Subject measurement device

Abstract

Provided is a subject measurement device capable of efficiently performing a subject inspection service including an inspection of malaria infection. A subject measurement device for measuring a subject collected from a subject includes: a measurement unit for preparing a measurement sample from the subject and a reagent and detecting at least an optical signal corresponding to cells in the measurement sample; and an analysis means for analyzing the cells on the basis of the measurement of the subject by the measurement means. The measurement unit is capable of selectively performing a plurality of measurement operations on a subject. The plurality of measurement operations include: a first measurement operation in which a subject is measured using a first reagent containing a first fluorescent dye for staining white blood cells for classification of white blood cells, and a second measurement operation in which the subject is measured using a second reagent containing a second fluorescent dye for staining white blood cells for classification of white blood cells; a second measurement operation in which the subject is measured using a second reagent containing a second fluorescent dye that stains cells suspected of being infected with malaria; and a third measurement operation in which the subject is measured using the first reagent and the second reagent.

Description

Technical Field

[0001] This invention relates to a subject measurement device for measuring a subject. Background Technology

[0002] Analytical devices for detecting blood cells such as white blood cells and malaria-infected red blood cells are known. For example, Patent Document 1 describes an analytical device that acquires a scattered light signal, a first fluorescence signal corresponding to the first dye, and a second fluorescence signal corresponding to the second dye from a test sample prepared by mixing a first dye that can stain blood samples, a hemolysin, and white blood cells with a second dye that can stain infected red blood cells. The device acquires optical information of white blood cells and infected red blood cells in a single test. In this analytical device, white blood cell parameters and infected red blood cell parameters can be detected simultaneously in a single examination. Therefore, compared to preparing two test samples for each parameter, the amount of blood used in the examination is reduced, and the examination cost is lowered.

[0003] [Existing Technical Documents] [Patent Literature] [Patent Document 1] International Publication No. 2022 / 115982 Summary of the Invention [The problem the invention aims to solve] However, for example, malaria testing is sometimes unnecessary for subjects from whom there is no suspicion of infection. In such cases, the analytical apparatus suffers from reduced efficiency in the subject testing process, such as wasted reagents or time.

[0004] In view of the aforementioned issues, the object of the present invention is to provide a subject testing device that can improve the efficiency of subject testing services, including malaria infection testing.

[0005] [Technical means to solve the problem] This invention relates to a subject measurement device for measuring a subject collected from a subject. The subject measurement device (1) of the present invention comprises: a measurement unit (10) for preparing a measurement sample from the subject and reagents, and detecting at least an optical signal corresponding to a cell in the measurement sample; and an analysis unit (30) for analyzing the cells based on the measurement of the subject by the measurement unit (10). The measurement unit (10) is capable of selectively performing multiple measurement actions on the subject, the multiple measurement actions including: (1) a first measurement action of measuring the subject using a first reagent containing a first fluorescent dye for staining white blood cells for classification; (2) a second measurement action of measuring the subject using a second reagent containing a second fluorescent dye for staining cells suspected of being infected with malaria; and (3) a third measurement action of measuring the subject using the first reagent and the second reagent.

[0006] According to the present invention, the subject testing device can, for example, select and perform either or both of the following: a test for white blood cell classification and a test for malaria-infected red blood cells, based on the test instruction, analysis results, medical history, test results from other devices, travel records to malaria-endemic areas, or the rainy season when malaria is prevalent. This improves the efficiency of subject testing services, including tests for malaria infection.

[0007] [The effects of the invention] This invention can streamline the process of examining patients, including those who are tested for malaria infection. Attached Figure Description

[0008] Figure 1 This is a perspective view showing the structure of the subject measurement device according to Embodiment 1.

[0009] Figure 2 This is a block diagram showing the functional structure of the measuring unit in Implementation Method 1.

[0010] Figure 3 This is a diagram showing the structure of the optical detection unit in Embodiment 1.

[0011] Figure 4 is a diagram showing the structure of the electrical detection unit and the hemoglobin detection unit of Embodiment 1.

[0012] Figure 5 This is a diagram illustrating the structure of Embodiment 1 for aspirating and ejecting the test subject via a suction tube.

[0013] Figure 6 This is a diagram showing the structure of the fluid circuit connected to the chamber and the optical detection unit in Embodiment 1.

[0014] Figure 7This is a diagram showing the structure of the fluid circuit connected to the chamber, the electrical detection unit, and the hemoglobin detection unit in Embodiment 1.

[0015] Figure 8 This is a block diagram illustrating the functional structure of the conveying unit and the analysis unit in Implementation Method 1.

[0016] Figure 9 This is a diagram illustrating an example of the relationship between the discreteness, measurement mode, and measurement items in Implementation Method 1.

[0017] Figure 10 This is a diagram showing the structure of the menu screen in Implementation Method 1.

[0018] Figure 11 is a diagram showing the structure of the measurement category switching dialog box, the manual measurement dialog box, and the measurement unit information display area in Embodiment 1.

[0019] Figure 12 This is a diagram showing the structure of the measurement command registration screen in Implementation Method 1.

[0020] Figure 13 This is a diagram of the measurement command registration screen when the standard mode is selected as the measurement command in Implementation 1.

[0021] Figure 14 This is an illustration of the measurement command registration screen when the malaria mode is selected as the measurement command in Implementation Method 1.

[0022] Figure 15 This is a diagram of the measurement command registration screen when the multi-function mode is selected as the measurement command in Implementation 1.

[0023] Figure 16 is a diagram showing the structure of the scatter plot WDF and scatter plot WNR of Embodiment 1.

[0024] Figure 17 is a diagram showing the structure of the scatter plot M and scatter plot RET in Embodiment 1.

[0025] Figure 18 This is a diagram showing the structure of the scatter plot PLT-F of Embodiment 1.

[0026] Figure 19 This is a diagram showing the structure of the analysis result display screen in Implementation Method 1.

[0027] Figure 20 This is an example of implementation method 1. Figure 13 The diagram shows the display screen with the measurement mode and discrete analysis results set as shown.

[0028] Figure 21 This is an example of implementation method 1. Figure 14The diagram shows the display screen with the measurement mode and discrete analysis results set as shown.

[0029] Figure 22 This is an example of implementation method 1. Figure 15 The diagram shows the display screen with the measurement mode and discrete analysis results set as shown.

[0030] Figure 23 This is a flowchart illustrating the processing performed by the control unit of the analysis unit in Implementation Method 1.

[0031] Figure 24 This is a diagram showing the structure of the reflection setting screen in Embodiment 2.

[0032] Figure 25 This is a flowchart illustrating the processing performed by the control unit of the analysis unit in Embodiment 2.

[0033] Figure 26 This is a flowchart illustrating the processing performed by the control unit of the analysis unit when, in the case of modified Example 1, a measurement action is selectively performed based on other information related to the subject.

[0034] Figure 27 This is a diagram showing the structure of the fluid circuit connected to the chamber and the optical detection unit in Modified Example 2.

[0035] Figure 28 This is a diagram showing the structure of the fluid circuit connected to the chamber and the optical detection unit in Modified Example 3.

[0036] Figure 29 This is a diagram showing the structure of the scatter plot WDF in modified Example 4.

[0037] Figure 30 This is a diagram showing the structure of the scatter plot WDF-1 of the modified example 5.

[0038] Explanation of icon numbers 1: Subject Measurement Device 10: Measurement Unit 30: Analysis Unit 31: Display Section 32: Operations Department 110: Optical Inspection Department (Organization) 120: Electrical Testing Department (Organization) 130: Hemoglobin Testing Department (Institution) 161: Reading Department (Organization) 162: Subject Container Transfer Department (Agency) 163: Betting Division (Institution) 164, 165: Liquid transfer unit (mechanism) 201, 202: Light source (mechanism) 301: Suction tube (mechanism) 311: Injection pump (mechanism, pump, sample preparation unit) 342: Injection pump (mechanism) 401: Control Department 520: Measurement Mode Selection Dialog Box (Screen) 540: Manual Measurement Dialog Box (Screen) 600: Command Registration Screen (Screen, Other Screens) C11~C15, C21, C22: Chambers (mechanisms, sample preparation sections) Detailed Implementation <Implementation Method 1> Figure 1 This is a three-dimensional diagram showing the structure of the test subject measuring device 1. Figure 1 The diagram shows the directions: up, down, left, right, front, and back.

[0039] The subject testing device 1 is a blood cell counting device that measures white blood cells, red blood cells, malaria-infected red blood cells, platelets, etc., contained in the subject, and performs classification and / or counting of each blood cell. The subject is whole blood collected from the subject. The subject testing device 1 includes a testing unit 10, a conveying unit 20, and an analysis unit 30.

[0040] The transport unit 20 is positioned in front of the measuring unit 10 to transport the sample holder R, which holds multiple sample containers T, to the measuring unit 10. The measuring unit 10 removes the sample containers T from the sample holder R, places them in the sample placement section 12, and moves them to the sample aspiration position within the frame 11. The measuring unit 10 aspirates samples from the sample containers T at the aspiration position and measures the blood cells contained within the samples. The measuring unit 10 returns the sample containers T, after measurement, to the sample holder R.

[0041] A switch 13, a start switch 14, and a cover 15 are provided on the front surface of the frame 11 of the measuring unit 10. When the switch 13 is operated, the cover 15 opens, and the subject placement section 12 moves forward of the frame 11. When the operator places the subject container T in the subject placement section 12 and operates the start switch 14, the measuring unit 10 drives the subject placement section 12 and moves the subject container T to the subject aspiration position to measure the subject inside the subject container T. Thus, the subject container T can be inserted into the transfer unit 20 for measurement of a specified subject container T.

[0042] The analysis unit 30 performs an analysis, including the classification and / or counting of blood cells, based on the measurement results obtained by the measurement unit 10, and generates analysis results. The analysis results may include, for example, result values ​​based on the analysis, graphs, charts, and labeling information assigned to the subject.

[0043] The analysis unit 30 includes a display unit 31 and an operation unit 32. The display unit 31 displays analysis results, and may include, for example, a liquid crystal display or an organic electroluminescence (EL) display. The operation unit 32 accepts operations performed by the operator, such as a mouse or keyboard. Furthermore, the display unit 31 and the operation unit 32 may be integrated, for example, a touchscreen display may be included.

[0044] Figure 2 This is a block diagram representing the functional structure of the measuring unit 10.

[0045] The measuring unit 10 includes: an optical detection unit 110, an electrical detection unit 120, a hemoglobin detection unit 130, an analog processing unit 141, an analog processing unit 142, an analog processing unit 143, an analog / digital (A / D) conversion unit 151, an A / D conversion unit 152, an A / D conversion unit 153, a reading unit 161, a sample container transfer unit 162, a dispensing unit 163, a liquid transfer unit 164, a liquid transfer unit 165, an interface (IF) unit 171, an IF unit 172, and a communication unit 173.

[0046] The optical detection unit 110 detects optical signals corresponding to blood cells in the sample using flow cytometry. The electrical detection unit 120 detects electrical signals corresponding to blood cells in the sample using direct current (DC) detection. The hemoglobin detection unit 130 detects optical signals corresponding to the hemoglobin concentration in the sample using the sodium lauryl sulfate (SLS)-hemoglobin method. The structures of the optical detection unit 110, electrical detection unit 120, and hemoglobin detection unit 130 will be described later. Figure 3 Figure 4 illustrates this.

[0047] Analog processing units 141, 142, and 143 respectively process the analog signals detected by optical detection unit 110, electrical detection unit 120, and hemoglobin detection unit 130, performing noise removal or smoothing processes. A / D conversion units 151, 152, and 153 convert the processed analog signals into digital signals and send them as measurement results to analysis unit 30 via IF unit 171 and communication unit 173.

[0048] The reading unit 161 includes a mechanism for reading the subject identifier (ID) from the barcode label affixed to the subject container T which is transferred into the frame 11. The subject container transfer unit 162 includes a mechanism for removing the subject container T from the subject rack R on the transfer unit 20, a subject placement unit 12, and a mechanism for moving the subject placement unit 12 back and forth.

[0049] Sub-section 163 contains Figure 5 The suction tube 301 is shown, and the suction tube transfer section moves the suction tube 301 within the frame 11. The liquid transfer section 164 includes... Figure 5 The flow path, syringe pumps and valves, and the mechanism for driving these syringe pumps and valves are shown. The liquid transfer unit 165 includes... Figure 6 , Figure 7 The flow path, chambers C11 to C14, chamber C21, chamber C22, syringe pump, diaphragm pump and valve, and the mechanism for driving these syringe pumps, diaphragm pumps and valves are shown.

[0050] The communication unit 173 includes, for example, a connection terminal based on the Universal Serial Bus (USB) standard, for communication with the analysis unit 30. Each part of the measurement unit 10 is controlled by the analysis unit 30 via the IF unit 171, the IF unit 172, and the communication unit 173.

[0051] Figure 3 This is a diagram showing the structure of the optical detection unit 110. Figure 3 For convenience, the mutually orthogonal X-axis, Y-axis, and Z-axis are appended. The Z-axis direction is the flow direction of the sample in the flow cell 211.

[0052] The optical detection unit 110 includes: a light source 201, a light source 202, a dichroic mirror 203, a flow cell 211, a light receiving unit 221, a dichroic mirror 231, a light receiving unit 232, a light receiving unit 233, a dichroic mirror 241, and light receiving units 242 and 243.

[0053] Light sources 201 and 202 are, for example, semiconductor laser light sources. Light source 201 emits light with a wavelength of λ10 along the Y-axis, and light source 202 emits light with a wavelength of λ20 along the X-axis. Wavelength λ10 is a blue-violet wavelength band, ranging from 315 nm to 490 nm. Wavelength λ20 is a red wavelength band, ranging from 610 nm to 750 nm. The dichroic mirror 203 is configured to reflect the light from light source 201 along the X-axis and allow the light from light source 202 to pass through. The dichroic mirror 203 is configured such that the light from light sources 201 and 202 illuminates the flow path 211a of the flow cell 211 in a state of mutual overlap.

[0054] The test sample supplied to the optical detection unit 110 flows in the flow path 211a of the flow cell 211. When light of wavelength λ10 from the light source 201 and light of wavelength λ20 from the light source 202 irradiates the blood cells in the test sample flowing in the flow path 211a, forward scattered light, side scattered light, and fluorescence are generated from the irradiated blood cells. Here, it is envisioned that when light of wavelength λ10 and wavelength λ20 irradiates the fluorescent dye used to stain the blood cells, light of wavelength λ11 and wavelength λ21 are generated, respectively.

[0055] 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 light intensity. The light-receiving unit 221 is, for example, a photodiode (PD).

