blood cells is abnormal, and a condition suggesting the presence of nucleated red blood cells.

[0163] According to this configuration, the second analysis result is obtained when blast cells, abnormal lymphocytes, atypical lymphocytes, or immature granulocytes are present, when the classified state of white blood cells is abnormal, etc. Therefore, the laboratory technician can refer to the second analysis result and accurately determine whether or not a smear sample needs to be prepared.

[0164] If the first analysis result meets the above-mentioned predetermined conditions (step S12: YES) and the second analysis result suggests the presence of abnormal cells (upper and middle rows of Figure 20), the control unit 31 generates a cell analysis result suggesting the presence of abnormal cells based on the second analysis result illustrated in Figure 19 (step S14 of Figure 14).

[0165] With this configuration, abnormal cells are suggested based on the second analysis result, which more accurately reflects the state of the cells in the specimen, out of the first and second analysis results. This allows the laboratory technician to accurately grasp the state of the abnormal cells, reducing the burden on the technician.

[0166] If the first analysis result meets the above-mentioned predetermined conditions (step S12: YES) and the second analysis result does not suggest the presence of any type of abnormal cell (lower part of Figure 20), the control unit 31 generates the cell analysis result that does not suggest the presence of abnormal cells (step S14 of Figure 14).

[0167] With this configuration, even if the first analysis result suggests the presence of abnormal cells, if the second analysis result, which more accurately reflects the state of the cells in the specimen, does not suggest the presence of any type of abnormal cells, a cell analysis result that does not suggest the presence of abnormal cells is generated. This allows the laboratory technician to accurately grasp the state of the abnormal cells, reducing the burden on the technician.

[0168] Sample analyzer 1 includes flow cell 101 (first flow cell) and flow cell 201 (second flow cell). Optical measurement unit 100 (first measurement unit) measures first optical information obtained when cells flowing through flow cell 101 (first flow cell) pass through beam spot BS. Optical measurement unit 200 (second measurement unit) measures second optical information obtained when cells flowing through flow cell 201 (second flow cell) pass through irradiation range R of second illumination light, in which multiple diffracted lights generated by diffractive optical element 215 upon which light is incident are distributed.

[0169] According to this configuration, since the acquisition of the first optical information and the acquisition of the second optical information are performed in separate flow cells, these steps can also be performed simultaneously.

[0170] The first light information includes information on scattered light and fluorescent light from the cells irradiated with the first illumination light.

[0171] According to this configuration, the size and internal structure of the cell can be determined based on the information on the scattered light of the first illumination light, and the amount of nucleic acid in the cell can be determined based on the information on the fluorescence of the first illumination light.

[0172] In generating the first analysis result (step S104 in FIG. 15), the control unit 31 groups multiple cell groups irradiated with the first illumination light, as illustrated in the lower part of FIG. 12, and in generating the second analysis result (step S203 in FIG. 16), it classifies each individual cell irradiated with the second illumination light into one of the types of cells.

[0173] According to this configuration, cells can be classified simply in the process of generating the first analysis result, and cells can be classified with high accuracy in the process of generating the second analysis result.

[0174] Control unit 31 controls optical measurement unit 200 (second measurement unit) so that the cells pass through irradiation range R of the second illumination light under fluid conditions according to the first analysis result (steps S302 and S303 in FIG. 21).

[0175] According to this configuration, the fluid conditions for the cells can be appropriately set in accordance with the results of the first analysis, so that the analysis based on the second optical information can be performed with high accuracy.

[0176] A sample analysis method for analyzing cells in a sample collected from a subject includes a step of acquiring first light information obtained by the cells passing through at least one beam spot BS of a first illumination light (step S103 in FIG. 15), a step of acquiring second light information obtained by the cells passing through an irradiation range R of a second illumination light in which multiple diffracted lights generated by a diffractive optical element 215 into which the light is incident are distributed (step S202 in FIG. 16), and a step of generating a cell analysis result based on the first analysis result and either the first analysis result or the second analysis result (steps S14 and S15 in FIG. 14).

[0177] According to this method, the measurement principle used to acquire the first optical information is different from the measurement principle used to acquire the second optical information. This makes it possible to provide test results that do not rely solely on a specific measurement principle (e.g., test results that provide classification and counting of cells in a specimen). For example, cell types that were difficult to classify in the first analysis results can be classified in the second analysis results, improving the accuracy of the test results.

[0178] <Modification 1 of Embodiment 1> In embodiment 1, when the second measurement process is performed, only the abnormal cell flag of the first analysis result is replaced with the second analysis result, but this is not limited to this, and the count value and abnormal cell flag of the first analysis result may also be replaced with the second analysis result.

[0179] FIG. 23 is a flowchart showing the control process for measurement by the control unit 30 according to this modified example.

[0180] In the control process of this modified example, steps S21 and S22 are added instead of steps S12 and S14 in comparison with the first embodiment shown in FIG.

[0181] In step S21, the control unit 31 of the control unit 30 determines whether a predetermined count value included in the first analysis result is outside a predetermined range. In this modified example, the predetermined count value is the white blood cell count. The predetermined range is a numerical range in which the reliability of the first analysis result is maintained. The predetermined range is composed of an upper limit value and a lower limit value, and is stored in advance in the memory unit 33 of the control unit 30.

[0182] If the predetermined count value included in the first analysis result is outside the predetermined range (step S21: YES), the control unit 31 performs the above-mentioned second measurement process in step S13. In this modified example, if the white blood cell count included in the first analysis result is greater than a predetermined upper limit value, or if the white blood cell count included in the first analysis result is smaller than a predetermined lower limit value, the control unit 31 determines the result of step S21 to be YES.

