Sample measuring device

Abstract

We provide a specimen measurement device that can streamline specimen testing operations, including malaria infection testing. [Solution] The specimen measuring device 1, which measures a specimen taken from a subject, includes a measuring unit 10 that prepares a measurement sample from the specimen and reagents and detects an optical signal corresponding to at least cells in the measurement sample, and an analysis unit 30 that analyzes cells in accordance with the measurement of the specimen by the measuring unit 10. The measuring unit 10 is capable of selectively performing a plurality of measurement operations on the specimen, including: (1) a first measurement operation in which the specimen is measured using a first reagent containing a first fluorescent dye for staining leukocytes for classification of leukocytes; (2) a second measurement operation in which the specimen is measured using a second reagent containing a second fluorescent dye for staining cells suspected of being infected with malaria; and (3) a third measurement operation in which the specimen is measured using the first reagent and the second reagent.

Description

Technical Field

[0001] The present invention relates to a specimen measurement device for measuring a specimen.

Background Art

[0002] There is known a specimen analysis device for detecting blood cells such as white blood cells and red blood cells infected with malaria. For example, in Patent Document 1 below, from a measurement sample prepared by mixing a blood sample, a hemolytic agent, a first dye capable of staining white blood cells, and a second dye capable of staining infected red blood cells, a scattered light signal, a first fluorescence signal corresponding to the first dye, and a second fluorescence signal corresponding to the second dye are acquired, and an analyzer that acquires white blood cell optical information and infected red blood cell optical information in a single test is described. In this analyzer, white blood cell parameters and infected red blood cell parameters can be detected simultaneously in a single test. As a result, compared with the case of preparing two measurement samples for detecting each parameter, the amount of blood used for the test is reduced, and the test cost is lowered.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] However, for example, for a specimen from a subject in whom no infection is suspected at all, a malaria infection test may not be necessary. In such a case, the above analyzer has a problem that the efficiency of the specimen examination work decreases, such as waste of reagents and time.

[0005] In view of such problems, an object of the present invention is to provide a specimen measurement device capable of improving the efficiency of specimen examination work including a malaria infection test.

Means for Solving the Problems

[0006] The present invention relates to a specimen measuring device for measuring specimens collected from a subject. The specimen measuring device (1) of the present invention includes a measuring unit (10) that prepares a measurement sample from a specimen and reagents and detects an optical signal corresponding to at least cells in the measurement sample, and an analysis unit (30) that analyzes cells in response to the measurement of the specimen by the measuring unit (10). The measuring unit (10) is capable of selectively performing a plurality of measurement operations on the specimen, including: (1) a first measurement operation in which the specimen is measured using a first reagent containing a first fluorescent dye for staining leukocytes for classification of leukocytes; (2) a second measurement operation in which the specimen is measured using a second reagent containing a second fluorescent dye for staining cells suspected of being infected with malaria; and (3) a third measurement operation in which the specimen is measured using the first reagent and the second reagent.

[0007] According to the specimen measurement device of the present invention, for example, depending on the measurement order, analysis results, medical history, test results from other devices, travel history to malaria-endemic areas, and the rainy season or other period when malaria is likely to occur, either one or both of the measurements for white blood cell classification and the measurement of malaria-infected red blood cells can be appropriately selected and performed. This makes specimen testing operations, including malaria infection testing, more efficient. [Effects of the Invention]

[0008] According to the present invention, specimen testing operations, including malaria infection testing, can be made more efficient. [Brief explanation of the drawing]

[0009] [Figure 1] Figure 1 is a perspective view showing the configuration of a sample measuring device according to Embodiment 1. [Figure 2] Figure 2 is a block diagram showing the functional configuration of the measurement unit according to Embodiment 1. [Figure 3] Figure 3 shows the configuration of the optical detection unit according to Embodiment 1. [Figure 4] Figure 4 shows the configuration of the electrical detection unit and the hemoglobin detection unit according to Embodiment 1. [Figure 5] Figure 5 shows a configuration for aspirating and discharging a sample via a suction tube according to Embodiment 1. [Figure 6] Figure 6 shows the configuration of the fluid circuit connected to the chamber and the optical detection unit according to Embodiment 1. [Figure 7] Figure 7 shows the configuration of a fluid circuit connected to a chamber, an electrical detection unit, and a hemoglobin detection unit according to Embodiment 1. [Figure 8] Figure 8 is a block diagram showing the functional configuration of the transport unit and the analysis unit according to Embodiment 1. [Figure 9] Figure 9 shows an example of the relationship between discrete components, measurement mode, and measurement items according to Embodiment 1. [Figure 10] Figure 10 is a diagram showing the configuration of the menu screen according to Embodiment 1. [Figure 11] Figure 11 shows the configuration of the measurement type switching dialog, manual measurement dialog, and measurement unit information display area according to Embodiment 1. [Figure 12] Figure 12 shows the configuration of the measurement order registration screen according to Embodiment 1. [Figure 13] Figure 13 is a diagram illustrating the measurement order registration screen when normal mode is selected as the measurement order according to Embodiment 1. [Figure 14] Figure 14 is a diagram illustrating the measurement order registration screen when malaria mode is selected as the measurement order according to Embodiment 1. [Figure 15] Figure 15 is a diagram illustrating the measurement order registration screen when multimode is selected as the measurement order according to Embodiment 1. [Figure 16] Figure 16 shows the configuration of the scattergram WDF and scattergram WNR according to Embodiment 1. [Figure 17] Figure 17 shows the configurations of scattergram M and scattergram RET according to Embodiment 1. [Figure 18]FIG. 18 is a diagram showing the configuration of the scattergram PLT-F according to Embodiment 1. [Figure 19] FIG. 19 is a diagram showing the configuration of the analysis result display screen according to Embodiment 1. [Figure 20] FIG. 20 is a diagram illustrating an analysis result display screen when the measurement mode and discrete values are set as shown in FIG. 13 according to Embodiment 1. [Figure 21] FIG. 21 is a diagram illustrating an analysis result display screen when the measurement mode and discrete values are set as shown in FIG. 14 according to Embodiment 1. [Figure 22] FIG. 22 is a diagram illustrating an analysis result display screen when the measurement mode and discrete values are set as shown in FIG. 15 according to Embodiment 1. [Figure 23] FIG. 23 is a flowchart showing the processing performed by the control unit of the analysis unit according to Embodiment 1. [Figure 24] FIG. 24 is a diagram showing the configuration of the reflex setting screen according to Embodiment 2. [Figure 25] FIG. 25 is a flowchart showing the processing performed by the control unit of the analysis unit according to Embodiment 2. [Figure 26] FIG. 26 is a flowchart showing the processing performed by the control unit of the analysis unit when the measurement operation is selectively executed based on other information regarding the subject according to Modification 1. [Figure 27] FIG. 27 is a diagram showing the configuration of the fluid circuit connected to the chamber and the optical detection unit according to Modification 2. [Figure 28] FIG. 28 is a diagram showing the configuration of the fluid circuit connected to the chamber and the optical detection unit according to Modification 3. [Figure 29] FIG. 29 is a diagram showing the configuration of the scattergram WDF according to Modification 4. [Figure 30] FIG. 30 is a diagram showing the configuration of the scattergram WDF-1 according to Modification 5.

BEST MODE FOR CARRYING OUT THE INVENTION

[0010] <Embodiment 1> Figure 1 is a perspective view showing the configuration of the sample measuring device 1. Figure 1 shows the directions of up, down, left, right, front, and back.

[0011] The specimen measuring device 1 is a blood cell counter that measures white blood cells, red blood cells, malaria-infected red blood cells, platelets, etc., contained in a specimen, and performs classification and / or counting of each blood cell. The specimen is whole blood collected from the subject. The specimen measuring device 1 comprises a measuring unit 10, a transport unit 20, and an analysis unit 30.

[0012] The transport unit 20 is positioned in front of the measurement unit 10 and transports a sample rack R holding multiple sample containers T to the measurement unit 10. The measurement unit 10 takes a sample container T from the sample rack R, sets the removed sample container T in the sample setting unit 12, and transfers it to the sample aspiration position in the housing 11. The measurement unit 10 aspirates a sample from the sample container T at the sample aspiration position and measures the blood cells contained in the sample. The measurement unit 10 returns the sample container T, after measurement is complete, to the sample rack R.

[0013] The front of the housing 11 of the measurement unit 10 is provided with a changeover switch 13, a start switch 14, and a cover 15. When the changeover switch 13 is operated, the cover 15 opens and the sample setting unit 12 moves to the front of the housing 11. When the operator sets the sample container T in the sample setting unit 12 and operates the start switch 14, the measurement unit 10 drives the sample setting unit 12 to move the sample container T to the sample aspiration position and measures the sample in the sample container T. This allows the measurement to be performed on a predetermined sample container T by interrupting the sample container T on the transport unit 20.

[0014] The analysis unit 30 performs an analysis, including classification and / or counting of blood cells, based on the measurement results obtained by the measurement unit 10, and generates an analysis result. The analysis result includes, for example, result values ​​based on the analysis, graphs, charts, and flag information assigned to the sample.

[0015] The analysis unit 30 includes a display unit 31 and an operation unit 32. The display unit 31 displays analysis results, etc., and is composed of, for example, a liquid crystal display or an organic EL display. The operation unit 32 receives operations from the operator and is composed of, for example, a mouse or keyboard. The display unit 31 and the operation unit 32 may be configured as an integrated unit, or they may be composed of, for example, a touch panel display.

[0016] Figure 2 is a block diagram showing the functional configuration of the measurement unit 10.

[0017] The measurement unit 10 includes an optical detection unit 110, an electrical detection unit 120, a hemoglobin detection unit 130, analog processing units 141, 142, 143, A / D conversion units 151, 152, 153, a reading unit 161, a sample container transfer unit 162, a dispensing unit 163, liquid transfer units 164, 165, IF (interface) units 171, 172, and a communication unit 173.

[0018] The optical detection unit 110 detects optical signals corresponding to blood cells in the sample based on flow cytometry. The electrical detection unit 120 detects electrical signals corresponding to blood cells in the sample based on sheath flow DC detection. The hemoglobin detection unit 130 detects optical signals corresponding to the hemoglobin concentration of the sample based on SLS-hemoglobin detection. The configurations of the optical detection unit 110, the electrical detection unit 120, and the hemoglobin detection unit 130 will be described later with reference to Figures 3 and 4, respectively.

[0019] The analog processing units 141, 142, and 143 perform processing such as noise reduction and smoothing on the analog signals detected by the optical detection unit 110, the electrical detection unit 120, and the hemoglobin detection unit 130, respectively. The A / D conversion units 151, 152, and 153 convert the analog signals processed by the analog processing units 141, 142, and 143 into digital signals, respectively, and transmit the measurement results to the analysis unit 30 via the IF unit 171 and the communication unit 173.

[0020] The reading unit 161 includes a mechanism for reading the sample ID from a barcode label attached to the sample container T that has been transferred into the housing 11. The sample container transfer unit 162 includes a mechanism for removing the sample container T from the sample rack R on the transport unit 20, a sample setting unit 12, and a mechanism for transferring the sample setting unit 12 back and forth.

[0021] The dispensing unit 163 includes a suction tube 301 as shown in Figure 5, and a suction tube transfer unit for transferring the suction tube 301 within the housing 11. The liquid transfer unit 164 includes a flow path, a syringe pump and a valve as shown in Figure 5, and a mechanism for driving these syringe pumps and valves. The liquid transfer unit 165 includes a flow path, chambers C11-C14, C21, C22, a syringe pump, a diaphragm pump and a valve as shown in Figures 6 and 7, and a mechanism for driving these syringe pumps, diaphragm pumps and valves.

[0022] The communication unit 173 is configured, for example, with a connection terminal based on the USB standard, and communicates with the analysis unit 30. Each part of the measurement unit 10 is controlled by the analysis unit 30 via the IF units 171, 172 and the communication unit 173.

[0023] Figure 3 shows the configuration of the optical detection unit 110. For convenience, the X, Y, and Z axes, which are orthogonal to each other, are indicated in Figure 3. The Z axis direction is the flow direction of the sample to be measured in the flow cell 211.

[0024] The optical detection unit 110 includes light sources 201 and 202, a dichroic mirror 203, a flow cell 211, a light receiving unit 221, a dichroic mirror 231, light receiving units 232 and 233, a dichroic mirror 241, and light receiving units 242 and 243.

[0025] Light sources 201 and 202 are, for example, semiconductor laser light sources. Light source 201 emits light with a wavelength of λ10 in the Y-axis direction, and light source 202 emits light with a wavelength of λ20 in the X-axis direction. Wavelength λ10 is in the blue-violet wavelength band, between 315 nm and 490 nm. Wavelength λ20 is in the red wavelength band, between 610 nm and 750 nm. The dichroic mirror 203 is configured to reflect light from light source 201 in the X-axis direction and transmit light from light source 202. The dichroic mirror 203 is positioned so that the light from light sources 201 and 202 overlaps and irradiates the flow channel 211a of the flow cell 211.

[0026] The sample to be measured, supplied to the optical detection unit 110, flows through the channel 211a of the flow cell 211. When blood cells in the sample flowing through channel 211a are irradiated with light of wavelength λ10 from light source 201 and light of wavelength λ20 from light source 202, forward scattered light, side scattered light, and fluorescence are generated from the irradiated area of ​​the blood cells. Here, it is assumed that when the fluorescent dye used to stain the blood cells is irradiated with light of wavelengths λ10 and λ20, light of wavelengths λ11 and λ21 are generated, respectively.

[0027] The light-receiving unit 221 receives forward-scattered light of wavelength λ20 based on light from the light source 202 and detects an optical signal corresponding to the received light intensity. The light-receiving unit 221 is, for example, a photodiode (PD).

[0028] The dichroic mirror 231 is configured to reflect side-scattered light of wavelength λ10 based on light from the light source 201 and transmit fluorescence of wavelength λ11 based on light from the light source 201. The light-receiving unit 232 receives the side-scattered light of wavelength λ10 and detects an optical signal corresponding to the light-receiving intensity. The light-receiving unit 232 is, for example, a photodiode (PD). The light-receiving unit 233 receives fluorescence of wavelength λ11 and detects an optical signal corresponding to the light-receiving intensity. The light-receiving unit 233 is, for example, a photomultiplier tube (PMT), an avalanche photodiode (APD), or a photodiode (PD).

[0029] The dichroic mirror 241 is configured to reflect side-scattered light of wavelength λ20 based on light from the light source 202 and transmit fluorescence of wavelength λ21 based on light from the light source 202. The light-receiving unit 242 receives the side-scattered light of wavelength λ20 and detects an optical signal corresponding to the light-receiving intensity. The light-receiving unit 242 is, for example, a photodiode (PD). The light-receiving unit 243 receives fluorescence of wavelength λ21 and detects an optical signal corresponding to the light-receiving intensity. The light-receiving unit 243 is, for example, a photomultiplier tube (PMT), an avalanche photodiode (APD), or a photodiode (PD).