[0056] The dichroic mirror 231 is configured to reflect side-scattered light of wavelength λ10 based on light from light source 201, and allow fluorescence of wavelength λ11 based on light from light source 201 to pass through. The light-receiving unit 232 receives the side-scattered light of wavelength λ10 and detects the optical signal corresponding to the intensity of the received light. The light-receiving unit 232 is, for example, a photodiode (PD). The light-receiving unit 233 receives the fluorescence of wavelength λ11 and detects the optical signal corresponding to the intensity of the received light. The light-receiving unit 233 is, for example, a photomultiplier tube (PMT), an avalanche photodiode (APD), or a photodiode (PD).

[0057] The dichroic mirror 241 is configured to reflect side-scattered light of wavelength λ20 based on light from light source 202, and to transmit fluorescence of wavelength λ21 based on light from light source 202. The light-receiving unit 242 receives the side-scattered light of wavelength λ20 and detects an optical signal corresponding to the intensity of the received light. 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 intensity of the received light. The light-receiving unit 243 is, for example, a photomultiplier tube (PMT), an avalanche photodiode (APD), or a photodiode (PD).

[0058] Figure 4 is a diagram showing the structure of the electrical detection unit 120 and the hemoglobin detection unit 130.

[0059] 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 orifice 124, a recovery tube 125, and a chamber 126.

[0060] The sample nozzle 122 ejects the test sample supplied to the electrical detection unit 120 upwards. The chamber 123 has a tapered shape that tapers upwards. Sheath fluid is supplied into the chamber 123. The test sample, enveloped in sheath fluid, passes through the aperture 124 and proceeds towards the recovery tube 125. The blood cells contained in the test sample pass through the aperture 124 in a line. Electrodes are provided in the aperture 124. A direct current is supplied between the electrodes of the aperture 124, and the electrical signal corresponding to the change in DC resistance as the test sample passes through the aperture 124 is detected. The electrical signal reflects information about the blood cells passing through the aperture 124.

[0061] Sheath fluid is supplied to chamber 126 in a downward-flowing manner on the outer region of the recovery tube 125. The sheath fluid flowing on the outer side of the recovery tube 125 flows into the interior of the recovery tube 125 after reaching the lower end of chamber 126. This prevents blood cells that have passed through aperture 124 from returning to aperture 124, thereby preventing false detection of blood cells.

[0062] As shown in the lower part of Figure 4, the hemoglobin detection unit 130 includes: a pool 131, a light source unit 132, and a light receiving unit 133.

[0063] Cell 131, made of a light-transmitting material, contains the measurement sample supplied to the hemoglobin detection unit 130. Light source 132 irradiates cell 131 with light of a wavelength based on the high absorbance of SLS-hemoglobin. Light receiving unit 133 is disposed opposite to light source 132, separated from cell 131. Light receiving unit 133 receives transmitted light from the light source 132 that has not been absorbed by the sample, and detects an optical signal corresponding to the intensity of the transmitted light. This signal corresponds to absorbance.

[0064] Figure 5 This diagram shows the structure used to aspirate and eject the test subject via the suction tube 301.

[0065] The suction tube 301 is conveyed by the suction tube transfer section and inserted into the specimen container T and the interior of chambers C11 to C14, C21, and C22. The upper end of the suction tube 301 is connected to the syringe pump 311 via a flow path, in which a valve 312 is disposed. The syringe pump 311 includes a piston and a motor, configured to apply a predetermined pressure to the flow path, draw a predetermined amount of specimen from the specimen container T via the suction tube 301, and eject a predetermined amount of specimen drawn through the suction tube 301.

[0066] The sample aspirated by the aspiration tube 301 is dispensed into at least one of the chambers C11-C14, C21, and C22 based on a predetermined measurement command. In each chamber C11-C14, C21, and C22, the sample is mixed with a prescribed liquid reagent to prepare the measurement sample. When the dispensing of the sample is complete, the syringe pump 311 introduces the remaining sample from the aspiration tube 301 and discards it via valve 313.

[0067] Figure 6 This is a diagram showing the structure of the fluid circuit connected to chambers C11 to C14 and the optical detection unit 110.

[0068] Chambers C11 to C14 have identical structures. Chambers C11 to C14 may also have different structures. Chambers C11 to C14 are containers open at the top. The sample aspirated from the sample container T via the suction tube 301 is ejected into the chambers C11 to C14 through the opening at the top. Each chamber C11 to C14 includes: an inlet 321 for supplying reagents; an outlet 322 for discharging the test sample prepared within the chamber; and a waste outlet 323 for discarding the liquid within the chamber. Chambers C11 to C14 are connected to a common optical detection unit 110 via a common flow path 341.

[0069] Hemolysis reagent WDF and staining reagent WDF are supplied to chamber C11 via inlet 321. In chamber C11, the sample, hemolysis reagent WDF, and staining reagent WDF are mixed to prepare the assay sample WDF. The hemolysis reagent WDF is a reagent that hemolyzes red blood cells and damages the cell membranes of white blood cells to a degree permeable to fluorescent dye. For example, the hemolysis reagent WDF is Lysercell (registered trademark) WDF II (manufactured by Sysmex Corporation). The staining reagent WDF contains a fluorescent dye for staining white blood cells for classification. The fluorescent dye contained in the staining reagent WDF is, for example, an anthocyanin-based fluorescent dye that can be excited by light at wavelength λ20 and can bind to nucleic acids. For example, the staining reagent WDF is Fluorocell (registered trademark) WDF (manufactured by Sysmex Corporation). The assay sample WDF is supplied to the optical detection unit 110. The WDF of the sample is measured for white blood cell classification. Furthermore, in this specification, "white blood cell classification" refers to classifying white blood cells into two or more subgroups.

[0070] The hemolytic reagent WDF is not particularly limited, for example, it may contain a nonionic surfactant represented by the following formula (I). In formula (I), R1 is an alkyl, alkenyl or alkynyl group having 8 or more carbon atoms and less than 25 carbon atoms, and R2 is an oxygen atom, (COO) or represented by the following formula (II).

[0071] R1-R2-(CH2CH2O)nH(I) [Chemistry 1]

[0072] 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 alcohols with 1 to 6 carbon atoms, ethylene glycol, diethylene glycol, polyethylene glycol, dimethyl sulfoxide (DMSO), etc.

[0073] The hemolytic reagent WDF may contain a buffering substance to maintain a constant pH. Examples of buffering substances include: inorganic acid salts, organic acid salts, excellent 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 excellent buffers include: 2-morpholinoethanesulfonic acid (MES), bis(2-hydroxyethyl)amino-tris(hydroxymethyl)methane (Bis-Tris), N-(2-acetamido)iminodiacetic acid (ADA), piperazine-1,4-bisethanesulfonic acid (PIPES), 1,3-Bis((trishydroxymethyl)methylamino)propane (Bis-Tris-Propane), N-(2-acetamido)-2-aminoethanesulfonic acid (ACES), and 3-morpholinopropanesulfonic acid. Acid (MOPS), 3-(N-morpholino)-2-hydroxypropanesulfonic acid (MOPSO), N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (BES), N-Tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid (TES), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), 4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid (HEPPS), N-Tris(hydroxymethyl)methylglycine (N-Tris(hydroxymethyl)methyl glycine (Tricine), tris(hydroxymethyl)aminomethane (Tris), N,N-bis(2-hydroxyethyl)glycine (Bicine), N-Tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid (TAPS), and combinations thereof, etc.

[0074] In the hemolytic reagent WDF, the nonionic surfactant represented by formula (I) may include, for example, polyoxyethylene alkyl ethers, polyoxyethylene sterols, polyoxyethylene castor oil, polyoxyethylene sorbitol fatty acid esters, polyoxyethylene alkylamines, polyoxyethylene polyoxypropylene alkyl ethers, and combinations thereof. Preferably, polyoxyethylene alkyl ethers are included. As polyoxyethylene alkyl ethers, polyoxyethylene (23) cetyl ether, polyoxyethylene (25) cetyl ether, polyoxyethylene (30) cetyl ether, and at least one selected from the group thereof are preferred. More preferably, polyoxyethylene (23) cetyl ether, polyoxyethylene (25) cetyl ether, and combinations thereof are preferred, and even more preferably, polyoxyethylene (23) cetyl ether is preferred. Furthermore, in the hemolytic reagent WDF, there may be one or more nonionic surfactants. Additionally, the hemolytic reagent WDF may also include cationic surfactants or nonionic surfactants other than those represented by formula (I).

[0075] The fluorescent dyes contained in the staining reagent WDF are not particularly limited and can be selected appropriately based on factors such as the wavelength of the light irradiated by the light source. For example, when the wavelength of the light irradiated by the light source is in the blue-violet wavelength band, the following can be listed: propidium iodide, ethidium bromide, ethidium-acridinium heterodimer, ethidium diazide, ethidium homodimer-1, ethidium homodimer-2, ethidium monoazide, and trimethylenebis[[3-[[4-[[(3-methylbenzothiazo-3-onyl)-2-yl]methylene]-1,4-dihydroxyquinoline]-1-yl]propyl]dimethylammonium]·tetraiodide (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)-ylide)methyl]-1-[3-(trimethylamino)propyl]quinolineonium diiodide (4-[(3-m ethylbenzothiazole-2(3H)-ylidene)methyl]-1-[3-(trimethylaminio)propyl]quinolinium·diiodide, TO-PRO-1), N,N,N',N'-tetramethyl-N,N'-bis[3-[4-[3-[(3-methylbenzothiazole-3-onyl)-2-yl]-2-propenylene]-1,4-dihydroquinolin-1-yl]propyl]-1,3-propanediammonium·tetramethyl ...ium-1-yl]propyl]-1,3-propanediammonium·tetramethyl[3-[4-[3-[(3-methylbenzothiazole-3-onyl]-2- Iodides (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, TOTO-3), or 2-[3-[[1-[3-(trimethylamino)propyl]-1,4-dihydroquinoline]-4-ylidene]-1-propenyl]-3-methylbenzothiazole-3-onium·diiodide (2-[3-[[1-[3-(trimethylaminio)propyl]-1,4-dihydroquinoline]-4-ylidene]-1-propenyl]-3-methylbenzothiazole-3-ium·diiodide, TOPO-3), combinations thereof, etc.

[0076] In addition, fluorescent pigments contained in the staining reagent WDF can be listed as fluorescent pigments represented by the following general formula (III).

[0077] [Chemistry 2]

[0078] In formula (III), R1 and R4 may be the same or different from each other, and are hydrogen atoms, alkyl groups, alkyl chains with hydroxyl groups, alkyl chains with ether groups, alkyl chains with ester groups, or benzyl groups that may have substituents. R2 and R3 may be the same or different from each other, and are hydrogen atoms, hydroxyl groups, halogens, alkyl groups, alkenyl groups, alkoxy groups, alkylsulfonyl groups, or phenyl groups. Z is a sulfur atom, an oxygen atom, or a carbon atom with a methyl group. n is 0, 1, 2, or 3. n is appropriately selected according to the wavelength of the light irradiated from the light source. X - It is an anion.

[0079] In formula (III), the alkyl group can be either straight-chain or branched-chain. 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 fewer than 6 carbon atoms. Among the alkyl groups having 6 to 18 carbon atoms, alkyl groups having 6, 8, or 10 carbon atoms are preferred.

[0080] In formula (III), the substituents for the benzyl groups of R1 and R4 can be, for example, alkyl groups having 1 to 20 carbon atoms, alkenyl groups having 2 to 20 carbon atoms, or alkynyl groups having 2 to 20 carbon atoms. Among these, methyl or ethyl groups are particularly preferred.

[0081] In formula (III), alkenyl groups, such as those with 2 to 20 carbon atoms, can be used as R2 and R3. Alkoxy groups, such as those with 1 to 20 carbon atoms, can also be used as R2 and R3. Of these, methoxy or ethoxy groups are particularly preferred.

[0082] In equation (III), X is the anion. - Examples include: F - Cl - ,Br - and I - Such halide ions, CF3SO3 - BF4 - wait.

[0083] As a hemolytic reagent and a staining reagent, WDF may be used as described in U.S. Patent Application Publication No. 2022 / 0268763, which is incorporated herein by reference.

[0084] Return to Figure 6The hemolytic reagent WNR and staining reagent WNR are supplied to chamber C12 via inlet 321. In chamber C12, the sample, hemolytic reagent WNR, and staining reagent WNR are mixed to prepare the assay sample WNR. The hemolytic reagent WNR is a reagent that causes hemolysis of red blood cells and damages the cell membrane of white blood cells to a degree permeable to fluorescent dye. Examples of hemolytic reagent WNR include Lysercell (registered trademark) WNR (manufactured by Sysmex Corporation). The staining reagent WNR contains fluorescent dye for staining white blood cells and nucleated red blood cells for counting white blood cells, basophils, and nucleated red blood cells. Examples of fluorescent dyes contained in the staining reagent WNR include fluorescent dyes that can be excited by light at wavelength λ20 and can bind to nucleic acids. Examples of staining reagent WNR include Fluorocell (registered trademark) WNR (manufactured by Sysmex Corporation). The WNR test sample is supplied to the optical detection unit 110. The WNR test sample is used to count white blood cells, basophils, and nucleated red blood cells. Furthermore, in this specification, counting white blood cells means counting the total number of all subsets of white blood cells.

[0085] Hemolysis reagent M and staining reagent M are supplied to chamber C13 via inlet 321. In chamber C13, the sample, hemolysis reagent M, and staining reagent M are mixed to prepare the assay sample M. Hemolysis reagent M is a reagent that partially dissolves the cell membrane of red blood cells so that fluorescent dye can pass through while keeping the malaria parasite inside the red blood cells. Hemolysis reagent M is, for example, Lysercell (registered trademark) M (manufactured by Sysmex Corporation). Staining reagent M contains 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 at a wavelength of λ10 and stains deoxyribonucleic acid (DNA) more strongly than ribonucleic acid (RNA). Staining reagent M is, for example, Fluorocell (registered trademark) M (manufactured by Sysmex Corporation). The test sample M is supplied to the optical detection unit 110. The test sample M is used to count malaria-infected red blood cells.

[0086] In addition, by injection pump 311 (refer to) Figure 5The amount of sample dispensed into chamber C13 is preferably greater than the amount dispensed into chamber C11 by syringe pump 311. Therefore, syringe pump 311 is preferably operated differently for preparing the test sample WDF and for preparing the test sample M. Since the number of malaria-infected red blood cells is generally less than the number of normal white blood cells, the malaria-infected red blood cells can be counted with good accuracy by operating syringe pump 311 as described above.

[0087] The hemolytic agent M is not particularly limited, but may include, for example, a first surfactant with a specified solubility in the cell membrane of red blood cells, and a second surfactant with a weaker solubility than the first surfactant, a pH of 5 to 7, and an osmotic pressure of 200 mOsm / kg·H2O to 300 mOsm / kg·H2O.