[0183] If the determination result in step S21 is YES, it is assumed that the white blood cell grouping as shown in FIG. 12 has not been performed properly, and the count values ​​for each white blood cell classification and the abnormal cell flags for white blood cells included in the first analysis results are unreliable. Alternatively, if the determination result in step S21 is YES, it is assumed that the white blood cell grouping as shown in FIG. 12 has been performed properly, and the count values ​​for each white blood cell classification included in the first analysis results are correct, but the abnormal cell flags are unreliable. Therefore, in this modified example, a second measurement process is performed in such a case, and detailed analysis results for white blood cells are obtained. As described above, in step S21, the control unit 31 selectively determines whether to generate cell analysis results based on the first analysis results or based on the first analysis results and the second analysis results.

[0184] In step S22, the control unit 31 generates a cell analysis result for the target specimen based on the first analysis result obtained in step S11 and the count value and abnormal cell flag of the second analysis result obtained in step S13.

[0185] On the other hand, if the specified count value included in the first analysis result is within the specified range (step S21: NO), as in embodiment 1, in step S15, the control unit 31 generates a cell analysis result for the target specimen based on the first analysis result obtained in step S11.

[0186] FIG. 24 is a diagram schematically showing the configuration of the cell analysis result screen 300 when the second measurement process is performed according to this modified example.

[0187] In the cell analysis result screen 300 of this modified example, a label 312a is added to the display area 312, as compared to the first embodiment shown in Fig. 17. The number 1 or 2 is displayed in the label 312a. The label 312a with "1" displayed indicates that the count value displayed in the display area 312 is based on the first analysis result, and the label 312a with "2" displayed indicates that the count value displayed in the display area 312 is based on the second analysis result.

[0188] In this modified example, when the second measurement process is performed, the count value and abnormal cell flag based on the first analysis result are displayed in display areas 311, 313, 314 and display areas 322, 323. Meanwhile, the count value in DIFF mode based on the second analysis result is displayed in display area 312, and the abnormal cell flag based on the second analysis result is displayed in display area 321. In this case, as shown in FIG. 24 , a “2” is displayed in label 312a to indicate that the count value based on the second analysis result is displayed in display area 312, and a “2” is displayed in label 321a to indicate that the abnormal cell flag based on the second analysis result is displayed in display area 321. In other words, in this modified example, at least a portion of the results based on the first analysis result are supplemented based on the second analysis result.

[0189] On the other hand, if the second measurement process has not been performed, the cell analysis result screen 300 displays the cell analysis result based only on the first analysis result, and the labels 312a and 321a display "1."

[0190] In this modified example, when the second measurement process is performed, the measurement values ​​and abnormal cell flags related to white blood cells in the first analysis results are replaced with the second analysis results, but the second analysis results may also be displayed together with the first analysis results.

[0191] In this case, as shown in Fig. 25, compared to Fig. 24, display area 315 displaying count values ​​based on the second analysis results and display area 324 displaying abnormal cell flags based on the second analysis results are added. In this case, display area 312 displays only count values ​​from the first analysis results, display area 315 displays only count values ​​from the second analysis results, display area 321 displays only abnormal cell flags related to white blood cells from the first analysis results, and display area 324 displays only abnormal cell flags related to white blood cells from the second analysis results. In addition, labels 311a-315a and 321a-324a indicating whether the displayed content is based on the first analysis results or the second analysis results are added to display areas 311-315 and 321-324, respectively.

[0192] 23 is low reliability, a low reliability label 301 is displayed on the cell analysis result screen 300. By referring to the low reliability label 301, the laboratory technician can understand that the first analysis result includes a low reliability result.

[0193] In step S21 of FIG. 23 , the control unit 31 may determine the count value based on a first range and a second range wider than the first range. For example, when the count value of white blood cells included in the first analysis result is outside the first range but within the second range, it is assumed that the white blood cells have been grouped properly and the count values ​​of each white blood cell classification included in the first analysis result are correct, but the reliability of the abnormal cell flag for the white blood cells included in the first analysis result is low. In this case, the control unit 31 performs a second measurement process and displays only the abnormal cell flag of the second analysis result on the cell analysis result screen 300, as in the first embodiment shown in FIG. 19 . On the other hand, if the count value is outside the second range, the control unit 31 performs steps S13, S22, and S16, as in FIG. 23 , and displays the count value and abnormal cell flag of the second analysis result on the cell analysis result screen 300.

[0194] <Effects of the sample analyzer and sample analysis method according to Modification 1 of Embodiment 1> The acquisition of the second optical information by the optical measurement unit 200 (second measurement unit) and the analysis of the second optical information by the control unit 31 (step S13 in Figure 23) are performed when the number of cells of a predetermined type is outside a predetermined range (when the first analysis result meets a predetermined condition) (step S21 in Figure 23: YES).

[0195] According to this configuration, if the white blood cell count (the number of cells of a predetermined type) is outside a predetermined range in the analysis of the first optical information, for example, there is a possibility that the grouping of cells based on the first optical information has not been performed properly. Even in this case, the analysis of the second optical information provides an analysis result that reflects the morphology of each cell, so that, for example, the number of each type of white blood cell in the sample can be obtained with high accuracy.

[0196] The above-mentioned predetermined range is a numerical range in which the reliability of the analysis results is maintained.

