Sample measurement device and sample measurement method

Abstract

A sample measuring apparatus according to an embodiment may be a sample measuring apparatus for measuring a platelet aggregation function of a blood sample. The apparatus may include: a detection section configured to measure optical information of platelet rich plasma and platelet poor plasma prepared from a blood sample; a control section configured to acquire information on a platelet aggregation function of the blood sample based on optical information of platelet rich plasma and platelet poor plasma; and a display configured to display information on a platelet aggregation function. The controller is configured to obtain evaluation information on suitability of the platelet-rich plasma as a sample based on a measurement result of the platelet-rich plasma by the detection portion, and display the evaluation information on the display.

Description

Technical Field

[0001] The present invention relates to a sample measurement device and a sample measurement method, and more particularly, to a sample measurement device and a sample measurement method for measuring platelet aggregation function of a blood sample. Background Art

[0002] Currently, platelet aggregation function is tested using a blood coagulation tester. To measure platelet aggregation function, whole blood samples collected from patients are subjected to two centrifugation processes to prepare a platelet-rich plasma (PRP) sample containing many platelets and a platelet-poor plasma (PPP) sample containing virtually no platelets. Calculations are performed based on the optical information obtained from measuring the platelet-poor plasma sample and the optical information obtained from measuring the platelet-rich plasma sample to which a reagent that induces platelet aggregation has been added. However, if the platelet count in the platelet-rich plasma sample is low (less than 150×10 9 / L), correct results may not be obtained.

[0003] Prior art literature Non-patent literature Non-patent document 1: Guidelines of the International Society on Thrombosis and Haemostasis (ISTH): “Recommendations for the standardization of light transmission aggregometry: a consensus of the working party from the platelet physiology subcommittee of SSC / ISTH,” Journal of Thrombosis and Haemostasis, 11: 1183–1189, 2013. Summary of the Invention

[0004] Problems to be solved by the invention In order to accurately measure platelet aggregation function, it is desirable to use a platelet count of 150 × 10 9 Therefore, the platelet count of the prepared platelet-rich plasma sample is measured using a blood cell counting device separate from the blood coagulation test device to confirm whether it is suitable for the platelet aggregation function test. This confirmation operation consumes labor and time.

[0005] Technical solutions to solve problems One aspect of the present invention provides a sample measuring device (1) for measuring the platelet aggregation function of a blood sample, characterized in that the sample measuring device (1) comprises: a measuring section (13) for measuring optical information of platelet-rich plasma and platelet-poor plasma prepared from the blood sample; a control section (3) for acquiring information related to the platelet aggregation function of the blood sample based on the optical information of the platelet-rich plasma and the platelet-poor plasma; and a display section (4) for displaying information related to platelet aggregation, wherein the control section (3) acquires evaluation information related to the suitability of the platelet-rich plasma as a sample based on the measurement result of the platelet-rich plasma by the measuring section (13), and displays the information on the display section (4).

[0006] One aspect of the present invention provides a sample measurement method for measuring the platelet aggregation function of a blood sample, characterized in that the sample measurement method includes: a step of obtaining optical information of platelet-poor plasma and platelet-rich plasma; a step of obtaining information related to the platelet aggregation function of the blood sample based on the optical information obtained from the platelet-poor plasma and the platelet-rich plasma; and a step of obtaining evaluation information related to the suitability of the platelet-rich plasma as a specimen based on the optical information obtained from the platelet-rich plasma.

[0007] Effects of the Invention According to the sample measurement device and sample measurement method of the present invention, the suitability of platelet-rich plasma as a sample can be easily determined. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 1 is a diagram showing the appearance of a sample measurement device as an example of an embodiment.

[0009] Figure 2 It is a top view showing the structure of the sample measurement device.

[0010] Figure 3 This is a block diagram showing the structure of a sample measurement device.

[0011] Figure 4 This is a diagram showing an example of the main menu screen.

[0012] Figure 5 It is a diagram showing an example of an instruction screen.

[0013] Figure 6 is a flowchart illustrating an example of a sample measurement method.

[0014] Figure 7 is a flowchart illustrating an example of a sample measurement method.

[0015] Figure 8 is a flowchart illustrating an example of a sample measurement method.

[0016] Figure 9 This is a diagram showing an example of a setting screen related to sample suitability evaluation.

[0017] Figure 10 This is a graph showing the relationship between the initial absorbance of a platelet-rich plasma sample and the number of platelets.

[0018] Figure 11 This is a graph showing the distribution of initial absorbance of platelet-rich plasma samples.

[0019] Figure 12 This is a diagram showing an example of a setting screen related to sample suitability evaluation.

[0020] Figure 13 This is a diagram showing an example of a setting screen related to sample suitability evaluation.

[0021] Figure 14 This is a diagram showing an example of a setting screen related to sample suitability evaluation.

[0022] Figure 15 is a flowchart illustrating an example of a sample measurement method including a specimen suitability evaluation.

[0023] Figure 16 This is a graph showing the change over time in absorbance of a sample after addition of an inducer.

[0024] Figure 17 is a flowchart illustrating an example of a sample measurement method including a specimen suitability evaluation.

[0025] Figure 18 is a flowchart illustrating an example of a sample measurement method including a specimen suitability evaluation.

[0026] Figure 19 It is a diagram showing an example of a display screen of measurement results.

[0027] Figure 20 It is a diagram showing an example of a display screen of measurement results. DETAILED DESCRIPTION

[0028] Below, embodiments of the sample measurement device and sample measurement method of the present invention are described in detail with reference to the accompanying drawings. The embodiments described below are merely illustrative, and the present invention is not limited to these embodiments. Furthermore, the present invention encompasses selective combinations of components from the various embodiments and variations described below.

[0029] Figure 11 is a perspective view showing the appearance of a sample measurement device 1 as an example of an embodiment. Figure 1 As shown, the sample measurement device 1 includes a housing 10 having a generally rectangular parallelepiped shape. The sample measurement device 1 is a blood coagulation measurement device configured to measure the platelet aggregation function of a blood sample. The housing 10 includes a freely openable and closable front cover 10a. The front cover 10a slides vertically or rotates, and opening the front cover 10a allows the interior of the device to be exposed. The sample measurement device 1 also includes a transport unit 102 for transporting the sample and a measurement start button 30.

[0030] The transport unit 102 is located in the center of the height of the front portion of the sample measurement device 1. The transport unit 102 includes a rack loading section 102a, where the sample rack 105 is placed, and a rack collection section 102b, where the sample rack 105 is removed from the interior of the housing 10 after measurement. The sample rack 105 holds multiple sample containers 104 containing samples. As will be described in detail later, when sample measurement begins, the sample rack 105 placed on the rack loading section 102a is transported into the interior of the housing 10. After sample measurement is completed, the sample rack 105 is removed from the interior of the housing 10 to the rack collection section 102b.

[0031] The measurement start button 30 is provided above the rack mounting portion 102a at the front of the sample measurement device 1. When the operator places the sample rack 105 holding the sample container 104 on the rack mounting portion 102a and then presses the measurement start button 30, the sample rack 105 is transported into the interior of the housing 10 and the measurement of the sample is started. It should be noted that when manually inputting sample information such as the sample identification number (sample ID) and measurement items, the instruction screen 700 (see below) is displayed. Figure 5 ) After inputting the sample information, the measurement start button 30 is operated.

[0032] The sample measurement device 1 further includes an analysis device 3 and a display 4. The analysis device 3 is a computer that analyzes the results of the measurement performed by the device body 2 and is connected to the device body 2 so as to be communicable. In this embodiment, the device body 2 refers to the unit that measures the optical information of the sample and is the part other than the analysis device 3 and the display 4. Figure 1 In the illustrated example, the display 4 is attached to a side surface of the housing 10 , and the analyzer 3 is housed in a side frame 10 b attached to the rear of the display 4 .

[0033] The analysis device 3 can also be communicatively connected to a host computer in which sample information such as the sample ID and measurement items are registered. The display 4 is a display unit that displays information related to platelet aggregation, etc. In addition, the display 4 is a touch panel display that also functions as an input unit. The display 4 is connected to the analysis device 3 and is communicatively connected to the device body 1 via the analysis device 3. For example, operation signals from the display 4, which is a touch panel, are transmitted to the device body 2 via the analysis device 3. It should be noted that the functions of the analysis device 3 can be built into the device body 2, and the display 4 can also be integrated with the device body 2.

[0034] The sample measurement device 1 is a device for analyzing blood coagulation function by, for example, coagulation method, synthetic matrix method, immunoturbidimetry, and agglutination method. The structure and method related to the measurement of platelet aggregation function (agglutination method) are described in detail below.

[0035] Figure 2 FIG is a top view showing the internal structure of the sample measurement device 1. Figure 2 As shown, the sample measurement device 1 includes a dilute reagent solution preparation unit 11 that automatically prepares a dilute reagent solution containing a reagent, a measurement sample preparation unit 12 that prepares a measurement sample, and a measurement unit 13 that performs optical measurements of the measurement sample. The dilute reagent solution is prepared by mixing a reagent that induces platelet aggregation in the sample with a diluent such as physiological saline. The measurement sample is prepared, for example, by mixing the dilute reagent solution prepared by the dilute reagent solution preparation unit 11 with the sample. The samples used to measure platelet aggregation function are platelet-rich plasma (PRP) samples and platelet-poor plasma (PPP) samples. The measurement unit 13 measures optical information of the PRP sample and the PPP sample prepared from the blood sample.