[0088] As the first and second surfactants, any one of anionic surfactants, nonionic surfactants, and cationic surfactants can be used, but cationic surfactants are preferred.

[0089] Specifically, as cationic surfactants, the following can be used: Octyltrimethyl ammonium bromide (OTAB), Decyltrimethyl ammonium bromide (DTAB), Lauryltrimethyl ammonium chloride (LTAC), Myristyltrimethyl ammonium bromide (MTAB), Cetyl pyridinium chloride (CPC), Stearyltrimethyl ammonium chloride (STAC), etc.

[0090] The solubility of a surfactant in red blood cell membranes depends primarily on the number of carbon atoms in the surfactant. Specifically, a higher carbon number, especially in the case of quaternary ammonium salts, results in a longer carbon chain of the straight-chain alkyl group, leading to stronger solubility, but also a tendency to solidify at room temperature. Therefore, by using surfactants with a lower carbon number in red blood cell membrane dissolving agents, the solubility of the agent in the solvent can be improved, and the influence on the red blood cell membrane can be adjusted. Thus, when both the first and second surfactants are quaternary ammonium salts with long-chain alkyl groups, it is preferable that the number of carbon atoms in the long-chain alkyl group of the second surfactant is less than that in the first surfactant.

[0091] Specifically, a combination of a first surfactant being stearyltrimethylammonium chloride (STAC) and a second surfactant being lauryltrimethylammonium chloride (LTAC) can be preferably used.

[0092] The combination of the first and second surfactants, and the specific combination of their concentrations in the reagent, are selected to achieve a degree to which the red blood cell membrane dissolves into fluorescent dye that can permeate the red blood cells while maintaining their shape. For example, in the case of a combination of STAC with 21 carbon atoms (the longest alkyl chain is 18 carbons) and LTAC with 15 carbon atoms (the longest alkyl chain is 12 carbons), it is preferable to use a mixture in the range of 40 ppm to 600 ppm for STAC and 500 ppm to 1400 ppm for LTAC.

[0093] To maintain the pH at 5–7, the hemolytic reagent M may contain a buffer. By maintaining this pH range, the cell membranes of red blood cells can be partially dissolved, allowing fluorescent dye to pass through while keeping the malaria parasite inside the red blood cells.

[0094] Citric acid, phosphoric acid, succinic acid, tris(hydroxymethyl)glycine, etc., can be used as buffers. Hydrochloric acid or sodium hydroxide can be added as pH adjusters to regulate pH.

[0095] Furthermore, in order to maintain the osmotic pressure within the range of 200 mOsm / kg·H2O to 300 mOsm / kg·H2O, the hemolytic reagent M preferably contains an osmotic pressure regulator. When the osmotic pressure is less than 200 mOsm / kg·H2O, the liquid components in the reagent or blood tend to be drawn into the erythrocytes and swell, which may lead to hypotonic lysis of the erythrocytes. When the osmotic pressure exceeds 300 mOsm / kg·H2O, the fluorescent dyes used for malaria parasite detection (described later) have difficulty entering the erythrocytes, and structural changes may occur due to erythrocyte contraction.

[0096] As an osmotic pressure regulator, alkali metal halides such as sodium chloride or alkaline earth halides such as magnesium chloride, carboxylic acid metal salts such as propionic acid, and sugars such as glucose and mannose can be used.

[0097] Furthermore, depending on the requirements, the hemolytic reagent M may also contain preservatives such as sodium 2-pyridylthio-1-oxide or β-phenylethanol.

[0098] In addition, the hemolytic reagent M can be diluted with purified water, ethanol, etc., to adjust its concentration within a range that does not affect pH or osmotic pressure.

[0099] The hemolytic agent M is preferably a nonionic surfactant that also contains cell membranes that are substantially insoluble in red blood cells. This allows for more accurate classification of malaria-infected red blood cells based on the growth stage of the malaria parasite.

[0100] As nonionic surfactants, specifically, the following are preferred: polyoxyethylene (20) sorbitan monoisostearate, polyoxyethylene (20) sorbitan monooleate, and other polyoxyethylene sorbitan fatty acid esters; polyoxyethylene (30) hydrogenated castor oil, polyoxyethylene (50) hydrogenated castor oil, and other castor oils; polyoxyethylene (20) phytosterols (hereinafter abbreviated as "polyoxyethylene (POE) (20) phytosterols"), polyoxyethylene (2... 5) Polyoxyethylene phytosterols (hereinafter abbreviated as "POE(25) phytosterols") and other polyoxyethylene phytosterols; polyoxyethylene (21) lauryl ether, polyoxyethylene (16) oleyl ether, polyoxyethylene (20) oleyl ether and other polyoxyethylene alkyl ethers; polyoxyethylene (20)·polyoxypropylene (6) decyltetradecyl ether, polyoxyethylene (20) polyoxypropylene (8) cetyl ether and other polyoxyethylene·polyoxypropylene alkyl ethers; polyoxyethylene (10) monolaurate and other polyoxyethylene fatty acid esters, etc. Furthermore, the numerical value within the parentheses of polyoxyethylene indicates the number of carbon atoms in the polyethylene chain.

[0101] The fluorescent reagent contained in staining reagent M is not particularly limited; for example, it may be a DNA-selective fluorescent dye, preferably a DNA-selective bisbenzoimide-based fluorescent dye. A DNA-selective fluorescent dye is a fluorescent dye that stains DNA more strongly than RNA, and a DNA-selective bisbenzoimide-based fluorescent dye is a fluorescent dye with a bisimide backbone.

[0102] As such a pigment, a pigment having a structure as shown in formula (IV) can be preferably used (e.g., Hoechst 34580 from Invitrogen).

[0103] [Chemistry 3]

[0104] In addition to the pigments listed above, DNA-selective bisbenzoimide fluorescent dyes include Hoechst 33258 and Hoechst 33342. These dyes have different side chains than Hoechst 34580, but can be excited in the blue-violet wavelength band (above 315 nm and below 490 nm).

[0105] 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, which is incorporated herein by reference.

[0106] Return to Figure 6 A diluent RET and a 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 assay sample RET. The diluent RET is used to dilute the sample. For example, Cellpack (registered trademark) DFL (manufactured by Sysmex Corporation). The staining reagent RET is used to stain blood cell components. For example, Fluorocell (registered trademark) RET (manufactured by Sysmex Corporation). The assay sample RET is supplied to the optical detection unit 110. The assay sample RET is used to count reticulocytes.

[0107] Additionally, when chamber C14 is not used to prepare the RET test sample, diluent PLT-F and staining reagent PLT-F are supplied to chamber C14 via inlet 321. In chamber C14, the test sample, diluent PLT-F, and staining reagent PLT-F are mixed to prepare the RET test sample PLT-F. The diluent PLT-F is used to dilute the test sample. For example, Cellpack DFL (manufactured by Sysmex Corporation) is a registered trademark. The staining reagent PLT-F is used to stain blood cell components. For example, Fluorocell PLT (manufactured by Sysmex Corporation) is a registered trademark. The RET test sample PLT-F is supplied to the optical detection unit 110. The RET test sample PLT-F is used for platelet counting.

[0108] The outlets 322 of chambers C11 to C14 are connected to flow path 341 via valve 331. An injection pump 342, valve 343, and optical detection unit 110 are connected to flow path 341. A diaphragm pump 344 is connected to flow path 341 via valve 343. A valve 345 is connected to the flow path between valve 343 and diaphragm pump 344. The waste outlets 323 of chambers C11 to C14 are connected to the waste flow path via valve 332.

[0109] When in Figure 6When the preparation of the test sample in each of the shown chambers is completed, the diaphragm pump 344 introduces the prepared test sample from the corresponding chamber into the flow path 341. The syringe pump 342 supplies the test 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 test sample stored in the flow path 341 to the optical detection unit 110 by applying a predetermined pressure to the flow path 341.

[0110] The optical detection unit 110 causes the test sample and sheath fluid to pass through the flow cell 211 (see reference). Figure 3 The sample flows through the blood cells and the optical signals corresponding to the blood cells in the sample are detected by flow cytometry.

[0111] Specifically, the optical detection unit 110 measures the WDF of the test sample, thereby detecting optical signals corresponding to white blood cells, etc., in the WDF. The optical detection unit 110 measures the WNR of the test sample, thereby detecting optical signals corresponding to white blood cells, nucleated red blood cells, etc., in the WNR. The optical detection unit 110 measures the M of the test sample, thereby detecting optical signals corresponding to white blood cells, malaria-infected red blood cells, etc., in the M. The optical detection unit 110 measures the RET of the test sample, thereby detecting optical signals corresponding to reticulocytes, etc., in the RET. The optical detection unit 110 measures the PLT-F of the test sample, thereby detecting optical signals corresponding to platelets, etc., in the PLT-F. The optical detection unit 110 measures each test sample individually. Test samples passing through the flow cell 211 of the optical detection unit 110 are discarded.

[0112] Furthermore, the measurement time for the test sample M based on the optical detection unit 110 is preferably longer than the measurement time for the test sample WDF. The measurement time can be adjusted by changing the amount of test sample supplied to the optical detection unit 110 by the syringe pump 342 and / or changing the flow rate of the test sample supplied to the optical detection unit 110 by the syringe pump 342. Since the number of malaria-infected red blood cells is generally less than the number of normal white blood cells, the malaria-infected red blood cells can be counted with good accuracy by operating the syringe pump 342 and the optical detection unit 110 as described above.

[0113] When the optical detection unit 110 finishes measuring a test sample, it supplies cleaning fluid to the chamber in which the test sample was prepared. The cleaning fluid in the chamber is discarded through the waste port 323 and valve 332, and discharged into the flow path 341 through the outlet 322. The cleaning fluid discharged into the flow path 341 is discarded through valve 345.

[0114] Figure 7This is a diagram showing the structure of the fluid circuit connected to chamber C21, chamber C22, electrical detection unit 120, and hemoglobin detection unit 130.

[0115] Chambers C21 and C22 have the same structure as chambers C11 to C14. Chamber C22 further includes an inlet 324 for supplying reagents. The sample aspirated from the sample container T through the suction tube 301 is ejected into chambers C21 and C22 through the opening at the upper end.

[0116] A diluent RBC / PLT is supplied to chamber C21 via inlet 321. In chamber C21, the sample is mixed with the diluent RBC / PLT to prepare the assay sample RBC / PLT. The diluent RBC / PLT is used to dilute the sample. For example, the diluent RBC / PLT is Cellpack (registered trademark) DCL (manufactured by Sysmex Corporation). The assay sample RBC / PLT is supplied to the electrical detection unit 120. The assay sample RBC / PLT is used to count red blood cells and platelets.

[0117] A hemolysin HGB is supplied to chamber C22 via inlet 324, and a diluent HGB is supplied via inlet 321. In chamber C22, the test sample, hemolysin HGB, and diluent HGB are mixed to prepare the assay sample HGB. The hemolysin HGB is a reagent used to dissolve hemoglobin from red blood cells. For example, the hemolysin HGB is SULFOLYSER (registered trademark) (manufactured by Sysmex Corporation). The hemolysin HGB is a reagent used to dilute the test sample. For example, the hemolysin HGB is Cellpack DCL (registered trademark) (manufactured by Sysmex Corporation). The assay sample HGB is supplied to the hemoglobin detection unit 130. The assay sample HGB is used to obtain the hemoglobin concentration.

[0118] The outlet 322 of chamber C21 is connected to flow path 361 via valve 351. Flow path 361 is connected to an injection pump 362, valve 363, and an electric detection unit 120. The outlet 322 of chamber C22 is connected to a hemoglobin detection unit 130 via valve 353. The hemoglobin detection unit 130 is connected to flow path 364 via valve 354. Flow path 364 is connected to valves 363 and 365. A diaphragm pump 366 is connected to flow path 364 via valve 365. A valve 367 is connected in the flow path between valve 365 and diaphragm pump 366. The waste ports 323 of chambers C21 and C22 are connected to waste flow paths via valves 352 and 355, respectively.

[0119] When the preparation of the RBC / PLT sample in chamber C21 is complete, the diaphragm pump 366 introduces the RBC / PLT sample from chamber C21 into flow path 361. The syringe pump 362 supplies the RBC / PLT sample stored in 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 flow path 361 to the electrical detection unit 120 by applying a predetermined pressure to flow path 361.

[0120] The electrical detection unit 120 causes the test sample RBC / PLT and sheath fluid to flow in the flow cell 121 (see the upper part of Figure 4), and detects the electrical signals corresponding to red blood cells and platelets in the test sample RBC / PLT based on the sheath flow DC detection method. The test sample RBC / PLT that has passed through the flow cell 121 of the electrical detection unit 120 is discarded.

[0121] When the electrical detection unit 120 finishes measuring the RBC / PLT of the test sample, it supplies cleaning fluid to the chamber C21. The cleaning fluid in the chamber C21 is discarded through the waste port 323 and discharged into the flow path 361 through the outlet 322. The cleaning fluid discharged into the flow path 361 is discarded through the valve 367.

[0122] When 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 the 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.

[0123] When the hemoglobin detection unit 130 finishes measuring the HGB sample, cleaning fluid is supplied to chamber C22. The cleaning fluid in chamber C22 is discarded through waste port 323 and discharged into the hemoglobin detection unit 130 through outlet 322. The cleaning fluid discharged into the hemoglobin detection unit 130 passes through the interior of the hemoglobin detection unit 130 and is discharged into flow path 364. The cleaning fluid discharged into flow path 364 is discarded through valve 367.

[0124] Figure 8 This is a block diagram representing the functional structure of the conveying unit 20 and the analysis unit 30.

[0125] The transfer unit 20 includes a reading unit 21, a subject frame transfer unit 22, and a communication unit 23.

[0126] The reading unit 21 includes a mechanism for reading the rack ID and the subject ID from the barcode labels affixed to the subject rack R and subject container T, which are transferred on the transport unit 20. The subject rack transfer unit 22 includes a mechanism for transferring the subject rack R on the transport unit 20. The communication unit 23 includes a USB-based connection terminal for communication with the analysis unit 30. Each part of the transport unit 20 is controlled by the analysis unit 30 via the communication unit 23.

[0127] The analysis unit 30 includes a control unit 401, a storage unit 402, and a communication unit 403. Additionally, the analysis unit 30 includes... Figure 1 The display unit 31 and the operation unit 32 shown are shown.

[0128] The control unit 401 includes, for example, a central processing unit (CPU). The control unit 401 executes a computer program stored in the storage unit 402 to analyze the subject and control the measurement unit 10 and the transport unit 20. The storage unit 402 includes, for example, a solid-state drive (SSD) and a hard disk drive (HDD). The storage unit 402 stores measurement results received from the measurement unit 10, analysis results based on the measurement results, and programs for controlling the analysis unit 30, the measurement unit 10, and the transport unit 20.