[0197] According to this configuration, when the reliability of the number of cells of a predetermined type based on the first analysis result is not maintained, the second optical information is acquired and analyzed, thereby making it possible to accurately acquire the number of each type of cell, for example, white blood cells, in the sample based on the second analysis result.

[0198] If the first analysis result indicates that the number of cells of a predetermined type is outside a predetermined range (step S21 in Figure 23: YES), the control unit 31 generates a cell analysis result including the number of cells of the predetermined type based on the second analysis result (step S22 in Figure 23).

[0199] According to this configuration, the number of each type of white blood cell, for example, is generated as the number of cells of a predetermined type based on the second analysis result, allowing the laboratory technician to accurately grasp the number of cells of a predetermined type.

[0200] <Modification 2 of Embodiment 1> In Modification 1 of Embodiment 1, when the second measurement process is performed, not only the second analysis result but also the first analysis result is displayed as the cell analysis result, but this is not limited to this, and the first analysis result does not necessarily have to be displayed.

[0201] FIG. 26 is a flowchart showing the control process for measurement by the control unit 30 according to this modified example.

[0202] In the control process of this modified example, step S31 is added instead of step S14, compared to embodiment 1 shown in Fig. 14. In step S31, the control unit 31 of the control unit 30 generates a cell analysis result based only on the second analysis result.

[0203] FIG. 27 is a diagram schematically showing the configuration of the cell analysis result screen 300 when the second measurement process is performed according to this modified example.

[0204] In this modified example, only a display area 315 displaying the count value based on the second analysis result shown in Fig. 25 and a label 315a added to the display area 315 are displayed in the count value display area 310. Also, in this modified example, only a display area 324 displaying the abnormal cell flag for the white blood cells based on the second analysis result shown in Fig. 25 and a label 324a added to the display area 324 are displayed in the abnormal cell flag display area 320. That is, in this modified example, when the second measurement process is performed, only the second analysis result is displayed on the cell analysis result screen 300.

[0205] In this modified example, the second analysis result allows the laboratory technician to, for example, reduce the number of times smear samples and other samples need to be prepared and checked because the number of false positive samples is reduced, and the technician can check smear samples and other samples by referring to more accurate cell analysis results, thereby eliminating the need to prepare and check smear samples. This reduces the burden on the technician.

[0206] <Embodiment 2> In the first embodiment, the first measurement process and the second measurement process were performed in the first measurement unit 10 and the second measurement unit 20, respectively. In contrast, in the second embodiment, the first measurement process and the second measurement process are both performed in the third measurement unit 70. The configuration and process of the second embodiment are the same as those of the first embodiment, except for the points mentioned below.

[0207] FIG. 28 is a front view schematically showing the configuration of a sample analyzer 1 according to the second embodiment.

[0208] Compared to the first embodiment shown in FIG. 1, the sample analyzer 1 of the second embodiment includes a third measurement unit 70 instead of the first measurement unit 10 and the second measurement unit 20.

[0209] FIG. 29 is a block diagram showing the functional configuration of the third measurement unit 70. As shown in FIG.

[0210] Compared to the second measurement unit 20 of the first embodiment shown in FIG. 6, the third measurement unit 70 includes an electrical measurement unit 16a and an HGB measurement unit 16b shown in FIG. 2, and includes a sample preparation unit 27 and an optical measurement unit 400 instead of the sample preparation unit 25 and the optical measurement unit 200. The fluid adjustment unit 400a in the optical measurement unit 400 adjusts the flow rate per unit time of the measurement sample in the flow cell 201 of the optical measurement unit 400 and is configured similarly to the fluid adjustment unit 200a in FIG. 6. The sample preparation unit 27 will be described later with reference to FIG. 30. The optical system of the optical measurement unit 400 will be described later with reference to FIG. 31.

[0211] The electrical measurement unit 16a and the HGB measurement unit 16b perform signal processing on the detection signals obtained by measurement and output the measurement information after the signal processing to the measurement control unit 21. The optical measurement unit 400 performs signal processing on the detection signals obtained by measurement and outputs the first optical information and second optical information after the signal processing to the measurement control unit 21. The measurement control unit 21 stores the measurement information, first optical information, and second optical information output from the measurement unit 26 in the memory unit 22. When the measurement of one sample is completed, the measurement control unit 21 associates the measurement information, first optical information, and second optical information stored in the memory unit 22 with the sample ID read by the reading unit 24 and transmits them to the control unit 30.

[0212] FIG. 30 is a block diagram showing the functional configuration of the sample preparation unit 27.

[0213] Compared to the sample preparation unit 25 of the first embodiment shown in Fig. 7, the sample preparation unit 27 includes reaction chambers C11, C12, and C21 to C24 shown in Fig. 3. The reaction chambers C11 and C12 are connected to the electrical measurement unit 16a and the HGB measurement unit 16b, respectively, and the reaction chambers C21 to C24 and C30 are connected to the optical measurement unit 400.

[0214] The aspirating tube 25b aspirates the specimen from the specimen container 51 that has been stirred by the stirring unit 25a, and dispenses the aspirated specimen into the reaction chambers C11, C12, C21 to C24, and C30 as appropriate.

[0215] The measurement samples prepared in reaction chambers C21 to C24 and C30 are each individually flowed into flow cell 201 and measured by optical measurement unit 400. Optical measurement unit 400 measures the measurement samples prepared in reaction chambers C21 to C24 to obtain detection signals, and performs signal processing on the obtained detection signals to obtain first optical information. Optical measurement unit 400 measures the measurement sample prepared in reaction chamber C30 to obtain detection signals, and performs signal processing on the obtained detection signals to obtain second optical information.