[0036] PRP samples and PPP samples are prepared by subjecting whole blood samples collected from patients to two types of centrifugation. For example, a PRP sample is the supernatant obtained by centrifuging blood to which an anticoagulant such as sodium citrate has been added at 200×g for 10 minutes. It should be noted that ×g is a unit of centrifugal force. For example, a PPP sample is the supernatant obtained by centrifuging blood to which an anticoagulant has been added at 200×g for 10 minutes and then at 1500×g for 15 minutes. The sample container 104 for storing the PRP sample and the sample container 104 for storing the PPP sample are arranged in pairs on the sample rack 105.

[0037] The reagent contains a substance (inducer) that induces platelet aggregation. Examples of inducers include adenosine diphosphate (ADP), collagen, epinephrine, arachidonic acid, ristocetin, and protease-activated receptor 1-activating peptide (PAR1-AP). Revohem ADP (registered trademark) can be used as ADP. Revohem collagen (registered trademark) can be used as collagen. Revohem epinephrine (registered trademark) can be used as epinephrine. Revohem arachidonic acid (registered trademark) can be used as arachidonic acid. Revohem ristocetin (registered trademark) can be used as ristocetin.

[0038] The reagent containing the inducer is dispensed (divided or dispensed) only into the container containing the PRP sample. As will be described in detail later, the measurement sample preparation unit 12 dispenses the diluted reagent solution containing the reagent prepared by the diluted reagent solution preparation unit 11 into the reaction container 108 containing the PRP sample, and dispenses the diluted solution into the reaction container 108 containing the PPP sample. In addition, in order to promote the reaction between the inducer and the platelets in the sample and to homogenize the reaction, the measurement sample preparation unit 12 heats the reaction container 108 containing the PRP sample to a specified temperature before dispensing the diluted reagent solution. It should be noted that the reaction container 108 containing the PPP sample is not heated. In addition, an evaluation related to suitability as a measurement sample (sample suitability evaluation) is performed on the measurement sample containing the PRP sample.

[0039] The diluted reagent solution preparation unit 11 includes a reagent preparation table 180. The reagent preparation table 180 is a circular workbench. Multiple container racks 100 and 300 are arranged on the reagent preparation table 180 along the circumference of the workbench. Reagent containers 90 for storing solutions containing reagents, diluent containers 50 for storing diluents, and diluted reagent solution containers 60 are arranged on the container racks 100 and 300. When the operator opens the front cover 10a to expose the interior of the apparatus, the reagent containers 90, diluent containers 50, and diluted reagent solution containers 60 are arranged on the container racks 100 and 300, and the container racks 100 and 300 are arranged on the reagent preparation table 180.

[0040] The reagent preparation table 180 includes a first work table 181 having a circular shape in plan view and a second work table 182 having an annular shape in plan view provided on the outer periphery of the first work table 181. Figure 1 In the illustrated example, four container racks 100 are arranged circumferentially on a first workbench 181. Three large container racks 300 are arranged circumferentially on a second workbench 182. The first workbench 181 and the second workbench 182 can be independently rotated circumferentially about a rotation axis 183 by a rotation mechanism equipped with an electric motor. This rotation can move the reagent container 90, the diluent container 50, and the diluted reagent solution container 60 to predetermined positions.

[0041] The diluted reagent solution preparation unit 11 includes a reagent information reader 184 that reads information assigned to each of the reagent container 90, diluent container 50, diluted reagent solution container 60, and container racks 100 and 300. For example, this information is assigned to each container and rack in the form of a barcode, and the reagent information reader 184 includes a barcode reader. The first workbench 181 and the second workbench 182 are capable of moving the container racks 100 and 300 and the containers held therein to a reading position relative to the reagent information reader 184. By reading information using the reagent information reader 184, the positions of the reagent container 90, diluent container 50, and diluted reagent solution container 60 on the reagent preparation station 180 can be determined.

[0042] The information assigned to the reagent container 90 includes, for example, the identification number (ID) of the reagent container 90, the name of the reagent, the type of reagent, the concentration of the reagent, the lot number, and the expiration date. The information assigned to the diluent container 50 includes, for example, the identification number (ID) of the diluent container 50, the name of the diluent, the type of diluent, the lot number, and the expiration date. The information assigned to the diluted reagent solution container 60 includes, for example, the identification number (ID) of the diluted reagent solution container 60. The information assigned to the container racks 100 and 300 includes, for example, the identification numbers (ID) of the container racks 100 and 300.

[0043] The diluted reagent solution preparation unit 11 includes first dispensing units 150a and 150b. Each of the first dispensing units 150a and 150b includes a dispensing arm that rotatably holds a pipette 153 for dispensing. The pipette 153 is connected to a pump and is configured to aspirate and dispense a predetermined amount of fluid. The first dispensing units 150a and 150b move the pipette 153 to the diluent container 50, aspirate a predetermined amount of diluent from the diluent container 50, and dispense the predetermined amount of diluent into the diluted reagent solution container 60. Furthermore, the first dispensing units 150a and 150b move the pipette 153 to the reagent container 90, aspirate a predetermined amount of reagent from the reagent container 90, and dispense the predetermined amount of reagent into the diluted reagent solution container 60. Thus, the reagent and the diluent are mixed within the diluted reagent solution container 60, thereby preparing a diluted reagent solution containing the reagent.

[0044] The sample measurement device 1 includes a transport unit 102 that includes a rack loading unit 102a and a rack collecting unit 102b, as described above. The transport unit 102 transports a sample rack 105 placed by an operator on the rack loading unit 102a into the housing 10 and positions the sample containers 104 held on the sample rack 105 at predetermined sample aspiration positions 501 and 502. Furthermore, the transport unit 102 includes a sample information reader 103 positioned along the transport path of the sample rack 105. The sample information reader 103 includes a barcode reader.

[0045] A label having sample information recorded thereon in the form of a barcode or the like is affixed to the sample container 104. The sample information includes, for example, information such as the sample ID, the type of sample, the provider of the sample, and measurement items. Information related to the type of sample may include information indicating whether the sample is a PRP sample or a PPP sample. When the sample information is registered in the host computer, the operator does not need to input the sample information on the instruction screen 700. The operator only needs to place the sample rack 105 on the rack loading portion 102a of the transport portion 102 and operate the measurement start button 30. In this case, the sample information reading portion 103 reads the barcode of the sample container 104 held on the sample rack 105, queries the host computer for information required for measurement, and automatically registers the measurement instruction.

[0046] The measurement sample preparation unit 12 has a rotating table 160 for transporting the reaction container 108. The rotating table 160 is arranged on the outer side of the reagent preparation table 180. The rotating table 160 has a ring shape when viewed from above and can rotate in the circumferential direction. A plurality of retaining holes 161 arranged in the circumferential direction are provided on the rotating table 160. The reaction containers 108 can be arranged one by one in the retaining holes 161. The PRP sample and the diluted reagent solution prepared by the diluted reagent solution preparation unit 11 are distributed in the reaction container 108, and the measurement sample is prepared in the reaction container 108. The reaction container 108 is, for example, a reaction cup. A stirring member is pre-placed in the reaction container 108.

[0047] The first dispensing units 150a and 150b of the diluted reagent solution preparation unit 11 dispense the sample into the reaction container 108. The first dispensing unit 150a moves the pipette 153 to aspirate a predetermined amount of sample from the sample container 104 positioned at the sample aspirating position 501 of the transport unit 102. The first dispensing unit 150b moves the pipette 153 to aspirate a predetermined amount of sample from the sample container 104 positioned at the sample aspirating position 502 of the transport unit 102. After aspirating the sample, the first dispensing units 150a and 150b dispense the sample into the reaction container 108 positioned at the sample dispensing positions 503 and 504 of the rotary table 160.

[0048] The measurement sample preparation unit 12 includes a gripping mechanism 170 capable of transporting a reaction vessel 108 and a heating stage 190 for holding and heating the reaction vessel 108. The gripping mechanism 170 grips and transports the reaction vessel 108, removes the reaction vessel 108 containing the PRP sample from the holding hole 161 of the rotating stage 160, and places it on the heating stage 190. Furthermore, the gripping mechanism 170 places the reaction vessel 108 containing the PPP sample at the reagent dispensing position 508.

[0049] The heating stage 190 is a circular worktable with a built-in heater. It includes multiple holding holes 191 for holding multiple reaction vessels 108 containing PRP samples, and a clamping mechanism 192 for clamping and transferring the reaction vessels 108. Multiple holding holes 191 are arranged along the circumference of the heating stage 190. The heating stage 190 is rotatable, heating the reaction vessels 108 to a predetermined temperature using the heater while simultaneously rotating to transfer the reaction vessels 108 held in the multiple holding holes 191. The clamping mechanism 192 removes the reaction vessel 108 from the holding hole 191 and places the reaction vessel 108 at either of the reagent dispensing positions 507 and 508.