[0129] Communication unit 403 includes a USB standard-based connection terminal, which connects to communication unit 173 of measurement unit 10 via a USB standard-based cable (see reference). Figure 2 The control unit 401 communicates with the communication unit 23 of the conveying unit 20. The control unit 401 receives data from the reading unit 161 (see reference 161) of the measuring unit 10 via the communication unit 403. Figure 2 The control unit 401 receives the subject ID, the measurement results obtained by the measurement unit 10, and information indicating the operation of the switching switch 13 and the start switch 14 via the reading unit 21 of the transport unit 20. In addition, the control unit 401 receives the rack ID and subject ID read by the reading unit 21 of the transport unit 20, as well as information indicating that a subject rack R is provided in the transport unit 20, via the communication unit 403.

[0130] As described below, the operator specifies discrete values ​​for multiple pre-associated test items, such as Complete Blood Count (CBC), CBC + Differential Leukocyte Count (DIFF), CBC + DIFF + Reticulocyte Count (RET), CBC + Malaria Infected (MI), CBC + DIFF + RET, and MI, and sets test instructions including the test content of the subject. When the control unit 401 receives a test instruction from the operator, it stores the received test instruction in the storage unit 402. When the control unit 401 receives a test instruction from the reading unit 161 of the test unit 10 (see reference 161), it stores the received test instruction in the storage unit 402. Figure 2 When the subject ID is read, the measurement command corresponding to the received subject ID is read from the storage unit 402, and the measurement unit 10 is controlled to perform the measurement of the subject based on the measurement command.

[0131] Figure 9 This is a diagram illustrating an example of the relationship between discrete, measurement modes, and measurement items.

[0132] Discrete corresponds to a combination of specified measurement items. Figure 9 In this context, “CBC”, “DIFF”, “RET”, “platelet count fluorescent (PLT-F)”, and “MI” (hereinafter referred to as subdiscrete) correspond to different specified measurement items from other subdiscrete, and are discretized into one subdiscrete or a combination of multiple subdiscrete.

[0133] "CBC" is a discrete process as follows: The RBC / PLT ratio of the test sample is measured by the electrical detection unit 120, the HGB ratio of the test sample is measured by the hemoglobin detection unit 130, and the WNR ratio of the test sample is measured by the optical detection unit 110. Hemoglobin concentration, hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) are obtained by counting red blood cells, platelets, and white blood cells. Since the test sample WDF is not prepared in "CBC," white blood cell classification is not performed. “DIFF” is a sub-discretion defined as follows: The WDF and WNR of the test sample are measured by the optical detection unit 110, and white blood cells are classified into five subgroups (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), and each of the five subgroups is counted. “RET” is a sub-discretion defined as follows: The RET of the test sample is measured by the optical detection unit 110, and reticulocytes are counted. “PLT-F” is a sub-discretion defined as follows: The PLT-F of the test sample is measured by the optical detection unit 110, and platelets are counted. “MI” is a sub-discretion defined as follows: The RBC / PLT ratio of the test sample is measured by the electrical detection unit 120, and the M of the test sample is measured by the optical detection unit 110, malaria-infected red blood cells are counted, and the ratio of malaria-infected red blood cells to the total number of red blood cells is calculated. Furthermore, in “MI”, the red blood cell count can be obtained from the analysis results of the electrical detection unit 120 for the determination of RBC / PLT in the test sample.

[0134] In this embodiment, such as Figure 9 As shown, 13 discrete types were preset, and the measurement items correspond to the 13 discrete types respectively.

[0135] Measurements corresponding to the discrete "CBC" include, for example, white blood cell count (WBC), red blood cell count (RBC), hemoglobin concentration (HGB), hemoglobin concentration (HCT), mCV, mCH, mCHC, pLT, nucleated red blood cell count (NRBC#), and nucleated red blood cell percentage (NRBC%). NRBC# represents the number of nucleated red blood cells, and NRBC% represents the ratio of nucleated red blood cells to white blood cells. The measurements corresponding to the discrete "DIFF" include, for example, neutrophil count (NEUT#), lymphocyte count (LYMPH#), monocyte count (MONO#), eosinophil count (EO#), basophil count (BASO#), neutrophil percentage (NEUT%), lymphocyte percentage (LYMPH%), monocyte percentage (MONO%), eosinophil percentage (EO%), and basophil percentage (BASO%). NEUT#, LYMPH#, MONO#, EO#, and BASO# represent the number of neutrophils, lymphocytes, monocytes, eosinophils, and basophils, respectively. NEUT%, LYMPH%, MONO%, EO%, and BASO% represent the ratios of neutrophils, lymphocytes, monocytes, eosinophils, and basophils to the white blood cell count, respectively. Measurements corresponding to the subdiscrete "RET" include, for example, RET% and RET#. RET% represents the ratio of reticulocytes to the total number of mature and reticulocytes, while RET# represents the number of reticulocytes. Measurements corresponding to the subdiscrete "PLT-F" include, for example, IPF, IPF#, and PLT. The Immature Platelet Fraction (IPF) is the ratio of immature platelets to the total number of mature and immature platelets, while IPF# represents the number of immature platelets. PLT is the total number of mature platelets and immature platelets.Measurements corresponding to the discrete "MI" include, for example, MI-RBC# and MI-RBC% (indicating MI-RBC%). MI-RBC# represents the ratio of the number of malaria-infected red blood cells to the total number of uninfected and malaria-infected red blood cells. MI-RBC# represents the number of malaria-infected red blood cells.

[0136] Control unit 401 when specified Figure 9 When any of the 13 discrete types shown is used, the corresponding test sample is measured, the corresponding test item is analyzed, and the analysis results are obtained.

[0137] In this embodiment, the classification of white blood cells and the classification and counting of red blood cells not infected with malaria are discretely performed (“CBC+DIFF”, “CBC+DIFF+RET”, “CBC+DIFF+PLT-F”, “CBC+DIFF+RET+PLT-F”). Figure 9 The measurement mode is shown in the figure, corresponding to the "standard mode". Discrete red blood cell counts for malaria infection without white blood cell differential ("CBC+MI", "MI", "RET+MI") are shown below. Figure 9 The measurement pattern shown corresponds to the "malaria pattern". It includes white blood cell classification and discrete counts of malaria-infected red blood cells ("CBC+DIFF+MI", "CBC+DIFF+RET+MI") as shown below. Figure 9 The measurement mode is shown in the figure, corresponding to "multi-functional mode". Figure 9 The discrete values ​​other than those shown do not correspond to any of the "Standard Mode", "Malaria Mode", and "Multifunctional Mode".

[0138] When the discrete sample corresponding to the "standard mode" is selected, the measurement unit 10 performs at least the measurement action of measuring the subject using the staining reagent WDF (first measurement action). 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 sent from the measurement unit 10, the analysis unit 30 generates a scatter plot WDF as shown in the upper part of Figure 16, classifying white blood cells into multiple subpopulations. Furthermore, in the discrete sample corresponding to the "standard mode", the measurement unit 10 does not perform the measurement action of measuring the subject using the staining reagent M (second measurement action).

[0139] When the discrete sample corresponding to the "malaria pattern" is selected, the measurement unit 10 performs at least the measurement action of measuring the subject using the staining reagent M (second measurement action). Specifically, the measurement unit 10 prepares the test sample M and detects the optical signal corresponding to the cells in the test sample M using the optical detection unit 110. Based on the measurement results sent from the measurement unit 10, the analysis unit 30 generates a scatter plot M as shown in the upper part of Figure 17 and counts the red blood cells infected with malaria. Furthermore, in the discrete sample corresponding to the "malaria pattern", the measurement unit 10 does not perform the measurement action of measuring the subject using the staining reagent WDF (first measurement action).

[0140] When the discrete method corresponding to the "multi-functional mode" is selected, the measurement unit 10 performs at least the measurement action (third measurement action) of measuring the subject using staining reagent WDF and staining reagent M. Specifically, the measurement unit 10 prepares the measurement sample WDF and detects the optical signal corresponding to the cells in the measurement sample WDF through the optical detection unit 110, prepares the measurement sample M, and detects the optical signal corresponding to the cells in the measurement sample M through the optical detection unit 110. That is, when the discrete method corresponding to the "multi-functional mode" is selected, the measurement unit 10 performs at least the first measurement action and the second measurement action. Based on the measurement results sent from the measurement unit 10, the analysis unit 30 generates the scatter plot WDF shown in the upper part of Figure 16, classifies white blood cells, generates the scatter plot M shown in the upper part of Figure 17, and counts the red blood cells infected with malaria.

[0141] Figure 10 This is a diagram showing the structure of menu screen 500.

[0142] When the control unit 401 receives a display instruction from the menu screen 500, it displays the menu screen 500 on the display unit 31 and processes the operator's actions on the menu screen 500. Furthermore, as shown in Figures 11-14 below… Figure 15 In the shown screen, the control unit 401 also displays the screen on the display unit 31 and processes the operation according to the operation of the operator corresponding to the screen.

[0143] The menu screen 500 includes: a measurement registration button 501, a measurement mode selection button 502, and a measurement unit information display area 510.

[0144] When the measurement registration button 501 is pressed, the instruction registration screen 600, described later, is displayed on the display unit 31. The instruction registration screen 600 will be referred to later. Figures 12-15 Please provide an explanation.

[0145] When the measurement mode selection button 502 is operated, such as Figure 10As shown, a test mode selection dialog box 520 is displayed. The test mode selection dialog box 520 includes: a standard mode button 521, a malaria mode button 522, and a multi-function mode button 523. When any of the standard mode button 521, malaria mode button 522, and multi-function mode button 523 is operated, only the operated button is set to the selection state. Figure 10 In the diagram, a solid line indicates that the standard mode button 521 is selected, while a dashed line indicates that the malaria mode button 522 and the multi-function mode button 523 are not selected.

[0146] When any of the standard mode button 521, malaria mode button 522, and multi-function mode button 523 is selected, pressing the OK button confirms the selected measurement mode. When the control unit 401 accepts the measurement mode, it will... Figure 12 The instruction registration screen 600 shown is displayed on the display unit 31. In addition, the acceptance of the measurement mode via the measurement mode selection dialog box 520 can be performed for each subject, or a temporarily accepted measurement mode can be applied to multiple subjects until another measurement mode is accepted.

[0147] Various information about the measurement unit 10 (name of the measurement unit 10, information about the subject being measured, reagent status, etc.) is displayed in the measurement unit information display area 510. In addition, during the measurement of the subject using the transport unit 20 (sampler measurement), the sampler measurement button 511 is displayed in the measurement unit information display area 510.

[0148] For reference Figure 1 As explained, in the subject measurement device 1, in addition to sampler measurement, it is also possible to perform measurements (manual measurement) by individually supplying subject containers T to the measurement unit 10 from the front surface of the frame 11 of the measurement unit 10. When the switch 13 of the measurement unit 10 is operated, the cover 15 is opened, the subject placement section 12 moves forward, and the operator places the subject container T of the subject to be measured in the subject placement section 12. At this time, as shown on the left side of FIG11, the measurement category switching dialog box 530 is displayed above the measurement unit information display area 510.

[0149] The left side of Figure 11 shows the structure of the measurement unit information display area 510 and the measurement category switching dialog box 530 displayed during manual measurement.

[0150] During manual measurement, in the measurement unit information display area 510, instead of Figure 10 The sampler measurement button 511 displays the measurement category switching button 512 and the manual measurement button 513.

[0151] The test category switching dialog box 530 includes radio buttons 531 to 533, which are used to set the subject to be manually tested to one of three test categories (whole blood test, low white blood cell count test using whole blood, and dilution test). When the confirmation button is pressed, the control unit 401 accepts the test category of the subject to be manually tested according to the selection state of radio buttons 531 to 533. Then, instead of the test category switching dialog box 530, as shown on the right side of FIG11, the manual test dialog box 540 is displayed above the test unit information display area 510.

[0152] The right side of Figure 11 shows the structure of the measurement unit information display area 510 and the manual measurement dialog box 540 during manual measurement.

[0153] Manual measurement dialog box 540 and Figure 10 The test mode selection dialog box 520 also includes a standard mode button 541, a malaria mode button 542, and a multi-function mode button 543. Additionally, the manual test dialog box 540 includes a subject ID input area 544, which serves as a text box for inputting the subject ID. After selecting the test mode and inputting the subject ID, pressing the confirmation button receives the test mode and subject ID from the control unit 401. Figure 12 The instruction registration screen 600 shown is displayed on the display unit 31.

[0154] In addition, the measurement category switching dialog box 530 shown on the left side of Figure 11 is... Figure 10 The test mode selection dialog box 520 shown may similarly include a standard mode button, a malaria mode button, and a multi-function mode button. In this case, after selecting the test category and test mode in the test category switching dialog box 530, pressing the confirmation button will, for example, not display the manual test dialog box 540, but instead display... Figure 12 The instruction registration screen shown is 600.

[0155] Figure 12 This is a diagram showing the structure of the instruction registration screen 600. Figures 13-15 This is a diagram of an instruction registration screen 600 that shows the status of the drop-down menu of the discrete selection area 612 when the standard mode, malaria mode and multi-functional mode are selected as the test modes respectively.

[0156] like Figure 12 As shown, the instruction registration screen 600 includes: a measurement mode display area 601, a subject ID input area 611, a discrete selection area 612, a subject annotation input area 613, a subject ID input area 614, a free selection checkbox 615, and a measurement item display area 620.

[0157] exist Figure 10 When a measurement mode is set in the measurement mode selection dialog box 520 or the manual measurement dialog box 540 on the right side of Figure 11, and the instruction registration screen 600 is displayed, the set measurement mode is automatically displayed in the measurement mode display area 601. Thus, as... Figures 13-15 As illustrated, the set measurement mode is displayed in the measurement mode display area 601. When no measurement mode is set, the measurement mode display area 601 is empty.

[0158] In addition, the instruction registration screen 600 can be configured as a test mode display area 601 including a drop-down menu, which allows selection of any one of the standard mode, malaria mode and multi-function mode.

[0159] The subject ID input area 611 is a text box where the subject ID can be entered. When the subject ID is entered in the manual measurement dialog box 540 on the right side of Figure 11 and the instruction registration screen 600 is displayed, the entered subject ID is automatically displayed in the subject ID input area 611.

[0160] Discrete selection region 612 is selectable Figure 9 A drop-down menu for any of the multiple discrete options shown. The discrete options displayed as candidates in the discrete selection area 612 vary depending on the measurement mode displayed in the measurement mode display area 601.

