Automatic analysis apparatus and automatic analysis method

Abstract

The purpose of the present invention is to provide an automatic analysis device that can make a determination according to a cross-mixing test, even when there is a preparation specimen for which a coagulation time cannot be calculated. An automatic analysis device of the present invention comprises: a specimen dispenser mechanism; a reagent dispenser mechanism; a measuring unit; an analysis operation control unit that controls the operation of the specimen dispenser mechanism, the reagent dispenser mechanism and the measuring unit; a coagulation time arithmetic unit that calculates a coagulation time on the basis of light intensity measured at the measuring unit; a graph generating unit that generates a graph pertaining to the coagulation time of each preparation specimen calculated at the coagulation time arithmetic unit; and a display unit that displays the graph generated by the graph generating unit, wherein if a preparation specimen exists for which a coagulation time cannot be calculated, the graph generating unit generates a graph using at least either a coagulation time calculated by the coagulation time arithmetic unit with respect to a preparation specimen prepared outside the automatic analysis device, or a coagulation time estimated by the coagulation time arithmetic unit on the basis of the light intensity measured at the measuring unit.

Description

Technical Field

[0001] The present invention relates to an automatic analyzer and an automatic analysis method.

Background Art

[0002] Blood coagulation tests are performed for purposes such as understanding the pathological conditions of the blood coagulation fibrinolytic system, diagnosing DIC (disseminated intravascular coagulation syndrome), confirming the therapeutic effect of thrombus treatment, and diagnosing hemophilia. In particular, the blood coagulation time measurement measures the time until a fibrin clot is formed after mixing a specimen and a reagent. When there are congenital or acquired abnormalities, the coagulation time is prolonged. The causes of the prolonged coagulation time include a decrease in activity due to a deficiency of coagulation factors (deficiency type) and a decrease in activity due to inhibition of the coagulation reaction by an antibody against a component constituting the coagulation system or a component in the coagulation time measurement reagent (inhibitor type). Therefore, as a method for determining whether it is a deficiency type or an inhibitor type, a crossmixing test is known. The crossmixing test determines by graphing the degree of correction of the coagulation time of a prepared specimen obtained by adding normal plasma to a test plasma. For example, Patent Document 1 discloses an automatic analyzer that automates the preparation of a mixed plasma obtained by mixing a test plasma and a normal plasma at a predetermined mixing ratio.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] However, in the crossmixing test, for example, when the coagulation time of a prepared specimen containing only the test plasma becomes long and the coagulation reaction does not complete within a predetermined time, the coagulation time cannot be calculated. If there is even one prepared specimen for which the coagulation time cannot be calculated, a graph is not output, and it may be difficult to determine whether it is a deficiency type or an inhibitor type.

[0005] An object of the present invention is to provide an automatic analyzer and an automatic analysis method capable of making a determination by a cross mixing test even when there is a prepared specimen for which the coagulation time cannot be calculated.

Means for Solving the Problems

[0006] To solve the above problems, the automatic analyzer of the present invention includes a specimen dispensing mechanism, a reagent dispensing mechanism, a measurement unit, an analysis operation control unit that controls the operations of the specimen dispensing mechanism, the reagent dispensing mechanism, and the measurement unit, a coagulation time calculation unit that calculates a coagulation time based on the light intensity measured by the measurement unit, a graph creation unit that creates a graph regarding the coagulation time of each prepared specimen calculated by the coagulation time calculation unit, and a display unit that displays the graph created by the graph creation unit. When there is a prepared specimen for which the coagulation time cannot be calculated, the graph creation unit creates a graph using at least one of the coagulation time calculated by the coagulation time calculation unit for a prepared specimen prepared outside the automatic analyzer and the coagulation time estimated by the coagulation time calculation unit based on the light intensity measured by the measurement unit.

[0007] Further, the automatic analysis method of the present invention is an automatic analysis method using an automatic analyzer having a specimen dispensing mechanism, a reagent dispensing mechanism, a measurement unit, a coagulation time calculation unit, a graph creation unit, and a display unit, and includes a step in which the coagulation time calculation unit calculates a coagulation time based on the light intensity measured by the measurement unit, a step in which the graph creation unit creates a graph regarding the coagulation time of each prepared specimen calculated by the coagulation time calculation unit, and a step in which the display unit displays the graph created by the graph creation unit. When there is a prepared specimen for which the coagulation time cannot be calculated, the graph creation unit further includes a step of creating a graph using at least one of the coagulation time calculated for a prepared specimen prepared outside the automatic analyzer and the coagulation time estimated by the coagulation time calculation unit based on the light intensity measured using another prepared specimen.

Effects of the Invention

[0008] According to the present invention, even when there is a prepared specimen for which the coagulation time cannot be calculated, an automatic analyzer and an automatic analysis method capable of determination by a crossmixing test can be provided. As a result, not only can the time for re-measuring the light intensity to calculate the coagulation time be suppressed, but re-sampling due to insufficient plasma volume required for re-measurement can also be suppressed.

[0009] Problems, configurations, and effects other than those described above will be clarified by the description of the following embodiments.

Brief Description of the Drawings

[0010]

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Mode for Carrying Out the Invention

[0011] In this specification, "test plasma" includes plasma of inpatients or outpatients, plasma of examinees in health checkups, etc., and "normal plasma" includes pooled plasma, commercially available plasma with normal coagulation time, etc. Pooled plasma is a collection of plasma from at least 20 clearly healthy people. Also, in this specification, the specimens for measuring the coagulation time of blood may sometimes be referred to generically as "test plasma", "normal plasma", and "mixed plasma in which test plasma and normal plasma are mixed (at a predetermined mixing ratio)".

[0012] FIG. 1 is an example of a graph used in a crossmixing test. In the crossmixing test, for specimens (prepared specimens) prepared such that the ratio of the test plasma becomes 0, 10, 20, 50, 80, 90, 100% by adding normal plasma to the test plasma, the APTT (Activated Partial Thromboplastin Time, hereinafter sometimes simply referred to as "coagulation time") is measured and graphed. The horizontal axis in FIG. 1 is the ratio (%) of the test plasma in the prepared specimen, and the vertical axis in FIG. 1 is the APTT (seconds).

[0013] In the deficiency type, like the broken line (a) connecting the points plotted as circles in FIG. 1, the APTT is corrected by adding normal plasma, showing a downward convex pattern. On the other hand, in the inhibitor type, like the broken line (b) connecting the points plotted as squares in FIG. 1, it is difficult to correct the APTT even when normal plasma is added, showing an upward convex pattern. However, since the reaction of the inhibitor against factor VIII has a dependence on time and temperature, in the reaction immediately after mixing (hereinafter referred to as the "immediate reaction"), it does not show a clear upward convex shape, and may show an upward convex shape in the reaction after incubation at 37°C for a certain period of time (hereinafter referred to as the "delayed reaction"). Therefore, in the crossmixing test, it is recommended to judge in both the immediate reaction and the delayed reaction.