[0030] Figure 4 shows the configuration of the electrical detection unit 120 and the hemoglobin detection unit 130.

[0031] As shown in the upper part of Figure 4, the flow cell 121 of the electrical detection unit 120 includes a sample nozzle 122, a chamber 123, an aperture 124, a recovery tube 125, and a chamber 126.

[0032] The sample nozzle 122 sends the sample supplied to the electrical detection unit 120 upward. The chamber 123 has a tapered shape that narrows as it goes upward. Sheath fluid is supplied into the chamber 123. The sample, encased in the sheath fluid, passes through the aperture 124 to the recovery tube 125. The blood cells contained in the sample pass through the aperture 124 in a single line. Electrodes are provided on the aperture 124. A direct current is supplied between the electrodes of the aperture 124, and an electrical signal corresponding to the change in DC resistance as the sample passes through the aperture 124 is detected. The electrical signal reflects information about the blood cells passing through the aperture 124.

[0033] Sheath fluid is supplied to the chamber 126 so that it flows downward over the outer region of the recovery tube 125. The sheath fluid flowing outside the recovery tube 125 reaches the lower end of the chamber 126 and then flows into the interior of the recovery tube 125. This prevents blood cells that have passed through the aperture 124 from returning to the aperture 124, thereby preventing false detection of blood cells.

[0034] As shown in the lower part of Figure 4, the hemoglobin detection unit 130 comprises a cell 131, a light source unit 132, and a light receiving unit 133.

[0035] Cell 131 is made of a light-transmitting material and contains the sample to be measured supplied to the hemoglobin detection unit 130. The light source unit 132 irradiates cell 131 with light of a wavelength that has a high absorbance rate due to SLS-hemoglobin. The light receiving unit 133 is positioned opposite the light source unit 132, with cell 131 in between. The light receiving unit 133 receives the transmitted light from the light source unit 132 that was not absorbed by the sample to be measured, and detects an optical signal corresponding to the intensity of the transmitted light. This signal corresponds to the absorbance.

[0036] Figure 5 shows the configuration for aspirating and discharging a sample via the suction tube 301.

[0037] The suction tube 301 is transported by the suction tube transfer unit and inserted into the specimen container T and chambers C11-C14, C21, and C22. The upper end of the suction tube 301 is connected to the syringe pump 311 via a flow path, and a valve 312 is located in this flow path. The syringe pump 311 is equipped with a piston and a motor and is configured to apply a predetermined pressure to the flow path, thereby aspirating a predetermined amount of specimen from the specimen container T via the suction tube 301 and discharging a predetermined amount of the aspirated specimen via the suction tube 301.

[0038] The sample aspirated by the suction tube 301 is dispensed into at least one of the chambers C11-C14, C21, and C22, based on the measurement order set for the sample. In each chamber C11-C14, C21, and C22, the sample is mixed with a predetermined liquid reagent to prepare the measurement sample. Once the dispensing of the sample is complete, the syringe pump 311 draws in any remaining sample from the suction tube 301 and discards it via the valve 313.

[0039] Figure 6 shows the configuration of the fluid circuit connected to chambers C11 to C14 and the optical detection unit 110.

[0040] Chambers C11 to C14 have similar configurations. Chambers C11 to C14 may have different configurations. Chambers C11 to C14 are containers with open tops. Samples aspirated from sample container T by the suction tube 301 are discharged into the chambers C11 to C14 through the openings at the tops. Each chamber C11 to C14 also includes an inlet 321 for supplying reagents, an outlet 322 for discharging the measurement sample prepared in the chamber, and a waste port 323 for discarding the liquid in the chamber. Chambers C11 to C14 are connected to a common optical detection unit 110 by a common flow path 341.

[0041] Chamber C11 is supplied with hemolytic reagent WDF and staining reagent WDF via inlet 321. In chamber C11, the sample, hemolytic reagent WDF, and staining reagent WDF are mixed to prepare the measurement sample WDF. The hemolytic reagent WDF is a reagent that lyses red blood cells and causes damage to the cell membrane of white blood cells to the extent that a fluorescent dye can penetrate it. An example of the hemolytic reagent WDF is LyzaCell® WDF II (manufactured by Sysmex Corporation). The staining reagent WDF contains a fluorescent dye that stains white blood cells for classification. The fluorescent dye contained in the staining reagent WDF is, for example, a cyanine-based fluorescent dye that can be excited by light of wavelength λ20 and can bind to nucleic acids. An example of the staining reagent WDF is FluoroCell® WDF (manufactured by Sysmex Corporation). The measurement sample WDF is supplied to the optical detection unit 110. The measurement sample WDF is used to classify white blood cells. In this specification, classifying leukocytes means classifying them into two or more subgroups.

[0042] The hemolytic reagent WDF is not particularly limited and includes, for example, a nonionic surfactant represented by the following formula (I). In formula (I), R1 is an alkyl group, alkenyl group, or alkynyl group having 8 to 25 carbon atoms, and R2 is an oxygen atom, (COO), or represented by the following formula (II).

[0043] R1-R2-(CH2CH2O)nH (I)

[0044] [ka]

[0045] In the hemolytic reagent WDF, the solvent is not particularly limited as long as it can dissolve the nonionic surfactant represented by formula (I). Examples include water, organic solvents, and mixtures thereof. Examples of organic solvents include C1-C6 alcohols, ethylene glycol, diethylene glycol, polyethylene glycol, and dimethyl sulfoxide (DMSO).

[0046] The hemolytic reagent WDF may contain a buffering agent to maintain a constant pH. Examples of buffering agents include inorganic acid salts, organic acid salts, Good's buffers, and combinations thereof. Examples of inorganic acid salts include phosphates, borates, and combinations thereof. Examples of organic acid salts include citrates, malates, and combinations thereof. Examples of Good's buffers include MES, Bis-Tris, ADA, PIPES, Bis-Tris-Propane, ACES, MOPS, MOPSO, BES, TES, HEPES, HEPPS, Tricin, Tris, Bicine, TAPS, and combinations thereof.

[0047] In the hemolytic reagent WDF, the nonionic surfactant represented by formula (I) may be, for example, polyoxyethylene alkyl ether, polyoxyethylene sterol, polyoxyethylene castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene alkylamine, polyoxyethylene polyoxypropylene alkyl ether, or combinations thereof. Among these, the inclusion of polyoxyethylene alkyl ether is preferred. The polyoxyethylene alkyl ether is preferably at least one selected from polyoxyethylene (23) cetyl ether, polyoxyethylene (25) cetyl ether, polyoxyethylene (30) cetyl ether, and the group thereof. More preferably, it is polyoxyethylene (23) cetyl ether, polyoxyethylene (25) cetyl ether, or combinations thereof, and even more preferably polyoxyethylene (23) cetyl ether. In the hemolytic reagent WDF, there may be one type of nonionic surfactant or two or more types. Furthermore, the hemolytic reagent WDF may also contain cationic surfactants or nonionic surfactants other than the nonionic surfactant represented by formula (I).

[0048] The fluorescent dyes contained in the staining reagent WDF are not particularly limited and can be appropriately selected depending on the wavelength of light emitted from the light source. When the wavelength of light emitted from the light source is in the blue-violet wavelength range, for example, propidium iodide, ethidium bromide, ethidium-acridine heterodimer, ethidium diazide, ethidium homodimer-1, ethidium homodimer-2, ethidium monoazide, trimethylene bis[[3-[[4-[[(3-methylbenzothiazole-3-ium)-2-yl]methylene]-1,4-dihydroquinoline]-1-yl]propyl]dimethylaminium]·tetraiodide (TOTO-1), 4-[(3-methylbenzothiazole-2(3H)-ylidene)methyl]-1-[3-(trimethylaminium] Examples include nio)propyl]quinolinium diiodide (TO-PRO-1), N,N,N',N'-tetramethyl-N,N'-bis[3-[4-[3-[(3-methylbenzothiazole-3-ium)-2-yl]-2-propenylidene]-1,4-dihydroquinoline-1-yl]propyl]-1,3-propanediaminium tetraiodide (TO-3), or 2-[3-[[1-[3-(trimethylaminio)propyl]-1,4-dihydroquinoline]-4-ylidene]-1-propenyl]-3-methylbenzothiazole-3-ium diiodide (TOPRO-3), and combinations thereof.

[0049] Furthermore, the fluorescent dyes contained in the staining reagent WDF include fluorescent dyes represented by the following general formula (III).

[0050] [ka]

[0051] In formula (III), R1 and R4 are the same or different from each other and are a hydrogen atom, an alkyl group, an alkyl chain having a hydroxyl group, an alkyl chain having an ether group, an alkyl chain having an ester group, or a benzyl group which may have a substituent. R2 and R3 are the same or different from each other and are a hydrogen atom, a hydroxyl group, a halogen, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylsulfonyl group, or a phenyl group. Z is a sulfur atom, an oxygen atom, or a carbon atom having a methyl group. n is 0, 1, 2, or 3. n is appropriately selected depending on the wavelength of light irradiated from the light source. - It is an anion.

[0052] In formula (III), the alkyl group may be linear or branched. Furthermore, if either R1 or R4 is an alkyl group having 6 to 18 carbon atoms, the other is preferably a hydrogen atom or an alkyl group having less than 6 carbon atoms. Among alkyl groups having 6 to 18 carbon atoms, alkyl groups having 6, 8, or 10 carbon atoms are preferred.

[0053] In formula (III), examples of substituents on the benzyl groups R1 and R4 include C1-C20 alkyl groups, C2-C20 alkenyl groups, or C2-C20 alkynyl groups. Among these, methyl groups or ethyl groups are particularly preferred.

[0054] In formula (III), examples of alkenyl groups for R2 and R3 include alkenyl groups having 2 to 20 carbon atoms. Examples of alkoxy groups for R2 and R3 include alkoxy groups having 1 to 20 carbon atoms. Among these, methoxy or ethoxy groups are particularly preferred.

[0055] In equation (III), anion X - F - Cl - , Br - and I - Halogen ions like CF3SO3 - BF4 - These are some examples.

[0056] As the hemolytic reagent WDF and staining reagent WDF, the hemolytic reagent and staining reagent described in U.S. Patent Application Publication No. 2022 / 0268763 may be used, and U.S. Patent Application Publication No. 2022 / 0268763 is incorporated herein by reference.

[0057] Returning to Figure 6, the hemolytic reagent WNR and the staining reagent WNR are supplied to chamber C12 via inlet 321. In chamber C12, the sample, the hemolytic reagent WNR, and the staining reagent WNR are mixed to prepare the measurement sample WNR. The hemolytic reagent WNR is a reagent that lyses red blood cells and causes damage to the cell membrane of white blood cells to the extent that a fluorescent dye can penetrate it. An example of the hemolytic reagent WNR is LyzaCell® WNR (manufactured by Sysmex Corporation). The staining reagent WNR contains a fluorescent dye that stains white blood cells and nucleated red blood cells for the counting of white blood cells, basophils, and nucleated red blood cells. The fluorescent dye contained in the staining reagent WNR is, for example, a fluorescent dye that can be excited by light of wavelength λ20 and can bind to nucleic acids. An example of the staining reagent WNR is FluoroCell® WNR (manufactured by Sysmex Corporation). The measurement sample WNR is supplied to the optical detection unit 110. The WNR sample is used to count leukocytes, basophils, and nucleated red blood cells. In this specification, counting leukocytes means counting the total number of all subpopulations of leukocytes.

[0058] Chamber C13 is supplied with hemolytic reagent M and staining reagent M via inlet 321. In chamber C13, the sample, hemolytic reagent M, and staining reagent M are mixed to prepare the measurement sample M. Hemolytic reagent M is a reagent that partially lyses the cell membrane of red blood cells so that a fluorescent dye can pass through while retaining malaria parasites inside the red blood cells. An example of hemolytic reagent M is LyzaCell® M (manufactured by Sysmex Corporation). Staining reagent M contains a fluorescent dye that stains red blood cells suspected of being infected with malaria. The fluorescent dye contained in staining reagent M is, for example, a DNA-selective fluorescent dye that can be excited by light of wavelength λ10 and stains DNA more strongly than RNA. An example of staining reagent M is FluoroCell® M (manufactured by Sysmex Corporation). The measurement sample M is supplied to the optical detection unit 110. The measurement sample M is used to count malaria-infected red blood cells.

[0059] Furthermore, it is preferable that the amount of sample dispensed into chamber C13 by syringe pump 311 (see Figure 5) is greater than the amount of sample dispensed into chamber C11 by syringe pump 311. For this reason, it is preferable that the operation of syringe pump 311 for preparing the measurement sample WDF and the operation for preparing the measurement sample M are different. Since the number of red blood cells infected with malaria is often less than the number of normal white blood cells, the syringe pump 311 can accurately count red blood cells infected with malaria by operating as described above.

[0060] The hemolytic reagent M is not particularly limited, and for example, it includes a first surfactant having a predetermined dissolving power against the cell membrane of red blood cells and a second surfactant having a weaker dissolving power than the first surfactant, has a pH of 5 to 7, and an osmotic pressure of 200 to 300 mOsm / kg·H2O.

[0061] Any of anionic surfactants, nonionic surfactants, or cationic surfactants can be used as the first and second surfactants, but cationic surfactants are preferred.

[0062] Specifically, cationic surfactants that can be used include octyltrimethylammonium bromide (OTAB), decyltrimethylammonium bromide (DTAB), lauryltrimethylammonium chloride (LTAC), myristyltrimethylammonium bromide (MTAB), cetylpyridinium chloride (CPC), and stearyltrimethylammonium chloride (STAC).

[0063] The dissolving power of a surfactant on red blood cell membranes primarily depends on the number of carbon atoms in the surfactant. Specifically, the greater the number of carbon atoms, and in the case of quaternary ammonium salts, the longer the carbon chain of the linear alkyl group, the stronger the dissolving power, but the more likely it is to solidify at room temperature. Therefore, by using a surfactant with a small number of carbon atoms as a red blood cell membrane partial lysis reagent, the solubility of the red blood cell membrane partial lysis reagent in the solvent can be increased, and its influence on the red blood cell membrane can be adjusted. Accordingly, when the first and second surfactants are quaternary ammonium salts having long-chain alkyl groups, it is preferable to have fewer carbon atoms in the long-chain alkyl group of the second surfactant than in the long-chain alkyl group of the first surfactant.

[0064] Specifically, a combination in which the first surfactant is stearyltrimethylammonium chloride (STAC) and the second surfactant is lauryltrimethylammonium chloride (LTAC) is preferably used.