[0161] For example, when the measurement mode is the standard mode, such as Figure 13 As shown, Figure 9 Four discrete CBC+DIFF, CBC+DIFF+RET, CBC+DIFF+PLT-F, and CBC+DIFF+RET+PLT-F corresponding to the standard model were listed as candidates for discrete selection regions 612. In the case where the measurement model is the malaria model, such as... Figure 14 As shown, Figure 9 Three discrete CBC+MI, MI, and RET+MI corresponding to the malaria pattern were listed as candidate discrete selection regions 612. In the case of a multi-functional measurement mode, such as... Figure 15 As shown, Figure 9 The two discrete CBC+DIFF+MI and CBC+DIFF+RET+MI corresponding to the multi-functional mode are listed as candidates for selection in discrete selection region 612. In the case where no measurement mode is selected... Figure 9 All 13 discrete types shown are listed as candidates for the discrete selection region 612.

[0162] The subject annotation input area 613 is a text box where annotations for the subject can be entered. For example, the medical history of the subject whose data was collected, or travel records to malaria-endemic areas, can be entered in the subject annotation input area 613. The subject ID input area 614 is a text box where the subject ID can be entered.

[0163] The measurement item display area 620 indicates the selection status of measurement items that can be set in the subject measurement device 1. Checkboxes are attached to each measurement item, and the corresponding checkbox for the measurement item is automatically selected based on the discrete selection in the discrete selection area 612. Measurement items selected based on the discrete selection are as follows: Figure 9 This refers to the predetermined measurement items.

[0164] For example, if "CBC+DIFF+PLT-F" is selected in the discrete selection region 612, then in the measurement item display region 620, such as Figure 13 Select the measurement item as shown. If "CBC+MI" is selected in the discrete selection area 612, then in the measurement item display area 620, as shown... Figure 14 Select the measurement item as shown. If "CBC+DIFF+RET+MI" is selected in the discrete selection area 612, then in the measurement item display area 620, as shown... Figure 15 Select the measurement items as shown.

[0165] The measurement items selected (checked) in the measurement item display area 620 correspond one-to-one with the discrete items selected in the discrete selection area 612, and cannot be changed by default. On the other hand, when the operator checks the free selection checkbox 615 by operating the operation unit 32, the control unit 401 can also accept the deselection of measurement items automatically selected according to the selected discrete items, and the addition of unselected measurement items not automatically selected according to the selected discrete items, through the operation unit 32. In addition, when the free selection checkbox 615 is checked, the control unit 401 can also, through the operation unit 32, display the measurement items in the measurement item display area 620 before discrete selection (refer to...). Figure 12 The selection of the test items in the )

[0166] When a measurement command is entered on the command registration screen 600 and the confirmation button is pressed, the control unit 401 stores the contents of the command registration screen 600 as a measurement command in the storage unit 402. When the test subject container T is supplied to the measurement unit 10, the control unit 401 performs a measurement in the measurement unit 10 based on the measurement command corresponding to the test subject in the test subject container T, obtains the measurement result, and generates an analysis result based on the measurement result.

[0167] Next, refer to Figure 16~ Figure 18 The analysis of blood cells based on the scatter plot generated from the measurement results obtained using the optical detection unit 110 and the scatter plot is explained.

[0168] In addition, in Figure 16~ Figure 18 The scatter plots shown illustrate the curves corresponding to blood cells, but for convenience, these curves illustrate the distribution based on the subjects. Furthermore, for convenience, the following descriptions... Figures 20-22 The curves in the scatter plot and the degree of the histogram shown also illustrate the distribution of curves and degrees based on the subject.

[0169] The upper part of Figure 16 shows a scatter plot of WDF generated based on the measured WDF of the sample. In the scatter plot WDF, the horizontal axis corresponds to the level of the optical signal detected based on the side-scattered light generated by the light of wavelength λ20 (red wavelength band) emitted from the light source 202 (red-light side scattering, R-SSC), and the vertical axis corresponds to the level of the optical signal detected based on the fluorescence generated by the light of wavelength λ20 (red wavelength band) emitted from the light source 202 (red-light side fluorescence, R-SFL).

[0170] The control unit 401 generates a scatter plot WDF by plotting blood cells based on the measurement results of the measured sample WDF in the scatter plot containing the vertical and horizontal axes as described above. Then, for the scatter plot WDF, as shown by the dashed lines, the control unit 401 sets four regions where neutrophils and basophils are distributed respectively: (B11) neutrophils and basophils, (B12) lymphocytes, (B13) monocytes, and (B14) eosinophils.

[0171] To define the four regions, the control unit 401 performs a classification process to categorize the curves corresponding to the blood cells as follows: The control unit 401 defines initial regions corresponding to the blood cells to be classified (in the case of a scatter plot WDF, four initial regions (B11) to (B14) are defined). For each of these initial regions, the control unit 401 defines the curves within the initial region as clusters belonging to the initial region and calculates the centroid position of the curves belonging to the clusters. The control unit 401 calculates the distance from the curves not belonging to the clusters to the centroid position of each cluster, and changes the initial regions so that the curves not belonging to the clusters are included in the clusters with the shortest distance. Then, the control unit 401 calculates the centroid position of the curves belonging to each cluster again, and repeats the process until the difference between the previous centroid position and the current centroid position becomes a reference value or less. This classification process is described, for example, in U.S. Patent No. 5,555,198. U.S. Patent No. 5,555,198 is incorporated herein by reference.

[0172] The control unit 401 performs the classification process, classifying the blood cells plotted in the scatter plot WDF into any one of (B11) to (B14), and obtaining the number of blood cells in each region. Thus, white blood cells are classified, and the total number of neutrophils and basophils, the number of lymphocytes, the number of monocytes, and the number of eosinophils are obtained.

[0173] The lower section of Figure 16 shows a scatter plot of WNR generated based on the measured sample WNR. In the scatter plot WNR, the horizontal axis corresponds to the level of the optical signal detected based on the fluorescence generated 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 the forward scattered light generated by light of wavelength λ20 (red wavelength band) emitted from light source 202 (Red-light Forward Scatter (R-FSC)).

[0174] The control unit 401 generates a scatter plot WNR by plotting blood cells using the measurement results based on the measured sample WNR in the scatter plot containing the vertical and horizontal axes as described above. Then, the control unit 401 performs the classification process, defining three regions for the scatter plot WNR as shown by the dashed lines: (B21) nucleated red blood cells, (B22) basophils, and (B23) neutrophils, lymphocytes, monocytes, and eosinophils. The control unit 401 obtains the number of blood cells in each region (B21) to (B23). Furthermore, the control unit 401 calculates the total number of blood cells in (B22) and (B23) to obtain the white blood cell count. Thus, 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.

[0175] The control unit 401 obtains the difference between the number of blood cells in (B11) and the number of blood cells in (B22) as the neutrophil count. Therefore, the control unit 401 counts the white blood cells in the subject and classifies them into five categories: neutrophils, lymphocytes, monocytes, eosinophils, and basophils, obtaining the number of blood cells in each of these five categories. Furthermore, if the classification of neutrophils and basophils is not required, the preparation of the sample WNR and the creation of the scatter plot WNR can be omitted. In this case, the control unit 401 can also obtain the total count of blood cells in (B11) to (B14) as the white blood cell count.

[0176] The upper section of Figure 17 shows a scatter plot M generated based on the measured sample M. In scatter plot M, the horizontal axis corresponds to the level of the optical signal detected based on fluorescence generated by light of wavelength λ10 (blue-violet wavelength band) emitted from light source 201 (violet-light side fluorescence, V-SFL), and the vertical axis corresponds to the level of the optical signal detected based on forward scattered light generated by light of wavelength λ20 (red wavelength band) emitted from light source 202 (R-FSC). The vertical axis can also correspond to the level of the optical signal detected based on forward scattered light generated by light of wavelength λ10 (blue-violet wavelength band) emitted from light source 201 (violet-light forward scattering, V-FSC).

[0177] Control unit 401 generates a scatter plot M by plotting blood cells based on the measurement results of the measured sample M in a scatter plot including the vertical and horizontal axes as described above. Then, control unit 401 performs the classification process described above, and for scatter plot M, as shown by the dashed lines, sets three regions where (B30) malaria-infected red blood cells, (B31) malaria-uninfected red blood cells, and (B36) white blood cells are distributed respectively. As a subgroup of malaria-infected red blood cells, control unit 401 may also set four regions where (B32) ringforms (single), (B33) ringforms (multiple), (B34) trophozoites, and (B35) schizonts are distributed respectively within the region of (B30). Control unit 401 obtains the number of blood cells in each region of (B30), (B31), and (B36), or the number of blood cells in each region of (B31) to (B36). Thus, the number of malaria-infected red blood cells, the number of malaria-uninfected red blood cells and white blood cells, or the number of malaria-infected red blood cells, the number of single ring bodies, the number of multiple ring bodies, the number of trophozoites, the number of schizonts, the number of malaria-uninfected red blood cells and white blood cells can be obtained.

[0178] A ring-shaped body is a red blood cell infected with Plasmodium parasites that have a ring-shaped form. A single ring-shaped body is a red blood cell containing one ring-shaped Plasmodium parasite. Multiple ring-shaped bodies are red blood cells containing multiple ring-shaped Plasmodium parasites. A trophozoite is a red blood cell infected with Plasmodium parasites that have a trophozoite form. A schizont is a red blood cell infected with Plasmodium parasites that have a schizont form.

[0179] The intraerythrocytic life cycle of Plasmodium begins when it invades red blood cells via merozoites, one of the parasite's forms. During this intraerythrocytic life cycle, the parasite's morphology changes in the order of ring body, trophozoite, and schizont. The schizont divides into multiple merozoites, destroying red blood cells. This releases a large number of merozoites into the bloodstream. The merozoites then invade the next red blood cell, and the intraerythrocytic life cycle begins again. This cycle repeats, allowing the Plasmodium to multiply.

[0180] As described above, the control unit 401 analyzes cells (blood cells) by using clustering of scatter plots. The horizontal axis, vertical axis, and initial region of scatter plots WDF, WNR, and M are different from each other. That is, the control unit 401 applies different clustering to scatter plots WDF, WNR, and M to analyze cells.

[0181] The lower section of Figure 17 shows a scatter plot RET generated based on the measured sample RET. In the scatter plot RET, the horizontal axis corresponds to the level of the optical signal detected based on the fluorescence generated 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 the forward scattered light generated by light of wavelength λ20 (red wavelength band) emitted from light source 202 (R-FSC).

[0182] The control unit 401 plots blood cells in a scatter plot containing the vertical and horizontal axes as described above, using the measurement results based on the RET of the measured sample, and generates a scatter plot RET. Then, the control unit 401 performs the classification process, defining three regions for the scatter plot RET, as shown by the dashed lines: (B41) mature erythrocytes, (B42) reticulocytes, and (B46) platelets. The control unit 401 can also segment (B42) reticulocytes based on the R-SFL size, defining three regions: (B43) low-fluorescence reticulocytes, (B44) medium-fluorescence reticulocytes, and (B45) high-fluorescence reticulocytes. The control unit 401 obtains the number of blood cells in each region of (B41), (B42), and (B46), or the number of blood cells in each region of (B41) to (B46). Thus, the number of mature erythrocytes, reticulocytes, and platelets can be obtained, or the number of mature erythrocytes, reticulocytes, low-fluorescence reticulocytes, medium-fluorescence reticulocytes, high-fluorescence reticulocytes, and platelets can be obtained.

[0183] exist Figure 18The figure shows a scatter plot PLT-F generated based on the measured sample PLT-F. In the scatter plot PLT-F, the horizontal axis corresponds to the level of the optical signal detected based on the fluorescence generated by the light emitted from the light source 202 at wavelength λ20 (the red wavelength band) (R-SFL), and the vertical axis corresponds to the level of the optical signal detected based on the forward scattered light generated by the light emitted from the light source 202 at wavelength λ20 (the red wavelength band) (R-FSC).

[0184] The control unit 401 generates a scatter plot PLT-F, which includes a vertical axis and a horizontal axis, by plotting blood cells based on the measurement results of the measured sample PLT-F. Then, the control unit 401 performs the classification process, defining two regions for the scatter plot PLT-F, as shown by the dashed lines: (B51) for red blood cells and (B52) for platelets. Additionally, the control unit 401 defines a region (B53) for immature platelets within (B52). The control unit 401 obtains the number of blood cells in each region (B51) to (B53). Thus, the number of red blood cells, platelets, and immature platelets are obtained.

[0185] Figure 19 This is a diagram showing the structure of screen 700 displaying the analysis results. Figures 20-22 Examples are as follows Figures 13-15 The measurement mode and the analysis results display screen 700 are set as shown in the figure.

[0186] When the control unit 401 receives a display instruction from the analysis result display screen 700, it displays the analysis result display screen 700 on the display unit 31 and processes the operator's operation on the analysis result display screen 700. The display content of the analysis result display screen 700 is based on the analysis results corresponding to a subject ID.

[0187] like Figure 19 As shown, the analysis result display screen 700 includes an analysis information display area 701, a result value display area 710, a chart display area 720, a marker display area 731, and a measurement need setting area 732.

[0188] The analysis information display area 701 displays the subject ID, measurement mode, and dispersion. The result value display area 710 displays lists corresponding to the sub-discrete CBC, sub-discrete DIFF, sub-discrete MI, sub-discrete RET, and sub-discrete PLT-F, respectively. The result values ​​for each measurement item are displayed in each list. The chart display area 720 displays scatter plots WDF, WNR, M, RET, PLT-F, histogram RBC, and histogram PLT. The RBC histogram is a histogram related to red blood cells generated based on the measured sample's RBC / PLT ratio, and the PLT histogram is a histogram related to platelets generated based on the measured sample's RBC / PLT ratio.

[0189] For example, in the case of discrete form "CBC+DIFF+PLT-F", such as Figure 20 As shown, the result value display area 710 displays a list of result values ​​representing CBC, DIFF, and PLT-F, and the chart display area 720 displays scatter plots WDF, WNR, PLT-F, RBC, and PLT. In the case of discretization as "CBC+MI", as shown... Figure 21 As shown, the result value display area 710 displays a list of result values ​​representing CBC and MI, and the chart display area 720 displays scatter plots WNR, M, RBC, and PLT. In the case of discretization as "CBC+DIFF+RET+MI", as shown... Figure 22 As shown, the result value display area 710 displays a list of result values ​​representing CBC, DIFF, RET, and MI, and the chart display area 720 displays scatter plots WDF, WNR, M, RET, RBC, and PLT.

[0190] In the marked display area 731, if a specified disease is suspected based on the analysis results, the suspected disease is displayed.

[0191] For example, when the measurement mode is the standard mode, if the control unit 401 determines that a curve group exists in the scatter plot WDF shown in the upper part of Figure 16, in a region further to the left of region (B11) and further below region (B12), a marker for malaria-infected red blood cells is added to the analysis results. In this case, such as Figure 20 As shown, "Suspected malaria infection" is displayed in the label display area 731. For example, when the test mode is malaria mode or multi-function mode, the control unit 401 adds a malaria-positive label to the analysis results when it determines that the number of malaria-infected red blood cells (MI-RBC#) in the result value display area 710 is above a predetermined value. In this case, as... Figure 21 , Figure 22As shown, “malaria positive” is displayed in the marked display area 731.