[0014] Hereinafter, examples of the present invention will be described.

Examples

[0015] FIG. 2 is an overall schematic configuration diagram of the automatic analyzer 100. As shown in FIG. 2, the automatic analyzer 100 includes a specimen dispensing mechanism 101, a specimen disk 102, a reagent dispensing mechanism 106, a reagent disk 107, a reaction vessel stock unit 111, a reaction vessel transport mechanism 112, a detection unit 113, a reaction vessel disposal unit 117, an input / output unit 118, a storage unit 119, and a control unit 120.

[0016] The sample dispensing mechanism 101 sucks the sample contained in the sample container 103 arranged on the sample disk 102 that rotates clockwise and counterclockwise, and discharges it into the reaction vessel 104 contained in the reaction vessel stock section 111. The sample dispensing mechanism 101 is provided with a sample dispensing probe 101a at its tip, and sucks and discharges the sample by the operation of a syringe pump 105 for samples controlled by the control unit 120.

[0017] The reagent dispensing mechanism 106 sucks the reagent contained in the reagent container 108 arranged on the reagent disk 107, and discharges it into the reaction vessel 104 contained in the reaction vessel stock section 111. The reagent dispensing mechanism 106 is provided with a reagent dispensing probe 106a at its tip, and sucks and discharges the reagent by the operation of a syringe pump 110 for reagents controlled by the control unit 120. Further, the reagent dispensing mechanism 106 incorporates a reagent heating mechanism 109, and the reagent sucked by the reagent dispensing mechanism 106 is heated to a predetermined temperature by the reagent heating mechanism 109.

[0018] The reaction vessel transfer mechanism 112 transports and installs the reaction vessel 104 contained in the reaction vessel stock section 111. The reaction vessel transfer mechanism 112 grips the reaction vessel 104 and rotates it horizontally, thereby transporting and installing the reaction vessel 104 from the reaction vessel stock section 111 to the reaction vessel installation section 114 of the detection unit 113. Further, the reaction vessel transfer mechanism 112 grips the reaction vessel 104 after the measurement is completed and discards it to the reaction vessel disposal section 117.

[0019] The detection unit 113 (measurement unit) includes a reaction vessel installation section 114 for placing the reaction vessel 104, a light source 115, and a light receiving section 116. The detection unit 113 measures the light intensity of the sample in the reaction vessel 104 inserted into the reaction vessel installation section 114. In this embodiment, a configuration in which one detection unit 113 is arranged is shown, but a configuration in which a plurality of detection units 113 are arranged may also be used.

[0020] An example of the detection principle in the detection unit 113 is described below. The light irradiated from the light source 115 is scattered by the reaction solution (specimen) in the reaction vessel 104. The light receiving unit 116 is composed of a photodiode or the like. The light receiving unit 116 receives the scattered light scattered by the reaction solution in the reaction vessel 104, and by performing photo / electric conversion, outputs a photometric signal indicating the intensity of the received scattered light to the A / D converter 121. The measurement signal of the scattered light A / D-converted by the A / D converter 121 is input to the control unit 120 via the interface 122.

[0021] Note that the light receiving unit 116 is not limited to a configuration that detects the intensity of the scattered light scattered by the reaction solution in the reaction vessel 104. For example, the light receiving unit 116 may be a configuration that detects the intensity of the transmitted light transmitted through the reaction solution in the reaction vessel 104. Further, a light receiving unit 116 that can detect both scattered light and transmitted light may be used. Furthermore, the light receiving unit 116 may utilize viscosity.

[0022] The control unit 120 is composed of an analysis operation control unit 120a, a coagulation time calculation unit 120b, and a graph creation unit 120c. Each function of the analysis operation control unit 120a, the coagulation time calculation unit 120b, and the graph creation unit 120c is realized by a processor such as a CPU reading a program stored in a ROM or a storage unit 119 (not shown) and executing the read program.

[0023] The analysis operation control unit 120a controls the specimen dispensing mechanism 101 and the specimen disk 102 to dispense normal plasma added to correct the coagulation time of the test plasma and / or the test plasma into a plurality of specimen containers 103. Further, the analysis operation control unit 120a controls the specimen dispensing mechanism 101 and the specimen disk 102 to dispense a prepared specimen containing only the test plasma, only the normal plasma, or a mixed plasma in which the test plasma and the normal plasma are mixed, from the specimen container 103 into the reaction container 104. Furthermore, the analysis operation control unit 120a controls the reagent dispensing mechanism 106 and the reagent disk 107 to dispense a reagent into the reaction container 104. Furthermore, the analysis operation control unit 120a controls the detection unit 113 to irradiate the prepared specimen with the reagent added thereto in the reaction container 104 with light from the light source 115 and measure the light intensity of the resulting scattered light. In addition, the analysis operation control unit 120a controls the reagent temperature raising mechanism 109 to raise the temperature of the reagent to a predetermined temperature, or controls the reaction container transport mechanism 112 to transport, install, and discard the reaction container 104.

[0024] The coagulation time calculation unit 120b calculates the coagulation time based on the light intensity measured by the detection unit 113. The graph creation unit 120c creates a graph regarding the coagulation time of each prepared specimen calculated by the coagulation time calculation unit 120b.

[0025] The input / output unit 118 is composed of a mouse 118a and a keyboard 118b which are input units, and a display 118c (display unit) which is an output unit. When the operator uses the input unit to input the analysis items of the specimen to be analyzed by the automatic analyzer 100, the input information is transmitted to the control unit 120. The display unit displays the analysis results, alarms, etc., and also displays the coagulation time calculated by the coagulation time calculation unit 120b and the graph created by the graph creation unit 120c.

[0026] The storage unit 119 stores the analysis results, coagulation time, etc. Note that the analysis results, coagulation time, etc. may be printed out by a printer 123 connected to the input / output unit 118 via the interface 122.

[0027] In addition, in FIG. 2, for the sake of convenience in showing all the components, the reaction vessel stock unit 111, the specimen disk 102, and the reagent disk 107 appear to be spaced apart. However, actually, the specimen disk 102 and the reaction vessel stock unit 111 are arranged within the range of the arc-shaped movement locus of the specimen dispensing probe 101a that constitutes the specimen dispensing mechanism 101. Also, the reagent disk 107 and the reaction vessel stock unit 111 are arranged within the range of the arc-shaped movement locus of the reagent dispensing probe 106a that constitutes the reagent dispensing mechanism 106. Therefore, when viewing the automatic analyzer 100 from above, these specimen disk 102, reaction vessel stock unit 111, and reagent disk 107 are arranged in a substantially triangular shape. Further, the automatic analyzer 100 may further include an incubator 124 for warming the specimen before the measurement start reagent is added, for the purpose of improving the processing capacity.