[0065] The combination of the first and second surfactants, and the concentrations of each surfactant in the reagent, are specifically selected so that the red blood cell membrane is dissolved to the extent that the fluorescent dye can penetrate into the red blood cells and the shape of the red blood cells can be maintained. For example, in the case of a combination of STAC with 21 carbon atoms (longest alkyl group is 18 carbon chains) and LTAC with 15 carbon atoms (longest alkyl group is 12 carbon chains), conditions in which STAC is mixed in the range of 40-600 ppm and LTAC in the range of 500-1400 ppm are preferably used.

[0066] Hemolytic reagent M may contain a buffer to maintain a pH of 5-7. Maintaining this pH range allows for partial lysis of the red blood cell membrane, enabling the fluorescent dye to pass through while retaining the malaria parasites within the red blood cells.

[0067] Citric acid, phosphoric acid, succinic acid, and trichine can be used as buffering agents. Hydrochloric acid or sodium hydroxide may be added as pH adjusters to adjust the pH.

[0068] Furthermore, it is preferable that the hemolytic reagent M contains an osmotic regulator to maintain the osmotic pressure in the range of 200-300 mOsm / kg·H2O. Below osmotic pressure of less than 200 mOsm / kg·H2O, the reagent or liquid components in the blood tend to be taken up into the red blood cells, causing them to swell and potentially leading to hypotonic lysis of red blood cells. Above 300 mOsm / kg·H2O, the fluorescent dyes described later for detecting malaria parasites become less likely to enter the red blood cells, and structural changes due to red blood cell contraction may occur.

[0069] Preferably used as osmotic pressure regulators are alkali metal halides such as sodium chloride, alkaline earth halides such as magnesium chloride, metal carboxylate salts such as propionic acid, and sugars such as glucose and mannose.

[0070] Furthermore, the hemolytic reagent M may contain preservatives such as 2-pyridylthio-1-oxide sodium or β-phenethyl alcohol, if necessary.

[0071] Furthermore, the hemolytic reagent M may be diluted with purified water, ethanol, or other substances to adjust its concentration, provided that it does not affect pH or osmotic pressure.

[0072] The hemolytic reagent M preferably further contains a nonionic surfactant that does not substantially dissolve the cell membrane of red blood cells. This allows for more accurate classification of malaria-infected red blood cells according to the developmental stage of the malaria parasite.

[0073] Nonionic surfactants include, specifically, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene(20) sorbitan monoisostearate and polyoxyethylene(20) sorbitan monooleate; castor oils such as polyoxyethylene(30) hydrogenated castor oil and polyoxyethylene(50) hydrogenated castor oil; polyoxyethylene phytosterols such as polyoxyethylene(20) phytosterol (hereinafter abbreviated as "POE(20) phytosterol") and polyoxyethylene(25) phytostanol (hereinafter abbreviated as "POE(25) phytostanol"); polyoxyethylene alkyl ethers such as polyoxyethylene(21) lauryl ether, polyoxyethylene(16) oleyl ether, and polyoxyethylene(20) oleyl ether; and polyoxyethylene(20) · polyoxypropylene(6) decyltetradecyl ether. Polyoxyethylene / polyoxypropylene alkyl ethers such as polyoxypropylene(8) cetyl ether; polyoxyethylene fatty acid esters such as polyoxyethylene(10) monolaurate ester are preferably used. The number in parentheses for polyoxyethylene indicates the number of carbon atoms in the polyethylene chain.

[0074] The fluorescent reagent included in staining reagent M is not particularly limited, and is, for example, a DNA-selective fluorescent dye, preferably a DNA-selective bisbenzimide-based fluorescent dye. A DNA-selective fluorescent dye is a fluorescent dye that stains DNA more strongly than RNA, and a DNA-selective bisbenzimide-based fluorescent dye is one whose skeleton is bisimide-based.

[0075] As such dyes, dyes having a structure like that of formula (IV) below (e.g., Hoechst 34580 from Invitrogen) are preferably used.

[0076] [ka]

[0077] DNA-selective bisbenzimide fluorescent dyes include the above-mentioned dyes, as well as Hoechst 33258 and Hoechst 33342. These dyes have different side chains from Hoechst 34580, but can be excited in the blue-violet wavelength range (315 nm to 490 nm).

[0078] As the hemolytic reagent M and staining reagent M, the hemolytic reagent and staining reagent described in U.S. Patent Application Publication No. 2006 / 0223137 may be used, and U.S. Patent Application Publication No. 2006 / 0223137 is incorporated herein by reference.

[0079] Returning to Figure 6, the diluent RET and staining reagent RET are supplied to chamber C14 via inlet 321. In chamber C14, the sample, diluent RET, and staining reagent RET are mixed to prepare the measurement sample RET. The diluent RET is a reagent for diluting the sample. An example of the diluent RET is Cellpack® DFL (manufactured by Sysmex Corporation). The staining reagent RET is a reagent for staining blood cell components. An example of the staining reagent RET is Fluorocell® RET (manufactured by Sysmex Corporation). The measurement sample RET is supplied to the optical detection unit 110. The measurement sample RET is used to count reticulocytes.

[0080] Furthermore, when chamber C14 is not being used for preparing the measurement sample RET, diluent PLT-F and staining reagent PLT-F are supplied to chamber C14 via inlet 321. In chamber C14, the sample, diluent PLT-F, and staining reagent PLT-F are mixed to prepare the measurement sample PLT-F. Diluent PLT-F is a reagent for diluting the sample. Diluent PLT-F is, for example, Cellpack® DFL (manufactured by Sysmex Corporation). Staining reagent PLT-F is a reagent for staining blood cell components. Staining reagent PLT-F is, for example, Fluorocell® PLT (manufactured by Sysmex Corporation). The measurement sample PLT-F is supplied to the optical detection unit 110. The measurement sample PLT-F is used to count platelets.

[0081] The outlets 322 of chambers C11 to C14 are each connected to a flow path 341 via valves 331. A syringe pump 342, a valve 343, and an optical detection unit 110 are connected to the flow path 341. A diaphragm pump 344 is connected to the flow path 341 via valve 343. A valve 345 is connected to the flow path between valve 343 and the diaphragm pump 344. The waste ports 323 of chambers C11 to C14 are each connected to the waste flow path via valves 332.

[0082] When the preparation of the measurement sample is completed in each chamber shown in Figure 6, the diaphragm pump 344 draws the prepared measurement sample from the corresponding chamber into the flow path 341. The syringe pump 342 supplies the measurement sample stored in the flow path 341 to the optical detection unit 110. The syringe pump 342 is configured to transfer a predetermined amount of the measurement sample stored in the flow path 341 to the optical detection unit 110 by applying a predetermined pressure to the flow path 341.

[0083] The optical detection unit 110 flows the sample to be measured and the sheath fluid into the flow cell 211 (see Figure 3) and detects the optical signal corresponding to the blood cells in the sample to be measured based on the flow cytometry method.

[0084] Specifically, the optical detection unit 110 measures the WDF of the measurement sample and detects optical signals corresponding to leukocytes, etc., in the WDF. The optical detection unit 110 measures the WNR of the measurement sample and detects optical signals corresponding to leukocytes, nucleated red blood cells, etc., in the WNR. The optical detection unit 110 measures the M of the measurement sample and detects optical signals corresponding to leukocytes, malaria-infected red blood cells, etc., in the M. The optical detection unit 110 measures the RET of the measurement sample and detects optical signals corresponding to reticulocytes, etc., in the RET. The optical detection unit 110 measures the PLT-F of the measurement sample and detects optical signals corresponding to platelets, etc., in the PLT-F. The optical detection unit 110 measures each measurement sample individually. The measurement samples that have passed through the flow cell 211 of the optical detection unit 110 are discarded.

[0085] Furthermore, it is preferable that the measurement time for the measurement sample M by the optical detection unit 110 is longer than the measurement time for the measurement sample WDF. The measurement time can be adjusted by changing the amount of measurement sample supplied to the optical detection unit 110 by the syringe pump 342, and / or by changing the flow rate of the measurement sample supplied to the optical detection unit 110 by the syringe pump 342. Since the number of red blood cells infected with malaria is often less than the number of normal white blood cells, the syringe pump 342 and the optical detection unit 110 can be operated as described above to accurately count red blood cells infected with malaria.

[0086] Once measurement by the optical detection unit 110 is completed for one sample, cleaning solution is supplied to the chamber in which the sample was prepared. The cleaning solution in the chamber is then discarded through the waste port 323 and valve 332, and also discharged into the flow path 341 via the outlet 322. The cleaning solution discharged into the flow path 341 is then discarded through valve 345.

[0087] Figure 7 shows the configuration of the fluid circuit connected to chambers C21 and C22, the electrical detection unit 120, and the hemoglobin detection unit 130.

[0088] Chambers C21 and C22 have the same configuration as chambers C11 to C14 described above. However, chamber C22 further includes an inlet 324 for supplying reagents. The sample aspirated from the sample container T by the suction tube 301 is discharged into the chambers C21 and C22 through the opening at the upper end.

[0089] The diluent RBC / PLT is supplied to chamber C21 via inlet 321. In chamber C21, the sample and the diluent RBC / PLT are mixed to prepare the measurement sample RBC / PLT. The diluent RBC / PLT is a reagent used to dilute the sample. The diluent RBC / PLT is, for example, CellPak® DCL (manufactured by Sysmex Corporation). The measurement sample RBC / PLT is supplied to the electrical detection unit 120. The measurement sample RBC / PLT is used to count red blood cells and platelets.

[0090] Chamber C22 is supplied with hemolytic reagent HGB via inlet 324 and diluent HGB via inlet 321. In chamber C22, the sample, hemolytic reagent HGB, and diluent HGB are mixed to prepare the measurement sample HGB. Hemolytic reagent HGB is a reagent for eluting hemoglobin from red blood cells. Examples of hemolytic reagent HGB include Sulfolyzer® (manufactured by Sysmex Corporation). Hemolytic reagent HGB is a reagent for diluting the sample. Examples of hemolytic reagent HGB include Cellpack® DCL (manufactured by Sysmex Corporation). The measurement sample HGB is supplied to the hemoglobin detection unit 130. The measurement sample HGB is used to obtain the hemoglobin concentration.

[0091] The outlet 322 of chamber C21 is connected to the flow path 361 via valve 351. The syringe pump 362, valve 363, and electric detection unit 120 are connected to the flow path 361. The outlet 322 of chamber C22 is connected to the hemoglobin detection unit 130 via valve 353. The hemoglobin detection unit 130 is connected to the flow path 364 via valve 354. Valves 363 and 365 are connected to the flow path 364. The diaphragm pump 366 is connected to the flow path 364 via valve 365. Valve 367 is connected to the flow path between valve 365 and the diaphragm pump 366. The waste ports 323 of chambers C21 and C22 are connected to the waste flow paths via valves 352 and 355, respectively.

[0092] Once the preparation of the RBC / PLT sample in chamber C21 is complete, the diaphragm pump 366 draws the RBC / PLT sample from chamber C21 into the flow path 361. The syringe pump 362 supplies the RBC / PLT sample stored in the flow path 361 to the electrical detection unit 120. The syringe pump 362 is configured to transfer a predetermined amount of the sample stored in the flow path 361 to the electrical detection unit 120 by applying a predetermined pressure to the flow path 361.

[0093] The electrical detection unit 120 flows the measurement sample RBC / PLT and sheath fluid into the flow cell 121 (see upper part of Figure 4) and detects electrical signals corresponding to red blood cells and platelets in the measurement sample RBC / PLT based on the sheath flow DC detection method. The measurement sample RBC / PLT that has passed through the flow cell 121 of the electrical detection unit 120 is discarded.

[0094] When the measurement of the RBC / PLT sample by the electrical detection unit 120 is completed, cleaning solution is supplied to the chamber C21. The cleaning solution in the chamber C21 is discarded through the waste port 323 and discharged into the flow path 361 through the outlet 322. The cleaning solution discharged into the flow path 361 is discarded through the valve 367.

[0095] Once the preparation of the HGB sample in chamber C22 is complete, the HGB sample is supplied to the hemoglobin detection unit 130 via valve 353. The hemoglobin detection unit 130 detects an optical signal corresponding to the hemoglobin concentration based on the HGB sample using the SLS-hemoglobin method. The HGB sample used for measurement in the hemoglobin detection unit 130 is discarded.

[0096] When the measurement of the HGB sample by the hemoglobin detection unit 130 is completed, washing solution is supplied to the chamber C22. The washing solution in the chamber C22 is discarded through the waste port 323 and discharged to the hemoglobin detection unit 130 through the outlet 322. The washing solution discharged to the hemoglobin detection unit 130 passes through the inside of the hemoglobin detection unit 130 and is discharged into the flow path 364. The washing solution discharged into the flow path 364 is discarded through the valve 367.

[0097] Figure 8 is a block diagram showing the functional configuration of the transport unit 20 and the analysis unit 30.

[0098] The transport unit 20 includes a reading unit 21, a sample rack transport unit 22, and a communication unit 23.

[0099] The reading unit 21 includes a mechanism for reading the rack ID and sample ID from barcode labels attached to the sample rack R and sample container T being transported on the transport unit 20. The sample rack transport unit 22 includes a mechanism for transporting the sample rack R on the transport unit 20. The communication unit 23 is composed of connection terminals based on the USB standard and communicates with the analysis unit 30. Each part of the transport unit 20 is controlled by the analysis unit 30 via the communication unit 23.

[0100] The analysis unit 30 comprises a control unit 401, a storage unit 402, and a communication unit 403. The analysis unit 30 also includes a display unit 31 and an operation unit 32 as shown in Figure 1.

[0101] The control unit 401 is composed of, for example, a CPU. The control unit 401 performs sample analysis and controls the measurement unit 10 and the transport unit 20 by executing a computer program stored in the storage unit 402. The storage unit 402 is composed of, for example, an SSD and an HDD. The storage unit 402 stores the measurement results received from the measurement unit 10, the analysis results based on the measurement results, and a program for controlling the analysis unit 30, the measurement unit 10, and the transport unit 20.

[0102] The communication unit 403 is composed of connection terminals based on the USB standard and communicates with the communication unit 173 of the measurement unit 10 (see Figure 2) and the communication unit 23 of the transport unit 20 via a cable based on the USB standard. The control unit 401 receives, via the communication unit 403, the sample ID read by the reading unit 161 of the measurement unit 10 (see Figure 2), the measurement result acquired by the measurement unit 10, and information indicating that the changeover switch 13 and the start switch 14 have been operated. The control unit 401 also receives, via the communication unit 403, the rack ID and sample ID read by the reading unit 21 of the transport unit 20, and information indicating that the sample rack R has been installed in the transport unit 20.