[0192] In the determination of whether or not a determination is required setting area 732, if a suspected prescribed disease is displayed in the mark display area 731, the name of the determination for detailed examination of the prescribed disease and a check box for setting whether or not to perform the determination are displayed.

[0193] For example, when the testing mode is standard, if the control unit 401 displays "suspected malaria infection" in the label display area 731, then... Figure 20 As shown, the message "Malaria test required" and a checkbox are displayed in the test requirement setting area 732. In this case, when the operator selects the checkbox, a marker indicating that a malaria-related test (e.g., discrete MI test) is preferred is added to the analysis results. When the test mode is malaria mode, the control unit 401 displays "Malaria positive" in the marker display area 731, as shown... Figure 21 As shown, the message "White blood cell differential assay required" and a checkbox are displayed in the assay requirement setting area 732. In this case, when the operator selects the checkbox, a mark indicating that an assay related to white blood cell differential (e.g., discrete CBC+DIFF assay) is preferably performed is added to the analysis results.

[0194] When the determination area 732 for a specific subject is selected, and a marker indicating that a malaria-related test or a white blood cell differential test is preferably performed is added to the analysis results, the doctor or other operator can determine the presence of the required test for the subject by referring to the analysis results display screen 700 for that subject. Thus, the doctor or other operator can smoothly perform the required test.

[0195] Furthermore, when the measurement mode is in multi-functional mode, Figure 22 The analysis results display screen 700 can also be divided into a screen related to white blood cell classification and a screen related to malaria-infected red blood cells. In this case, for example, the screen related to white blood cell classification displays the result values ​​and scatter plots other than discrete MI, while the screen related to malaria-infected red blood cells displays only the result values ​​and scatter plots of discrete MI. Histograms RBC and PLT can be displayed in at least one screen. Alternatively, in this case, buttons for switching between displaying each other can be configured in both the screen related to white blood cell classification and the screen related to malaria-infected red blood cells.

[0196] Figure 23 This is a flowchart showing the processing performed by the control unit 401 of the analysis unit 30.

[0197] In step S11, the control unit 401 waits for processing before receiving a measurement instruction. In sampler mode, when a subject holder R is placed in the transport unit 20, the control unit 401 receives the measurement instruction by receiving information from the transport unit 20 indicating that the subject holder R is placed. In manual mode, when the start switch 14 is operated, the control unit 401 receives the measurement instruction by receiving information from the transport unit 20 indicating that the start switch 14 has been operated. When a measurement instruction is received (step S11: YES), the control unit 401 moves the subject container T into the frame 11 and controls the reading unit 161 to read the subject ID from the subject container T. Based on the read subject ID, the control unit 401 reads the measurement command stored in the storage unit 402.

[0198] Furthermore, in sampler mode, control unit 401 repeatedly performs the following steps S12 and S13 for each of the multiple subjects continuously supplied to measurement unit 10, and in manual mode, performs the following steps S12 and S13 on the subjects placed in subject placement unit 12.

[0199] In step S12, the control unit 401 controls the measuring unit 10 to selectively execute any one of the first measuring action, the second measuring action, and the third measuring action based on the measuring command. The first measuring action is when a measuring command is selected... Figure 9 The standard model shown is a discrete-time measurement for white blood cell classification. The second measurement is performed after selecting... Figure 9 The discrete-time measurement action for counting malaria-infected red blood cells in the malaria pattern shown is performed. The third measurement action is performed after selecting... Figure 9 The multi-functional mode shown is a discrete-time measurement operation for white blood cell classification and malaria-infected red blood cell counting. Furthermore, in step S12, the control unit 401 can read measurement commands input via the command registration screen 600 and stored in the storage unit 402, and can also receive measurement commands sent from a host computer capable of communicating with the analysis unit 30.

[0200] That is, the control unit 401 controls the measurement unit 10 to selectively perform multiple measurement actions, which include: a first measurement action to measure the subject using a staining reagent WDF containing fluorescent dye for staining white blood cells for classification; a second measurement action to measure the subject using a staining reagent M containing fluorescent dye for staining red blood cells suspected of being infected with malaria; and a third measurement action to measure the subject using staining reagent WDF and staining reagent M.

[0201] In addition, Figure 9 In the discrete CBC, discrete CBC+RET, discrete CBC+PLT-F, and discrete CBC+RET+PLT-F measurements, the measurement unit 10 performs only other measurement actions that do not correspond to any of the first, second, and third measurement actions. That is, in this embodiment, the measurement unit 10 can selectively perform multiple measurement actions on the subject, including the first, second, third, and other measurement actions.

[0202] The measurement unit 10 generates a measurement result through the measurement action in step S12 and sends the generated measurement result to the analysis unit 30. In step S13, the control unit 401 analyzes the measurement result received from the measurement unit 10 and generates an analysis result.

[0203] Subsequently, when the control unit 401 receives a display instruction from the operator for the analysis result display screen 700, in step S14, the analysis result display screen 700 is displayed on the display unit 31 based on the analysis result of the subject ID as the object.

[0204] <Effects of the Subject Measurement Device Based on Implementation Method 1> The subject measurement device 1 for measuring a subject collected from a subject includes: a measurement unit 10, which prepares a measurement sample WDF, a measurement sample M, etc. from the subject and reagents, and detects at least the optical signal corresponding to the cells in the measurement sample; and an analysis unit 30, which analyzes the cells based on the measurement of the subject by the measurement unit 10. The measurement unit 10 can selectively perform multiple measurement actions on the subject, the multiple measurement actions including: (1) a first measurement action of measuring the subject using a staining reagent WDF (first reagent) containing a fluorescent dye (first fluorescent dye) for staining white blood cells for classification; (2) a second measurement action of measuring the subject 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 action of measuring the subject using staining reagent WDF (first reagent) and staining reagent M (second reagent).

[0205] Based on the aforementioned structure, for example, based on testing instructions, analysis results, medical history, test results from other devices, travel records to malaria-endemic areas, and periods when malaria is prevalent, such as rainy seasons, either or both of the assay for white blood cell classification and the assay for malaria-infected red blood cells can be appropriately selected and performed. This improves the efficiency of patient examination procedures, including malaria infection testing.

[0206] The measuring 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, a liquid transfer unit 164, a liquid transfer unit 165, a light source 201, a light source 202, a suction tube 301, a syringe pump 311, a syringe pump 342, and chambers C11 to C14, C21, and C22 (multiple mechanisms for measuring the sample). The measuring unit 10 shares at least one of these multiple mechanisms in the first measuring action, the second measuring action, and the third measuring action.

[0207] According to the structure described above, the structure of the subject measurement device 1 can be simplified compared to the case where a mechanism is set up for each measurement action.

[0208] The measurement unit 10 includes an optical detection unit 110, which is used to detect optical signals corresponding to cells in the measurement sample. The measurement unit 10 shares the optical detection unit 110 in the first measurement operation, the second measurement operation, and the third measurement operation.

[0209] According to the structure described above, the structure of the subject measurement device 1 can be simplified compared to the case where an optical detection unit is set for each measurement action.

[0210] The measuring unit 10 includes a light source 201 and a light source 202 (at least one light source) for irradiating the sample. The measuring unit 10 shares the at least one light source in the first measuring action, the second measuring action, and the third measuring action.

[0211] According to the structure described above, the structure of the subject measurement device 1 can be simplified compared to the case where a light source is set for each measurement action.

[0212] The measuring unit 10 includes a light source 201 for irradiating the measuring sample with light of wavelength λ10 (first wavelength) and a light source 202 for irradiating the measuring sample with light of wavelength λ20 (second wavelength). In a first measuring operation, the measuring unit 10 irradiates the measuring sample with light of at least wavelength λ10 (first wavelength) and light of wavelength λ20 (second wavelength), and in a second measuring operation, it irradiates the measuring sample with light of wavelength λ10 (first wavelength) and light of wavelength λ20 (second wavelength).

[0213] According to the structure described above, the structure of the subject measurement device 1 can be simplified compared to the case where light sources are respectively set up to correspond to the first measurement action and the second measurement action.

[0214] The measuring unit 10 includes a suction tube 301, which is used to aspirate the sample supplied to the sample measuring device 1. The measuring unit 10 shares the suction tube 301 in the first measuring action, the second measuring action, and the third measuring action.

[0215] According to the structure described above, the structure of the subject measurement device 1 can be simplified compared to the case where a suction tube is set for each measurement action.

[0216] The measuring unit 10 includes: a suction tube 301 for aspirating the sample supplied to the sample measuring device 1; and an injection pump 311 for aspirating the sample through the suction tube 301. The measuring unit 10 shares the suction tube 301 and the injection pump 311 in the first measuring action, the second measuring action, and the third measuring action.

[0217] According to the structure described above, the structure of the subject measurement device 1 can be simplified compared to the case where a suction tube and pump are set for each measurement action.

[0218] The measuring unit 10 performs the first measuring action and the second measuring action in the third measuring action.

[0219] According to the structure described above, compared with the case where the test sample WDF-M1 containing both staining reagent WDF (first reagent) and staining reagent M (second reagent) is measured in the third measurement operation as described in Modified Example 2 below, the possibility of obtaining highly accurate analytical results can be increased.

[0220] The measuring 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, a liquid transfer unit 164, a liquid transfer unit 165, a light source 201, a light source 202, a suction tube 301, a syringe pump 311, a syringe pump 342, and chambers C11 to C14, C21, and C22 (multiple mechanisms for measuring the sample). At least one of the multiple mechanisms performs different actions in the first measuring action and the second measuring action, respectively.

[0221] For example, in Embodiment 1, the amount of sample dispensed in the first measurement action is different from the amount of sample dispensed in the second measurement action, and the measurement time of the optical detection unit 110 in the first measurement action is different from the measurement time of the optical detection unit 110 in the second measurement action. Therefore, the syringe pump 311 and syringe pump 342 perform different actions in the first and second measurement actions, respectively. According to the above structure, the target mechanism can be made to perform appropriate actions corresponding to the measurement actions in both the first and second measurement actions.

[0222] The measurement unit 10 includes an optical detection unit 110, which is used to detect optical signals corresponding to cells in the measurement sample. The measurement time based on the optical detection unit 110 in the first measurement operation is different from the measurement time based on the optical detection unit 110 in the second measurement operation.

[0223] According to the structure, in the first measurement operation and the second measurement operation, the optical detection unit 110 can perform the measurement of an appropriate measurement time corresponding to the measurement operation.

[0224] The measurement unit 10 includes chambers C11 to C14, chamber C21, and chamber C22, and a syringe pump 311, etc. (sample preparation unit), for preparing the test sample from the subject and reagents. In the first measurement operation, chambers C11 and C13, and syringe pump 311, etc. (sample preparation unit) prepare the test sample WDF (first test sample) from the subject and staining reagent WDF (first reagent), and in the second measurement operation, prepare the test sample M (second test sample) from the subject and staining reagent M (second reagent).

[0225] According to the structure, the test sample WDF and the test sample M can be successfully prepared in the first and second test actions, respectively.

[0226] In the first measurement action, chambers C11 and C13 (sample preparation section) prepare the test sample WDF (first test sample) from the test subject, staining reagent WDF (first reagent) and hemolysis reagent WDF (first hemolysis reagent). In the second measurement action, the test sample M (second test sample) is prepared from the test subject, staining reagent M (second reagent) and hemolysis reagent M (second hemolysis reagent).

[0227] According to the structure, in the first measurement action, the measurement sample WDF can be appropriately prepared using the hemolyzing reagent WDF, and in the second measurement action, the measurement sample M can be appropriately prepared using the hemolyzing reagent M.

[0228] In the second measurement action, the measurement unit 10 measures the count of cells suspected of being infected with malaria (the count of blood cells in region (B30) of scatter plot M) and the count of white blood cells (the count in region (B36) of scatter plot M) on the subject.

[0229] According to the structure, malaria can be detected with good accuracy based on the measurement results obtained through the second measurement action and with reference to the number of red blood cells and white blood cells infected with malaria.

[0230] 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 both the first measurement operation and the second measurement operation.

[0231] According to the aforementioned structure, both the optical detection unit 110 and the electrical detection unit 120 are used in the first and second measurement operations, thereby enabling more detailed analysis of the sample. Specifically, the optical detection unit 110 can be used to classify or count white blood cells, while the electrical detection unit 120 can be used to count red blood cells or platelets.

[0232] In the first and second measurement actions, the analysis unit 30 analyzes the cells by using different clusters.

[0233] According to the structure, appropriate cell analysis can be performed in the first and second measurement actions, respectively.

[0234] In the analysis corresponding to the first measurement action, the analysis unit 30 classifies white blood cells into multiple subgroups.

[0235] Based on the described structure, white blood cell-based examinations can be performed with good accuracy.

[0236] In the analysis corresponding to the second measurement action, the analysis unit 30 obtains information related to the life cycle of malaria for cells suspected of being infected with malaria.

[0237] Based on the structure described, information related to the life cycle (life stages) of malaria, such as the circosome, trophosome, and schizont, can be obtained, thus providing a detailed understanding of the status of the malaria parasites in the infected subject.

[0238] The analysis unit 30 selects the measurement action to be performed by the measurement unit 10 based on the measurement instruction (information related to the test subject). Figure 23 Step S12).

[0239] According to the structure, the first measurement action, the second measurement action, and the third measurement action are automatically selected according to the measurement command. Therefore, by pre-registering the measurement command, the measurement action can be executed smoothly.

[0240] The analysis unit 30 includes a control unit 401, a display unit 31, and an operation unit 32. The control unit 401 causes the display unit 31 to display a measurement mode selection dialog box 520 and a manual measurement dialog box 540 (screen) for selecting a measurement mode from three measurement modes, namely, dividing multiple measurement actions into a first measurement action, a second measurement action, and a third measurement action. The control unit 32 accepts the measurement mode selected via the measurement mode selection dialog box 520 and the manual measurement dialog box 540 (screen) and causes the display unit 31 to display an instruction registration screen 600 (other screen) for selecting the measurement action corresponding to the accepted measurement mode.

[0241] According to the structure described above, by selecting a measurement mode, the operator can display an instruction registration screen 600 for selecting the measurement action corresponding to the measurement mode. Thus, the operator can easily select the measurement action via the instruction registration screen 600.

[0242] The analysis unit 30 includes a control unit 401, a display unit 31, and an operation unit 32. The control unit 401 causes the display unit 31 to display an instruction registration screen 600 (screen) for selecting a first measurement action, a second measurement action, and a third measurement action from multiple measurement actions. The operation unit 32 is used to accept the measurement action selected via the instruction registration screen 600 (screen).