[0050] The measurement sample preparation section 12 has second distribution sections 120a and 120b. The second distribution sections 120a and 120b each have a pipette 121 for distribution. The second distribution sections 120a and 120b move the pipette 121 to the dilution reagent liquid container 60 arranged at the specified reagent aspiration positions 505 and 506 on the reagent preparation table 180, and aspirate a specified amount of dilution reagent liquid from the dilution reagent liquid container 60. Thereafter, the second distribution sections 120a and 120b move to the reaction container 108 arranged at the reagent distribution positions 507 and 508, and distribute a specified amount of dilution reagent liquid into the reaction container 108 containing the PRP sample. Thus, the dilution reagent liquid and the PRP sample are mixed in the reaction container 108 to prepare a measurement sample containing a reagent of a specified concentration. It should be noted that in the reaction container 108 containing the PPP sample, the dilution liquid is distributed at the reagent distribution position 508.

[0051] The measurement sample preparation unit 12 also includes a gripping mechanism 175 for transporting reaction containers 108. The gripping mechanism 175 includes a mechanism for movement in three orthogonal axes: the X, Y, and Z directions. It grips and transports the reaction containers 108. The gripping mechanism 175 transfers the reaction containers 108 containing the measurement samples from the reagent dispensing positions 507 and 508 to the container placement unit 131 of the measurement unit 13. Furthermore, the gripping mechanism 175 transfers the reaction containers 108 after measurement from the container placement unit 131 to the disposal port 106.

[0052] The measuring unit 13 measures the absorbance or transmittance of the measurement sample. The measuring unit 13 includes a container placement unit 131 for placing the reaction container 108 containing the measurement sample, a light transmitting unit 132 for illuminating the reaction container 108 with light for signal detection, and a light receiving unit 133 positioned opposite the light transmitting unit 132 across the reaction container 108. The container placement unit 131 includes a stirring mechanism that rotates a stirrer within the reaction container 108. Multiple container placement units 131 are provided in the measuring unit 13. In this manner, measurement samples in multiple reaction containers 108 can be measured simultaneously.

[0053] The measuring unit 13 measures the time-dependent changes in absorbance or transmittance during the aggregation reaction of platelets or other cells in the measurement sample within the reaction vessel 108, which is located in the vessel placement unit 131. The light transmitting unit 132 irradiates the measurement sample within the reaction vessel 108, which is located in the vessel placement unit 131, with light. The light transmitting unit 132 includes a light source such as a light-emitting diode or a halogen lamp. The light receiving unit 133 receives transmitted or scattered light from the light irradiating the measurement sample within the reaction vessel 108 and outputs an electrical signal corresponding to the amount of light received. The light receiving unit 133 includes a photoelectric conversion element that converts the received light into an electrical signal and outputs the signal, which is then transmitted to the analysis device 3.

[0054] The analyzing device 3 analyzes the platelet aggregation function of the sample based on the electrical signal output from the light receiving unit 133, that is, the measurement result of the optical information of the sample obtained by the measuring unit 13. The analyzing device 3 generates the platelet aggregation function described below based on, for example, the absorbance or transmittance of the measured sample. Figure 19 Based on the reaction curve shown, calculations were made for vWF:RCo (von Willebrand factor ristocetin cofactor) activity, adenosine diphosphate (ADP) maximum aggregation rate, collagen maximum aggregation rate, epinephrine maximum aggregation rate, arachidonic acid maximum aggregation rate, ristocetin maximum aggregation rate, and protease-activated receptor 1-activating peptide (PAR1-AP) maximum aggregation rate. Furthermore, analysis device 3 evaluated sample suitability based on the measurement results of the PRP sample.

[0055] Figure 3 : is a block diagram showing the structure of the device body 2 and the analysis device 3. Figure 3 As shown, device main body 2 includes a communication unit 209, and analysis device 3 includes a communication unit 212. Device main body 2 and analysis device 3 transmit and receive information via communication units 209 and 212. Control unit 210 includes a processor such as a CPU (Central Processing Unit) and an FPGA (Field-Programmable Gate Array), and storage devices such as ROM (Read Only Memory), RAM (Random Access Memory), and a hard disk.

[0056] The processor of the control unit 210 controls the various components of the apparatus main body 2 via the I / O board 211 by executing a control program stored in the storage device. The control unit 210 controls, for example, the dispensing operation of the second dispensing unit 120, the dispensing operation of the first dispensing units 150a and 150b, the operation of the reagent preparation table 180, the operation of each workstation and each clamping mechanism, and the operation of the measuring unit 13.

[0057] The analysis device 3 includes a control unit 213 including a processor such as a CPU and a storage device such as a ROM, RAM, and a hard disk. In this embodiment, the control unit 213 of the analysis device 3 analyzes the platelet aggregation function of the sample based on the electrical signal output from the light receiving unit 133 of the device body 2, and also analyzes the suitability of the measurement sample containing the PRP sample as a sample. The analysis device 3 is connected to a display 4, which will be described later. Figure 19 and Figure 20 The analysis results of the analysis device 3 , such as the measurement results of the platelet aggregation function and the evaluation results of the sample suitability, are displayed on the display 4 .

[0058] It should be noted that in Figure 3 While the illustrated example shows a configuration with two control units 210 and 213, the number of control units is not particularly limited. A single control unit can control both the device body 2 and the analyzer 3, or three or more control units can control both. Furthermore, the placement of the control units is not particularly limited and can be located in only one of the device body 2 and the analyzer 3. Furthermore, as mentioned above, the functions of the analyzer 3 can also be integrated into the device body 2.

[0059] Figure 4 The main menu screen 600 is displayed. Figure 5 The main menu screen 600 and the command screen 700 are displayed on the display 4 .

[0060] like Figure 4 As shown, the main menu screen 600 includes a tool bar 610 containing buttons for main functions, a status display area 620 containing indicators showing information such as the status of the device, the status of the main unit, and the remaining amounts of reagents and consumables, and a menu icon display area 630. Tool bar 610 also includes a maintenance button 611 operated to perform maintenance on the device, a shutdown button 612 operated to shut down the device, and a command button 613 for displaying the command screen 700.

[0061] The menu icon display area 630 displays a plurality of buttons (icons) for performing various operations or displaying information. The same buttons as those included in the tool bar 610 may also be displayed. The menu icon display area 630 includes a reagent and consumables button 631, a calibration curve button 632, a QC chart button 633, a maintenance button 634, an error history button 635, a setting button 636, and a close button 637. The setting button 636 displays the setting screen for the suitability evaluation of the measurement sample (see the following description). Figure 9 ) button is operated when performing sample suitability evaluation.

[0062] like Figure 5As shown, the instruction screen 700 includes an instruction registration section 701 for registering sample information such as sample ID and measurement items, and a measurement category selection section 702 that displays the selected measurement category. If the sample information has not been registered with the host, the operator needs to input the sample information required for measurement into the instruction registration section 701. In addition, the operator selects the measurement category using the measurement category selection section 702. A pull-down button is provided in the measurement category selection section 702, which functions as a measurement category selection button. Figure 5 9 shows that the text “Platelet Aggregation Command” is displayed in the measurement type selection portion 702 , and the measurement of the platelet aggregation function is selected as the measurement type.

[0063] The instruction registration section 701 is displayed in the form of a table in which sample information can be input. In the measurement of platelet aggregation function, PRP samples and PPP samples are arranged in pairs on the sample rack 105, and the paired PRP samples and PPP samples are managed according to the same sample ID. A plurality of measurement items are displayed in the instruction registration section 701. The operator can select the desired measurement item for each sample from the table in the instruction registration section 701 and register the instruction for the selected measurement item. In the case of performing a sample suitability evaluation before measuring the platelet aggregation function, the instruction is also registered based on the information read by the sample information reading section 103 or based on the information entered on the instruction screen 700.

[0064] Below, refer to Figures 6 to 8 The method for measuring platelet aggregation function is described.

[0065] like Figure 6 As shown, the method for measuring platelet aggregation function includes the steps of registering a measurement instruction (step S10), preparing a measurement sample and measuring optical information (steps S11 and S12), and analyzing and outputting the measurement results (steps S13 and S14). In step S10, the control unit 210 controls the sample information reader 103 to read the barcode on the sample container 104, query the host computer for information required for measurement, and register the instruction. If the sample information is not registered in the host computer, the control unit 210 registers the instruction based on the information entered on the instruction screen 700.

[0066] In step S11, the control unit 210 controls the dilution reagent solution preparation unit 11 and the measurement sample preparation unit 12 to prepare a measurement sample containing a PPP sample, and controls the measurement unit 13 to measure optical information of the measurement sample. Furthermore, in step S12, the control unit 210 controls the dilution reagent solution preparation unit 11 and the measurement sample preparation unit 12 to prepare a measurement sample containing a PRP sample, and controls the measurement unit 13 to measure optical information of the measurement sample. Details of steps S11 and S12 will be described later. In this embodiment, absorbance is measured as optical information.

[0067] In step S13, the control unit 210 sends the measurement data acquired in steps S11 and S12 to the control unit 213 of the analysis device 3, and the control unit 213 performs analysis of the measurement data. For example, the control unit 213 calculates the time-dependent change in the agglutination rate of the PRP sample when the initial absorbance after adding the diluted reagent solution to the PRP sample is set to 0% and the absorbance of the PPP sample is set to 100%, and creates the following Figure 19 and Figure 20 The reaction curve shown is (aggregation waveform obtained by converting absorbance into aggregation rate). In addition, the maximum aggregation rate is calculated based on the maximum change in absorbance accompanying platelet aggregation reaction.