[0028] Next, regarding the method for preparing a specimen used in the crossmixing test, it will be described with reference to FIGS. 3 and 4. FIG. 3 is a flowchart showing a method for preparing a mixed plasma used in the crossmixing test. FIG. 4 is an example of a preparation setting screen for the mixed plasma used in the crossmixing test.

[0029] The operator confirms a request for a crossmixing test (hereinafter sometimes simply referred to as measurement) (step S300) and prepares the specimen (step S301). Next, while looking at the setting screen shown in FIG. 4 output to the display unit, the operator sets the test items and the ratios of the test plasma for the immediate type and the delayed type respectively, using the input unit (step S302). As the ratios of the test plasma, those stored in the storage unit 119 in advance before the measurement request may be used, or they may be changed each time the measurement is performed.

[0030] Based on the test items and the ratio of the plasma sample to be tested set in step S302, the analysis operation control unit 120a calculates the required amount of normal plasma and the amount of plasma sample to be tested for the measurement, and displays them on the setting screen of FIG. 4 (step S303). In this way, since the required amount of normal plasma and the amount of plasma sample to be tested are notified to the operator via the display unit, not only can the burden on the operator to calculate the required amount be reduced, but also the shortage of the plasma amount during the preparation can be prevented.

[0031] Next, the operator sets the installation positions of the specimen container 103a filled with normal plasma, the specimen container 103b filled with the plasma sample to be tested, and the installation positions of the empty specimen containers 103c to 103g (step S304). Here, each position represents the installation position of the specimen container 103 on the specimen disk 102, and is not necessarily specified only by numbers. For example, a combination of alphabet and numbers may be used. Also, each position may be automatically set by the analysis operation control unit 120a instead of being set by the operator.

[0032] The operator installs the specimen container 103a filled with normal plasma, the specimen container 103b filled with the plasma sample to be tested, and the empty specimen containers 103c to 103g at the positions set in step S304 (step S305). The analysis operation control unit 120a calculates the time required for the preparation of the mixed plasma and outputs it to the display unit (step S306). Next, the analysis operation control unit 120a performs a container installation check, that is, checks whether there is an empty specimen container and whether there is a required amount of normal plasma and plasma sample to be tested (step S307).

[0033] FIG. 5 is a diagram showing a state when the specimen dispensing mechanism 101 checks for the presence of an empty specimen container. As shown in FIG. 5, the check for the presence of an empty specimen container is performed by whether the specimen dispensing probe 101a provided at the tip of the specimen dispensing mechanism 101 detects a physical abnormality when it contacts the bottom of the empty specimen container.

[0034] On the one hand, to confirm whether there is a required amount of normal plasma and abnormal plasma, it is performed using the liquid level detection function of the specimen dispensing mechanism 101. The liquid level detection function is a function of detecting the liquid level by capturing electrical characteristics such as capacitance and resistance value that change when the specimen dispensing probe 101a provided at the tip of the specimen dispensing mechanism 101 contacts or approaches the liquid level. When confirming the amount of normal plasma, the analysis operation control unit 120a rotates the specimen disk 102 so that the specimen container 103a filled with normal plasma among the specimen containers 103 installed on the specimen disk 102 is located at the dispensing position of the specimen dispensing mechanism 101 (see FIG. 6 described later). Then, the analysis operation control unit 120a confirms the amount of normal plasma in the specimen container 103a by the liquid level detection function of the specimen dispensing probe 101a. When confirming the amount of the test plasma, the analysis operation control unit 120a rotates the specimen disk 102 so that the specimen container 103b filled with the test plasma among the specimen containers 103 installed on the specimen disk 102 is located at the dispensing position of the specimen dispensing mechanism 101 (see FIG. 7 described later). Then, the analysis operation control unit 120a confirms the amount of the test plasma in the specimen container 103b by the liquid level detection function of the specimen dispensing probe 101a.

[0035] In step S307, if it is determined that the amount of normal plasma or the amount of the test plasma is less than the required amount, or if the required number of empty specimen containers are not installed at the predetermined positions, the analysis operation control unit 120a aborts the preparation of the mixed plasma and outputs a system alarm to the display unit (step S308). Thereby, it is possible to avoid plasma shortage during preparation and measurement, contamination of the specimen disk 102 by dispensing into a place where an empty specimen container is not installed, mixing by further dispensing the specimen (normal plasma, test plasma, mixed plasma) into the specimen container where the specimen has already been dispensed, and the like. Note that the system alarm may also output voice (the same applies to the following system alarms).

[0036] On the other hand, in step S307, when it is determined that the normal plasma volume and the test plasma volume satisfy the required amounts and the required number of empty specimen containers are installed, the analysis operation control unit 120a starts dispensing the normal plasma into the empty specimen containers 103c to 103g (step S309).

[0037] Here, the dispensing operation of the normal plasma will be described. First, due to the rotation of the specimen disk 102, as shown in FIG. 6, after the specimen container 103a filled with normal plasma moves to the dispensing position of the specimen dispensing mechanism 101, the specimen dispensing probe 101a of the specimen dispensing mechanism 101 sucks the normal plasma. In this embodiment, it is assumed that the specimen disk 102 rotates step by step clockwise, and the moving distance in each step corresponds to the pitch of two adjacent specimen containers 103.

[0038] Thereafter, the specimen disk 102 further rotates, and as shown in FIG. 7, the specimen container 103b filled with the test plasma moves to the dispensing position of the specimen dispensing mechanism 101. At this time, the specimen dispensing mechanism 101 does not discharge the normal plasma sucked from the specimen container 103a into the specimen container 103b.

[0039] Next, the specimen disk 102 further rotates. As shown in FIG. 8, after the empty specimen container 103c moves to the dispensing position of the specimen dispensing mechanism 101, the specimen dispensing probe 101a of the specimen dispensing mechanism 101 discharges the normal plasma into the empty specimen container 103c. At this time, the tip of the specimen dispensing probe 101a is at a height that does not contact the liquid surface of the normal plasma discharged into the specimen container 103c. Thereafter, the specimen dispensing probe 101a descends, and when the liquid surface is detected by the liquid surface detection function, the specimen dispensing probe 101a ascends. By this operation, it becomes possible to move the normal plasma attached to the tip of the specimen dispensing probe 101a into the specimen container 103c. Furthermore, it becomes possible to minimize the contamination of the specimen dispensing probe 101a by the plasma.