[0243] According to the structure, the operator can cause the measuring unit 10 to perform the measuring actions required for the subject.

[0244] The analysis unit 30 includes a control unit 401, a display unit 31, and an operation unit 32. The control unit 401 can also cause the display unit 31 to display an instruction registration screen 600 (screen) for selecting at least one measurement item from multiple measurement items that respectively define a first measurement action, a second measurement action, and a third measurement action, and the operation unit 32 can accept the measurement item selected via the instruction registration screen 600 (screen).

[0245] According to the structure, the operator can set the required measurement actions for the subject in more detail, and the measurement unit 10 can perform the set measurement actions.

[0246] The analysis unit 30 includes a control unit 401, a display unit 31, and an operation unit 32. The control unit 401 causes the display unit 31 to display an instruction registration screen 600 (screen) for registering the following measurement instructions: that is, indicating which of the following measurement instructions to execute: the first measurement action, the second measurement action, and the third measurement action. The operation unit 32 accepts the measurement instructions registered via the instruction registration screen 600 (screen).

[0247] According to the structure, by pre-registering the measurement instructions, the measurement actions required for the subject can then be smoothly performed.

[0248] <Implementation Method 2> Based on the analysis results obtained by the subject measurement device 1, it can be determined whether, for the same subject, further measurements of other discrete (measurement items) are required by the subject measurement device 1, i.e., whether reflectance measurement is necessary. In this case, when it is determined that reflectance measurement is necessary, the measurement of the subject is performed automatically. Hereinafter, a structure and process different from Embodiment 1 will be described.

[0249] Figure 24 This is a diagram showing the structure of the reflection setting screen 800 in this embodiment.

[0250] When the control unit 401 receives a display instruction from the reflection setting screen 800, it displays the reflection setting screen 800 on the display unit 31 and processes the operation of the reflection setting screen 800 by the operator.

[0251] The reflection setting screen 800 includes a reflection rule display area 810 and a reflection rule addition area 820.

[0252] The reflection rules used to determine whether a reflection measurement is required are displayed in the reflection rule display area 810. Each row corresponds to one reflection rule. The reflection rule includes a name, a conditional expression for determining that a reflection measurement is required, and a specified operation for automatic processing when a reflection measurement is determined to be required.

[0253] For example, the reflection rules include performing discrete MI when a marker for malaria-infected red blood cells is added to the analysis results of the standard pattern, as shown in the first row of the reflection rules display area 810. In this case, the number of malaria-infected red blood cells that cannot be obtained in the white blood cell classification can be obtained, thus allowing for a high-precision determination of whether someone has malaria. Additionally, the reflection rules include performing discrete CBC+DIFF when a marker for malaria positivity is added to the analysis results of the malaria pattern, as shown in the second row of the reflection rules display area 810. In this case, the number of white blood cells in each category that cannot be obtained in the malaria-infected red blood cell classification can be obtained, thus allowing for an accurate assessment of the subject's condition.

[0254] The reflection rule addition area 820 includes text boxes 821 to 823 corresponding to the name, condition, and operation of the reflection rule, respectively, and an addition button 824. When the name, condition, and operation are entered via the operation unit 32, and the addition button 824 is operated, the control unit 401 accepts the contents of the reflection rule addition area 820 and stores them in the storage unit 402, and adds and displays the accepted reflection rule in the reflection rule display area 810.

[0255] Figure 25 This is a flowchart showing the processing performed by the control unit 401 of the analysis unit 30.

[0256] exist Figure 25 In the process of handling, with Figure 23 Compared to the processing in Implementation Method 1, steps S21 and S22 are added. In step S21, the control unit 401 determines whether there is an analysis result in the analysis results generated in step S13 that matches the conditional expression of the reflection rule stored in the storage unit 402. If there is an analysis result that matches the conditional expression of the reflection rule (step S21: Yes), in step S22, the control unit 401 moves the subject container T, which contains the subject to be determined by the reflection rule, back to the subject aspiration position in the frame 11. Then, the control unit 401 selectively performs a measurement operation on the subject in the subject container T according to the operation of the consistent reflection rule.

[0257] <Effects of the Subject Measurement Device Based on Implementation Method 2> Based on the analysis results (information related to the subject), the analysis unit 30 selects the measurement action to be performed by the measurement unit 10. Figure 25 Step S22).

[0258] Based on the structure, the first measurement action, the second measurement action, and the third measurement action are automatically selected according to the analysis results, thus eliminating the need for the operator to select the measurement action by referring to the analysis results.

[0259] <Example 1 of the amendment> In Implementation 1, the measurement action is selectively performed based on the measurement command; in Implementation 2, the measurement action is selectively performed again based on the analysis results. However, the measurement action is not limited to information related to the subject, such as the measurement command and analysis results; it can also be selectively performed based on other information related to the subject. For example, other information related to the subject may include the subject's medical history, examination results of other devices, travel records to malaria-endemic areas, etc.

[0260] Figure 26 This is a flowchart illustrating the processing performed by the control unit 401 of the analysis unit 30 when selectively performing measurement actions based on information related to the subject.

[0261] Figure 26 Flowcharts and Figure 23 Compared with Implementation 1, steps S31 to S34 are added instead of step S12.

[0262] In step S31, the control unit 401, for example, obtains and collects other information about the subject being tested from the electronic medical record system via a computer network. In step S32, the control unit 401 determines whether the subject is suspected of being 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 travel history to malaria-endemic areas, the control unit 401 determines that the subject is suspected of being infected with malaria.

[0263] If malaria infection is suspected (step S32: Yes), the control unit 401 controls the measurement unit 10 to perform a second measurement action or a third measurement action. If malaria infection is not suspected (step S32: No), the control unit 401 controls the measurement unit 10 to perform a first measurement action.

[0264] Furthermore, the operator can pre-set which of the second and third measurement actions will be performed in step S33. Additionally, the operator can pre-set the discreteness of the malaria pattern performed during the second measurement action and the discreteness of the multi-functional pattern performed during the third measurement action.

[0265] <Effects of the Subject Measurement Device Based on Modified Example 1> The analysis unit 30 selects the measurement action to be performed by the measurement unit 10 based on other information related to the subject. Figure 26 Steps S31 to S34).

[0266] According to the structure, the first measurement action, the second measurement action, and the third measurement action are automatically selected based on other information related to the subject, thus eliminating the need for the operator to select the measurement action by referring to other information related to the subject.

[0267] Analysis unit 30 is used when the subject is obtained from a subject suspected of being infected with malaria. Figure 26 Step S32: Yes), select the second measurement action or the third measurement action (step S33).

[0268] For subjects suspected of having malaria, it is desirable to perform a second or third testing action, including the testing of test sample M. According to the aforementioned structure, for test samples obtained from subjects suspected of having malaria, the second or third testing action is automatically selected, thus eliminating the need for determining the required testing action.

[0269] Analysis unit 30 is used when the subject is a subject who has never been suspected of having malaria ( Figure 26Step S32: No), select the first measurement action (step S34).

[0270] For subjects who are not suspected of having malaria, the second and third testing actions, including the testing of sample M, are unnecessary. According to this structure, for subjects obtained from subjects who are never suspected of having malaria, the first testing action is automatically selected, thus preventing the selection of unnecessary testing actions.

[0271] <Amendment Example 2> In Embodiment 1, during the discrete phase of the multifunctional mode, a measurement sample WDF and a measurement sample M are prepared separately, and measurements are performed based on the measurement sample WDF and the measurement sample M, respectively. However, this is not a limitation; a measurement sample WDF-M1 corresponding to both the measurement sample WDF and the measurement sample M may also be prepared, and the same analytical results as those based on the measurement sample WDF and the measurement sample M may be obtained based on the measurement of measurement sample WDF-M1.

[0272] Figure 27 This is a diagram showing the structure of the fluid circuit connected to chambers C12, C14, C15 and the optical detection unit 110.

[0273] In this example of change, with Figure 6 Compared to embodiment 1, chamber C15 is added instead of chambers C11 and C13. Chamber C15 has the same structure as the other chambers C12 and C14, and is connected to flow path 341 in the same way as the other chambers C12 and C14. In addition, staining reagent WDF, staining reagent M, and hemolysis reagent WDF-M are supplied through inlet 321 of chamber C15.

[0274] In this modified example, when the multi-functional mode of discrete CBC+DIFF+MI or discrete CBC+DIFF+RET+MI is selected in the measurement instruction, instead of preparing the test sample WDF and test sample M separately, the test sample WDF-M1 is prepared in chamber C15 by mixing the test subject, staining reagent WDF, staining reagent M, and hemolytic reagent WDF-M. The hemolytic reagent WDF-M is a reagent that partially dissolves 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 the malaria parasite is held inside the red blood cells. The hemolytic power of the hemolytic reagent WDF-M on the cell membrane of red blood cells is preferably stronger than that of the hemolytic reagent M and weaker than that of the hemolytic reagent WDF. The hemolytic reagent WDF-M may contain, for example, a nonionic surfactant, a cationic surfactant, an anionic surfactant, an amphiphilic surfactant, or a combination thereof.

[0275] When the preparation of the test sample WDF-M1 is completed, the test sample WDF-M1 is supplied to the optical detection unit 110 via the flow path 341, and the optical detection unit 110 uses the light source 201 and the light source 202 to perform the measurement.

[0276] When the test sample WDF-M1 is measured, the scatter plot WDF in the upper part of Figure 16 and the scatter plot M in the upper part of Figure 17 are generated based on the measurement results of the test sample WDF-M1. Then, the control unit 401 classifies the blood cells drawn in the scatter plot WDF into any one of (B11) to (B14) and obtains the number of blood cells in each region. Similarly, the control unit 401 classifies the blood cells drawn in the scatter plot M into any one of (B30), (B31), and (B36), or any one of (B31) to (B36), and obtains the number of blood cells in each region.

[0277] Furthermore, when the standard mode discrete method is selected, in chamber C15, test sample WDF-M2 is prepared by mixing the test subject, hemolysis reagent WDF-M, and staining reagent WDF. The scatter plot WDF in the upper part of Figure 16 is generated based on the measurement results of test sample WDF-M2. When the malaria mode discrete method is selected, in chamber C15, test sample WDF-M3 is prepared by mixing the test subject, hemolysis reagent WDF-M, and staining reagent M. The scatter plot M in the upper part of Figure 17 is generated based on the measurement results of test sample WDF-M3. That is, in this modified example, test samples WDF-M1, WDF-M2, and WDF-M3 are prepared in the common chamber C15.

[0278] <Effects of the Subject Measurement Device Based on Modified Example 2> In the third measurement action, the measurement unit 10 prepares a common measurement sample WDF-M1 for the classification of white blood cells 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.

[0279] According to the structure, in the third measurement action, only one test sample needs to be prepared for the examination of white blood cells and malaria infection. Therefore, the third measurement action can be performed more efficiently than the case where test sample WDF for the examination of white blood cells and test sample M for the examination of malaria infection are prepared separately.

[0280] Furthermore, according to the aforementioned structure, in the first measurement action, the second measurement action, and the third measurement action, the measurement sample WDF-M1 / M2 / M3 can be prepared using a common hemolytic reagent WDF-M, thereby suppressing the number of reagents connected to the test subject measurement device 1.

[0281] Furthermore, in Modification Example 2, reflectance measurement can also be performed as in Embodiment 2. In this case, the reflectance rule may include, for example, adding a marker of malaria-infected red blood cells to the analysis results of the standard mode, performing discretization of the multifunctional mode. This allows for further acquisition of analysis results based on the measured sample WDF-M1, thus enabling more accurate determination of whether or not the individual has malaria.

[0282] Furthermore, in Modification Example 2, when the discrete multi-functional mode is selected in the measurement command, the control unit 401 performs an analysis based on the measurement sample WDF-M1. However, it is not limited to this; it can also receive instructions from the operator in advance regarding which of the following analyses should be performed: a first analysis based on measurement samples WDF-M2 and WDF-M3, or a second analysis based on measurement sample WDF-M1. Thus, for example, it is possible to determine which of the first and second analyses should be performed based on the facility's operational guidelines.

[0283] In addition, in Modified Example 2, a common chamber C15 for preparing test samples WDF-M1, WDF-M2 and WDF-M3 is provided, but it is not limited to this. A separate chamber for preparing at least one of test samples WDF-M1, WDF-M2 and WDF-M3 may also be provided separately from chamber C15.

[0284] <Example 3 of the amendment> In modified example 2, staining reagent WDF, staining reagent M, and hemolysis reagent WDF-M are connected to chamber C15. However, it is not limited to this, such as... Figure 28 As shown, hemolysis reagent WDF, staining reagent WDF, hemolysis reagent M and staining reagent M can also be connected to chamber C15.

[0285] In this modified example, with the multi-functional discrete mode selected, the test sample WDF is prepared in chamber C15 by mixing the test subject, hemolysis reagent WDF, and staining reagent WDF. The scatter plot of WDF in the upper part of Figure 16 is generated based on the measurement results of the test sample WDF. The test sample WDF is discharged from chamber C15, chamber C15 is cleaned, and then the test sample M is prepared in chamber C15 by mixing the test subject, hemolysis reagent M, and staining reagent M. The scatter plot of M in the upper part of Figure 17 is generated based on the measurement results of the test sample M. The preparation of the test sample WDF and the test sample M can be performed either first.

[0286] When the standard mode discrete method is selected, the test sample WDF is prepared in chamber C15 by mixing the test subject, hemolysis reagent WDF, and staining reagent WDF. The scatter plot WDF in the upper part of Figure 16 is generated based on the measurement results of the test sample WDF. When the malaria mode discrete method is selected, the test sample M is prepared in chamber C15 by mixing the test subject, hemolysis reagent M, and staining reagent M. The scatter plot M in the upper part of Figure 17 is generated based on the measurement results of the test sample M. That is, in this modified example, the test sample WDF and the test sample M are prepared in the common chamber C15.

[0287] Furthermore, in this modified example, reflection measurement can also be performed as in Embodiment 2.

[0288] <Amendment Example 4> In Embodiment 1, during the determination of subdiscrete DIFF, the subject measuring device 1 prepares a test sample WDF and a test sample WNR, and generates a scatter plot WDF and a scatter plot WNR. In this modified example, during the determination of subdiscrete DIFF, the subject measuring device 1 does not prepare a test sample WNR or generate a scatter plot WNR, but instead prepares a test sample WDF and generates a scatter plot WDF.

[0289] Figure 29 This is an example of a scatter plot WDF. The scatter plot WDF is prepared in the same manner as in Embodiment 1, based on the measurement results of the WDF of the measured sample.