[0216] FIG. 31 is a diagram showing a schematic configuration of the optical measurement section 400. As shown in FIG.

[0217] Compared to the optical measurement unit 200 of Figure 8, the optical measurement unit 400 includes the light source 111, collimator lens 112, cylindrical lens 113, beam stopper 122, optical filters 123, 132, 142, and light receiving units 124, 133, 143 of the optical measurement unit 100 shown in Figure 4, and further includes dichroic mirrors 115, 125, 134, 144, and a condenser lens 126.

[0218] The dichroic mirror 115 reflects light of wavelength λ10 from the light source 111 and transmits light of wavelength λ20 from the light source 211. The dichroic mirror 115 aligns the optical axis of the light from the light source 111 with the central axis of the light from the diffractive optical element 215. The condenser lens 216 condenses the light from the light sources 111 and 211 into the flow channel 201a of the flow cell 201. The condenser lens 216 is configured to suppress chromatic aberration for the light of wavelengths λ10 and λ20. The beam spot BS (see FIG. 5) of the first illumination light from the light source 111 is positioned at the center position of the illumination range R shown in FIG. 9. The second illumination light from the light source 211 is irradiated onto the illumination range R, as in FIG. 9.

[0219] The collimator lens 112, the cylindrical lens 113, the dichroic mirror 115, and the condenser lens 216 constitute an illumination optical system 206 that irradiates cells passing through the flow cell 201 with light from the light source 111 as first illumination light.

[0220] As in the first embodiment, when the first illumination light of wavelength λ10 is irradiated onto cells flowing through flow cell 201, forward scattered light of wavelength λ10, side scattered light of wavelength λ10, and fluorescence of wavelength λ11 are generated from the site of the cells irradiated with the light. When the second illumination light of wavelength λ20 is irradiated onto cells flowing through flow cell 201, forward scattered light of wavelength λ20, side scattered light of wavelength λ20, and fluorescence of wavelength λ21 are generated from the site of the cells irradiated with the light.

[0221] The dichroic mirror 125 reflects the first illumination light and forward scattered light based on the first illumination light, and transmits the second illumination light and forward scattered light based on the second illumination light. The first illumination light and second illumination light that have passed through the flow cell 201 are blocked by beam stoppers 122 and 222, respectively. The condenser lens 126 condenses the forward scattered light based on the second illumination light that has passed through the beam stopper 122 onto the light receiving unit 124. The dichroic mirror 134 reflects the side scattered light based on the first illumination light and transmits the side scattered light based on the second illumination light. The dichroic mirror 144 reflects the fluorescence based on the first illumination light and transmits the fluorescence based on the second illumination light. The light receiving units 124, 133, 143, 225, 233, and 243 receive the corresponding light and output detection signals.

[0222] FIG. 32 is a flowchart showing the control process regarding measurement by the control unit 30.

[0223] 14, the control process in FIG. 32 differs from that in the first embodiment shown in FIG. 14 in that the second measurement process in step S13 is executed between steps S11 and S12. That is, in the second embodiment, the second measurement process is executed regardless of the first analysis result. In the first measurement process in the second embodiment, the third measurement unit 70 performs the same process as in FIG. 15, and in the second measurement process in the second embodiment, the third measurement unit 70 performs the same process as in FIG. 16.

[0224] <Effects of the sample analyzer and sample analysis method according to embodiment 2> The acquisition of second optical information by optical measurement section 400 (second measurement section) (step S202 in FIG. 16) and the generation of second analysis results by control section 31 (step S203 in FIG. 16) are performed regardless of the first analysis results.

[0225] This configuration eliminates the need to determine whether to perform the second measurement process, allowing the first and second measurement processes to be performed smoothly. Furthermore, since both the first and second measurement processes are performed, a wide range of results can be obtained as cell analysis results, for example.

[0226] If the first analysis result includes an abnormal cell flag (if the first analysis result meets a predetermined condition) (step S12 in Figure 32: YES), the control unit 31 generates a cell analysis result based on at least the second analysis result (step S14 in Figure 32).

[0227] According to this configuration, when the first analysis result satisfies a predetermined condition, the cellular analysis result is generated based on at least the second analysis result, allowing the laboratory technician to accurately understand the condition of the specimen by referring to the cellular analysis result based on the highly accurate second analysis result.

[0228] If the first analysis result includes an abnormal cell flag (if the first analysis result meets a predetermined condition) (step S12 in Figure 32: YES), the control unit 31 generates a cell analysis result based on the first analysis result and the second analysis result (step S14 in Figure 32).

[0229] According to this configuration, if the first analysis result satisfies a predetermined condition, the cell analysis result is generated based on both the first analysis result and the second analysis result, which allows the generation of an analysis result that more accurately reflects the state of the specimen than when the cell analysis result is generated based only on the second analysis result.

[0230] Sample analyzer 1 includes flow cell 201. Optical measurement unit 400 (first measurement unit) measures first optical information obtained when cells flowing through flow cell 201 pass through beam spot BS. Optical measurement unit 400 (second measurement unit) measures second optical information obtained when cells flowing through flow cell 201 pass through irradiation range R of second illumination light, in which multiple diffracted lights generated by diffractive optical element 215 upon which light is incident are distributed.

[0231] According to this configuration, two measurements can be performed using a common flow cell 201, and therefore the configuration for acquiring the first light information and the second light information can be simplified.