[0040] When this operation is repeated and normal plasma is dispensed into the empty specimen containers 103d to 103g, the analysis operation control unit 120a determines whether or not the dispensing of normal plasma has been completed (step S310). In step S310, if it is determined that the dispensing of normal plasma has not been completed, the analysis operation control unit 120a aborts the preparation of the mixed plasma and outputs a system alarm to the display unit (step S311). On the other hand, in step S310, if it is determined that the dispensing of normal plasma has been completed, the analysis operation control unit 120a continues to start the dispensing of the test plasma (step S312).

[0041] Here, the dispensing operation of the test plasma will be described. First, due to the rotation of the specimen disk 102, after the specimen container 103b filled with the test plasma moves to the dispensing position of the specimen dispensing mechanism 101, the specimen dispensing probe 101a of the specimen dispensing mechanism 101 sucks the test plasma.

[0042] Thereafter, the specimen disk 102 rotates further. After the specimen container 103c into which normal plasma was discharged in step S309 moves to the dispensing position of the specimen dispensing mechanism 101, the specimen dispensing probe 101a of the specimen dispensing mechanism 101 discharges the test plasma into the specimen container 103. At this time, it is assumed that the tip of the specimen dispensing probe 101a is at a height that does not contact the liquid surface of the test plasma discharged into the specimen container 103c. Thereafter, when the specimen dispensing probe 101a descends and the liquid surface is detected by the liquid surface detection function, the specimen dispensing probe 101a ascends. By this operation, it becomes possible to move the test plasma adhering to the tip of the specimen dispensing probe 101a into the specimen container 103c. Furthermore, it is also possible to prevent the specimen dispensing probe 101a from being contaminated by normal plasma and contaminating the test plasma.

[0043] When the test plasma is dispensed into the specimen container 103c, the specimen dispensing mechanism 101 stirs the mixed plasma composed of the normal plasma and the test plasma in the specimen container 103c (step S313). For example, the specimen dispensing probe 101a stirs the mixed plasma in the specimen container 103 by repeatedly sucking and discharging it while using the discharge pressure of the specimen syringe pump 105. The specimen dispensing probe 101a also descends in accordance with the drop in the liquid level during suction and ascends in accordance with the rise in the liquid level during discharge. By this operation, it becomes possible to minimize the contamination of the specimen dispensing probe 101a by the plasma. Since this stirring method does not require dedicated parts for stirring, the automatic analyzer 100 can be made more space-saving. However, the mixed plasma may be stirred by other stirring methods, such as a stirring method using ultrasonic waves.

[0044] For the specimen containers 103d to 103g into which the normal plasma has been discharged in step S309, the test plasma is also dispensed in the same procedure as for the specimen container 103c, and the mixed plasma is stirred by the specimen dispensing probe 101a. After this operation is repeated, the analysis operation control unit 120a determines whether or not the dispensing and stirring of the test plasma have been completed (step S314).

[0045] In step S314, if it is determined that the dispensing and stirring of the test plasma have not been completed, the analysis operation control unit 120a stops the dispensing and stirring and outputs a system alarm to the display unit (step S315). On the other hand, in step S314, if it is determined that the dispensing and stirring have been completed, the analysis operation control unit 120a notifies the display unit that the preparation of the mixed plasma has been completed (step S316).

[0046] Note that the amount of normal plasma discharged from the specimen dispensing probe 101a in step S309 and the amount of test plasma discharged from the specimen dispensing probe 101a in step S312 are automatically calculated by the analysis operation control unit 120a based on the test plasma ratio set in step S302. When the dispensing amount for one empty specimen container exceeds the maximum dispensing amount of the specimen dispensing probe 101a, the specimen dispensing mechanism 101 performs dispensing in several times, and the number of times is also automatically calculated by the analysis operation control unit 120a.

[0047] Also, in the flowchart of FIG. 3, after the dispensing of normal plasma (step S309), the dispensing of test plasma (step S312) is performed. Conversely, after the dispensing of test plasma, the dispensing of normal plasma may be performed. Further, in the flowchart of FIG. 3, from the viewpoint of preventing contamination between normal plasma and test plasma, the dispensing of normal plasma and the dispensing of test plasma are performed independently, but it is not limited to this. For example, when the cleaning of the specimen dispensing mechanism 101 is sufficient and there is no concern about contamination, mixed plasma may be prepared one by one. In this case, after the specimen dispensing mechanism 101 dispenses the required amount of normal plasma into the empty specimen container 103c, before dispensing normal plasma into the next specimen container 103d, the specimen dispensing mechanism 101 dispenses the required amount of test plasma into the specimen container 103c. Then, when the preparation of the mixed plasma in the specimen container 103c is completed, the specimen dispensing mechanism 101 prepares the mixed plasma in the empty specimen container 103d, and thereafter, prepares the mixed plasma sequentially for each empty specimen container.

[0048] Next, the process until a graph for the cross-mixing test is created using the prepared specimen will be described in detail. FIG. 9 is a flowchart showing a method for measuring and creating a graph of the prepared specimen. In the cross-mixing test, first, an immediate-type measurement is performed using the mixed plasma immediately after the preparation is completed, and then a delayed-type measurement is performed using the mixed plasma after being incubated for a certain time after the preparation is completed. The following is a specific description.

[0049] When the preparation of the mixed plasma is completed, the analysis operation control unit 120a not only outputs a message to that effect to the display unit as in step S316 of FIG. 3, but also outputs information for confirming whether to perform an immediate measurement (step S901). FIG. 10 shows an example of a screen for notifying the completion of preparation and confirming an immediate measurement. In the example shown in FIG. 10, it is assumed that the mixed plasma automatically prepared by the automatic analyzer 100 according to the flow of FIG. 3 is directly used for an immediate measurement. However, a mixed plasma prepared outside the automatic analyzer 100, for example, a mixed plasma manually prepared by an operator, may also be used for an immediate measurement.

[0050] When the operator instructs an immediate measurement using the input unit (step S902), the measurement unit measures the scattered light intensity of each prepared specimen for a certain period of time, and based on the measurement results, the coagulation time calculation unit 120b calculates the coagulation time of each mixed plasma (step S903).

[0051] As methods for calculating the coagulation time, as shown in Patent Document [Japanese Patent Laid-Open No. 6-27115], a method of directly using the light quantity, a method of using the differential value of the scattered light quantity, etc. are known. Here, the coagulation time calculation unit 120b calculates the coagulation time by a method of directly using the light quantity. Hereinafter, the method of directly using the light quantity will be specifically described.