[0068] In step S14, the control unit 213 of the analyzer 3 displays the measurement results of the platelet aggregation function, such as the reaction curve and the maximum aggregation rate, on the display 4. Although described in detail later, the evaluation results of the sample suitability of the PRP sample may also be displayed on the measurement result display screen together with the measurement results of the platelet aggregation function.

[0069] Figure 7 Yes Figure 6 Flowchart of an example of a method for measuring PPP samples in step S11. Figure 7 As shown, in step S111, the control unit 210 controls the first dispensing unit 150a of the dilution reagent solution preparing unit 11 to aspirate a predetermined amount of PPP sample from the sample container 104 containing the PPP sample and dispense it into the reaction container 108. In step S112, the control unit 210 controls the second dispensing unit 120a of the measurement sample preparing unit 12 to aspirate a predetermined amount of diluent from the diluent container 50 and dispense it into the reaction container 108 to prepare a measurement sample containing the PPP sample.

[0070] In step S113 , the control unit 210 controls the clamping mechanism 175 of the measurement sample preparation unit 12 to transfer the reaction container 108 containing the diluted PPP sample to the measurement unit 13 , and controls the measurement unit 13 to measure the absorbance of the PPP sample for a predetermined time.

[0071] Figure 8 Yes Figure 6 Flowchart of an example of a method for measuring a PRP sample in step S12. Figure 8As shown, in step S121, the control unit 210 controls the first dispensing unit 150a to aspirate a predetermined amount of the PRP sample from the sample container 104 containing the PRP sample and dispense the PRP sample into the reaction container 108, into which the stirring element has been placed. In step S122, the control unit 210 controls the clamping mechanism 170 of the measurement sample preparation unit 12 to transfer the reaction container 108 containing the PRP sample to the heating stage 190, where the reaction container 108 is heated for a predetermined time and at a predetermined temperature.

[0072] In step S123, the control unit 210 controls the second dispensing unit 120a to aspirate a predetermined amount of diluted reagent solution from the diluted reagent solution container 60 and dispense it into the reaction container 108 containing the PRP sample, thereby preparing a measurement sample containing the PRP sample. Based on the measurement items registered in the command, the control unit 210 dispenses a predetermined reagent at a predetermined concentration to prepare one or more measurement samples for each PRP sample. In step S124, the control unit 210 controls the gripping mechanism 175 to transfer the reaction container 108 containing the measurement sample to the container placement unit 131 of the measurement unit 13 and rotate the stirring element within the reaction container 108 to stir the measurement sample.

[0073] In step S125, the control unit 210 controls the measuring unit 13 to measure the absorbance of the measurement sample, which contains a reagent at a predetermined concentration and a PRP sample, for a predetermined time while stirring the measurement sample. It should be noted that if multiple measurement items, each with different reagent types and concentrations, are registered for a single PRP sample instruction, steps S121 through S125 are repeated based on the number of measurement items. This allows for simultaneous preparation and measurement of measurement samples corresponding to multiple measurement items.

[0074] Below, refer to Figures 9 to 20 The evaluation functions related to the suitability of PRP samples as measurement specimens are described in detail.

[0075] Figure 9 FIG. 1 is a diagram showing an example of a setting screen related to suitability evaluation as a sample. Figure 9 As shown, the setting screen 800 includes a display area 801 that lists multiple measurement items and a parameter registration section 802 for confirming, setting, and changing the conditions for each measurement item. The setting screen 800 is used to confirm, set, and change the conditions for each measurement item of the platelet aggregation function of the sample. New measurement items can also be registered or registered measurement items can be deleted on the setting screen 800. Furthermore, when performing a suitability evaluation of a measurement specimen containing a PRP sample, the setting screen 800 is used to set information required for the evaluation.

[0076] The setting screen 800 is displayed on the display 4 by operating the setting button 636 on the main menu screen 600. In the list display area 801, multiple measurement items are displayed side by side along the vertical direction of the screen. In the sample measurement device 1, multiple items with different types and concentrations of inducers are generally registered as measurement items for platelet aggregation function. On the setting screen 800, by selecting a measurement item (type and concentration of inducer) in the list display area 801, the selected measurement item is displayed in the parameter registration section 802. The parameter registration section 802 includes an edit button 803. By operating the edit button 803, the operator can set or change the conditions of the selected measurement item.

[0077] In the sample measuring device 1, evaluation information related to the suitability of the PRP sample as a sample is obtained based on the measurement result of the measurement sample containing the PRP sample by the measuring unit 13, and the information is displayed on the display 4 as the display unit. In the case where the number of platelets contained in the PRP sample is low, it may not be possible to obtain a correct result in the measurement of the platelet aggregation function. Therefore, the platelet number of the PRP sample is separately measured using a blood cell counting device to confirm whether it is suitable for the measurement of the platelet aggregation function. According to the sample measuring device 1, the suitability of the PRP sample as a sample can be easily known, and the platelet aggregation function can be measured following the determination of the suitability. Therefore, the user usability is greatly improved, and the reliability of the measurement results is also improved.

[0078] The optical information of the PRP sample required to obtain information evaluating the sample's suitability is absorbance or transmittance. The sample measurement device 1 includes a measuring unit 13 for measuring the absorbance or transmittance of the sample containing the PRP sample. Therefore, the absorbance or transmittance obtained by the measuring unit 13 can be used as information evaluating the sample's suitability. In this embodiment, the absorbance of the sample containing the PRP sample is measured by the control unit 210 of the device main body 2. Furthermore, the control unit 213 of the analysis device 3 analyzes the measurement results to obtain evaluation information related to the sample's suitability for measurement.

[0079] exist Figure 9In the example shown, "ADP2.0_m," "ADP2.0_s," and "ADP2.0_e" are displayed in parameter registration section 802, with "ADP2.0_s" selected. While "ADP2.0_s" is selected, operating edit button 803 allows the conditions for "ADP2.0_s" to be set or changed. In "ADP2.0_s," "ADP" refers to the type of inducer, "2.0" refers to the inducer concentration, and "s" refers to the initial absorbance. The initial absorbance refers to the absorbance immediately after the inducer is added to the PRP sample (details will be described later, for example, within 10 seconds) and is the initial absorbance before platelet aggregation is detected.

[0080] Although the details will be described later, the evaluation related to the suitability of the measurement sample containing the PRP sample is performed, for example, using the initial absorbance of the measurement sample containing the PRP sample. Therefore, in the case of performing the sample suitability evaluation, the conditions related to the initial absorbance are set on the setting screen 800. Since the initial absorbance does not vary significantly depending on the measurement item (the type and concentration of the inducer), the conditions related to the initial absorbance can be set for each measurement item, but can also be set to be shared by all measurement items. If the edit button 803 is operated in the state where "ADP2.0_s" is selected, for example, the setting screen 810 of the evaluation reference value of the initial absorbance is displayed (refer to the following description). Figure 12 ).

[0081] Figure 10 This is a graph showing the relationship between the initial absorbance ([PRP_s]) of a measurement sample containing a PRP sample and the platelet count (PLT). Figure 11 This is a graph showing the distribution of initial absorbance of a sample containing a PRP sample. Figure 10 and Figure 11 As can be understood from the data shown, the absorbance (initial absorbance) of the sample containing the PRP sample obtained by the measuring unit 13 can be used as information for evaluating the suitability of the sample. The initial absorbance of the sample containing the PRP sample obtained by the measuring unit 13 is the absorbance in the initial state after the inducing agent is added to the PRP sample as described above and before platelet aggregation is detected by the measuring unit 13.

[0082] Initial absorbance was measured at a wavelength of 660 nm using a blood coagulation analyzer (CS5100, fully automatic blood coagulation analyzer, manufactured by Sysmex Corporation). Platelet count was measured using a blood cell counter (XS-1000i, multi-item automatic blood analyzer, manufactured by Sysmex Corporation). Figure 10 The recommended lower limit of platelet count in PRP samples according to the ISTH guidelines (15×104 / μL).

[0083] Figure 10 The PRP samples and PPP samples used in the measurement of the data shown were prepared from the blood of 70 healthy volunteers. The preparation method of each sample is as follows.

[0084] (1) Blood was collected from healthy volunteers using blood collection tubes containing 3.2% sodium citrate (Venoject RRtubes (registered trademark) manufactured by Terumo Corporation).

[0085] (2) Two blood samples were sorted into 10 mL centrifuge tubes (sterile round-bottom Spitz tubes manufactured by Eiken Chemical Co., Ltd.) and centrifuged at 200 × g for 10 minutes using a high-speed refrigerated centrifuge (Model 7000 manufactured by Kubota Corporation). A portion of the supernatant was collected and used as a PRP sample.

[0086] (3) The remaining supernatant was further centrifuged at 1500 × g for 15 minutes, and the supernatant was recovered as the PPP sample.