[0232] In addition, in embodiment 2, as in modification example 1 of embodiment 1, steps S21 and S22 of FIG. 23 may be executed instead of steps S12 and S14 of FIG. 32, and as in modification example 2 of embodiment 1, step S31 of FIG. 26 may be executed instead of step S14 of FIG. 32.

[0233] <Modification 1 of Embodiment 2> In the second embodiment, as shown in Fig. 32, the first analysis result is determined in step S12, and either step S14 or S15 is executed depending on the first analysis result. However, this is not limiting, and the determination in step S12 may be omitted.

[0234] FIG. 33 is a flowchart showing the control process for measurement by the control unit 30 according to this modified example.

[0235] In the control process of this modified example, steps S41 and S42 are added instead of steps S12 and S14 to S16 in comparison with the second embodiment shown in FIG.

[0236] In step S41, the control unit 31 of the control unit 30 generates a cell analysis result based on the second analysis result. In this case, the cell analysis result includes at least one of the count value and the abnormal cell flag included in the second analysis result. In step S42, the control unit 31 displays the cell analysis result generated in step S41 on the cell analysis result screen 300, and also displays the first analysis result acquired in the first measurement process of step S11 as reference information. In this case, the first analysis result may be additionally displayed on the cell analysis result screen 300 when, for example, a button provided on the cell analysis result screen 300 is operated, or the first analysis result may be displayed on the cell analysis result screen 300 together with a label indicating that it is reference information.

[0237] 33, the cell analysis result is generated based on the second analysis result and the first analysis result is displayed as reference information, but the cell analysis result may be generated based on the first analysis result and the second analysis result may be displayed as reference information. For example, whether the cell analysis result is generated based on the first analysis result or the second analysis result may be selectively determined by the control unit 30. For example, whether the cell analysis result is generated based on the first analysis result or the second analysis result may be selectively determined by the control unit 30 depending on the settings and operations by the laboratory technician.

[0238] <Modification 2 of Embodiment 2> In embodiment 2, the measurement sample used in the second measurement process was prepared in reaction chamber C30, but this is not limited thereto, and an RBC / PLT measurement sample prepared in reaction chamber C11 may also be used in the second measurement process.

[0239] FIG. 34 is a block diagram showing the functional configuration of the sample preparation unit 27 according to this modified example.

[0240] 30, the sample preparation unit 27 of this modified example does not include the reaction chamber C30, and instead connects a reaction chamber C11 to an optical measurement unit 400. In this modified example, for the second measurement sample, an RBC / PLT measurement sample prepared in the reaction chamber C11 is flowed through the flow cell 201, and the measurement sample is irradiated with second illumination light to acquire second light information. In this case, fluorescence based on the second illumination light is not acquired, and therefore the second analysis result is acquired by analyzing the second light information based on the forward scattered light and side scattered light based on the second illumination light.

[0241] According to this modification, the configuration of the sample analyzer 1 can be simplified because the reaction chamber C30 can be omitted.

[0242] In this modified example, in the second measurement process, the RBC / PLT measurement sample is passed through the flow cell 201 to acquire the second optical information, but this is not limited to this, and the second optical information may be acquired by passing a WDF measurement sample through the flow cell 201.

[0243] In this case, the second measurement process may be performed simultaneously with the first measurement process. That is, when the WDF measurement sample prepared in reaction chamber C21 is flowed through flow cell 201, the first optical information and the second optical information regarding white blood cells may be acquired simultaneously. However, in this case, in order to properly acquire the second optical information, the flow rate per unit time of the WDF measurement sample flowing through flow cell 201 must be reduced by control of fluid adjustment unit 400a compared to when only the first optical information is acquired from the WDF measurement sample. However, since the first optical information and the second optical information regarding white blood cells can be acquired simultaneously, it is also possible to shorten the throughput of sample analysis.

[0244] <Embodiment 3> In the first and second embodiments, the count value and the abnormal cell flag are generated based on the second optical information, but as shown in FIG. 35, a reconstructed image of the cells may be generated based on the second optical information.

[0245] The upper part of FIG. 35 is a diagram schematically illustrating a state in which the second illumination light is irradiated onto the irradiation position of the flow cell 201.

[0246] At the irradiation position, the length of the second illumination light in the Z-axis direction (flow direction of the measurement sample) is L1. Also, at the irradiation position, a reconstruction range R2 is set for generating a reconstructed image of the cell to be measured. The length of the reconstruction range R2 in the Z-axis direction is L21, and the length of the reconstruction range R2 in the Y-axis direction is L22.

[0247] If the value of the reconstruction region is L21 × L22, when the value of the reconstruction region is equal to or less than the length L1 of the second illumination light, the control unit 31 generates a reconstructed image using an inverse matrix, as shown in the middle of Fig. 35. On the other hand, when the value of the reconstruction region is greater than the length L1, the control unit 31 generates a reconstructed image using compressed sensing, as shown in the bottom of Fig. 35. Whether the reconstructed image is generated using an inverse matrix or compressed sensing is determined in advance depending on the size of the target cell and the length L1 of the second illumination light.

[0248] The middle part of FIG. 35 is a diagram schematically showing the procedure for generating a reconstructed image using an inverse matrix.

[0249] If the matrix representing the cells to be measured is S, the matrix representing the diffracted light contained in the second illumination light is K, and the matrix representing the second light information is g, the second light information is information based on the light generated when the cells to be measured are irradiated with the second illumination light, and the relationship between S, K, and g is expressed by the following formula (1). Therefore, the matrix S representing the cells is obtained by dividing the inverse matrix of K by K. -1 is obtained by the following equation (2): The control unit 31 generates a reconstructed image based on the matrix S indicating the cells.