[0103] As described later, the operator sets a measurement order including the measurement details of the sample by specifying a discrete component to which multiple measurement items are pre-associated, such as CBC, CBC+DIFF, CBC+DIFF+RET, CBC+MI, CBC+DIFF+RET, and MI. When the control unit 401 receives a measurement order from the operator, it stores the received measurement order in the storage unit 402. When the control unit 401 receives the sample ID read by the reading unit 161 (see Figure 2) of the measurement unit 10, it reads the measurement order corresponding to the received sample ID from the storage unit 402 and controls the measurement unit 10 to perform the measurement of the sample based on the measurement order.

[0104] Figure 9 shows an example of the relationship between discrete components, measurement mode, and measurement items.

[0105] A discrete component corresponds to a predetermined combination of measurement items. In Figure 9, "CBC," "DIFF," "RET," "PLT-F," and "MI" (hereinafter referred to as sub-discrete components) each correspond to a predetermined measurement item that is different from other sub-discrete components, and a discrete component is either one sub-discrete component or a combination of multiple sub-discrete components.

[0106] "CBC" is a subdiscrete that measures the measurement sample RBC / PLT with an electrical detection unit 120, measures the measurement sample HGB with a hemoglobin detection unit 130, measures the measurement sample WNR with an optical detection unit 110, counts red blood cells, platelets and white blood cells, and obtains hemoglobin concentration, hematocrit value (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC), etc. Since the measurement sample WDF is not prepared in "CBC", white blood cell classification is not performed. "DIFF" is a subdiscrete that measures the measurement sample WDF and measurement sample WNR with an optical detection unit 110, classifies white blood cells into five subpopulations (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), and counts each of the five classified subpopulations. "RET" is a subdiscrete that measures the RET sample using an optical detection unit 110 and counts reticulocytes. "PLT-F" is a subdiscrete that measures the PLT-F sample using an optical detection unit 110 and counts platelets. "MI" is a subdiscrete that measures the RBC / PLT sample using an electrical detection unit 120, measures the M sample using an optical detection unit 110, counts malaria-infected red blood cells, and calculates the ratio of malaria-infected red blood cells to the total red blood cell count. In "MI", the red blood cell count can be obtained from the analysis results obtained by measuring the RBC / PLT sample using the electrical detection unit 120.

[0107] In this embodiment, as shown in Figure 9, 13 types of discrete components are pre-configured, and each of the 13 types of discrete components corresponds to a measurement item.

[0108] The measurement items corresponding to the subdiscrete "CBC" include, for example, WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NRBC#, and NRBC%. NRBC# is the number of nucleated red blood cells, and NRBC% is the ratio of nucleated red blood cells to white blood cells. The measurement items corresponding to the subdiscrete "DIFF" include, for example, NEUT#, LYMPH#, MONO#, EO#, BASO#, NEUT%, LYMPH%, MONO%, EO%, and BASO%. NEUT#, LYMPH#, MONO#, EO#, and BASO# represent the numbers of neutrophils, lymphocytes, monocytes, eosinophils, and basophils, respectively, while NEUT%, LYMPH%, MONO%, EO%, and BASO% represent the ratios of neutrophils, lymphocytes, monocytes, eosinophils, and basophils to white blood cells, respectively. The measurement items corresponding to the subdiscrete "RET" include, for example, RET%, RET#, etc. RET% is the ratio of reticulocytes to the total number of mature red blood cells and reticulocytes, and RET# is the number of reticulocytes. The measurement items corresponding to the subdiscrete "PLT-F" include, for example, IPF, IPF#, PLT, etc. IPF is the ratio of immature platelets to the total number of mature platelets and immature platelets, and IPF# is the number of immature platelets. PLT is the total number of mature platelets and immature platelets. The measurement items corresponding to the subdiscrete "MI" include, for example, MI-RBC#, MI-RBC%, etc. MI-RBC# is the ratio of malaria-infected red blood cells to the total number of malaria-free red blood cells and malaria-infected red blood cells. MI-RBC# is the number of malaria-infected red blood cells.

[0109] When one of the 13 types of discrete components shown in Figure 9 is selected, the control unit 401 measures the corresponding sample, performs analysis on the corresponding measurement item, and obtains the analysis results.

[0110] In this embodiment, discrete circuits that classify white blood cells but do not classify or count malaria-infected red blood cells ("CBC+DIFF", "CBC+DIFF+RET", "CBC+DIFF+PLT-F", "CBC+DIFF+RET+PLT-F") correspond to "Normal Mode" as shown in the Measurement Mode section of Figure 9. Discrete circuits that do not classify white blood cells but count malaria-infected red blood cells ("CBC+MI", "MI", "RET+MI") correspond to "Malaria Mode" as shown in the Measurement Mode section of Figure 9. Discrete circuits that classify white blood cells and count malaria-infected red blood cells ("CBC+DIFF+MI", "CBC+DIFF+RET+MI") correspond to "Multi-Mode" as shown in the Measurement Mode section of Figure 9. Discrete circuits other than those shown in Figure 9 do not correspond to "Normal Mode", "Malaria Mode", or "Multi-Mode".

[0111] When a discrete component corresponding to "normal mode" is selected, the measurement unit 10 performs at least one measurement operation (first measurement operation) to measure the sample using the staining reagent WDF. Specifically, the measurement unit 10 prepares the measurement sample WDF and detects the optical signal corresponding to the cells in the measurement sample WDF using the optical detection unit 110. Based on the measurement results transmitted from the measurement unit 10, the analysis unit 30 creates the scattergram WDF shown in the upper part of Figure 16 and classifies the leukocytes into several subpopulations. Note that the measurement unit 10 does not perform a measurement operation (second measurement operation) to measure the sample using the staining reagent M in the discrete component corresponding to "normal mode".

[0112] When the discrete component corresponding to "malaria mode" is selected, the measurement unit 10 performs at least one measurement operation (second measurement operation) to measure the sample using the staining reagent M. Specifically, the measurement unit 10 prepares the measurement sample M and detects the optical signal corresponding to the cells in the measurement sample M using the optical detection unit 110. Based on the measurement results transmitted from the measurement unit 10, the analysis unit 30 creates the scattergram M shown in the upper part of Figure 17 and counts the malaria-infected red blood cells. Note that the measurement unit 10 does not perform the measurement operation (second measurement operation) to measure the sample using the staining reagent WDF in the discrete component corresponding to "malaria mode".

[0113] When a discrete component corresponding to "multimode" is selected, the measurement unit 10 performs a measurement operation (third measurement operation) that measures the sample using at least staining reagent WDF and staining reagent M. Specifically, the measurement unit 10 prepares the measurement sample WDF, detects the optical signal corresponding to the cells in the measurement sample WDF with the optical detection unit 110, prepares the measurement sample M, and detects the optical signal corresponding to the cells in the measurement sample M with the optical detection unit 110. In other words, when a discrete component corresponding to "multimode" is selected, the measurement unit 10 performs at least the first and second measurement operations. Based on the measurement results transmitted from the measurement unit 10, the analysis unit 30 creates a scattergram WDF shown in the upper part of Figure 16, classifies the leukocytes, creates a scattergram M shown in the upper part of Figure 17, and counts the malaria-infected red blood cells.

[0114] Figure 10 shows the configuration of menu screen 500.

[0115] When the control unit 401 receives a display instruction for the menu screen 500, it displays the menu screen 500 on the display unit 31 and processes the information according to the operator's actions on the menu screen 500. Similarly, in the screens shown in Figures 11 to 15 below, the control unit 401 displays the screen on the display unit 31 and processes the information according to the operator's actions corresponding to that screen.

[0116] The menu screen 500 includes a measurement registration button 501, a measurement mode selection button 502, and a measurement unit information display area 510.

[0117] When the measurement registration button 501 is pressed, the order registration screen 600, which will be described later, is displayed on the display unit 31. The order registration screen 600 will be explained later with reference to Figures 12 to 15.

[0118] When the measurement mode selection button 502 is operated, the measurement mode selection dialog 520 is displayed as shown in Figure 10. The measurement mode selection dialog 520 includes a normal mode button 521, a malaria mode button 522, and a multi-mode button 523. When any one of the normal mode button 521, malaria mode button 522, or multi-mode button 523 is operated, only the operated button is set to a selected state. In Figure 10, the state in which the normal mode button 521 is selected is shown by a solid line frame, and the state in which the malaria mode button 522 and multi-mode button 523 are not selected is shown by a dashed line frame.

[0119] After one of the Normal Mode button 521, Malaria Mode button 522, or Multi-Mode button 523 is selected, if the OK button is pressed, the control unit 401 accepts the selected measurement mode. Upon accepting the measurement mode, the control unit 401 displays the order registration screen 600 shown in Figure 12 on the display unit 31. Note that the acceptance of the measurement mode via the measurement mode selection dialog 520 may be performed for each sample, or a measurement mode that has been accepted may be applied to multiple samples until a different measurement mode is accepted.

[0120] The measurement unit information display area 510 displays various information about the measurement unit 10 (name of the measurement unit 10, sample information being measured, reagent status, etc.). In addition, the sampler measurement button 511 is displayed in the measurement unit information display area 510 when sample measurement using the transport unit 20 (sampler measurement) is being performed.

[0121] As explained with reference to Figure 1, in addition to sampler measurement, the sample measurement device 1 can also perform manual measurement by individually supplying sample containers T to the measurement unit 10 from the front of the housing 11 of the measurement unit 10. When the changeover switch 13 of the measurement unit 10 is operated, the cover 15 opens and the sample setting unit 12 moves forward, and the operator sets the sample container T to be measured in the sample setting unit 12. At this time, as shown on the left side of Figure 11, the measurement type switching dialog 530 is displayed above the measurement unit information display area 510.

[0122] The left side of Figure 11 shows the configuration of the measurement unit information display area 510 and the measurement type switching dialog 530 that are displayed during manual measurement.

[0123] During manual measurement, the measurement unit information display area 510 displays a measurement type switching button 512 and a manual measurement button 513 instead of the sampler measurement button 511 shown in Figure 10.

[0124] The measurement type switching dialog 530 includes radio buttons 531 to 533 for determining which of three measurement types (whole blood measurement, low leukocyte count measurement using whole blood, and dilution measurement) to set the sample to be measured manually. When the OK button is pressed, the control unit 401 accepts the measurement type of the sample to be measured manually, according to the selection status of radio buttons 531 to 533. Then, instead of the measurement type switching dialog 530, the manual measurement dialog 540 is displayed above the measurement unit information display area 510, as shown on the right side of Figure 11.

[0125] The right side of Figure 11 shows the configuration of the measurement unit information display area 510 and the manual measurement dialog 540 that are displayed during manual measurement.

[0126] The manual measurement dialog 540, like the measurement mode selection dialog 520 shown in Figure 10, includes a normal mode button 541, a malaria mode button 542, and a multi-mode button 543. The manual measurement dialog 540 also includes a sample ID input area 544, which is a text box into which a sample ID can be entered. After the measurement mode is selected and the sample ID is entered, when the OK button is pressed, the control unit 401 accepts the measurement mode and sample ID and displays the order registration screen 600 shown in Figure 12 on the display unit 31.

[0127] Furthermore, the measurement type switching dialog 530 shown on the left side of Figure 11 may include a normal mode button, a malaria mode button, and a multi-mode button, similar to the measurement mode selection dialog 520 shown in Figure 10. In this case, after the measurement type and measurement mode are selected in the measurement type switching dialog 530, when the OK button is pressed, the order registration screen 600 shown in Figure 12 will be displayed without, for example, the manual measurement dialog 540.

[0128] Figure 12 shows the configuration of the order registration screen 600. Figures 13 to 15 illustrate the order registration screen 600 when normal mode, malaria mode, and multi-mode are selected as the measurement mode, and the pull-down menu of the discrete selection area 612 is displayed.

[0129] As shown in Figure 12, the order registration screen 600 includes a measurement mode display area 601, a sample ID input area 611, a discrete selection area 612, a sample comment input area 613, a subject ID input area 614, a free selection checkbox 615, and a measurement item display area 620.

[0130] If the measurement mode has been set in the measurement mode selection dialog 520 in Figure 10 or the manual measurement dialog 540 on the right side of Figure 11, and the order registration screen 600 is displayed, the set measurement mode will be automatically displayed in the measurement mode display area 601. As a result, the set measurement mode will be displayed in the measurement mode display area 601, as illustrated in Figures 13 to 15. If no measurement mode is set, the measurement mode display area 601 will be blank.

[0131] The order registration screen 600 may be configured such that the measurement mode display area 601 is configured by a pull-down menu, allowing the user to select from normal mode, malaria mode, or multi-mode.

[0132] The sample ID input area 611 is a text box into which the sample ID can be entered. If a sample ID is entered in the manual measurement dialog 540 on the right side of Figure 11 and the order registration screen 600 is displayed, the entered sample ID will be automatically displayed in the sample ID input area 611.

[0133] The discrete selection area 612 is a pull-down menu that allows selection of one of the multiple discrete components shown in Figure 9. The discrete components displayed as selection candidates in the discrete selection area 612 change according to the measurement mode displayed in the measurement mode display area 601.

[0134] For example, if the measurement mode is normal mode, the four discrete components CBC+DIFF, CBC+DIFF+RET, CBC+DIFF+PLT-F, and CBC+DIFF+RET+PLT-F, which correspond to normal mode in Figure 9, are listed as candidates for selection in the discrete selection area 612, as shown in Figure 13. If the measurement mode is malaria mode, the three discrete components CBC+MI, MI, and RET+MI, which correspond to malaria mode in Figure 9, are listed as candidates for selection in the discrete selection area 612, as shown in Figure 14. If the measurement mode is multi-mode, the two discrete components CBC+DIFF+MI and CBC+DIFF+RET+MI, which correspond to multi-mode in Figure 9, are listed as candidates for selection in the discrete selection area 612, as shown in Figure 15. If no measurement mode is selected, all 13 types of discrete components shown in Figure 9 are listed as candidates for selection in the discrete selection area 612.

[0135] The specimen comment input area 613 is a text box into which comments about the specimen can be entered. For example, the medical history of the subject from whom the specimen was collected, or their travel history to areas where malaria is prevalent, can be entered in the specimen comment input area 613. The subject ID input area 614 is a text box into which the subject ID can be entered.

[0136] The measurement item display area 620 shows the selected status of the measurement items that can be set in the sample measuring device 1. Each measurement item has a checkbox, and the checkbox of the corresponding measurement item is automatically selected according to the discrete component selected in the discrete component selection area 612. The measurement items selected according to the discrete component are predetermined measurement items as explained with reference to Figure 9.

[0137] For example, if "CBC+DIFF+PLT-F" is selected in the discrete selection area 612, the measurement item will be selected in the measurement item display area 620 as shown in Figure 13. If "CBC+MI" is selected in the discrete selection area 612, the measurement item will be selected in the measurement item display area 620 as shown in Figure 14. If "CBC+DIFF+RET+MI" is selected in the discrete selection area 612, the measurement item will be selected in the measurement item display area 620 as shown in Figure 15.