[0052] First, the coagulation time calculation unit 120b generates a coagulation reaction curve showing the change in scattered light intensity over time based on the measurement data by the detection unit 113. FIG. 11 is an example of the coagulation reaction curve. As shown in FIG. 11, at the start of measurement immediately after the reagent addition, almost no change in scattered light intensity is observed. However, thereafter, as coagulation progresses, the sample becomes turbid and a rapid increase in scattered light intensity is seen. When the coagulation reaction is almost complete, the change in scattered light intensity becomes small and then becomes substantially constant. Therefore, the coagulation time calculation unit 120b calculates the difference between the scattered light intensity at the time point when a certain specified time has elapsed from the reagent mixing time point T0 and the scattered light intensity at the time point T0 (coagulation reaction start level), and sets the time T from T0 until the time when the scattered light intensity increases by an amount corresponding to 1 / N (N is a predetermined number equal to or greater than 1) of the difference as the coagulation time. In other words, the coagulation time calculation unit 120b calculates a reference intensity difference, which is the intensity difference between the light intensity at the coagulation reaction start level and the light intensity at the coagulation reaction end level, and calculates the time until the intensity difference from the coagulation reaction start level reaches a predetermined ratio with respect to the reference intensity difference as the coagulation time. In this embodiment, this method is called the percentile method.

[0053] Returning to the description of FIG. 9, after the calculation of the coagulation time in step S903, the graph creation unit 120c creates an immediate-type graph based on the coagulation time of each mixed plasma calculated by the coagulation time calculation unit 120b (step S904), and the graph is output to the display unit.

[0054] The operator checks the immediate-type graph (step S905). If the operator continues to perform the delayed-type measurement, the containers of each mixed plasma after the immediate-type measurement are closed and incubated, for example, at 37°C for 2 hours (step S906). Here, the case where the incubation is performed outside the automatic analyzer 100 is described. However, if the automatic analyzer 100 has an incubator, the incubation may be performed inside the apparatus. When the incubation is complete, the operator opens the mixed plasma and places it on the specimen disk 102 (step S907).

[0055] Thereafter, when the operator instructs a delayed measurement using the input unit (step S908), the measurement unit measures the scattered light intensity of each mixed plasma for a certain period of time, and based on the measurement results, the coagulation time calculation unit 120b calculates the coagulation time of each mixed plasma (step S909). Further, the graph creation unit 120c creates a delayed graph based on the coagulation time of each mixed plasma calculated by the coagulation time calculation unit 120b (step S910). The graph created by the graph creation unit 120c is output to the display unit, and the operator checks the graph (step S911).

[0056] Here, when the immediate and delayed measurements are completed, a measurement result output screen (without error) as shown in FIG. 12 is output to the display unit. The operator refers to the immediate type broken line (A) connecting the points plotted in a circle in FIG. 12 and the delayed type broken line (B) connecting the points plotted in a square in FIG. 12. Also, on the screen of FIG. 12, the calculation result of the value of (measurement result at test plasma ratio 50% - measurement result at test plasma ratio 0%) / (measurement result at test plasma ratio 100%) × 100 for both the immediate and delayed types is also displayed as the Rosner Index (index of circulation anticoagulant: ICA). Thereby, the shape of the graph can be represented numerically and can be used as one of the objective evaluation indicators.

[0057] Here, if there is mixed plasma for which the clotting time cannot be calculated for some reason, the measurement result of the mixed plasma will be an error, and the graph may not be displayed. Also, even if the clotting time can be calculated but does not meet the predetermined judgment conditions, since the reliability of the measurement result may not be guaranteed, an alarm or the like may also be displayed together with the measurement result of the mixed plasma. Therefore, when the operator designates the measurement result of a predetermined mixed plasma on the screen of FIG. 12, the display unit makes a display prompting to delete the measurement result from the target for graph creation. At this time, when the operator performs an operation (selection) to delete from the graph, the graph creation unit 120c deletes the designated measurement result and creates a graph using only the measurement results of other mixed plasmas. Thereby, even if an error or the like occurs in the measurement results of some mixed plasmas, the operator can make a judgment by the crossmixing test.

[0058] Also, if the mixed plasma prepared by the automatic analyzer 100 contains one for which the clotting time cannot be calculated, the graph creation unit 120c may create a graph using the clotting time calculated for the mixed plasma prepared outside the automatic analyzer 100.

[0059] FIG. 13 is an example of a selection screen for measurement results used for graph creation. The example of FIG. 13 shows the case where APTT is selected as the test item. In addition to APTT, other test items such as PT (prothrombin time), dPT (diluted PT), dAPTT (diluted APTT), KCT (kaolin clotting time), and dRVVT (diluted Russell viper venom time) can also be selected. All the measurement results regarding APTT are displayed in the left column, and for each measurement result, in addition to the clotting time, specimen ID, date and time, comment (1) and comment (2) are also displayed. Comment (1) includes information such as whether the measurement was made using mixed plasma automatically prepared in the automatic analyzer 100 or manually prepared outside the automatic analyzer 100. On the other hand, comment (2) includes information such as the ratio of the test plasma and whether it is immediate type or delayed type. Note that comment (1) and comment (2) may be input by the operator using the input unit, or may be automatically input by the analysis operation control unit 120a.

[0060] Also, when the operator taps the right arrow button while selecting the desired measurement result in the left column, the said measurement result is added to the upper right column or the lower right column as the measurement result used for graph creation. The immediate-type measurement results are displayed in the upper right column, and the delayed-type measurement results are displayed in the lower right column.

[0061] Therefore, if an error is included in a part of the measurement results using the mixed plasma prepared in the automatic analyzer 100, it is possible to replace it with the measurement results using the mixed plasma prepared outside the automatic analyzer 100 and create a graph. For example, after an error occurs in the measurement results of a predetermined test plasma ratio automatically prepared for the immediate type, the operator manually prepares the mixed plasma of the test plasma ratio targeted by the error. And if the coagulation time calculation unit 120b can measure the coagulation time using the prepared specimen, the measurement results are displayed in the left column of the selection screen shown in FIG. 13, and as a result, even if an error occurs, it is possible to create a graph in a relatively short time.

[0062] However, if there is an error in a part of the delayed-type measurement results, since manual preparation requires incubation for a certain period of time, it takes a relatively long time to re-measure the coagulation time. Also, for example, when an error occurs in the coagulation time when the test plasma ratio is 100% exceeding a certain time, there is a possibility that an error will occur again even if the coagulation time is re-measured. In such a case, it is desirable to create a graph by estimating the coagulation time of the prepared specimen in which the error occurred. Note that even if there is an error in the delayed-type measurement results, the mixed plasma prepared manually may be used, or even if there is an error in the immediate-type measurement results, the coagulation time may be estimated.