[0250] S*K=g …(1) S=g*K -1 …(2)

[0251] The lower part of FIG. 35 is a diagram schematically showing the procedure for generating a reconstructed image by compressed sensing.

[0252] Let K be a matrix representing the diffracted light contained in the second illumination light, x be a matrix representing a reconstructed image of the cell to be measured, and y be a matrix representing the second light information, then the reconstructed image is obtained by the following equation (3). In the following equation (3), argmin indicates minimizing the expression in the parentheses. The first half of the term in the parentheses represents a least-squares solution, and the second half of the term in the parentheses is a term that adds a sparse condition called a regularization term. λ is a variable that determines the ratio between the least-squares solution and the regularization term. The control unit 31 generates a reconstructed image based on the matrix x representing the reconstructed image.

[0253]

number

[0254] In the inverse matrix and compressed sensing, the second light information may be based on any of forward scattered light, side scattered light, and fluorescence. When the second light information based on forward scattered light, side scattered light, and fluorescence is used, a reconstructed image based on forward scattered light, side scattered light, and fluorescence is generated.

[0255] In the third embodiment, when acquisition of the second optical information is completed in the second measurement process, the control unit 31 of the control unit 30 generates a reconstructed image of all cells in the specimen based on the second optical information. The control unit 31 also generates additional information for each cell based on the generated reconstructed image. The additional information includes, for example, cell size, nucleus size, amount of granules, basophilicity level, NC ratio, etc.

[0256] FIG. 36 is a diagram showing a schematic configuration of a reconstructed image display screen 500 for displaying a reconstructed image.

[0257] When the technician operates the input unit 35 to input a display instruction, the control unit 31 of the control unit 30 displays a reconstructed image display screen 500 on the display unit 34. The reconstructed image display screen 500 includes a reconstructed image display area 510 and a radar chart display area 520.

[0258] The reconstructed image display area 510 includes a pull-down menu 510a for selecting the type of light that is the source of the reconstructed image, an area 511 for displaying a plurality of reconstructed images, and a pull-down menu 512 for selecting the type of cell to be displayed in the area 511. In the example shown in Fig. 36, three areas 511 are provided in the reconstructed image display area 510, and reconstructed images corresponding to neutrophils, monocytes, and lymphocytes, respectively, are displayed in each area 511. Furthermore, because side scattered light is selected in the pull-down menu 510a, the reconstructed images displayed in each area 511 are reconstructed images based on side scattered light.

[0259] The radar chart display area 520 includes an area 521 that displays additional information for each cell generated based on the reconstructed image in the form of a radar chart.

[0260] <Effects of the sample analyzer and sample analysis method according to embodiment 3> The control unit 31 generates a reconstructed image (image) that visualizes the cells in the specimen based on the second light information.

[0261] With this configuration, by referring to the reconstructed image that visualizes the cells in addition to the cell analysis results, the laboratory technician can understand the shape of the cells in more detail. Also, by referring to the radar chart based on the additional information generated from the reconstructed image, the laboratory technician can understand the state of the cells in more detail. This reduces the burden on the laboratory technician.

[0262] <Other change examples> In the first to third embodiments, one first illumination light having a single beam spot BS is irradiated onto the cells flowing through the flow cell, but multiple first illumination lights having a single beam spot may be irradiated onto the cells flowing through the flow cell. That is, in the optical measurement unit 100 shown in FIG. 4, another first illumination light having a single beam spot based on light from another light source may be irradiated onto the cells flowing through the flow cell 101. Also, in the optical measurement unit 400 shown in FIG. 31, another first illumination light having a single beam spot based on light from another light source may be irradiated onto the cells flowing through the flow cell 201. The wavelength of the light irradiated from the other light source is preferably different from the wavelength of the light irradiated from the light source 111 or the light source 211.

[0263] In the first to third embodiments, the diffractive optical element 215 may have a light-collecting effect. In this case, for example, the diffraction pattern formed on the diffractive optical element 215 itself may have a light-collecting effect, or a diffraction pattern that generates diffracted light may be formed on the incident surface of the diffractive optical element 215, and a pattern or Fresnel lens having a lens effect may be formed on the exit surface of the diffractive optical element 215. Furthermore, in the first embodiment, when the diffractive optical element 215 has a light-collecting effect, the condenser lens 216 may be omitted.

[0264] In the first to third embodiments, the diffractive optical element 215 is a transmissive diffractive optical element, but it may also be a reflective diffractive optical element.

[0265] In embodiments 1 to 3, the calculation unit 32 of the control unit 30 classified the cells using the AI ​​algorithm 62 based on the detection signals of the light receiving units 225, 233, and 243, but this is not limited to this. The cells may also be classified by comparing the patterns of the detection signals of the light receiving units 225, 233, and 243 with patterns previously stored in the memory unit 33.

[0266] In the first to third embodiments, only the abnormal cell flag is displayed as the analysis result for the abnormal cells, but the count value of the abnormal cells included in the second analysis result may also be displayed.

[0267] In embodiments 1 to 3, count values ​​and abnormal cell flags for neutrophils, normal lymphocytes, monocytes, eosinophils, basophils, blasts, abnormal lymphocytes, atypical lymphocytes, immature granulocytes, and nucleated red blood cells are obtained in the second measurement process, but count values ​​and abnormal cell flags for cells other than these cells may also be obtained.