[0138] The measurement items selected (checked) in the measurement item display area 620 correspond one-to-one with the discrete components selected in the discrete component selection area 612, and by default, they cannot be changed. On the other hand, when the operator checks the free selection checkbox 615 by operating the operation unit 32, the control unit 401 may accept the deselection of measurement items that were automatically selected according to the selected discrete components, and the addition of unselected measurement items that were not automatically selected according to the selected discrete components, based on the operation of the operation unit 32. Also, when the free selection checkbox 615 is checked, the control unit 401 may accept the selection of measurement items in the measurement item display area 620 before discrete component selection (see Figure 12), based on the operation of the operation unit 32.

[0139] After a measurement order is entered on the order registration screen 600, when the OK button is pressed, the control unit 401 stores the contents of the order registration screen 600 as one measurement order in the storage unit 402. When a sample container T is supplied to the measurement unit 10, the control unit 401 performs a measurement on the measurement unit 10 based on the measurement order corresponding to the sample in the sample container T, obtains the measurement result, and generates an analysis result based on the measurement result.

[0140] Next, with reference to Figures 16-18, we will explain the scattergram generated based on the measurement results obtained using the optical detection unit 110, and the analysis of blood cells using the scattergram.

[0141] Note that the scattergrams shown in Figures 16-18 include plots corresponding to blood cells; however, these plots are for illustrative purposes only, illustrating the distribution of plots based on the sample. Similarly, the scattergram plots and histogram frequencies shown in Figures 20-22, described later, are also for illustrative purposes only, illustrating the distribution of plots and frequencies based on the sample.

[0142] The upper part of Figure 16 shows the scattergram WDF generated based on the measured sample WDF. In the scattergram WDF, the horizontal axis corresponds to the level of the optical signal (R-SSC) detected based on the side-scattered light produced by the light of wavelength λ20 (red wavelength band) emitted from the light source 202, and the vertical axis corresponds to the level of the optical signal (R-SFL) detected based on the fluorescence produced by the light of wavelength λ20 (red wavelength band) emitted from the light source 202.

[0143] The control unit 401 plots blood cells on a scattergram consisting of the vertical and horizontal axes as described above, using the measurement results based on the measured sample WDF, and generates a scattergram WDF. Then, the control unit 401 sets four regions on the scattergram WDF, as shown by the dashed lines, where (B11) neutrophils and basophils, (B12) lymphocytes, (B13) monocytes, and (B14) eosinophils are distributed.

[0144] The control unit 401 performs a classification step to classify plots corresponding to blood cells in order to set up the four regions described above. The control unit 401 sets up initial regions corresponding to the blood cells to be classified (four initial regions for setting (B11) to (B14) in the case of a scattergram WDF). For each of these initial regions, the control unit 401 sets the plots within the initial region into the cluster belonging to that initial region and calculates the centroid position of the plots belonging to the cluster. The control unit 401 calculates the distance from the plots that do not belong to a cluster to the centroid position of each cluster and changes the initial region so that the plots that do not belong to a cluster are placed in the cluster with the shortest distance. Then, the control unit 401 calculates the centroid position of the plots belonging to each cluster again and repeats the above process until the difference between the previous centroid position and the current centroid position is less than or equal to a reference value. Such a classification step is described, for example, in U.S. Patent No. 5555198. U.S. Patent No. 5555198 is incorporated herein by reference.

[0145] The control unit 401 performs the above classification process to classify the blood cells plotted on the scattergram WDF into one of (B11) to (B14) and obtains the number of blood cells in each region. This classifies the white blood cells and obtains the total number of neutrophils and basophils, the number of lymphocytes, the number of monocytes, and the number of eosinophils.

[0146] The lower part of Figure 16 shows the scattergram WNR generated based on the measured sample WNR. In the scattergram WNR, the horizontal axis corresponds to the level of the optical signal detected based on fluorescence produced by light of wavelength λ20 (red wavelength band) emitted from light source 202 (R-SFL), and the vertical axis corresponds to the level of the optical signal detected based on forward scattered light produced by light of wavelength λ20 (red wavelength band) emitted from light source 202 (R-FSC).

[0147] The control unit 401 plots blood cells on a scattergram consisting of the vertical and horizontal axes as described above, using the measurement results based on the measured sample WNR, and generates a scattergram WNR. Then, the control unit 401 performs the classification process described above and sets three regions in the scattergram WNR, as shown by the dashed lines, where (B21) nucleated red blood cells, (B22) basophils, and (B23) neutrophils, lymphocytes, monocytes, and eosinophils are distributed, respectively. The control unit 401 obtains the number of blood cells in each region from (B21) to (B23). The control unit 401 also calculates the total number of blood cells in (B22) and (B23) and obtains the white blood cell count. As a result, the total number of neutrophils, lymphocytes, monocytes, and eosinophils, as well as the number of nucleated red blood cells, basophils, and white blood cells are obtained.

[0148] The control unit 401 obtains the difference between the blood cell count in (B11) and the blood cell count in (B22) as the neutrophil count. This allows the control unit 401 to count the white blood cells in the sample and classify them into five categories: neutrophils, lymphocytes, monocytes, eosinophils, and basophils, obtaining the number of each of these five classifications. Note that if the classification of neutrophils and basophils is unnecessary, the preparation of the measurement sample WNR and the creation of the scattergram WNR may be omitted. In this case, the control unit 401 may obtain the total number of blood cells from (B11) to (B14) as the white blood cell count.

[0149] The upper part of Figure 17 shows the scattergram M generated based on the measurement sample M. In the scattergram M, the horizontal axis corresponds to the level of the optical signal detected based on fluorescence produced by light of wavelength λ10 (blue-violet wavelength band) emitted from light source 201 (V-SFL), and the vertical axis corresponds to the level of the optical signal detected based on forward scattered light (R-FSC) produced by light of wavelength λ20 (red wavelength band) emitted from light source 202. The vertical axis may also correspond to the level of the optical signal detected based on forward scattered light (V-FSC) produced by light of wavelength λ10 (blue-violet wavelength band) emitted from light source 201.

[0150] The control unit 401 plots blood cells on a scattergram consisting of a vertical axis and a horizontal axis as described above, using the measurement results based on the measurement sample M, and generates a scattergram M. Then, the control unit 401 performs the classification step described above and sets three regions in the scattergram M, as shown by the dashed lines, in which (B30) malaria-infected red blood cells, (B31) malaria-uninfected red blood cells, and (B36) white blood cells are distributed. The control unit 401 may also set four regions within the (B30) region as subpopulations of malaria-infected red blood cells, in which (B32) ring-form (single), (B33) ring-form (multi), (B34) tropozoite, and (B35) schizont are distributed. The control unit 401 obtains the number of blood cells for each region (B30), (B31), and (B36), or the number of blood cells for each region (B31) to (B36). This allows for the acquisition of malaria-infected red blood cell counts, malaria-free red blood cell counts, and white blood cell counts, or malaria-infected red blood cell counts, ring form (single) counts, ring form (multi) counts, tropozoite counts, schizont counts, malaria-free red blood cell counts, and white blood cell counts.

[0151] A ring-form malaria parasite is a red blood cell infected with a ring-form malaria parasite. A ring-form (single) malaria parasite is a red blood cell containing one ring-form malaria parasite. A ring-form (multiple) malaria parasite is a red blood cell containing multiple ring-form malaria parasites. A tropozoite malaria parasite is a red blood cell infected with a tropozoite malaria parasite. A schizont malaria parasite is a red blood cell infected with a schizont malaria parasite.

[0152] The intraerythroblastic life cycle of the malaria parasite begins when a merozoite, one of the morphologies of the parasite, invades a red blood cell. In the intraerythroblastic life cycle, the malaria parasite changes morphologically from ringform to tropozoite and then to schizont. The schizont divides into multiple merozoites, destroying red blood cells in the process. This releases a large number of merozoites into the bloodstream. The merozoites then invade the next red blood cell, and the intraerythroblastic life cycle begins again. The malaria parasite multiplies by repeating this cycle.

[0153] As described above, the control unit 401 analyzes cells (blood cells) by clustering using a scattergram. The horizontal axis, vertical axis, and initial region in scattergram WDF, scattergram WNR, and scattergram M are different from each other. In other words, the control unit 401 analyzes cells by applying different clustering methods to scattergram WDF, scattergram WNR, and scattergram M.

[0154] The lower part of Figure 17 shows the scattergram RET generated based on the measured sample RET. In the scattergram RET, the horizontal axis corresponds to the level of the optical signal (R-SFL) detected based on fluorescence produced by light of wavelength λ20 (red wavelength band) emitted from light source 202, and the vertical axis corresponds to the level of the optical signal (R-FSC) detected based on forward scattered light produced by light of wavelength λ20 (red wavelength band) emitted from light source 202.

[0155] The control unit 401 plots blood cells on a scattergram consisting of the vertical and horizontal axes as described above, using the measurement results based on the measured sample RET, and generates a scattergram RET. Then, the control unit 401 performs the above classification step and sets three regions in the scattergram RET where (B41) mature erythrocytes, (B42) reticulocytes, and (B46) platelets are distributed, as shown by the dashed lines. The control unit 401 may also divide (B42) reticulocytes based on the size of R-SFL and set three regions where (B43) low-fluorescence reticulocytes, (B44) medium-fluorescence reticulocytes, and (B45) high-fluorescence reticulocytes are distributed. The control unit 401 obtains the number of blood cells in each region (B41), (B42), and (B46), or the number of blood cells in each region (B41) to (B46). This allows for the acquisition of mature red blood cell count, reticulocyte count, and platelet count, or mature red blood cell count, reticulocyte count, low-fluorescence reticulocyte count, medium-fluorescence reticulocyte count, high-fluorescence reticulocyte count, and platelet count.

[0156] Figure 18 shows the scattergram PLT-F generated based on the measured sample PLT-F. In the scattergram PLT-F, the horizontal axis corresponds to the level of the optical signal (R-SFL) detected based on fluorescence produced by light of wavelength λ20 (red wavelength band) emitted from light source 202, and the vertical axis corresponds to the level of the optical signal (R-FSC) detected based on forward scattered light produced by light of wavelength λ20 (red wavelength band) emitted from light source 202.

[0157] The control unit 401 plots blood cells on a scattergram consisting of a vertical axis and a horizontal axis as described above, using the measurement results based on the measurement sample PLT-F, and generates a scattergram PLT-F. Then, the control unit 401 performs the classification process described above and sets two regions in the scattergram PLT-F, as shown by the dashed lines, where (B51) red blood cells and (B52) platelets are distributed. The control unit 401 also sets a region within (B52) where (B53) immature platelets are distributed. The control unit 401 obtains the number of blood cells in each region from (B51) to (B53). This allows the number of red blood cells, platelets, and immature platelets to be obtained.

[0158] Figure 19 shows the configuration of the analysis results display screen 700. Figures 20 to 22 illustrate the analysis results display screen 700 when the measurement mode and discrete settings are configured as shown in Figures 13 to 15, respectively.

[0159] When the control unit 401 receives a display instruction for the analysis result display screen 700, it displays the analysis result display screen 700 on the display unit 31 and processes the data according to the operator's operation on the analysis result display screen 700. The content displayed on the analysis result display screen 700 is based on the analysis results corresponding to a single sample ID.

[0160] As shown in Figure 19, the analysis result display screen 700 includes an analysis information display area 701, a result value display area 710, a graph display area 720, a flag display area 731, and a measurement necessity setting area 732.

[0161] The analysis information display area 701 displays the sample ID, measurement mode, and discrete components. The result value display area 710 displays lists corresponding to the sub-discrete components CBC, DIFF, MI, RET, and PLT-F. Each list displays the result value for the measured item. The graph display area 720 displays the scattergram WDF, scattergram WNR, scattergram M, scattergram RET, scattergram PLT-F, histogram RBC, and histogram PLT. The histogram RBC is a histogram of red blood cells generated based on the measured sample RBC / PLT, and the histogram PLT is a histogram of platelets generated based on the measured sample RBC / PLT.

[0162] For example, if the discrete component is "CBC+DIFF+PLT-F", as shown in Figure 20, a list showing the result values ​​of CBC, DIFF, and PLT-F will be displayed in the result value display area 710, and the scattergram WDF, scattergram WNR, scattergram PLT-F, histogram RBC, and histogram PLT will be displayed in the graph display area 720. If the discrete component is "CBC+MI", as shown in Figure 21, a list showing the result values ​​of CBC and MI will be displayed in the result value display area 710, and the scattergram WNR, scattergram M, histogram RBC, and histogram PLT will be displayed in the graph display area 720. When the discrete is "CBC+DIFF+RET+MI", as shown in Figure 22, a list of the result values ​​for CBC, DIFF, RET, and MI is displayed in the result value display area 710, and the scattergram WDF, scattergram WNR, scattergram M, scattergram RET, histogram RBC, and histogram PLT are displayed in the graph display area 720.

[0163] In the flag display area 731, if a predetermined disease is suspected based on the analysis results, that predetermined disease is suspected.

[0164] For example, when the measurement mode is normal mode, if the control unit 401 determines that a plot group exists in the area to the left of area (B11) and below area (B12) in the scattergram WDF shown in the upper part of Figure 16, it adds a malaria-infected red blood cell flag to the analysis results. In this case, as shown in Figure 20, "Suspected malaria infection" is displayed in the flag display area 731. For example, when the measurement mode is malaria mode or multi-mode, if the control unit 401 determines that the number of malaria-infected red blood cells (MI-RBC#) in the result value display area 710 is greater than or equal to a predetermined value, it adds a malaria-positive flag to the analysis results. In this case, as shown in Figures 21 and 22, "Malaria positive" is displayed in the flag display area 731.

[0165] In the measurement necessity setting area 732, if the flag display area 731 indicates that a specific disease is suspected, the name of the measurement to examine the specific disease in detail and a checkbox to set whether or not to perform the measurement are displayed.

[0166] For example, when the measurement mode is normal mode, if the control unit 401 displays "Suspected malaria infection" in the flag display area 731, it displays the message "Malaria measurement required" and a checkbox in the measurement requirement setting area 732, as shown in Figure 20. In this case, if the operator operates the checkbox to set it to checked state, a flag indicating that it is preferable to perform a malaria measurement (e.g., discrete MI measurement) is added to the analysis results. When the measurement mode is malaria mode, if the control unit 401 displays "Malaria positive" in the flag display area 731, it displays the message "Leukocyte classification measurement required" and a checkbox in the measurement requirement setting area 732, as shown in Figure 21. In this case, if the operator operates the checkbox to set it to checked state, a flag indicating that it is preferable to perform a leukocyte classification measurement (e.g., discrete CBC+DIFF measurement) is added to the analysis results.