[0290] Control unit 401 for Figure 29 The scatter plot WDF is used to set five initial regions corresponding to lymphocytes, monocytes, eosinophils, neutrophils, and basophils, and the classification process described in Embodiment 1 is performed. Therefore, compared with the scatter plot WDF in the upper part of FIG16, the control unit 401 sets regions for neutrophils (B15) and basophils (B16) instead of neutrophils (B11). Then, the control unit 401 obtains the number of blood cells in each region (B12) to (B14), (B15), and (B16). Furthermore, the control unit 401 obtains the total count of blood cells in (B12) to (B14), (B15), and (B16) as the white blood cell count. That is, in this modified example, the measurement unit 10 prepares a measurement sample WDF to count and classify white blood cells, and detects the optical signal corresponding to the cells in the measurement sample WDF.

[0291] <Effects of the Subject Measurement Device Based on Modified Example 4> In the first measurement action, the measurement unit 10 measures the subject for the counting and classification of white blood cells.

[0292] According to the structure described, only one test sample needs to be prepared for the counting and classification of white blood cells. Therefore, compared with the case of preparing test samples WDF and WNR separately, the measurement action for counting and classifying white blood cells can be performed more efficiently.

[0293] <Example 5 of the amendment> In implementation method 1, the vertical and horizontal axes of scatter plots WDF, WNR, M, RET, and PLT-F are shown in Figure 16. Figure 18 The settings are as shown. However, this is not a limitation; the optical signals used as axes for each scatter plot can be any optical signals based on light from light source 201 or light source 202. In either case, a region corresponding to the type of axis is set so that blood cells can be appropriately classified for each scatter plot.

[0294] However, when using an optical signal based on fluorescence generated by light from light source 201, the staining reagent mixed into the test sample contains a fluorescent dye that can be excited by light of wavelength λ10, and when using an optical signal based on fluorescence generated by light from light source 202, the staining reagent mixed into the test sample contains a fluorescent dye that can be excited by light of wavelength λ20.

[0295] Figure 30 This illustrates an example of a scatter plot WDF-1. The scatter plot WDF-1 is constructed based on the measurement results of the WDF of the sample. In the scatter plot WDF-1, the horizontal axis corresponds to the level of the optical signal detected based on the side-scattered light generated by light of wavelength λ10 (blue-violet wavelength band) emitted from light source 201 (violet-light side scatterer, V-SSC), and the vertical axis corresponds to the level of the optical signal detected based on the fluorescence generated by light of wavelength λ10 (blue-violet wavelength band) emitted from light source 201 (V-SFL).

[0296] For the scatter plot WDF-1, the control unit 401 sets five initial regions corresponding to lymphocytes, monocytes, eosinophils, neutrophils, and basophils, and performs the classification process described in Embodiment 1. Thus, the control unit 401 sets regions for (B12-1) lymphocytes, (B13-1) monocytes, (B14-1) eosinophils, (B15-1) neutrophils, and (B16-1) basophils. Then, the control unit 401 obtains the number of blood cells in each region (B12-1) to (B14-1), (B15-1), and (B16-1). Furthermore, the control unit 401 obtains the total number of blood cells in (B12-1) to (B14-1), (B15-1), and (B16-1) as the white blood cell count. That is, in this modified example, the measuring unit 10 prepares a measuring sample WDF in order to count and classify white blood cells, and detects the optical signal corresponding to the cells in the measuring sample WDF.

[0297] <Effects of the Subject Measurement Device Based on Modified Example 5> In the first measurement action, the measurement unit 10 measures the subject for the counting and classification of white blood cells.

[0298] According to the structure described, only one test sample needs to be prepared for the counting and classification of white blood cells. Therefore, compared with the case of preparing test samples WDF and WNR separately, the measurement action for counting and classifying white blood cells can be performed more efficiently.

[0299] Furthermore, in Embodiment 1, only a light-receiving unit 221 for detecting forward-scattered light based on wavelength λ20 is provided as the light-receiving unit corresponding to the forward-scattered light. However, when forward-scattered light based on wavelength λ10 is used in the analysis, the light-receiving unit for detecting forward-scattered light based on wavelength λ10 may replace the light-receiving unit 221 or be provided together with the light-receiving unit 221.

[0300] In addition, when using only optical signals based on light with wavelength λ10 from light source 201 as the optical signals used as axes of each scatter plot, a light receiving unit for detecting forward scattered light based on wavelength λ10 is arranged instead of light receiving unit 221, and light source 202, dichroic mirror 241, light receiving unit 242, and light receiving unit 243 are omitted.

[0301] <Example 6 of the amendment> In Embodiment 1, when a discrete sample including the sub-discrete MI is selected, the measurement unit 10 measures the RBC / PLT of the test sample using the electrical detection unit 120 and measures the test sample M using the optical detection unit 110. However, this is not a limitation; in the measurement operation (second measurement operation) of measuring the test sample M, the measurement unit 10 may also measure the test sample M using the optical detection unit 110 instead of the electrical detection unit 120. In this case, the control unit 401 calculates the total number of red blood cells in the regions (B30) and (B31) of the scatter plot M (refer to the upper part of Figure 17) as the number of red blood cells required to calculate the test item MI-RBC%.

[0302] <Effects of the Subject Measurement Device Based on Modified 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. The measurement unit 10 does not use the electrical detection unit 120 during the second measurement operation.

[0303] According to the structure, the electrical detection unit 120 is not used in the second measurement operation, thereby suppressing the amount of test subject and reagent used.

[0304] <Other Change Examples> In the described embodiments and modifications, when the measurement mode is selected, in Figure 12 The discrete selection area 612 displays only the discrete corresponding to the measurement mode. The operator determines the actual discrete to be executed by selecting a discrete in the discrete selection area 612. However, it is not limited to this; the actual discrete to be executed can also be uniquely determined based on the selected measurement mode. For example, if the discrete settings of the subject measurement device 1 are CBC+DIFF, MI, and CBC+DIFF+MI, when the standard mode, malaria mode, and multi-functional mode are selected, CBC+DIFF, MI, and CBC+DIFF+MI can be selected as the discrete, respectively.

[0305] In the described embodiments and variations, in the determination and analysis corresponding to the subdiscrete DIFF, white blood cells are classified into five subgroups, but white blood cells may also be classified into two, three, or four subgroups.

[0306] In the described embodiments and modifications, a predetermined amount of test sample is measured in either the first or second measurement action, but this is not a limitation. For example, in the measurement of test sample M included in the second measurement action, the measurement can be continued until a predetermined number of malaria-infected red blood cells are detected. That is, the measurement time of the second measurement action can also be variable. This allows for more reliable detection of malaria-infected red blood cells. Furthermore, in the measurement of test sample M included in the second measurement action, the emitted light power of light sources 201 and 202 can be higher than in the first measurement action. In this case, the detection sensitivity of malaria-infected red blood cells can be improved.

[0307] In the modified example 2, in Figure 22 In the analysis results display screen 700 related to the multi-functional mode, if "malaria positive" is displayed in the marker display area 731, a message "Individual tests of standard mode and malaria mode are required" and a checkbox may also be displayed in the test requirement setting area 732. In this case, when the operator selects the checkbox, a marker indicating that tests related to white blood cell differential (e.g., discrete CBC+DIFF test) and tests related to malaria (e.g., discrete MI test) are preferably performed can be added to the analysis results.

[0308] In the described embodiments and modifications, in Figure 20 , Figure 21 When the measurement requirement setting area 732 is set to the selected state, measurement commands related to the required measurement actions can also be automatically registered.

[0309] In the described embodiment and its variations, the measurement instructions are stored in the storage unit 402 of the analysis unit 30, but they may also be stored in a host computer capable of communicating with the analysis unit 30. In this case, when a measurement instruction is input into the subject measurement device 1 or other device, the input measurement instruction is sent to the host computer and centrally managed there. When the analysis unit 30 receives the subject ID read by the reading unit 161, it queries the host computer for the measurement instructions and receives the measurement instructions corresponding to the subject ID from the host computer.

[0310] The embodiments of the present invention can be adapted to various modifications within the scope of the technical concept shown in the claims.

Claims

1. A subject measurement device for measuring a subject collected from a subject, the subject measurement device comprising: The measurement unit prepares a measurement sample from the test subject and reagents, and detects at least the optical signal corresponding to the cells in the measurement sample; and The analysis unit analyzes the cells based on the measurements of the sample taken by the measurement unit. The measuring unit can selectively perform multiple measuring actions on the subject, the multiple measuring actions including: (1) A first measurement action of measuring the subject using a first reagent containing a first fluorescent dye for staining the white blood cells for classification. (2) A second assay step involving the use of a second reagent containing a second fluorescent dye for staining cells suspected of being infected with malaria to measure the subject, and (3) A third measurement action to measure the subject using the first reagent and the second reagent.

2. The subject measuring device according to claim 1, wherein, The measuring unit includes multiple mechanisms for measuring the test sample. The measuring unit shares at least one of the plurality of mechanisms in the first measuring action, the second measuring action, and the third measuring action.

3. The subject measuring device according to claim 1, wherein, The measurement unit includes an optical detection unit for detecting optical signals corresponding to the cells in the measurement sample. The measuring unit shares the optical detection unit in the first measuring action, the second measuring action, and the third measuring action.

4. The subject measuring device according to claim 1, wherein, The measuring unit includes at least one light source for irradiating the measuring sample with light. The measuring unit shares at least one light source in the first measuring action, the second measuring action, and the third measuring action.

5. The subject measuring device according to claim 1, wherein, The measuring unit includes a light source for irradiating the measuring sample with light of a first wavelength and a light source for irradiating the sample with light of a second wavelength. In the first measurement action, the measuring unit irradiates the measuring sample with light of at least the first wavelength and light of the second wavelength; in the second measurement action, the measuring unit irradiates the measuring sample with light of the first wavelength and light of the second wavelength.

6. The subject measuring device according to claim 5, wherein, The first wavelength is above 315 nm and below 490 nm. The second wavelength is above 610 nm and below 750 nm.

7. The subject measuring device according to claim 1, wherein, The measuring unit includes a suction tube for aspirating the sample supplied to the sample measuring device. The measuring unit shares the suction tube in the first measuring action, the second measuring action, and the third measuring action.

8. The subject measuring device according to claim 1, wherein, The measuring unit includes: a suction tube for suctioning the sample supplied to the sample measuring device; and a pump for suctioning the sample through the suction tube. The measuring unit shares the suction tube and the pump in the first measuring action, the second measuring action, and the third measuring action.

9. The subject measuring device according to claim 1, wherein, The measuring unit performs the first measuring action and the second measuring action in the third measuring action.

10. The subject measuring device according to claim 1, wherein, The measuring unit includes multiple mechanisms for measuring the test sample. At least one of the plurality of mechanisms performs different actions in the first measurement action and the second measurement action, respectively.

11. The subject measuring device according to claim 1, wherein, The measurement unit includes an optical detection unit for detecting optical signals corresponding to the cells in the measurement sample. The measurement time based on the optical detection unit in the first measurement operation is different from the measurement time based on the optical detection unit in the second measurement operation.

12. The subject measuring device according to claim 1, wherein, The measuring unit includes a sample preparation section for preparing the measuring sample from the test subject and the reagents. The sample preparation unit prepares a first test sample from the test subject and the first reagent during the first test operation, and prepares a second test sample from the test subject and the second reagent during the second test operation.

13. The subject measuring device according to claim 12, wherein, The sample preparation unit prepares the first test sample from the test subject, the first reagent, and the first hemolysing reagent in the first test operation, and prepares the second test sample from the test subject, the second reagent, and the second hemolysing reagent in the second test operation.

14. The subject measuring device according to claim 1, wherein, In the first measurement action, the measurement unit measures the subject for the purpose of counting and classifying white blood cells.

15. The subject measuring device according to claim 1, wherein, In the second measurement action, the measurement unit measures the number of cells suspected of being infected with malaria and the number of white blood cells in the subject.

16. The subject measuring device according to claim 1, wherein, In the third measurement action, the measurement unit prepares a common measurement sample for classifying the white blood cells and counting the cells suspected of being infected with the malaria, and detects the optical signal corresponding to the cells in the measurement sample.

17. The subject measuring device according to claim 1, wherein, The measurement unit includes: an optical detection unit for detecting optical signals corresponding to the cells in the measurement sample; and an electrical detection unit for detecting electrical signals corresponding to the cells in the measurement sample. The measuring unit uses both the optical detection unit and the electrical detection unit in the first measuring action and the second measuring action.

18. The subject measuring device according to claim 1, wherein, The measurement unit includes: an optical detection unit for detecting optical signals corresponding to the cells in the measurement sample; and an electrical detection unit for detecting electrical signals corresponding to the cells in the measurement sample. The measuring unit does not use the electrical detection unit in the second measuring action.

19. The subject measuring device according to claim 1, wherein, The analysis unit analyzes the cells by using different clusters in the first measurement action and the second measurement action.

20. The subject measuring device according to claim 1, wherein, In the analysis corresponding to the first measurement action, the analysis unit classifies the white blood cells into multiple subgroups.

21. The subject measuring device according to claim 1, wherein, In the analysis corresponding to the second measurement action, the analysis unit acquires information related to the life cycle of malaria for the cells suspected of being infected with malaria.

22. The subject measuring device according to claim 1, wherein, The analysis unit selects the measurement action to be performed by the measurement unit based on information related to the subject.

23. The subject measuring device according to claim 22, wherein, When the subject is obtained from a subject suspected of being infected with malaria, the analysis unit selects either the second or the third measurement action.

24. The subject measuring device according to claim 22, wherein, The analysis unit selects the first measurement action when the subject is a subject who has never been suspected of being infected with malaria.

25. The subject measuring device according to claim 1, wherein, The analysis unit includes a control unit, a display unit, and an operation unit. The control unit The display unit shows a screen for selecting one of three measurement modes from a set of measurement modes, namely, a first measurement mode, a second measurement mode, and a third measurement mode, respectively. The selected measurement mode is received by operating the operation unit via the screen. The display unit displays other screens for selecting the measurement action corresponding to the accepted measurement mode.

26. The subject measuring device according to claim 1, wherein, The analysis unit includes a control unit, a display unit, and an operation unit. The control unit The display unit displays a screen for selecting the first measurement action, the second measurement action, and the third measurement action from a plurality of measurement actions. The measurement action selected via the screen is received through the operation of the operating unit.

27. The subject measuring device according to claim 1, wherein, The analysis unit includes a control unit, a display unit, and an operation unit. The control unit The display unit displays a screen for selecting at least one of the measurement items from a plurality of measurement items that respectively define the first measurement action, the second measurement action, and the third measurement action. The measurement item selected via the screen is received through the operation of the operating unit.

28. The subject measuring device according to claim 1, wherein, The analysis unit includes a control unit, a display unit, and an operation unit. The control unit The display unit displays a screen indicating which of the following measurement commands—the first, second, and third—is being executed: the measurement command for registering the measurement instructions. The measurement command registered via the screen is received through the operation of the operating unit.

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