[0063] Therefore, when there is a prepared specimen for which the coagulation time cannot be calculated due to an error, the coagulation time calculation unit 120b in this embodiment estimates the coagulation time. Hereinafter, the method for estimating the coagulation time by the coagulation time calculation unit 120b will be described. In this embodiment, it is targeted at an error where the light intensity is measured by the detection unit 113 but the coagulation time calculation unit 120b cannot calculate the coagulation time, and errors before the measurement of the light intensity, such as insufficient specimen or insufficient reagent, are not targeted.

[0064] FIG. 14 is a flowchart regarding the method for estimating the coagulation time by the coagulation time calculation unit 120b of Example 1. First, the coagulation time calculation unit 120b determines whether there is an error (step S1401). If there is an error, it determines whether the scattered light intensity of the prepared specimen targeted by the error has reached the coagulation reaction end level (step S1402).

[0065] In step S1402, when the scattered light intensity has not reached the coagulation reaction end level, that is, when there is a prepared specimen for which the measurement of the light intensity has ended before reaching the coagulation reaction end level, the coagulation time calculation unit 120b estimates the reference intensity difference of the prepared specimen using the reference intensity differences of other prepared specimens (step S1403).

[0066] Here, the method for estimating the reference intensity difference will be described. The amount of change in the light intensity from the start to the end of the coagulation reaction is correlated with the fibrinogen concentration. That is, when the ratio of the test plasma in the mixed plasma is on the horizontal axis and the reference intensity difference is on the vertical axis, a generally linear correlation is obtained. The coagulation time calculation unit 120b utilizes this property to obtain an approximate formula of a linear line, for example, using the least squares method, from the reference intensity difference data of other prepared specimens that are not targeted by the error. Furthermore, the coagulation time calculation unit 120b estimates the reference intensity difference of the prepared specimen targeted by the error using this approximate formula. Note that the other prepared specimens used for the estimation of the reference intensity are not limited by whether they are of the delayed type or the immediate type, or where the preparation was performed.

[0067] Next, the coagulation time calculation unit 120b estimates the light intensity at the coagulation reaction end level of the preparation specimen targeted for the error, using the reference intensity difference estimated in step S1403 (step S1404). Note that the light intensity at the coagulation reaction end level is obtained by the following (Equation 1).

[0068] [Number] Thereafter, the coagulation time calculation unit 120b determines whether a coagulation reaction curve until the light intensity exceeds a predetermined percentage from the coagulation reaction start level has been obtained, that is, whether there is a preparation specimen for which the measurement of the light intensity has ended before reaching a predetermined ratio with respect to the estimated reference intensity difference (step S1405). When a coagulation reaction curve until exceeding the predetermined percentage (P%) has been obtained, the coagulation time calculation unit 120b estimates the coagulation time from the time corresponding to the light intensity at the predetermined percentage (P%) obtained by the following (Equation 2) (step S1406).

[0069] [Number] The coagulation time estimated by the coagulation time calculation unit 120b is output to the display unit as a measurement result output screen (with error) as shown in FIG. 15 (step S1409). In the example of FIG. 15, since the measurement result of the delayed type with a test plasma ratio of 100% was an error, it has been replaced with the estimation result by the coagulation time calculation unit 120b. In this way, the coagulation time estimated due to the error is displayed separately (with the annotation of "recalculation" in the example of FIG. 15) from the coagulation time calculated without error, so that the operator can grasp the accuracy of the coagulation time and the reliability of the crossmixing test is enhanced.

[0070] On the other hand, in step S1405, when a coagulation reaction curve until exceeding the predetermined percentage has not been obtained, since it is impossible to estimate the coagulation time by the percentile method, the coagulation time calculation unit 120b attempts to estimate the coagulation time by a method using the differential value of the scattered light amount.

[0071] Here, a method of using the differential value of the scattered light amount will be specifically described. Similar to the aforementioned percentile method, the coagulation time calculation unit 120b generates a coagulation reaction curve showing the change in scattered light intensity over time based on the measurement data by the detection unit 113. Then, the coagulation time calculation unit 120b sets the coagulation time as the time until the time when the first derivative value of the scattered light intensity peaks. In this embodiment, this method is called the first derivative method. Compared with the percentile method, although the calculation accuracy of the coagulation time decreases with this method, it has the advantage that the coagulation time can be calculated even when the coagulation reaction end level is unknown.

[0072] The coagulation time calculation unit 120b in this embodiment first attempts to calculate and estimate the coagulation time by preferentially using the percentile method, and when it is impossible to estimate by the percentile method, it estimates the coagulation time using the first derivative method. However, the first derivative method may also be preferentially used. In this specification, the case where the light intensity reaches the coagulation reaction end level and the coagulation time calculation unit 120b calculates a highly accurate coagulation time by the percentile method may be referred to as "(calculation of) the coagulation time". On the other hand, the case where the light intensity does not reach the coagulation reaction end level and the coagulation time calculation unit 120b calculates the coagulation time by the first derivative method, or as described later, the case where the coagulation time calculation unit 120b calculates a virtual coagulation time using the measurement results of other prepared specimens that have reached the coagulation reaction end level may be referred to as "(estimation of) the coagulation time".

[0073] Returning to the description of FIG. 14, based on the first derivative method, the coagulation time calculation unit 120b sets the coagulation reaction rate, which is the first derivative of the coagulation reaction curve, as A i and determines whether there is a measurement timing i at which A i > A i+1 after the coagulation reaction start level (step S1407). If there is no measurement timing i that satisfies this condition, that is, if there is no peak in the first derivative value of the light intensity, it is impossible to estimate the coagulation time by the first derivative method, so an error is output to the display unit.

[0074] In step S1407, when there exists a measurement timing i that satisfies the conditions, that is, when there exists a peak in the first derivative value of the light intensity, the coagulation time calculation unit 120b estimates the time until the first derivative value of the light intensity becomes a peak as the coagulation time (step S1408). The coagulation time estimated in step S1408 is output to the display unit (step S1409). Note that since the first derivative method and the percentile method are fundamentally different in the calculation method, when using the first derivative method, it is necessary to estimate the coagulation time using the first derivative method for all the prepared specimens used in the crossmixing test.

[0075] According to this embodiment, when an error occurs in some of the measurement results, it may be possible to make a determination by the crossmixing test without re-preparing the specimen or re-measuring the light intensity. If re-preparation of the specimen becomes unnecessary, plasma volume can be saved, which also leads to a reduction in the patient's burden due to re-blood collection. If re-measurement of the light intensity becomes unnecessary, it leads to a shortening of the time required for the crossmixing test. Also, in this embodiment, even when it is impossible to estimate the coagulation time by the percentile method, the coagulation time is estimated by the first derivative method, so the possibility of performing the crossmixing test is further increased. Note that when the estimated coagulation time is output, it is desirable to clarify whether the estimation method is the percentile method or the first derivative method.