[0167] If the measurement necessity setting area 732 for a particular sample is set to the checked state, and a flag indicating that it is preferable to perform measurements related to malaria or leukocyte classification is added to the analysis results, then physicians and other operators can see on the analysis results display screen 700 for that sample and understand that there are necessary measurements for that sample. This allows physicians and other operators to perform the necessary measurements smoothly.

[0168] Furthermore, if the measurement mode is multi-mode, the analysis result display screen 700 shown in Figure 22 may be divided into a screen for leukocyte classification and a screen for malaria-infected red blood cells. In this case, for example, the screen for leukocyte classification will display result values ​​and scattergrams other than discrete MI, and the screen for malaria-infected red blood cells will display result values ​​and scattergrams only for discrete MI. Histogram RBC and histogram PLT only need to be displayed on at least one of the screens. In this case, buttons for switching between the leukocyte classification screen and the malaria-infected red blood cell screen may also be provided on both screens.

[0169] Figure 23 is a flowchart showing the processing performed by the control unit 401 of the analysis unit 30.

[0170] In step S11, the control unit 401 waits to process until it receives a measurement instruction. In sampler mode, when the sample rack R is placed in the transport unit 20, the control unit 401 receives information from the transport unit 20 indicating that the sample rack R has been placed, thereby receiving a measurement instruction. In manual mode, when the start switch 14 is operated, the control unit 401 receives information from the transport unit 20 indicating that the start switch 14 has been operated, thereby receiving a measurement instruction. Upon receiving a measurement instruction (step S11: YES), the control unit 401 transports the sample container T into the housing 11 and controls the reading unit 161 to read the sample ID from the sample container T. Based on the read sample ID, the control unit 401 reads the measurement order stored in the storage unit 402.

[0171] In sampler mode, the control unit 401 repeatedly performs steps S12 and S13 for each of the multiple samples continuously supplied to the measurement unit 10. In manual mode, it performs steps S12 and S13 for the sample set in the sample setting unit 12.

[0172] In step S12, the control unit 401 controls the measurement unit 10 to selectively execute one of the first, second, or third measurement operations based on the measurement order. The first measurement operation is a measurement operation for leukocyte classification, performed when the normal mode discrete shown in Figure 9 is selected. The second measurement operation is a measurement operation for counting malaria-infected red blood cells, performed when the malaria mode discrete shown in Figure 9 is selected. The third measurement operation is a measurement operation for leukocyte classification and counting malaria-infected red blood cells, performed when the multi-mode discrete shown in Figure 9 is selected. In step S12, the control unit 401 may read a measurement order that has been entered via the order registration screen 600 and stored in the storage unit 402, or it may receive a measurement order transmitted from a host computer that can communicate with the analysis unit 30.

[0173] In other words, the control unit 401 controls the measurement unit 10 to selectively perform a plurality of measurement operations, including a first measurement operation in which the sample is measured using staining reagent WDF containing a fluorescent dye for staining white blood cells for classification of white blood cells; a second measurement operation in which the sample is measured using staining reagent M containing a fluorescent dye for staining red blood cells suspected of being infected with malaria; and a third measurement operation in which the sample is measured using staining reagent WDF and staining reagent M.

[0174] In the discrete CBC, CBC+RET, CBC+PLT-F, and CBC+RET+PLT-F configurations shown in Figure 9, the measurement unit 10 performs only measurement operations that do not fall under any of the first, second, or third measurement operations described above. In other words, in this embodiment, the measurement unit 10 can selectively perform multiple measurement operations on a sample, including the first, second, third, and other measurement operations.

[0175] The measurement unit 10 generates measurement results through the measurement operation in step S12 and transmits the generated measurement results to the analysis unit 30. In step S13, the control unit 401 performs analysis based on the measurement results received from the measurement unit 10 and generates analysis results.

[0176] Subsequently, when the control unit 401 receives a display instruction from the operator for the analysis result display screen 700, in step S14, it displays the analysis result display screen 700 on the display unit 31 based on the analysis results of the target sample ID.

[0177] <Effects of the specimen measuring device according to Embodiment 1> The specimen measuring device 1, which measures a specimen collected from a subject, includes a measuring unit 10 that prepares a measurement sample WDF, a measurement sample M, etc. from the specimen and reagents and detects an optical signal corresponding to at least cells in the measurement sample, and an analysis unit 30 that analyzes cells in accordance with the measurement of the specimen by the measuring unit 10. The measuring unit 10 is capable of selectively performing a number of measurement operations on the specimen, including: (1) a first measurement operation in which the specimen is measured using a staining reagent WDF (first reagent) containing a fluorescent dye (first fluorescent dye) for staining leukocytes for classification of leukocytes; (2) a second measurement operation in which the specimen is measured using a staining reagent M (second reagent) containing a fluorescent dye (second fluorescent dye) for staining cells suspected of being infected with malaria; and (3) a third measurement operation in which the specimen is measured using staining reagent WDF (first reagent) and staining reagent M (second reagent).

[0178] This configuration allows for the selection and execution of either or both of the following measurements: white blood cell classification and malaria-infected red blood cell measurement, depending on factors such as the measurement order, analysis results, medical history, test results from other devices, travel history to malaria-endemic areas, and the rainy season when malaria is more likely to occur. This streamlines specimen testing operations, including malaria infection testing.

[0179] The measurement unit 10 includes an optical detection unit 110, an electrical detection unit 120, a hemoglobin detection unit 130, a reading unit 161, a sample container transfer unit 162, a dispensing unit 163, liquid transfer units 164 and 165, light sources 201 and 202, a suction tube 301, syringe pumps 311 and 342, and chambers C11 to C14, C21 and C22 (multiple mechanisms for measuring the sample). The measurement unit 10 shares at least one of the above-mentioned multiple mechanisms in the first measurement operation, the second measurement operation, and the third measurement operation.

[0180] This configuration simplifies the structure of the sample measuring device 1 compared to a case where a mechanism is provided for each measurement operation.

[0181] The measurement unit 10 includes an optical detection unit 110 for detecting optical signals corresponding to cells in the measurement sample. The measurement unit 10 shares the optical detection unit 110 for the first measurement operation, the second measurement operation, and the third measurement operation.

[0182] This configuration simplifies the structure of the sample measuring device 1 compared to a case where an optical detection unit is provided for each measurement operation.

[0183] The measurement unit 10 includes light sources 201 and 202 (at least one light source) for irradiating the sample to be measured with light. The measurement unit 10 shares the above at least one light source for the first measurement operation, the second measurement operation, and the third measurement operation.

[0184] This configuration simplifies the setup of the sample measuring device 1 compared to the case where a light source is provided for each measurement operation.

[0185] The measurement unit 10 includes a light source 201 for irradiating the sample to be measured with light of wavelength λ10 (first wavelength) and a light source 202 for irradiating with light of wavelength λ20 (second wavelength). In the first measurement operation, the measurement unit 10 irradiates the sample to be measured with at least one of the light of wavelength λ10 (first wavelength) and the light of wavelength λ20 (second wavelength), and in the second measurement operation, it irradiates the sample to be measured with light of wavelength λ10 (first wavelength) and light of wavelength λ20 (second wavelength).

[0186] This configuration simplifies the structure of the sample measuring device 1 compared to the case where a light source is provided for each of the first and second measurement operations.

[0187] The measurement unit 10 includes a suction tube 301 for aspirating the sample supplied to the sample measuring device 1. The measurement unit 10 uses the suction tube 301 for the first measurement operation, the second measurement operation, and the third measurement operation.

[0188] This configuration simplifies the structure of the sample measuring device 1 compared to the case where a suction tube is provided for each measurement operation.

[0189] The measurement unit 10 includes a suction tube 301 for aspirating the sample supplied to the sample measuring device 1, and a syringe pump 311 (pump) used to aspirate the sample using the suction tube 301. The measurement unit 10 shares the suction tube 301 and the syringe pump 311 (pump) for the first measurement operation, the second measurement operation, and the third measurement operation.

[0190] This configuration simplifies the structure of the sample measuring device 1 compared to a case where a suction tube and pump are provided for each measurement operation.

[0191] In the third measurement operation, the measurement unit 10 performs the first measurement operation and the second measurement operation.

[0192] With this configuration, as shown in Modification Example 2 described later, the likelihood of obtaining highly accurate analytical results can be increased compared to the case where the measurement sample WDF-M1, which contains both staining reagent WDF (first reagent) and staining reagent M (second reagent), is measured in the third measurement operation.

[0193] The measurement unit 10 includes an optical detection unit 110, an electrical detection unit 120, a hemoglobin detection unit 130, a reading unit 161, a sample container transfer unit 162, a dispensing unit 163, liquid transfer units 164, 165, light sources 201, 202, a suction tube 301, syringe pumps 311, 342, and chambers C11-C14, C21, C22 (multiple mechanisms for measuring the sample). At least one of the above multiple mechanisms performs a different operation in each of the first and second measurement operations.

[0194] For example, in Embodiment 1, the amount of sample dispensed in the first measurement operation and the amount of sample dispensed in the second measurement operation are different, and the measurement time of the optical detection unit 110 in the first measurement operation and the measurement time of the optical detection unit 110 in the second measurement operation are different. Therefore, the syringe pumps 311 and 342 perform different operations in the first measurement operation and the second measurement operation, respectively. With the above configuration, in the first measurement operation and the second measurement operation, the target mechanism can be made to perform an appropriate operation according to the measurement operation.

[0195] The measurement unit 10 includes an optical detection unit 110 for detecting optical signals corresponding to cells in the measurement sample. The measurement time by the optical detection unit 110 in the first measurement operation is different from the measurement time by the optical detection unit 110 in the second measurement operation.

[0196] With this configuration, in the first and second measurement operations, the optical detection unit 110 can be instructed to measure an appropriate measurement time according to the measurement operation.

[0197] The measurement unit 10 includes chambers C11-C14, C21, C22 and a syringe pump 311, etc. (sample preparation section) for preparing measurement samples from the sample and reagents. Chambers C11, C13 and the syringe pump 311, etc. (sample preparation section) prepare a measurement sample WDF (first measurement sample) from the sample and staining reagent WDF (first reagent) in the first measurement operation, and prepare a measurement sample M (second measurement sample) from the sample and staining reagent M (second reagent) in the second measurement operation.

[0198] With this configuration, the measurement sample WDF and the measurement sample M can be smoothly prepared in the first and second measurement operations, respectively.

[0199] Chambers C11 and C13 (sample preparation units) prepare a measurement sample WDF (first measurement sample) from the sample, staining reagent WDF (first reagent), and hemolysis reagent WDF (first hemolysis reagent) in the first measurement operation, and prepare a measurement sample M (second measurement sample) from the sample, staining reagent M (second reagent), and hemolysis reagent M (second hemolysis reagent) in the second measurement operation.

[0200] With this configuration, in the first measurement operation, the measurement sample WDF can be properly prepared using the hemolytic reagent WDF, and in the second measurement operation, the measurement sample M can be properly prepared using the hemolytic reagent M.

[0201] In the second measurement operation, the measurement unit 10 measures the sample to count cells suspected of being infected with malaria (count of blood cells in area (B30) of scattergram M) and to count white blood cells (count in area (B36) of scattergram M).

[0202] With this configuration, based on the measurement results obtained from the second measurement operation, the number of malaria-infected red blood cells and white blood cells can be referenced to perform a malaria test with high accuracy.

[0203] The measurement unit 10 includes an optical detection unit 110 for detecting optical signals corresponding to cells in the measurement sample, and an electrical detection unit 120 for detecting electrical signals corresponding to cells in the measurement sample. The measurement unit 10 uses both the optical detection unit 110 and the electrical detection unit 120 in the first and second measurement operations.

[0204] With this configuration, by using both the optical detection unit 110 and the electrical detection unit 120 in the first and second measurement operations, the sample can be analyzed in more detail. Specifically, the optical detection unit 110 can classify and count white blood cells, while the electrical detection unit 120 can count red blood cells and platelets.

[0205] The analysis unit 30 analyzes cells using different clustering methods in the first and second measurement operations.

[0206] This configuration allows for proper cell analysis during both the first and second measurement operations.

[0207] The analysis unit 30 classifies white blood cells into several subpopulations in the analysis corresponding to the first measurement operation.

[0208] This configuration allows for accurate testing based on white blood cell counts.

[0209] In the analysis corresponding to the second measurement operation, the analysis unit 30 obtains information about the malaria life cycle for cells suspected of being infected with malaria.

[0210] This configuration allows for the acquisition of information about the life cycle (life stages) of malaria, such as ringform, tropozoite, and schizont, enabling a detailed understanding of the state of the malaria parasite infecting the subject.

[0211] The analysis unit 30 selects a measurement operation to be performed by the measurement unit 10 according to the measurement order (information about the sample) (step S12 in Figure 23).

[0212] With this configuration, the first, second, and third measurement operations are automatically selected according to the measurement order, allowing for smooth execution of measurement operations by registering the measurement order in advance.

[0213] The analysis unit 30 includes a control unit 401, a display unit 31, and an operation unit 32. The control unit 401 displays a measurement mode selection dialog 520 and a manual measurement dialog 540 (screen) on the display unit 31 for selecting one measurement mode from three measurement modes that divide multiple measurement operations into first, second, and third measurement operations. The operation unit 32 accepts the measurement mode selected via the measurement mode selection dialog 520 and manual measurement dialog 540 (screen), and displays an order registration screen 600 (other screen) on the display unit 31 for selecting a measurement operation corresponding to the accepted measurement mode.

[0214] With this configuration, the operator can select a measurement mode, which in turn displays an order registration screen 600 for selecting the measurement operation corresponding to that mode. This allows the operator to smoothly select the measurement operation via the order registration screen 600.

[0215] The analysis unit 30 includes a control unit 401, a display unit 31, and an operation unit 32. The control unit 401 displays an order registration screen 600 (screen) on the display unit 31 for selecting the first, second, and third measurement operations from a plurality of measurement operations, and accepts the selected measurement operation via the order registration screen 600 (screen) through operation of the operation unit 32.

[0216] With this configuration, the operator can have the measurement unit 10 perform the measurement actions necessary for the subject.

[0217] The analysis unit 30 includes a control unit 401, a display unit 31, and an operation unit 32. The control unit 401 may display an order registration screen 600 (screen) on the display unit 31 for selecting at least one measurement item from a plurality of measurement items that define the first, second, and third measurement operations, respectively, and may accept the selected measurement item via the order registration screen 600 (screen) by operating the operation unit 32.

[0218] With this configuration, the operator can further specify the measurement actions required for the subject and have the measurement unit 10 execute the set measurement actions.

[0219] The analysis unit 30 includes a control unit 401, a display unit 31, and an operation unit 32. The control unit 401 displays an order registration screen 600 (screen) on the display unit 31 for registering a measurement order indicating which of the first, second, or third measurement operations to perform, and accepts the measurement order registered via the order registration screen 600 (screen) through operation of the operation unit 32.