[0087] Figure 10 (a) shows the relationship between the initial absorbance [PRP_s] and platelet count (PLT) of a sample containing a PRP sample. Figure 10 (b) shows the relationship between the value [PRP_s]-[PPP_s] obtained by subtracting the initial absorbance [PPP_s] of the sample containing the PPP sample from [PRP_s] and the platelet count (PLT). Since PRP and PPP samples also contain components other than platelets, such as lipids, proteins, and amino acids, the influence of these components is excluded by calculating [PRP_s]-[PPP_s]. Figure 10 As shown, since a positive correlation between initial absorbance and platelet count is obtained in all cases, the suitability of a PRP sample for platelet aggregation function measurement can be determined based on the initial absorbance of PRP, even without measuring platelet count. By setting a reference value and comparing it with the initial absorbance of PRP, it is possible to determine whether the sample is suitable for measurement.

[0088] The regression equation for calculating the platelet count from the initial absorbance is as follows: Although details will be described later, either of the following regression equations 1 and 2 can be used to evaluate the suitability of the sample.

[0089] Formula 1: PLT = [PRP_s] / 5.71 - 336.92 / 5.71 Formula 2: PLT = [PRP_s] - [PPP_s] / 5.70 - 317.48 / 5.70 Figure 11(a) represents the distribution of [PRP_s], Figure 11 (b) shows the distribution of [PRP_s]-[PPP_s]. Figure 11 The PRP samples and PPP samples used in the measurement of the data shown were prepared from the blood of 130 healthy volunteers. The preparation method of each sample is as described above. Figure 11 Indicates the upper and lower limits of the 95% confidence interval.

[0090] Figure 11 The 95% confidence interval of the distribution of [PRP_s] shown in (a) is 419 to 828 mOD (optical density). Figure 11 The 95% confidence interval for the distribution of [PRP_s] - [PPP_s] shown in (b) is 401 to 787 mOD. Substituting the lower limit of the 95% confidence interval in the distribution of initial absorbance into the above regression equation yields a platelet count that is roughly consistent with the recommended lower limit of platelet count in the ISTH guidelines. Therefore, it can be understood that the initial absorbance of the sample obtained by the measuring unit 13 can be used as information for evaluating sample suitability.

[0091] The control unit 213 of the analysis device 3 compares the initial absorbance of the PRP sample measured by the measuring unit 13 with the reference value to obtain information for evaluating the suitability of the PRP sample as a specimen. The reference value is set, for example, in the range of 400 to 440 mOD. The value set in the range of 400 to 440 mOD is the lower limit reference value (lower limit value), which corresponds to the recommended lower limit value of the platelet count in the ISTH guidelines as described above. Therefore, by using this lower limit value, it is possible to evaluate the sample based on the recommended lower limit value of the ISTH guidelines. The value of [PRP_s]-[PPP_s] can also be used in the evaluation of the suitability of the sample. In this case, the lower limit value is set, for example, in the range of 380 to 420 mOD.

[0092] When the initial absorbance of the PRP sample is lower than the reference value, the control unit 213 outputs an error message. The error message is evaluation information indicating that the PRP sample used is not suitable as a sample. It should be noted that the details of the error message are described below. In the evaluation of sample suitability, an upper limit reference value (upper limit value) can also be further set. Based on the above discussion results, for example, the upper limit value is set in the range of 800 to 840 mOD. The value of [PRP_s]-[PPP_s] can also be used in the evaluation of sample suitability. In this case, the upper limit value is set in the range of 760 to 800 mOD, for example.

[0093] The control unit 213 can also compare the platelet count with the reference value to obtain evaluation information related to the sample suitability of the PRP sample. When the platelet count of the PRP sample is lower than the reference value, the control unit 213 outputs an error message. The platelet count of the PRP sample is calculated based on the initial absorbance of the PRP sample measured by the measuring unit 13, specifically, it is calculated using the above-mentioned regression formula 1. In this case, the recommended lower limit value of the ISTH guidelines can be used as the lower limit value. In addition, the upper limit value of the platelet count can also be further set based on the above-mentioned regression formula 2.

[0094] Figure 12 FIG. 8 is a diagram showing a setting screen 810 as an example of a screen for setting a reference value for sample suitability evaluation. Figure 12 As shown, setting screen 810 includes a selection button 811 for selecting whether to perform a sample suitability evaluation based on the initial absorbance of the PRP sample, and a reference value input section 812 for inputting a reference value required for the evaluation. Selection button 811 includes a checkbox. If the operator selects the checkbox in selection button 811, the sample suitability evaluation based on the initial absorbance is enabled. In other words, the sample suitability evaluation is performed. Furthermore, if the checkbox in selection button 811 is selected, a reference value can be input into reference value input section 812.

[0095] The reference value input section 812 includes two input sections for inputting upper and lower limit reference values. Since the evaluation conditions based on the initial absorbance of the PRP sample are set on the setting screen 810, the reference value of the initial absorbance is input to the reference value input section 812. Figure 12 In the example shown, an initial absorbance of "410" is entered as the lower limit, and an initial absorbance of "850" is entered as the upper limit. The operator can enter any reference value or select from predefined values. Alternatively, the setting screen displays only the select button 811, and the reference value can be a pre-registered fixed value.

[0096] Setting screen 810 also includes a selection button 813 for selecting whether to continue measurement based on the sample suitability evaluation information. Selection button 813 includes a checkbox. If the operator selects the checkbox in selection button 813, a query is executed regarding whether to continue subsequent measurements based on the sample suitability evaluation information. The query regarding whether to continue measurement is displayed on display 4 along with the button for selecting whether to continue measurement.

[0097] If the sample suitability evaluation result is positive, that is, if the initial absorbance of the PRP sample is within the upper and lower reference value ranges entered in the reference value input section 812, even if the checkbox for selection button 813 is selected, the control section 210 of the device body 2 does not execute the query and continues the platelet aggregation function measurement. From the perspective of improving user usability, it is preferable to automatically continue the measurement if the sample suitability evaluation result is within the reference value range. It should be noted that if the checkbox for selection button 813 is not selected, the platelet aggregation function measurement is continued to the end regardless of the evaluation result.

[0098] If the control unit 210 receives evaluation information indicating that the PRP sample is unsuitable as a specimen, it displays information on the display 4 confirming the operator's willingness to continue the measurement. In this case, the operator can use this information to determine whether to continue the measurement. Specifically, if the sample suitability evaluation result is negative, a query is made regarding whether to continue subsequent measurements. As a specific example, if the initial absorbance of the PRP sample is lower than the lower limit value entered in the reference value input unit 812, the query regarding whether to continue the measurement is displayed on the display 4 along with this information.

[0099] Based on the measurement results of the PRP sample or the evaluation information on the sample suitability, the control unit 210 can determine whether to add a reagent containing an inducer to the PRP sample to prepare the measurement sample, or can also determine whether to continue measuring the absorbance of the measurement sample to which the reagent containing an inducer has been added. In the case of the former determination, after the sample suitability evaluation is performed, the reagent containing an inducer is added to the PRP sample to prepare the measurement sample. On the other hand, in the case of the latter determination, after the reagent containing an inducer is added to the PRP sample, i.e., after the measurement sample is prepared, optical information of the PRP sample is measured within a predetermined time period to obtain evaluation information.

[0100] Figure 13 FIG. 8 is a diagram showing a setting screen 820 as another example of a screen for setting a reference value for sample suitability evaluation. Figure 13 As shown, setting screen 820 includes a selection button 821 for selecting whether to perform a sample suitability evaluation based on the platelet count of the PRP sample and a reference value input section 822 for inputting a reference value required for the evaluation. Selection button 821 includes a checkbox. If the operator checks the checkbox of selection button 821, the sample suitability evaluation based on the platelet count is enabled. Furthermore, if the checkbox of selection button 821 is checked, a reference value can be input into reference value input section 822.

[0101] Similar to the setting screen 810, the reference value input section 822 includes two input sections for inputting upper and lower limit reference values. Since the evaluation conditions based on the platelet count of the PRP sample are set on the setting screen 820, the reference value of the platelet count is input into the reference value input section 822. Figure 13 In the example shown, enter "15×10 4 / μL" as the lower limit, enter "80×10 4 The platelet count of 820 / μL is set as the upper limit. As for the reference value, the operator can input an arbitrary value or select from predetermined values. In addition, only the selection button 821 is displayed on the setting screen, and the reference value can also be a pre-registered fixed value.

[0102] A regression equation for calculating the platelet count based on the initial absorbance of the PRP sample can also be displayed on the reference value input section 822. As for the regression equation, the operator can also select from pre-registered equations. In addition, similar to the setting screen 810, the setting screen 820 can also include a selection button 813 for selecting whether to continue the measurement based on the evaluation information of the sample suitability. When the evaluation conditions are set based on the setting screen 820, the control section 213 estimates the platelet count based on the initial absorbance of the PRP sample and obtains evaluation information based on the platelet count. Specifically, the platelet count is calculated based on the initial absorbance of the PRP sample using the above-mentioned regression equation 1 or 2, and the calculated platelet count is compared with the reference value input to the reference value input section 822 to evaluate the sample suitability.