[0076] Furthermore, the coagulation time calculation unit 120b of this embodiment first attempts to calculate and estimate the coagulation time by preferentially using the percentile method, and when it is impossible to estimate by the percentile method, estimates the coagulation time using the first derivative method. However, as shown in FIG. 15, as the calculation method of the coagulation time by the coagulation time calculation unit 120b, a display prompting a switch to the percentile method or the first derivative method may be provided, and the calculation method may be switched by the operation of the operator.

Example

[0077] In Example 2, a part of the method for estimating the coagulation time by the coagulation time calculation unit 120b is different from that in Example 1. In Example 1, when there was a prepared specimen for which the measurement of the light intensity was completed before reaching the coagulation reaction end level, the reference intensity difference of the prepared specimen was estimated by using the reference intensity differences of other prepared specimens, thereby estimating the coagulation time of the prepared specimen. However, in Example 2, the coagulation time of the prepared specimen is estimated by estimating the coagulation reaction curve by using the second derivative value of the light intensity measured by the detection unit 113.

[0078] FIG. 16 is a second derivative curve of general APTT measurement results. In this example, since the second derivative value of the scattered light intensity is used for determining the plateau of the coagulation reaction curve, the coagulation reaction start point and the coagulation reaction end point can be regarded as the points when the second derivative value of the scattered light intensity becomes substantially zero. Also, the second derivative curve takes a minimum value after the peak value, and the time from the start of the coagulation reaction until this minimum value is reached is defined as T min .

[0079] FIG. 17 is a flowchart regarding the method for estimating the coagulation time by the coagulation time calculation unit 120b in Example 2. First, the coagulation time calculation unit 120b determines whether there is an error (step S1701). If there is an error, it is determined whether T min exists in the measurement result of the prepared specimen that is the error target (step S1702).

[0080] In step S1702, if it is determined that T min exists, the coagulation time calculation unit 120b estimates the second derivative curve (step S1703).

[0081] Here, the method for estimating the second derivative curve will be described. For example, in a specimen with a test plasma ratio of 100% and an extremely long coagulation time, the measurement may end without reaching a plateau after T min . In this case, the coagulation time calculation unit 120b calculates the second derivative curve after T min and the point (t, y) = (T minAn estimated curve is created by fitting the logistic curve of the following (Equation 3) to +600,0).

[0082] [Number] In (Equation 3), t represents time, y represents the second derivative value, and a, b, and c are parameters. The solidification time calculation unit 120b calculates the values of the parameters in the approximation function so that the difference between the approximation curve of the time-second derivative value represented by the approximation function of (Equation 3) and the second derivative value becomes as small as possible. For example, using regression analysis, the values of the parameters are obtained so that the squared error between the time-series light intensity data and the light intensity calculated by the approximation function becomes as small as possible.

[0083] When the second derivative curve is estimated in step S1703, the solidification time calculation unit 120b obtains the time until the estimated curve reaches the plateau, and sets the obtained time as the reaction end time (step S1704).

[0084] Next, the solidification time calculation unit 120b restores the first derivative value every 0.1 seconds starting from the measurement end time using the following (Equation 4) (step S1705).

[0085] [Number] Note that in (Equation 4), F is the first-order partial value. The solidification time calculation unit 120b completes the restoration when the first derivative value is restored until the reaction end time.

[0086] Furthermore, the solidification time calculation unit 120b restores the solidification reaction curve from the first derivative value in the same manner (step S1706).

[0087] Thereafter, the solidification time calculation unit 120b estimates the solidification time by the percentile method described in Example 1 based on the solidification reaction curve restored in step S1706 (step S1707). Thereafter, it is the same as in Example 1.

[0088] On the other hand, in step S1702, when it is determined that T min does not exist, the solidification time calculation unit 120b attempts to estimate the solidification time by the first derivative method. Thereafter, it is the same as in the first embodiment.

[0089] According to this embodiment, the same effects as those of the first embodiment can be obtained. Further, the estimation of the solidification time based on the estimated curve of the second derivative curve of this embodiment can also be used for analyses other than the crossmixing test.

Example

[0090] In the third embodiment, the specimens to be subjected to the crossmixing test are managed by test IDs. Since the configuration of the automatic analyzer and the processes related to the calculation of the solidification time in the third embodiment are the same as those in the first embodiment, the differences from the first embodiment will be described below. Also, the method for estimating the solidification time may be the same as that in the first or second embodiment.

[0091] FIG. 18 is an example of the mixed plasma adjustment setting screen in the third embodiment. As shown in FIG. 18, in this embodiment, the mixed plasma adjustment setting screen has a test ID input field. By the operator inputting a test ID for identifying the specimen to be subjected to the crossmixing test, it becomes possible to manage the measurement results for each of the immediate-type and delayed-type plasma ratios output thereafter with one test ID. Here, the test ID may be any character string. Also, when a barcode, RFID, etc. is attached to the test plasma, instead of the method of inputting the test ID from the operation screen, it can also be recognized by reading the request information from the host with a reading unit such as a handy barcode reader or the RFID reader of the automatic analyzer 100.

[0092] The method of associating the test ID with the measurement result will be described. In FIG. 18, by setting the installation positions of the specimen container 103a filled with normal plasma, the installation position of the specimen container 103b filled with the test plasma, and the installation positions of the empty specimen containers 103c to 103g in which mixed plasma of respective ratios is created, the test ID is associated with the measurement result. When associating by the installation position of the specimen container, at the time of delayed measurement, the mixed plasma after incubation is reinstalled at the set installation position. Alternatively, by setting the installation position again at the time of delayed measurement, it is possible to change the installation position of the mixed plasma at the time of delayed measurement. Also, if the test ID can be associated with the measurement result, a method other than setting the installation position may be used. In addition, a unique barcode including information such as the mixed plasma ratio of the target test plasma and the classification of immediate type / delayed type is attached to each of the containers storing the mixed plasma and read by an automatic analyzer, or the test ID attached to the test plasma is read, and a continuous set of specimens is identified as mixed plasma. The method for preparing the mixed plasma in this embodiment is the same as the adjustment method in Embodiment 1 shown in FIG. 3.

[0093] Next, the graph creation process in this embodiment will be described. FIG. 19 is a flowchart showing the method of measuring the prepared specimen and creating a graph. First, when the preparation of the mixed plasma is completed (step S1901), the analysis operation control unit 120a creates requests for the immediate type and the delayed type (step S1902), and on the screen shown in FIG. 10, the operator determines whether to continue the immediate type measurement (step S1903). The measurement unit measures the specimens of each mixing ratio, and based on the measurement results, the coagulation time calculation unit 120b calculates the coagulation time of each mixed plasma (step S1904).