[0220] With this configuration, by registering measurement orders in advance, the necessary measurement actions for the subject can be performed smoothly thereafter.

[0221] <Embodiment 2> Based on the analysis results obtained from the measurement by the sample measuring device 1, it may be determined whether or not to perform further measurements on other discrete components (measurement items) for the same sample using the sample measuring device 1, i.e., whether or not reflex measurement is necessary. In this case, if it is determined that reflex measurement is necessary, the relevant measurement is performed automatically. The following describes configurations and processes that differ from Embodiment 1.

[0222] Figure 24 is a diagram showing the configuration of the reflex settings screen 800 according to this embodiment.

[0223] When the control unit 401 receives a display instruction for the reflex setting screen 800, it displays the reflex setting screen 800 on the display unit 31 and processes the information according to the operator's actions on the reflex setting screen 800.

[0224] The reflex setting screen 800 includes a reflex rule display area 810 and a reflex rule addition area 820.

[0225] The reflex rule display area 810 displays reflex rules for determining whether reflex measurement is necessary. Each row corresponds to one reflex rule. A reflex rule includes a name, a conditional expression for determining whether reflex measurement is necessary, and an action that defines the process to be performed automatically if reflex measurement is determined to be necessary.

[0226] The reflex rule includes, for example, executing discrete MI if a malaria-infected red blood cell flag is added to the analysis results in normal mode, as shown in the first line of the reflex rule display area 810. In this case, the number of malaria-infected red blood cells, etc., which could not be obtained by white blood cell classification, can be obtained, allowing for an accurate determination of whether or not the person has malaria. The reflex rule also includes, for example, executing discrete CBC+DIFF if a malaria-positive flag is added to the analysis results in malaria mode, as shown in the second line of the reflex rule display area 810. In this case, the number of white blood cells for each classification, etc., which could not be obtained by malaria-infected red blood cell classification, can be obtained, allowing for an accurate understanding of the subject's condition.

[0227] The reflex rule addition area 820 includes text boxes 821 to 823 corresponding to the name, condition expression, and action of the reflex rule, respectively, and an add button 824. When the name, condition expression, and action are entered via the operation unit 32 and the add button 824 is operated, the control unit 401 receives the contents of the reflex rule addition area 820, stores them in the storage unit 402, and adds and displays the received reflex rule in the reflex rule display area 810.

[0228] Figure 25 is a flowchart showing the processing performed by the control unit 401 of the analysis unit 30.

[0229] In the process shown in Figure 25, steps S21 and S22 are added compared to the process in Embodiment 1 shown in Figure 23. In step S21, the control unit 401 determines whether there is an analysis result among the analysis results generated in step S13 that matches the condition expression of the reflex rule stored in the storage unit 402. If there is an analysis result that matches the condition expression of the reflex rule (step S21: YES), in step S22, the control unit 401 transports the sample container T containing the sample that was the subject of the reflex rule determination back to the sample aspiration position in the housing 11. Then, the control unit 401 selectively performs a measurement operation on the sample in the sample container T according to the action of the matched reflex rule.

[0230] <Effects of the specimen measuring device according to Embodiment 2> The analysis unit 30 selects a measurement operation to be performed by the measurement unit 10 according to the analysis results (information about the sample) (step S22 in Figure 25).

[0231] With this configuration, the first, second, and third measurement operations are automatically selected according to the analysis results, eliminating the need for the operator to refer to the analysis results and select the measurement operation.

[0232] <Example of change 1> In Embodiment 1, the measurement operation was selectively performed based on the measurement order, and in Embodiment 2, the measurement operation was selectively performed again based on the analysis results. However, the measurement operation may be selectively performed based on information other than that related to the sample, such as the measurement order and analysis results. For example, other information related to the sample may include information about the subject from whom the sample was collected, such as medical history, test results from other devices, and travel history to malaria-endemic areas.

[0233] Figure 26 is a flowchart showing the processes performed by the control unit 401 of the analysis unit 30 when the measurement operation is selectively performed based on information about the subject.

[0234] The flowchart in Figure 26, compared to Embodiment 1 in Figure 23, has steps S31 to S34 added in place of step S12.

[0235] In step S31, the control unit 401 obtains other information about the subject from whom the sample to be measured was collected, for example, from the electronic medical record system via a computer network. In step S32, the control unit 401 determines whether the subject is suspected to be infected with malaria, based on the other information about the subject obtained in step S31. For example, if the information obtained from the electronic medical record system includes information indicating that the subject has a history of travel to a malaria-endemic area, the control unit 401 determines that the subject is suspected to be infected with malaria.

[0236] If malaria infection is suspected (Step S32: YES), the control unit 401 controls the measurement unit 10 to perform a second or third measurement operation. If malaria infection is not suspected (Step S32: NO), the control unit 401 controls the measurement unit 10 to perform a first measurement operation.

[0237] In addition, the operator may pre-set whether to perform the second measurement operation or the third measurement operation in step S33. Furthermore, the malaria mode discrete circuitry executed when the second measurement operation is performed and the multi-mode discrete circuitry executed when the third measurement operation is performed may pre-set by the operator.

[0238] <Effects of the sample measuring device based on modification example 1> The analysis unit 30 selects the measurement operation to be performed by the measurement unit 10 according to other information about the subject (steps S31 to S34 in Figure 26).

[0239] With this configuration, the first, second, and third measurement actions are automatically selected based on other information about the subject, eliminating the need for the operator to refer to other information about the subject to select the measurement action.

[0240] If the sample is obtained from a subject suspected of being infected with malaria (step S32 in Figure 26: YES), the analysis unit 30 selects either a second or third measurement operation (step S33).

[0241] For subjects suspected of being infected with malaria, it is desirable to perform a second or third measurement operation, which includes measuring the sample M. With the above configuration, the second or third measurement operation is automatically selected for samples obtained from subjects suspected of being infected with malaria, thus eliminating the need to determine the necessary measurement operation.

[0242] If the analysis unit 30 obtains a sample from a subject who is not suspected of being infected with malaria (step S32: NO in Figure 26), it selects the first measurement operation (step S34).

[0243] For subjects not suspected of being infected with malaria, the second and third measurement operations, including the measurement of sample M, are unnecessary. With the above configuration, the first measurement operation is automatically selected for samples obtained from subjects not suspected of being infected with malaria, thus preventing the selection of unnecessary measurement operations.

[0244] <Example of change 2> In Embodiment 1, in a multimode discrete system, the measurement sample WDF and the measurement sample M were prepared separately, and measurements based on the measurement sample WDF and the measurement sample M were performed separately. However, the invention is not limited to this, and a single measurement sample WDF-M1 corresponding to both the measurement sample WDF and the measurement sample M may be prepared, and analytical results similar to those based on the measurement sample WDF-M1 may be obtained based on the measurement of the measurement sample WDF-M1.

[0245] Figure 27 shows the configuration of the fluid circuit connected to chambers C12, C14, C15 and the optical detection unit 110.

[0246] In this modified example, compared to Embodiment 1 in Figure 6, chamber C15 is added in place of chambers C11 and C13. Chamber C15 has the same configuration as the other chambers C12 and C14 and is connected to the flow path 341 in the same way as the other chambers C12 and C14. Furthermore, staining reagent WDF, staining reagent M, and hemolytic reagent WDF-M are supplied through the inlet 321 of chamber C15.

[0247] In this modified example, when multimode discrete CBC+DIFF+MI or CBC+DIFF+RET+MI is selected in the measurement order, instead of preparing measurement sample WDF and measurement sample M separately, the sample, staining reagent WDF, staining reagent M, and hemolytic reagent WDF-M are mixed in chamber C15 to prepare measurement sample WDF-M1. Hemolytic reagent WDF-M is a reagent that partially lyses the cell membrane of red blood cells so that the fluorescent dyes contained in staining reagent WDF and staining reagent M can pass through while retaining malaria parasites inside the red blood cells. The lytic power of hemolytic reagent WDF-M on the cell membrane of red blood cells is preferably stronger than that of hemolytic reagent M and weaker than that of hemolytic reagent WDF. Hemolytic reagent WDF-M includes, for example, a nonionic surfactant, a cationic surfactant, anionic surfactant, an amphiphilic surfactant, or a combination thereof.

[0248] Once the preparation of the measurement sample WDF-M1 is complete, the measurement sample WDF-M1 is supplied to the optical detection unit 110 via the flow path 341, and measurement is performed in the optical detection unit 110 using light sources 201 and 202.

[0249] When the sample WDF-M1 is measured, the scattergram WDF in the upper part of Figure 16 and the scattergram M in the upper part of Figure 17 are generated based on the measurement results of the sample WDF-M1. The control unit 401 then classifies the blood cells plotted in the scattergram WDF into one of (B11) to (B14) and obtains the number of blood cells in each region, and classifies the blood cells plotted in the scattergram M into one of (B30), (B31), or (B36), or one of (B31) to (B36), and obtains the number of blood cells in each region.

[0250] When the Normal Mode discrete is selected, the sample WDF-M2 is prepared in chamber C15 by mixing the sample with the hemolytic reagent WDF-M and the staining reagent WDF. Based on the measurement results of the sample WDF-M2, the scattergram WDF shown in the upper part of Figure 16 is generated. When the Malaria Mode discrete is selected, the sample WDF-M3 is prepared in chamber C15 by mixing the sample with the hemolytic reagent WDF-M and the staining reagent M. Based on the measurement results of the sample WDF-M3, the scattergram M shown in the upper part of Figure 17 is generated. In other words, in this modified example, the sample WDF-M1, the sample WDF-M2, and the sample WDF-M3 are prepared in a common chamber C15.

[0251] <Effects of the sample measuring device based on modification example 2> In the third measurement operation, the measurement unit 10 prepares a common measurement sample WDF-M1 for the classification of leukocytes and the counting of cells suspected of being infected with malaria, and detects the optical signal corresponding to the cells in the measurement sample WDF-M1.

[0252] With this configuration, in the third measurement operation, only one measurement sample needs to be prepared for the leukocyte and malaria infection tests. This allows the third measurement operation to be performed more efficiently compared to preparing the measurement sample WDF for the leukocyte test and the measurement sample M for the malaria infection test separately.

[0253] Furthermore, with this configuration, since the measurement samples WDF-M1 / M2 / M3 can be prepared using a common hemolytic reagent WDF-M in the first, second, and third measurement operations, the number of reagents connected to the sample measuring device 1 can be reduced.

[0254] In addition, in the modified example 2, reflex measurement may be performed as in embodiment 2. In this case, the reflex rule may include, for example, performing a multimode discrete analysis if a flag for malaria-infected red blood cells is added to the normal mode analysis results. This allows for obtaining further analysis results based on the measurement sample WDF-M1, making it possible to determine with even greater accuracy whether or not a person has contracted malaria.

[0255] Furthermore, in modification example 2, when a multimode discrete was selected in the measurement order, the control unit 401 performed an analysis based on the measurement sample WDF-M1. However, it is not limited to this, and the operator may be asked in advance whether to perform a first analysis based on measurement samples WDF-M2 and WDF-M3, or a second analysis based on measurement sample WDF-M1. This allows the operator to decide, for example, whether to perform the first or second analysis according to the facility's operational policy.

[0256] Furthermore, in Modification Example 2, a common chamber C15 is provided for preparing the measurement samples WDF-M1, WDF-M2, and WDF-M3. However, the design is not limited to this, and a separate chamber may be provided for preparing at least one of the measurement samples WDF-M1, WDF-M2, and WDF-M3, in addition to chamber C15.

[0257] <Example of change 3> In modification example 2, staining reagent WDF, staining reagent M, and hemolytic reagent WDF-M were connected to chamber C15. However, the configuration is not limited to this; as shown in Figure 28, hemolytic reagent WDF, staining reagent WDF, hemolytic reagent M, and staining reagent M may also be connected to chamber C15.

[0258] In this modified example, when multimode discrete is selected, the measurement sample WDF is prepared in chamber C15 by mixing the sample with hemolytic reagent WDF and staining reagent WDF, and the scattergram WDF shown in the upper part of Figure 16 is generated based on the measurement results of the measurement sample WDF. After the measurement sample WDF is discharged from chamber C15 and chamber C15 is washed, the measurement sample M is prepared in chamber C15 by mixing the sample with hemolytic reagent M and staining reagent M, and the scattergram M shown in the upper part of Figure 17 is generated based on the measurement results of the measurement sample M. The preparation of the measurement sample WDF and the measurement sample M may be performed in either order.

[0259] When the Normal Mode discrete is selected, the measurement sample WDF is prepared in chamber C15 by mixing the sample with the hemolytic reagent WDF and the staining reagent WDF. Based on the measurement results of the measurement sample WDF, the scattergram WDF shown in the upper part of Figure 16 is generated. When the Malaria Mode discrete is selected, the measurement sample M is prepared in chamber C15 by mixing the sample with the hemolytic reagent M and the staining reagent M. Based on the measurement results of the measurement sample M, the scattergram M shown in the upper part of Figure 17 is generated. In other words, in this modified example, the measurement sample WDF and measurement sample M are prepared in a common chamber C15.

[0260] In addition, reflex measurement may be performed in this modified example as in Embodiment 2.

[0261] <Example of change 4> In Embodiment 1, in the measurement of sub-discrete DIFF, the specimen measurement device 1 prepared measurement samples WDF and WNR, and created scattergrams WDF and WNR. In this modification example, the specimen measurement device 1 does not prepare the measurement sample WNR and create the scattergram WNR in the measurement of sub-discrete DIFF, but prepares the measurement sample WDF and creates the scattergram WDF.

[0262] FIG. 29 shows an example of the scattergram WDF. The scattergram WDF is created based on the measurement results of the measurement sample WDF, similar to Embodiment 1.

[0263] The control unit 401 sets five initial regions corresponding to lymphocytes, monocytes, eosinophils, neutrophils, and basophils for the scattergram WDF in FIG. 29, and performs the classification process described in Embodiment 1. As a result, compared with the scattergram WDF in the upper part of FIG. 16, the control unit 401 sets the regions of (B15) neutrophils and (B16) basophils instead of (B11) neutrophils and basophils. Then, the control unit 401 acquires the number of blood cells for each of the regions (B12) to (B14), (B15), and (B16). Also, the control unit 401 acquires the total number of blood cells in (B12) to (B14), (B15), and (B16) as the white blood cell count. That is, in this modification example, the measurement unit 10 prepares the measurement sample WDF and detects the optical signal for the cells in the measurement sample WDF in order to count and classify white blood cells.

[0264] <Effect of the Specimen Measurement Device According to Modification Example 4> The measurement unit 10 measures the specimen for counting and classifying white blood cells in the first measurement operation.

[0265] According to this configuration, since only one measurement sample needs to be prepared for counting and classifying white blood cells, the measurement operation for counting and classifying white blood cells can be performed more efficiently than when the measurement samples WDF and WNR are prepared separately.