[0103] Figure 14 FIG. 8 is a diagram showing a setting screen 830 as another example of a screen for setting a reference value for sample suitability evaluation. Figure 14 As shown, setting screen 830 includes a selection button 811 for selecting whether to evaluate the sample suitability based on the initial absorbance of the PRP sample, and a selection button 821 for selecting whether to evaluate the sample suitability based on the platelet count of the PRP sample. In this case, the operator can select whether to evaluate using the initial absorbance or the platelet count. Setting screen 830 also displays a reference value input section 812 for inputting a reference value for the initial absorbance, a reference value input section 822 for inputting a reference value for the platelet count, and a selection button 813 for selecting whether to query whether to continue the measurement.

[0104] Figure 15 This is a flow chart showing an example of a sample measurement method including a sample suitability evaluation. Figure 15Although not shown in the figure, the sample measurement method including the specimen suitability evaluation includes the steps of preparing a PPP sample and a PRP sample prepared from a blood sample.

[0105] exist Figure 15 In the example shown, the PPP sample and the PRP sample are measured in the same manner as in the usual platelet aggregation function measurement, and the sample suitability of the PRP sample is evaluated. In this case, the measurement operation of the PPP sample (step S22) is the same as that of the PRP sample. Figure 7 In addition, the measurement action of the PRP sample (step S23) is the same as Figure 8 When the measurement of the PRP sample in step S23 is completed, the display 4 displays the measurement result of the platelet aggregation function and the evaluation result of the sample suitability.

[0106] like Figure 15 As shown, when evaluating the suitability of a measurement sample containing a PRP sample, the control unit 210 sets the information required for the evaluation (step S20). The setting of the conditions for the suitability evaluation is performed based on the operator's operation. For example, if Figure 12 If the check box of the selection button 811 of the setting screen 810 shown is checked, the control units 210 and 213 execute the evaluation of the sample suitability based on the initial absorbance. Figure 13 In the case of the setting screen 820 shown, if the check box of the selection button 821 of the setting screen 820 is checked, the control units 210 and 213 execute the evaluation of the sample suitability based on the platelet count.

[0107] The control unit 210 sets the reference values entered in the reference value input section 812 of the setting screen 810 as the criteria for evaluating sample suitability. Specifically, the lower and upper limits of the initial absorbance are set as the reference values. Based on input in the reference value input section 822 of the setting screen 820, the lower and upper limits of the platelet count are set as the reference values. It should be noted that the reference values can be pre-registered values or automatically set using the functions of the control unit 210.

[0108] In step S21, the control unit 210 controls the sample information reading unit 103 to read the barcode of the sample container 104. When the sample information is registered in the host, the control unit 210 inquires the host for the information required for measurement and automatically registers the sample information. For example, the sample rack 105 holding the sample container 104 is placed on the rack loading unit 102a, and by operating the measurement start button 30, the sample rack 105 is transported to the interior of the frame 10 and the measurement of the sample is started, and the measurement instruction registration is executed. It should be noted that step S21 is the same as Figure 6 The same as step S10.

[0109] The control unit 210 prepares a sample containing a PPP sample and measures its absorbance (step S22: acquiring first optical information). Subsequently, it prepares a sample containing a PRP sample and measures its absorbance (step S23: acquiring second optical information). Each measurement sample is prepared by dispensing each sample from a sample container 104 located in the sample rack 105 on the rack mounting portion 102a. When measuring platelet aggregation function, the sample rack 105 holds sample containers 104 containing PPP and PRP samples, each with the same sample ID (i.e., provided by the same provider).

[0110] When the measurement of the PRP sample is completed, the control unit 213 obtains evaluation information related to the suitability of the PRP sample as a sample based on the absorbance of the PRP sample (step S24). Specifically, the initial absorbance of the PRP sample measured by the measuring unit 13 or the platelet count calculated based on the initial absorbance is compared with the reference value to evaluate the suitability of the PRP sample as a sample. Figure 15 In the example shown, since the PRP sample measurement has been completed in step S23, the control unit 213 performs platelet aggregation function analysis (step S25) regardless of the sample suitability evaluation result. The order of steps S24 and S25 is not particularly limited and may be reversed.

[0111] The control unit 213 outputs the sample suitability evaluation results to the display 4 (step S26). The sample suitability evaluation results are output together with the platelet aggregation function measurement results. Details will be described later, but the sample suitability evaluation results and the platelet aggregation function measurement results are displayed on the same screen. If the initial absorbance of the PRP sample measured by the measuring unit 13 or the platelet count calculated based on this initial absorbance is below the lower limit reference value, the control unit 213 outputs an error message indicating that the PRP sample used is not suitable as a sample.

[0112] exist Figure 15 In the example shown, after platelet aggregation function is measured as described above, sample suitability evaluation information is obtained using optical information from the PRP sample, which is the result of this measurement. In this case, control unit 210 measures the absorbance of the PRP sample for obtaining evaluation information within a predetermined time after adding a reagent containing an inducer to the PRP sample. The predetermined time is set, for example, to a period of 2 seconds to 10 seconds after adding the reagent containing the inducer.

[0113] Figure 16 This is a graph showing the temporal change in absorbance of a PRP sample after addition of a reagent containing an inducer. Figure 16As shown, after adding an inducer to a PRP sample, platelet aggregation proceeds and the absorbance decreases. However, the decrease in absorbance due to the aggregation reaction is detected after a predetermined time T2 has passed since the addition of the inducer. Therefore, by using the initial absorbance within the predetermined time T2 after the addition of the inducer, the sample suitability of the PRP sample to which the inducer has been added can be appropriately evaluated. The predetermined time T2, during which the absorbance remains substantially constant, varies depending on the type of inducer and is, for example, 4 to 10 seconds.

[0114] In this embodiment, a reagent containing an inducer is dispensed into the reaction vessel 108 containing the PRP sample, and after the measurement sample is prepared, the reaction vessel 108 is immediately transferred to the measurement unit 13. Therefore, in order to eliminate the impact of the transfer shock on the measurement, the initial absorbance measurement used to obtain evaluation information on the sample suitability is preferably performed after a predetermined time T1 has passed after the reaction vessel 108 is transferred to the measurement unit 13. An example of the predetermined time T1 is 0.5 to 2 seconds. Therefore, the control unit 210 performs the initial absorbance measurement within a period of 2 seconds or more and 10 seconds after adding the reagent containing the inducer to the PRP sample.

[0115] The initial absorbance is calculated, for example, by monitoring the absorbance for a predetermined time period, T1 to T2, and applying a linear approximation to the absorbance. Substituting 0 for the time period in the linear approximation formula allows the initial absorbance to be calculated using this formula. This reduces the influence of variation in the measured values, further improving the reliability of the evaluation results. Alternatively, the absorbance at the predetermined time period, T1, can be defined as the initial absorbance.

[0116] The control unit 210 may also measure the absorbance of the PRP sample to obtain sample suitability evaluation information after adding a reagent containing an inducer to the PRP sample to prepare the measurement sample and before starting to stir the measurement sample. The measurement unit 13 includes a stirring mechanism that rotates a stirrer within the reaction vessel 108. The absorbance measurement is performed while the stirrer is rotating. However, since rotating the stirrer accelerates the agglutination reaction, the absorbance measurement for reagent suitability evaluation may also be performed before starting to stir the measurement sample. For example, the control unit 210 may measure the initial absorbance of the PRP sample to obtain evaluation information within a specified time after adding a reagent containing an inducer to the PRP sample and before starting to stir the sample.

[0117] The control unit 213 compares the optical information of the PRP sample with the reference value to obtain evaluation information on the suitability of the sample. The evaluation information may also include information prompting the blood cell counter to measure the platelet count. In addition, the evaluation information may also include information related to whether the centrifugation conditions when preparing the PRP sample from the blood sample are appropriate. The control unit 213 may also infer the possibility of other diseases based on the measurement results or evaluation information of the PRP sample and display information related to other diseases on the display 4. Information related to other diseases may also be output as part of the evaluation information on the suitability of the sample.

[0118] If the initial absorbance or platelet count is below the lower limit reference value or exceeds the upper limit reference value, the control unit 213 outputs an error message as evaluation information indicating that the PRP sample used is not suitable as a specimen. The error message may include a text message such as "The platelet count may not be within the recommended range for measurement. Please measure the platelet count using a blood cell counter." or an error code indicating this information, prompting the blood cell counter to measure the platelet count.

[0119] The error message may also include information related to whether the centrifugation conditions when preparing the PRP sample from the blood sample are appropriate, such as a text message such as "There is a possibility that the platelet count is not within the recommended range for measurement. Please confirm the centrifugation conditions when preparing the sample." or an error code indicating this information. Centrifugation conditions can be cited as a major cause of platelet counts not being within the recommended range for measurement during PRP sample preparation. Therefore, by providing information related to centrifugation conditions, confirmation of centrifugation conditions and sample preparation under appropriate conditions can be encouraged.

[0120] Figure 17 This is a flowchart showing another example of a sample measurement method including sample suitability evaluation. In this regard, absorbance measurement for evaluating sample suitability is performed within a predetermined time after adding a reagent containing an inducer to a PRP sample. Figure 17 The example shown is the same as Figure 15 On the other hand, in Figure 17 In the example shown, when evaluation information indicating that the PRP sample is not suitable as a specimen is obtained, information for confirming the operator's willingness to continue the measurement is output. Figure 15 The examples shown are different. In addition, Figure 17 In the example shown, after evaluation of the sample suitability, absorbance measurements of the PPP samples were performed.