[0268] In the first to third embodiments, the specimen is blood, but it is not limited to this and may be a body fluid other than blood.

[0269] In the first embodiment, the second measurement process is executed when the first analysis result satisfies the predetermined condition shown in step S12 or step S21, but this is not limiting, and the second measurement process may be executed regardless of the first analysis result, as shown in Figure 32 or 33. Also, in the second embodiment, the second measurement process is executed regardless of the first analysis result, but this is not limiting, and the second measurement process may be executed when the first analysis result satisfies the predetermined condition shown in step S12 or step S21, as shown in Figure 14 or 23.

[0270] In embodiment 1, if the first analysis result satisfies the predetermined conditions shown in step S12 or step S21, the control unit 31 of the control unit 30 may place the specimen container 51 measured by the first measurement unit 10 at a specimen intake position (specimen supply position) by the second measurement unit 20, and if the first analysis result does not satisfy the predetermined conditions, the control unit 31 may control the transport device 40 to cause the specimen container 51 to pass through the second measurement unit 20.

[0271] The embodiments of the present invention can be modified in various ways as appropriate within the scope of the technical idea defined in the claims. [Explanation of symbols]

[0272] 1. Sample analyzer 31 Control Unit 32 Calculation unit (control unit) 40 Transport unit 62 AI Algorithms (Artificial Intelligence Algorithms) 100 Optical measurement section (1st measurement section) 101 Flow cell (first flow cell) 200 Optical measurement section (second measurement section) 201 Flow cell (1st flow cell, 2nd flow cell) 215 Diffractive Optical Elements 400 Optical measurement section (1st measurement section, 2nd measurement section) BS beam spot R illumination range

Claims

1. A sample analyzer for analyzing cells in a sample collected from a subject, comprising: a first measurement unit that measures first light information obtained when the cell passes through at least one beam spot of the first illumination light; a second measurement unit that measures second optical information obtained when the cell passes through an irradiation area of ​​the second illumination light in which a plurality of diffracted lights generated by a diffractive optical element on which the light is incident are distributed; and A sample analysis device comprising: (1) a first analysis result based on the first optical information; (2) a second analysis result based on the second optical information; and (3) a control unit that generates a cell analysis result based on either the first analysis result or the second analysis result.

2. the second measurement unit measures the second optical information, which contains more information corresponding to each of the cells than the first optical information. The sample analyzer according to claim 1 .

3. the second measurement unit measures the second optical information, which contains more information about the morphology of each of the cells than the first optical information. The sample analyzer according to claim 1 .

4. the control unit generates the first analysis result by a first analysis method and generates the second analysis result by a second analysis method; the first analysis method and the second analysis method are different from each other; The sample analyzer according to claim 1 .

5. The control unit selectively determines whether to generate the cell analysis result based on (1) the first analysis result, (2) the second analysis result, or (3) the first analysis result or the second analysis result. The sample analyzer according to claim 1 .

6. the control unit generates the cell analysis result based on the first analysis result and the second analysis result such that the first analysis result is complemented by the second analysis result. The sample analyzer according to claim 1 .

7. the first and second measurement units measure the sample transported to the sample analyzer by a transport unit. The sample analyzer according to claim 1 .

8. the control unit is capable of controlling the operations of the first and second measurement units so that the measurement frequency by the second measurement unit is lower than the measurement frequency by the first measurement unit. The sample analyzer according to claim 1 .

9. The control unit controlling the operations of the first and second measurement units so that the measurement frequency by the second measurement unit is lower than the measurement frequency by the first measurement unit; generating the cell analysis result based on the first analysis result and the second analysis result such that the first analysis result is complemented by the second analysis result; The sample analyzer according to claim 1 .

10. The control unit generates the second analysis result using an artificial intelligence algorithm. The sample analyzer according to claim 1 .

11. the control unit selectively determines whether to generate the cell analysis result based on (1) the first analysis result, (2) the second analysis result, or (3) the first analysis result or the second analysis result, so that the measurement frequency by the second measurement unit is lower than the measurement frequency by the first measurement unit; The sample analyzer according to claim 1 .

12. the acquisition of the second optical information by the second measurement unit and the generation of the second analysis result by the control unit are executed when the first analysis result satisfies a predetermined condition; The control unit generating the cell analysis result based on at least the second analysis result when the first analysis result satisfies the predetermined condition; The sample analyzer according to claim 1 .

13. the predetermined condition is a condition suggesting the presence of abnormal cells in the specimen; The sample analyzer of claim 12.

14. The conditions suggesting the presence of abnormal cells include at least one of the following: a condition suggesting the presence of blast cells, a condition suggesting the presence of abnormal lymphocytes, a condition suggesting the presence of atypical lymphocytes, a condition suggesting the presence of immature granulocytes, a condition suggesting that the classification state of white blood cells is abnormal, and a condition suggesting the presence of nucleated red blood cells. The sample analyzer of claim 13.

15. The control unit generating the cell analysis result suggesting the presence of abnormal cells based on the second analysis result when the first analysis result satisfies the predetermined condition and the second analysis result suggests the presence of abnormal cells; The sample analyzer of claim 13.

16. The control unit generating the cell analysis result that does not suggest the presence of abnormal cells when the first analysis result satisfies the predetermined condition and the second analysis result does not suggest the presence of any type of abnormal cells; The sample analyzer of claim 13.

17. The predetermined condition is a condition in which the number of a predetermined type of cell is outside a predetermined range. The sample analyzer of claim 12.