[0266] <Modification Example 5> In Embodiment 1, the vertical and horizontal axes of the scattergrams WDF, WNR, M, RET, and PLT were set as shown in Figures 16-18. However, the optical signals used for the axes of each scattergram may be any optical signals based on light from light sources 201 and 202. In either case, regions corresponding to the type of axis are set for each scattergram so that blood cells can be properly classified.

[0267] However, when an optical signal based on fluorescence generated by light from light source 201 is used, the staining reagent mixed with the sample contains a fluorescent dye that can be excited by light of wavelength λ10, and when an optical signal based on fluorescence generated by light from light source 202 is used, the staining reagent mixed with the sample contains a fluorescent dye that can be excited by light of wavelength λ20.

[0268] Figure 30 shows an example of a scattergram WDF-1. The scattergram WDF-1 is created based on the measurement results of the sample WDF. In the scattergram WDF-1, the horizontal axis corresponds to the level of the optical signal (V-SSC) detected based on the side-scattered light produced by the light of wavelength λ10 (blue-violet wavelength band) emitted from the light source 201, and the vertical axis corresponds to the level of the optical signal (V-SFL) detected based on the fluorescence produced by the light of wavelength λ10 (blue-violet wavelength band) emitted from the light source 201.

[0269] The control unit 401 sets five initial regions corresponding to lymphocytes, monocytes, eosinophils, neutrophils, and basophils in the scattergram WDF-1 and performs the classification process described in Embodiment 1. As a result, the control unit 401 sets the regions (B12-1) lymphocytes, (B13-1) monocytes, (B14-1) eosinophils, (B15-1) neutrophils, and (B16-1) basophils. The control unit 401 then obtains the number of blood cells for each region (B12-1) to (B14-1), (B15-1), and (B16-1). The control unit 401 also obtains the total number of blood cells in (B12-1) to (B14-1), (B15-1), and (B16-1) as the white blood cell count. In other words, in this modified example, the measurement unit 10 prepares a measurement sample WDF to count and classify leukocytes and detects an optical signal for cells in the measurement sample WDF.

[0270] <Effects of the sample measuring device based on modification example 5> In the first measurement operation, the measurement unit 10 measures the sample for the purpose of counting and classifying white blood cells.

[0271] With this configuration, only one measurement sample needs to be prepared for leukocyte counting and classification, which allows for more efficient measurement operations for leukocyte counting and classification compared to preparing the measurement sample WDF and measurement sample WNR separately.

[0272] In Embodiment 1, only a light-receiving unit 221 that detects forward-scattered light based on light with wavelength λ20 was provided as a light-receiving unit corresponding to forward-scattered light. However, if forward-scattered light based on light with wavelength λ10 is used for analysis, a light-receiving unit that detects forward-scattered light based on light with wavelength λ10 may be provided in place of or together with the light-receiving unit 221.

[0273] Furthermore, if only optical signals based on wavelength λ10 light from the light source 201 are used as the optical signals for the axes of each scattergram, a light-receiving unit that detects forward scattered light based on wavelength λ10 light is provided in place of the light-receiving unit 221, and the light source 202, dichroic mirror 241, and light-receiving units 242 and 243 are omitted.

[0274] <Example of change 6> In Embodiment 1, when a discrete component containing subdiscrete MI is selected, the measurement unit 10 measures the measurement sample RBC / PLT with the electrical detection unit 120 and the measurement sample M with the optical detection unit 110. However, it is not limited to this, and in the measurement operation for measuring the measurement sample M (second measurement operation), the measurement unit 10 may measure the measurement sample M with the optical detection unit 110 without using the electrical detection unit 120. In this case, the control unit 401 calculates the sum of the blood cell counts in the (B30) and (B31) regions of the scattergram M (see upper part of Figure 17) as the number of red blood cells necessary for calculating the measurement item MI-RBC%.

[0275] <Effects of the sample measuring device based on modification example 6> The measurement unit 10 includes an optical detection unit 110 for detecting optical signals corresponding to cells in the measurement sample, and an electrical detection unit 120 for detecting electrical signals corresponding to cells in the measurement sample. In the second measurement operation, the measurement unit 10 does not use the electrical detection unit 120.

[0276] With this configuration, the amount of sample and reagent used can be reduced by not using the electrical detection unit 120 in the second measurement operation.

[0277] <Other examples of changes> In the above embodiment and its modifications, when a measurement mode is selected, only the discrete components corresponding to the measurement mode are displayed in the discrete selection area 612 of Figure 12, and the discrete component to be actually executed is determined by the operator selecting a discrete component in the discrete selection area 612. However, the operator is not limited to this, and the discrete component to be actually executed may be uniquely determined according to the selected measurement mode. For example, if there are three types of discrete components provided in the sample measuring device 1, namely CBC+DIFF, MI, and CBC+DIFF+MI, then when normal mode, malaria mode, and multi-mode are selected, CBC+DIFF, MI, and CBC+DIFF+MI may be determined as the discrete components, respectively.

[0278] In the above embodiments and modifications, leukocytes were classified into five subpopulations in the measurement and analysis corresponding to subdiscrete DIFF, but leukocytes may be classified into two, three, or four subpopulations.

[0279] In the above embodiments and modifications, a predetermined amount of sample was measured in both the first and second measurement operations. However, the method is not limited to this. For example, in the measurement of sample M included in the second measurement operation, the measurement may be continued until a predetermined number of malaria-infected red blood cells are detected. In other words, the measurement time of the second measurement operation may be variable. This allows for more reliable detection of malaria-infected red blood cells. Furthermore, in the measurement of sample M included in the second measurement operation, the light emission power of light sources 201 and 202 may be increased compared to the first measurement operation. In this case, the detection sensitivity of malaria-infected red blood cells can be increased.

[0280] In the above-described Modification Example 2, when "Malaria positive" is displayed in the flag display area 731 on the analysis result display screen 700 related to the multi-mode shown in FIG. 22, a message "Measurement requirements for both the normal mode and the malaria mode" and a check box may be displayed in the measurement necessity setting area 732. In this case, when the operator operates the check box to set it to the checked state, a flag indicating that it is preferable that measurement related to white blood cell classification (for example, measurement of discrete CBC+DIFF) and measurement related to malaria (for example, measurement of discrete MI) are performed may be added to the analysis result.

[0281] In the above-described embodiments and modification examples, when the measurement necessity setting area 732 shown in FIGS. 20 and 21 is set to the checked state, a measurement order related to the necessary measurement operation may be automatically registered.

[0282] In the above-described embodiments and modification examples, the measurement order is stored in the storage unit 402 of the analysis unit 30, but it may be stored in a host computer communicable with the analysis unit 30. In this case, when a measurement order is input in the specimen measurement device 1 or another device, the input measurement order is transmitted to the host computer and is centrally managed in the host computer. When the analysis unit 30 receives the specimen ID read by the reading unit 161, it inquires the host computer about the measurement order and receives the measurement order corresponding to the specimen ID from the host computer.

[0283] In the embodiments of the present invention, various modifications can be appropriately made within the scope of the technical idea shown in the claims.

Explanation of Reference Numerals

[0284] 1 Specimen measurement device 10 Measurement unit 30 Analysis unit 31 Display unit 32 Operation unit 110 Optical detection unit (mechanism) 120 Electrical detection unit (mechanism) 130 Hemoglobin detection unit (mechanism) 161 Reading Unit (Mechanism) 162 Sample container transfer unit (mechanism) 163 Dispensing Unit (Mechanism) 164, 165 Liquid transfer section (mechanism) 201, 202 Light source (mechanism) 301 Suction tube (mechanism) 311 Syringe pump (mechanism, pump, sample preparation unit) 342 Syringe pump (mechanism) 401 Control Unit 520 Measurement Mode Selection Dialog (Screen) 540 Manual Measurement Dialog (Screen) 600 Order registration screen (screen, other screens) C11-C15, C21, C22 Chambers (Mechanism, Sample Preparation Section)

Claims

1. A specimen measuring device for measuring specimens collected from a subject, A measurement unit that prepares a measurement sample from the aforementioned sample and reagents and detects an optical signal corresponding to at least the cells in the measurement sample, The analysis unit includes an analysis unit that analyzes the cells in accordance with the measurement of the sample by the measurement unit, The measurement unit measures the sample as follows: (1) A first measurement operation in which the sample is measured using a first reagent containing a first fluorescent dye for staining the leukocytes in order to classify the leukocytes, (2) A second measurement operation in which the sample is measured using a second reagent containing a second fluorescent dye for staining the cells suspected of being infected with malaria, (3) A third measurement operation in which the sample is measured using the first reagent and the second reagent, Multiple measurement operations, including the following, can be selectively performed. Sample measuring device.

2. The measurement unit includes a plurality of mechanisms for measuring the sample to be measured, The measurement unit shares at least one of the plurality of mechanisms in the first measurement operation, the second measurement operation, and the third measurement operation. A specimen measuring device according to claim 1.

3. The measurement unit includes an optical detection unit for detecting an optical signal corresponding to the cells in the measurement sample. The measurement unit shares the optical detection unit for the first measurement operation, the second measurement operation, and the third measurement operation. A specimen measuring device according to claim 1.

4. The measurement unit includes at least one light source for irradiating the sample to be measured with light, The measurement unit shares the at least one light source for the first measurement operation, the second measurement operation, and the third measurement operation. A specimen measuring device according to claim 1.

5. The measurement unit includes a light source for irradiating the sample to be measured with light of a first wavelength and a light source for irradiating light of a second wavelength. In the first measurement operation, the measurement unit irradiates the sample to be measured with at least one of the first wavelength of light and the second wavelength of light, and in the second measurement operation, irradiates the sample to be measured with the first wavelength of light and the second wavelength of light. A specimen measuring device according to claim 1.

6. The first wavelength is 315 nm or more and 490 nm or less. The second wavelength is 610 nm or more and 750 nm or less. A specimen measuring device according to claim 5.

7. The measurement unit includes a suction tube for aspirating the sample supplied to the sample measuring device. The measurement unit uses the suction tube for the first measurement operation, the second measurement operation, and the third measurement operation. A specimen measuring device according to claim 1.

8. The measurement unit includes a suction tube for aspirating the sample supplied to the sample measuring device, and a pump used to aspirate the sample by the suction tube. The measurement unit uses the suction tube and the pump for the first measurement operation, the second measurement operation and the third measurement operation. A specimen measuring device according to claim 1.

9. The measurement unit performs the first measurement operation and the second measurement operation in the third measurement operation. A specimen measuring device according to claim 1.

10. The measurement unit includes a plurality of mechanisms for measuring the sample to be measured, At least one of the aforementioned plurality of mechanisms performs a different operation in each of the first measurement operation and the second measurement operation. A specimen measuring device according to claim 1.

11. The measurement unit includes an optical detection unit for detecting an optical signal corresponding to the cells in the measurement sample. The measurement time by the optical detection unit in the first measurement operation is different from the measurement time by the optical detection unit in the second measurement operation. A specimen measuring device according to claim 1.

12. The measurement unit includes a sample preparation unit for preparing the measurement sample from the sample and the reagent, The sample preparation unit prepares a first measurement sample from the sample and the first reagent in the first measurement operation, and prepares a second measurement sample from the sample and the second reagent in the second measurement operation. A specimen measuring device according to claim 1.

13. The sample preparation unit prepares a first measurement sample from the sample, the first reagent, and the first hemolytic reagent in the first measurement operation, and prepares a second measurement sample from the sample, the second reagent, and the second hemolytic reagent in the second measurement operation. A specimen measuring device according to claim 12.

14. The measurement unit measures the sample for the purpose of counting and classifying the white blood cells in the first measurement operation. A specimen measuring device according to claim 1.

15. In the second measurement operation, the measurement unit measures the sample for the purpose of counting the cells suspected of being infected with malaria and counting the white blood cells. A specimen measuring device according to claim 1.

16. In the third measurement operation, the measurement unit prepares a common measurement sample for classifying the leukocytes and counting the cells suspected of being infected with malaria, and detects the optical signal corresponding to the cells in the measurement sample. A specimen measuring device according to claim 1.

17. The measurement unit includes an optical detection unit for detecting an optical signal corresponding to the cells in the measurement sample, and an electrical detection unit for detecting an electrical signal corresponding to the cells in the measurement sample. The measurement unit uses both the optical detection unit and the electrical detection unit in the first measurement operation and the second measurement operation. A specimen measuring device according to claim 1.

18. The measurement unit includes an optical detection unit for detecting an optical signal corresponding to the cells in the measurement sample, and an electrical detection unit for detecting an electrical signal corresponding to the cells in the measurement sample. The measurement unit does not use the electrical detection unit in the second measurement operation. A specimen measuring device according to claim 1.

19. The analysis unit analyzes the cells using different clustering methods in the first and second measurement operations. A specimen measuring device according to claim 1.

20. The analysis unit, in the analysis corresponding to the first measurement operation, classifies the white blood cells into multiple subgroups. A specimen measuring device according to claim 1.

21. The analysis unit, in the analysis corresponding to the second measurement operation, obtains information on the malaria life cycle for the cells suspected of being infected with malaria. A specimen measuring device according to claim 1.

22. The analysis unit selects the measurement operation to be performed by the measurement unit according to the information about the sample. A specimen measuring device according to claim 1.

23. The analysis unit selects either the second measurement operation or the third measurement operation if the sample is obtained from a subject suspected of being infected with malaria. The specimen measuring device according to claim 22.

24. The analysis unit selects the first measurement operation if the sample is obtained from a subject who is not suspected of being infected with malaria. The specimen measuring device according to claim 22.

25. The analysis unit has a control unit, a display unit, and an operation unit. The control unit, The display unit displays a screen for selecting one of three measurement modes, each of which divides multiple measurement operations into the first, second, and third measurement operations, and the operation unit accepts the selected measurement mode via the screen. The display unit is shown another screen for selecting the measurement operation corresponding to the accepted measurement mode. A specimen measuring device according to claim 1.

26. The analysis unit has a control unit, a display unit, and an operation unit. The control unit, The display unit is shown a screen for selecting the first, second, and third measurement operations from among multiple measurement operations. The operation unit accepts the measurement operation selected via the screen. A specimen measuring device according to claim 1.

27. The analysis unit has a control unit, a display unit, and an operation unit. The control unit, A screen for selecting at least one of the multiple measurement items that define the first, second, and third measurement operations is displayed on the display unit. The operation unit accepts the measurement item selected via the screen. A specimen measuring device according to claim 1.

28. The analysis unit has a control unit, a display unit, and an operation unit. The control unit, A screen for registering a measurement order indicating which of the first, second, or third measurement operations to perform is displayed on the display unit. The operation of the control unit accepts the measurement order registered via the screen. A specimen measuring device according to claim 1.

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