[0121] like Figure 17 As shown in FIG. 2 , the control unit 210 sets the information required for evaluating the suitability of the sample (step S30). Figure 15 In addition, if the measurement start button 30 is operated and the sample rack 105 is transported to the interior of the housing 10, the control unit 210 controls the sample information reading unit 103 to read the barcode of the sample container 104 and register the measurement instruction (step S31). Step S31 is the same as Figure 6 Step S10, Figure 15 The same as step S21.

[0122] The control unit 210 dispenses a predetermined amount of PRP sample from the sample container 104 containing the PRP sample into the reaction container 108, and transfers the reaction container 108 to the heating stage 190 for heating at a predetermined temperature for a predetermined time (step S32). Figure 8 The control unit 210 dispenses the diluted reagent solution containing the inducer into the reaction vessel 108 containing the PRP sample to prepare a measurement sample containing the PRP sample (step S33). If multiple measurement items are registered for a single PRP sample instruction, a number of measurement samples corresponding to the number of measurement items are prepared.

[0123] The control unit 210 measures the initial absorbance of the sample containing the PRP sample (step S34). The sample absorbance measurement is performed while the stirrer in the reaction vessel 108 is rotating to stir the sample. However, the initial absorbance for sample suitability evaluation can also be measured without stirring the sample for a specified time after adding the reagent containing the inducer. Next, the control unit 213 evaluates the sample suitability of the PRP sample based on the measurement data from step S34 (step S35). If the initial absorbance or platelet count is below the lower limit reference value or exceeds the upper limit reference value, the control unit 213 outputs an error message indicating that the PRP sample being used is not suitable as a sample.

[0124] If evaluation information indicating that the PRP sample is unsuitable as a specimen is obtained, the control unit 213 displays a message on the display 4 confirming the operator's willingness to continue the measurement and determines whether to continue the measurement (steps S36 and S37). If the initial absorbance or platelet count of the PRP sample falls below the lower limit reference value or exceeds the upper limit reference value, the control units 210 and 213 may automatically terminate the measurement (No in step S37). Preferably, the operator is provided with a message confirming his or her willingness to continue the measurement.

[0125] If the sample suitability evaluation result in step S35 is positive, that is, if the initial absorbance or platelet count of the PRP sample is within the upper and lower limit reference values, the control units 210 and 213 preferably automatically continue the measurement (Yes in step S37). In this case, from the perspective of improving user usability, it is preferable to omit the confirmation with the operator in step S36.

[0126] In this embodiment, if the sample suitability evaluation result is negative (i.e., if the initial absorbance or platelet count of the PRP sample is below the lower limit reference value or exceeds the upper limit reference value), a message confirming the desire to continue the measurement is displayed on the display 4. Specifically, a text message such as "Do you want to continue the measurement?" or an error code indicating this information is displayed along with an error message indicating that the PRP sample is not suitable as a sample, along with a button for selecting "Continue the measurement." For example, if an operation signal to continue the measurement is received, the control units 210 and 213 continue the absorbance measurement of the measurement sample containing the PRP sample (Yes in step S37, step S38). If an operation signal to continue the measurement is not received, the measurement is terminated (No in step S37).

[0127] In step S38, the control unit 210 measures the absorbance of the sample containing the PRP sample, and then measures the absorbance of the sample containing the PPP sample (step S39). Note that if the sample was not stirred in step S34, stirring of the sample is initiated in step S38, and absorbance measurement is performed. Once the absorbance measurement of the PPP sample is completed, the control unit 213 analyzes the platelet aggregation function (step S40) and displays the platelet aggregation function measurement results along with the sample suitability evaluation results on the display 4 (step S41). If the measurement was aborted in step S37, the control unit 213 displays only the sample suitability evaluation results on the display 4 in step S41.

[0128] Figure 18 This is a flowchart showing another example of a sample measurement method including sample suitability evaluation. When evaluation information indicating that a PRP sample is not suitable as a sample is obtained, information for confirming the operator's willingness to continue the measurement is output. Figure 18 The example shown is the same as Figure 17 On the other hand, the absorbance measurement for evaluating the suitability of the sample is performed before adding the reagent containing the inducer to the PRP sample, which is similar to the example shown in FIG. Figure 17 The examples shown are different. Figure 18In the example shown, since the measurement sample containing the inducer has not been prepared when the evaluation information on the reagent suitability is acquired, the control units 210 and 213 can determine whether to prepare the measurement sample based on the evaluation information on the sample suitability.

[0129] like Figure 18 As shown, the control unit 210 sets the information required for the suitability evaluation of the measurement sample containing the PRP sample (step S50). In addition, if the measurement start button 30 is operated to transport the sample rack 105 into the device, the control unit 210 controls the sample information reading unit 103 to read the barcode of the sample container 104 and register the measurement instruction (step S51). Thereafter, a predetermined amount of the PRP sample is dispensed from the sample container 104 containing the PRP sample into the reaction container 108 (step S52). Steps S50 to S52 are similar to the steps in the embodiment of the present invention. Figure 17 However, in step S52, the reaction container 108 may not be heated.

[0130] The control unit 210 measures the initial absorbance of the PRP sample (step S53: acquiring third optical information) and, based on the measurement results, evaluates the sample suitability of the PRP sample (step S54). If the initial absorbance or platelet count falls below a lower limit reference value or exceeds an upper limit reference value, the control unit 213 outputs an error message indicating that the PRP sample being used is unsuitable as a sample.

[0131] If the PRP sample is evaluated as unsuitable as a specimen, the control unit 213 displays information on the display 4 confirming the operator's willingness to continue the measurement and determines whether to continue the measurement (steps S55 and S56). If the initial absorbance or platelet count of the PRP sample falls below the lower limit reference value or exceeds the upper limit reference value, the control unit 213 interrupts the series of measurements and confirms the operator's willingness to continue the measurement. The control unit 213 may automatically terminate the measurement (No in step S56), but preferably, the control unit 213 provides the operator with information confirming the operator's willingness to continue the measurement.

[0132] If the sample suitability evaluation result is negative, for example, a text message such as "Do you want to prepare a measurement sample and continue measurement?" or an error code indicating this message is displayed along with a button for selecting "Continue measurement" along with an error message indicating that the PRP sample is unsuitable as a sample. If the control units 210 and 213 receive an operation signal to continue measurement, they continue the platelet aggregation function measurement (Yes in step S56). If they do not receive an operation signal to continue measurement, they terminate the measurement (No in step S56).

[0133] If the measurement is continued in step S56, the control unit 210 prepares a measurement sample containing a PRP sample in step S57 and measures the absorbance of the measurement sample (step S58: acquisition of second optical information). Thereafter, the control unit 210 measures the absorbance of a sample containing a PPP sample (step S59: acquisition of first optical information). Figure 18 In the exemplary method, third optical information for sample suitability evaluation is obtained from the PRP sample before obtaining the second optical information. Here, the second optical information is measured after a predetermined time has passed since the addition of a platelet aggregation-inducing agent to the platelet-rich plasma, after the reaction has fully progressed. The third optical information is measured within a predetermined time after the addition of the platelet aggregation-inducing agent to the platelet-rich plasma.

[0134] like Figure 18 As shown, the movement of the reaction container 108 is as follows: in measuring the initial absorbance of the sample containing the PRP sample (step S53), the control unit 210 controls the reaction container 108 to be moved to the measurement unit 13 to obtain the third optical information; when the measurement is to be continued (yes in step S56), the control unit 210 controls the reaction container 108 to be moved to the measurement sample preparation unit 12, and heated at a predetermined temperature for a predetermined time (similar to the predetermined temperature). Figure 8 The control unit 210 controls the reaction container 108 to be moved to the dilution reagent solution preparation unit 11 to dispense a predetermined amount of dilution reagent solution into the reaction container 108 and prepare a measurement sample containing a PRP sample (similar to step S122 in FIG. 1 ); Figure 8 The control unit 210 controls the reaction container 108 to be moved to the measurement unit 13 to obtain the second optical information.

[0135] Once the absorbance measurement of the PPP sample is completed, the control unit 213 analyzes the platelet aggregation function (step S60) and displays the platelet aggregation function measurement results along with the sample compatibility evaluation results on the display 4 (step S61). If the measurement is terminated in step S56, the control unit 213 displays only the sample compatibility evaluation results on the display 4 in step S61.

[0136] Figure 19 and Figure 20 Result display screens 900 and 910 are respectively shown as examples of display screens of measurement results. Figure 19 The result display screen 900 shown includes a reaction curve display area 901 that displays a reaction curve (agglutination waveform) obtained by converting absorbance into agglutination rate. Figure 20Result display screen 910 also includes a reaction curve display area 911 that displays a reaction curve. Result display screen 900 displays the details of the results of the measurement item selected by measurement item tab 902. In contrast, result display screen 910 simultaneously displays the results of multiple measurement items. Display 4 can display either result display screen 900 or 910, and the screen can be switched based on the operator's selection.