18. The predetermined range is a numerical range in which the reliability of the analysis results is maintained. The sample analyzer of claim 17.

19. The control unit generating the cell analysis result including the number of the predetermined type of cells based on the second analysis result when the first analysis result indicates that the number of the predetermined type of cells is outside the predetermined range; The sample analyzer of claim 17.

20. The acquisition of the second optical information by the second measurement unit and the generation of the second analysis result by the control unit are performed regardless of the first analysis result. The sample analyzer according to claim 1 .

21. The control unit generating a cell analysis result based on at least the second analysis result when the first analysis result satisfies a predetermined condition; The sample analyzer according to claim 1 .

22. The control unit generating the cell analysis result based on the first analysis result and the second analysis result when the first analysis result satisfies a predetermined condition; The sample analyzer of claim 21.

23. the predetermined condition is a condition suggesting the presence of abnormal cells in the specimen; The sample analyzer of claim 21.

24. The conditions suggesting the presence of abnormal cells include at least one of the following: a condition suggesting the presence of blast cells, a condition suggesting the presence of abnormal lymphocytes, a condition suggesting the presence of atypical lymphocytes, a condition suggesting the presence of immature granulocytes, a condition suggesting that the classification state of white blood cells is abnormal, and a condition suggesting the presence of nucleated red blood cells. The sample analyzer of claim 23.

25. The control unit generating the cell analysis result suggesting the presence of abnormal cells based on the second analysis result when the first analysis result satisfies the predetermined condition and the second analysis result suggests the presence of abnormal cells; The sample analyzer of claim 23.

26. The control unit generating the cell analysis result that does not suggest the presence of abnormal cells when the first analysis result satisfies the predetermined condition and the second analysis result does not suggest the presence of any type of abnormal cells; The sample analyzer of claim 23.

27. a first flow cell and a second flow cell; the first measurement unit measures first optical information obtained when the cells flowing through the first flow cell pass through the beam spot; the second measurement unit measures second optical information obtained when the cells flowing through the second flow cell pass through an irradiation area of ​​second illumination light in which a plurality of diffracted lights generated by a diffractive optical element on which light is incident are distributed. The sample analyzer according to claim 1 .

28. a flow cell; the first measurement unit measures first optical information obtained when the cells flowing through the flow cell pass through the beam spot; the second measurement unit measures second optical information obtained when the cells flowing through the flow cell pass through an irradiation area of ​​second illumination light in which a plurality of diffracted lights generated by a diffractive optical element on which light is incident are distributed. The sample analyzer according to claim 1 .

29. the second illumination light is light having a structured illumination pattern; The sample analyzer according to claim 1 .

30. the first light information includes scattered light information and fluorescent light information from the cells irradiated with the first illumination light; The sample analyzer according to claim 1 .

31. The control unit In generating the first analysis result, a plurality of cell groups irradiated with the first illumination light are grouped; In generating the second analysis result, each cell irradiated with the second illumination light is classified into one of the types of cells. The sample analyzer according to claim 1 .

32. the control unit controls the second measurement unit so that the cells pass through an irradiation area of ​​the second illumination light under fluid conditions according to the first analysis result. The sample analyzer according to claim 1 .

33. the control unit generates an image in which cells in the specimen are visualized based on the second light information. The sample analyzer according to claim 1 .

34. A sample analysis method for analyzing cells in a sample collected from a subject, comprising: acquiring first light information obtained by the cell passing through at least one beam spot of first illumination light; acquiring second optical information obtained by the cell passing through an illumination range of second illumination light in which a plurality of diffracted lights generated by a diffractive optical element on which light is incident are distributed; A sample analysis method comprising the steps of: (1) generating a first analysis result based on the first optical information; (2) generating a second analysis result based on the second optical information; and (3) generating a cell analysis result based on either the first analysis result or the second analysis result.

35. In the step of acquiring the second optical information, the second optical information includes more information corresponding to each of the cells than the first optical information.

35. The method for analyzing a sample according to claim 34.

36. In the step of acquiring the second optical information, the second optical information is measured, the second optical information containing more information about the morphology of each of the cells than the first optical information.

35. The method for analyzing a sample according to claim 34.

37. generating the first analysis result by a first analysis method; generating the second analysis result by a second analysis method; the first analysis method and the second analysis method are different from each other; 35. The method for analyzing a sample according to claim 34.

38. In the step of generating the cell analysis result, (1) the first analysis result, (2) the second analysis result, and (3) selectively determining whether the cell analysis result is generated based on the first analysis result or the second analysis result.

35. The method for analyzing a sample according to claim 34.

39. In the step of generating the cell analysis result, generating the cell analysis result based on the first analysis result and the second analysis result such that the first analysis result is complemented by the second analysis result; 35. The method for analyzing a sample according to claim 34.

40. In the step of acquiring the first optical information and the step of acquiring the second optical information, measuring the sample transported by the transport unit; 35. The method for analyzing a sample according to claim 34.

41. a measurement frequency in the step of acquiring the second light information is lower than a measurement frequency in the step of acquiring the first light information; 35. The method for analyzing a sample according to claim 34.

42. generating the second analysis result using an artificial intelligence algorithm; 35. The method for analyzing a sample according to claim 34.

43. (1) the first analysis result, (2) the second analysis result, and (3) selectively determining whether the cell analysis result is generated based on the first analysis result or the second analysis result, so that the measurement frequency by the second measurement unit is lower than the measurement frequency by the first measurement unit.

35. The method for analyzing a sample according to claim 34.

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