[0137] The result display screen 900 also includes a detailed information display area 903 and an error information display area 904. Figure 19 In the example shown, the measurement item "ADP 1.0%" is selected, and the measurement results related to this measurement item are displayed. Result display screen 900 shows the reaction curve when ADP is added to the PRP sample. Detailed information display area 903 displays a value of 300 mOD as the initial absorbance of the sample containing the PRP sample, "Abs PRP_s." Error information display area 904 displays an error code. In other words, result display screen 900 displays information related to platelet aggregation function and information evaluating the sample suitability of the PRP sample.

[0138] The lower limit of the initial absorbance of a sample containing a PRP sample is set to, for example, 410 mOD. In this case, if the initial absorbance of 300 mOD is lower than the lower limit, an error message indicating that the PRP sample used is not suitable as a sample, i.e., abnormal, is displayed as evaluation information on the sample suitability. Figure 19 In the example shown, the error code displayed in the error message display area 904 corresponds to the error message. In addition to the error code, text indicating the error, such as "PLT number low," may be displayed in the error message display area 904. "PLT number low" indicates that the platelet count in the sample is low.

[0139] The result display screen 910 also includes a result summary display area 912. The reaction curve display area 911 and the result summary display area 912 of the result display screen 910 display the results of multiple measurement items, making it easy to compare the measurement results. As long as the PRP sample is the same, the initial absorbance of the sample containing the PRP sample will not change significantly depending on the type of inducer. Figure 20 The initial absorbance displayed in the result list display area 912 is a value lower than the lower limit reference value. The error code displayed on the result display screen 900 is not displayed on the result display screen 910, but an error message clearly indicating that the PRP sample used is not suitable as a specimen may be displayed on the result display screen 910.

[0140] If the initial absorbance of the PRP sample or the platelet count calculated according to the above-mentioned regression equation is within the reference value range, information clearly indicating that the PRP sample used is suitable as a sample (normal) may be displayed on the display 4 along with the initial absorbance or platelet count value as sample suitability evaluation information. Alternatively, if the sample is normal, only the initial absorbance or platelet count value may be displayed, and only if the sample is abnormal, an error message clearly indicating that the sample is abnormal may be displayed along with the initial absorbance or platelet count value.

[0141] The evaluation information of the sample suitability when the initial absorbance or platelet count of the PRP sample is not within the reference value range may include information that prompts the blood cell counting device to measure the platelet count as described above, and may also include information related to whether the centrifugation conditions when preparing the PRP sample from the blood sample are appropriate. In addition, both of these information can also be displayed on the result display screen. For example, a text message such as "There is a possibility that the platelet count is not within the recommended range for measurement. Please measure the platelet count with the blood cell counting device. In addition, there is a possibility that the centrifugation conditions when preparing the sample are not appropriate. Please confirm the centrifugation conditions." or an error code indicating the information may be displayed.

[0142] If the initial absorbance or platelet count of the PRP sample is outside the reference range, the information displayed on the result display screen may include information related to other diseases inferred from the measured initial absorbance or platelet count of the PRP sample. For example, if the platelet count in the PRP sample is below the lower limit of the reference value, it may be caused by Birch-Soe syndrome. Therefore, the result display screen may display a text message such as "There is a possibility that the platelet count is outside the recommended range for measurement. Birch-Soe syndrome is suspected." or a code indicating this information.

[0143] As described above, according to the sample measurement device 1 and the sample measurement method having the above-described configuration, the suitability of the PRP sample as a specimen can be easily determined.

[0144] Description of Reference Numerals 1. Sample measurement device 2 Device body 3 Analysis device 4 monitors 10 Frame 10a Front mask 10b Side frame 11. Dilution reagent solution preparation section 12. Measurement sample preparation section 13. Measurement Department 30 Measurement start button 50 diluent containers 60 dilution reagent container 90 Reagent Containers 100, 300 container racks 102 Conveying Department 102a rack mounting portion 102b rack recycling department 103 Sample information reading unit 104 sample containers 105 sample rack 106 Waste outlet 108 reaction vessel 120a, 120b Second distribution unit 150a, 150b first distribution unit 121, 152 pipette 131 Container Configuration Department 132 Light sending department 133 Light Receiving Unit 160 Rotary Table 161, 191 retaining holes 170, 175, 192 clamping mechanism 180 Reagent Preparation Station 181 First Workbench 182 Second workbench 183 Rotation Axis 184 Reagent information reading unit 190 Heating Table 209, 212 Ministry of Communications 210, 213 Control Department 211 I / O base board 501, 502 Sample aspiration positions 503, 504 sample allocation location 505, 506 reagent aspiration position 507, 508 Reagent distribution position 600 Menu Screen 610 Toolbar 611, 634 maintenance buttons 612, 637 Close button 613 Command Button 620 Status display area 630 Menu icon display area 631 Reagent Consumables Button 632 Calibration line button 633 QC chart button 635 Error History Button 636 Setting button 700 Command screen 701 Instruction Registration Department 702 Measurement Category Selection Section 800, 810, 820, 830 setting screen 801 Overview display area 802 Parameter Registration Department 803 Edit Button 811, 813, 821 selection buttons 812, 822 Reference value input unit 900, 910 result display screen 901, 911 reaction curve display area 902 Measurement Item Tags 903, 912 Detailed information display area 904 Error message display area

Claims

1. A coagulation analyzer, comprising: a sample dispensing portion configured to dispense a first sample into a first container and a second sample into a second container, wherein the first sample is platelet-poor plasma prepared from a blood sample and the second sample is platelet-rich plasma prepared from the blood sample; a reagent dispensing portion configured to dispense a reagent for inducing platelet aggregation into the second container; a detection unit configured to measure first optical information of the first sample and second optical information of the second sample; a control unit configured to analyze the first optical information and the second optical information to provide an analysis result of the platelet aggregation function of the blood sample, The control unit is configured to check whether the second sample contains a sufficient amount of platelets to obtain an accurate analysis result of the platelet aggregation function.

2. The coagulation analyzer according to claim 1, wherein The detection section is configured to measure third optical information from the second sample, and The control section is configured to check whether the second sample contains a sufficient amount of platelets based on the third optical information.

3. The coagulation analyzer according to claim 2, wherein: The third optical information is the absorbance or transmittance of the second sample.

4. The coagulation analyzer according to claim 1, wherein The second container contains a stirring member, and The detection section is configured to rotate the stirring member in the second container while measuring the second optical information.

5. The coagulation analyzer according to claim 1, wherein The detection section is configured to start rotating the stirring member after obtaining the third optical information.

6. The coagulation analyzer according to claim 2, wherein: The third optical information is obtained within 10 seconds after the reagent is dispensed into the second container.

7. The coagulation analyzer according to claim 2, wherein: The third optical information is obtained before adding the agent for inducing platelet aggregation to the second container.

8. The coagulation analyzer according to claim 2, wherein: The control section is configured to check whether the second sample contains a sufficient amount of platelets by comparing the third optical information with a reference value.

9. The coagulation analyzer according to claim 1, further comprising a display, wherein: The control section is configured to cause the display to display an analysis result regarding the platelet aggregation function and a check result regarding whether the second sample contains a sufficient amount of platelets.

10. The coagulation analyzer according to claim 9, wherein: The control section is configured to cause the display to display an error message in response to determining that the second sample does not contain a sufficient amount of platelets.

11. The coagulation analyzer according to claim 9, wherein: The control section is configured to cause the display to display a prompt for measuring the platelet count of the second sample using the blood cell counting section in response to determining that the second sample does not contain a sufficient amount of platelets.

12. The coagulation analyzer according to claim 2, wherein: The control section is configured to estimate the platelet count from the third optical information.

13. The coagulation analyzer according to claim 12, wherein: The control section is configured to check whether the second sample contains a sufficient amount of platelets by comparing the platelet count with a reference value.

14. The coagulation analyzer according to claim 1, wherein: The control section is configured to analyze the first optical information and the second optical information to generate a curve representing a change in platelet aggregation over time.

15. The coagulation analyzer according to claim 1, wherein: The control section is configured to analyze the first optical information and the second optical information to obtain an index of platelet aggregation.

16. A method for measuring platelet aggregation function of a blood sample using a coagulation analyzer, the method comprising: preparing a first sample and a second sample, wherein the first sample is platelet-poor plasma prepared from a blood sample, and the second sample is platelet-rich plasma prepared from the blood sample; combining a platelet aggregation-inducing agent with the second sample; acquiring first optical information of the first sample and second optical information of the second sample bound to the reagent; analyzing the first optical information and the second optical information to provide an analysis result of the platelet aggregation function of the blood sample; as well as Check whether the second sample contains a sufficient amount of platelets to obtain an accurate analysis result of the platelet aggregation function.

17. The sample measurement method according to claim 16, further comprising: Information on the platelet aggregation function is displayed, and a test result of whether the second sample contains a sufficient amount of platelets is displayed.

18. The sample measurement method according to claim 16, wherein: The third optical information as absorbance or transmittance is measured to check whether the second sample contains a sufficient amount of platelets.

19. The sample measurement method according to claim 16, further comprising: The third optical information is obtained within 10 seconds after the reagent is added to the second sample.

20. The sample measurement method according to claim 19, further comprising: A curve representing the temporal change of platelet aggregation is generated based on the first optical information and the second optical information.

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