[0094] FIG. 20 is an example of a selection screen for measurement results in Example 3. In this example, when the operator selects a test ID for which the operator wants to create a graph from the list of measurement results shown in FIG. 20, the measurement results associated with the test ID are automatically displayed in the left column, the upper right column, and / or the lower right column. All the measurement results associated with the test ID are displayed in the left column, the measurement results related to the immediate type are displayed in the upper right column, and the measurement results related to the delayed type are displayed in the lower right column. Since only the immediate type of measurement is completed by step S1904, the measurement results of the immediate type are automatically displayed in the left column and the upper right column. When the operator taps the graph creation button to instruct graph creation (S1905), the graph creation unit 120c creates an immediate type graph using the measurement results displayed in the upper right column (S1906), and the graph is displayed on the display unit. The operator checks the immediate type graph (step S1907). In Example 1, the measurement results used for graph creation were manually added to the upper right column and / or the lower right column. In this example, the specimen measurement results to be subjected to the crossmixing test are managed for one test ID, and when the test ID is selected, the measurement results associated with the test ID can be automatically selected, reducing the operator's effort during graph creation.

[0095] When continuing with the delayed type of measurement, the operator closes the plasma containers at each mixing ratio after the immediate type of measurement and incubates them, for example, at 37° C. for 2 hours (step S1908). In this example, although the mixed plasma for the delayed type of measurement is described as being incubated outside the automatic analyzer 100, it is not limited to this example. The specimen incubated outside the automatic analyzer 100 is placed on the specimen disk 102 by the operator (step S1909). When associating the test ID and the measurement results at the installation position of the specimen container 103 on the mixed plasma adjustment setting screen of FIG. 18 as described above, the operator places the incubated specimen at the position set on the mixed plasma adjustment setting screen. Here, when it is desired to change the installation position, it is possible to change the position from the operation screen.

[0096] After that, the operator uses the input unit to instruct a delayed measurement. On the measurement instruction screen (not shown), the installation position of the specimen container filled with mixed plasma can be set. If the operator wants to change the installation position of the specimen container during the delayed measurement, the operator sets the installation position again in this step (step S1910). The measurement unit measures the plasma of each mixing ratio, and based on the measurement results, the coagulation time calculation unit 120b calculates the coagulation time of each mixed plasma (step S1911). When the operator selects a test ID for which the operator wants to create a graph from the list of measurement results shown in FIG. 20, the measurement results associated with the test ID are automatically displayed in the left column, upper right column, and / or lower right column. Here, since the immediate and delayed measurements are completed, the immediate and delayed measurement results are automatically displayed in the left column, the immediate measurement results are displayed in the upper right column, and the delayed measurement results are displayed in the lower right column. When the operator taps the graph creation button to instruct graph creation (step 1912), the graph creation unit 120c creates an immediate and a delayed graph based on the coagulation time of each mixed plasma calculated by the coagulation time calculation unit 120b (step S1913). The immediate and delayed graphs created by the graph creation unit 120c are output on one screen to the display unit, and the operator checks the graph (step S1914).

[0097] In this embodiment, the case of associating the test ID with the measurement results according to the installation position has been described in detail as an example, but the method is not limited thereto. As other methods, for each container storing the mixed plasma, a unique barcode including information such as the mixing plasma ratio of the target test plasma and the classification of immediate / delayed types is attached and read by the device, or when the test ID attached to the test plasma is read and the subsequent specimen set is identified as the mixed plasma, if it is installed at an arbitrary position, the device can read the individual identification number and automatically recognize it.

[0098] Also, in this embodiment, the example of associating the test ID with the immediate and delayed measurement results has been described in detail. However, when performing either the immediate or delayed measurement and graph creation, the test ID may be input and the measurement results may be associated with the test ID. In this case as well, it is possible to reduce the labor of graph creation.

[0099] When the measurement results displayed on the list screen of the measurement results shown in FIG. 20 include error measurement results, the coagulation time estimation method described in Example 1 or Example 2 may be used. Alternatively, the error measurement results may be deleted from the list screen, and a graph may be created using the measurement results excluding the error measurement results, or a graph may be created using the coagulation time calculated for the mixed plasma prepared outside the automatic analyzer 100.

Example

[0100] Example 4 enables selection of whether to continuously measure from the preparation to the measurement of the mixed plasma. FIG. 21 is an example of a selection screen in Example 4. On the screen shown in FIG. 21, before performing the preparation of the mixed plasma used in the crossmixing test, the measurement of the prepared specimen, and the graph creation, the operator selects one from (1) only the mixed plasma preparation, (2) only the measurement (using the prepared specimen), and (3) the mixed plasma preparation + measurement. When (1) only the mixed plasma preparation is selected and executed, the preparation of the mixed plasma is performed as shown in the flowchart of FIG. 3 in Example 1, and the operation is completed without performing the measurement of the prepared specimen or the graph creation. When (2) only the measurement (using the prepared specimen) is selected and executed, the measurement of the prepared specimen and the graph creation are performed as shown in the flowchart of FIG. 9 in Example 1 or FIG. 19 in Example 3 without performing the preparation of the mixed plasma. By providing a selection screen as shown in FIG. 21, it becomes possible to analyze the mixed plasma adjusted outside the automatic analyzer 100.

[0101] (3) When "Mixing Plasma Preparation + Measurement" is selected and executed, the system transitions to the mixing plasma adjustment setting screen in FIG. 4 of Example 1 or FIG. 18 of Example 3, and the preparation of the mixing plasma is executed as shown in the flowchart of FIG. 3 in Example 1. Then, the measurement of the prepared sample and the graph creation are executed. In this example, since it is possible to give an instruction in advance to perform the measurement up to the selection screen as shown in FIG. 21, the immediate-type instruction request in step S902 and the delayed-type instruction request in step S908 in Example 1, the immediate-type measurement instruction in step S1903 and the delayed-type instruction request in step S1910 in Example 2 can be omitted, and the work of the operator can be reduced. This example is basically the same as the aforementioned Example 1 in other respects and is also applicable to Example 3. Also, regarding the method for estimating the coagulation time in this example, the method described in Example 2 may be applied.

Explanation of Reference Numerals

[0102] 100…Automatic analyzer, 101…Sample dispensing mechanism, 101a…Sample dispensing probe, 102…Sample disk, 103…Sample container, 104…Reaction vessel, 105…Sample syringe pump, 106…Reagent dispensing mechanism, 106a…Reagent dispensing probe, 107…Reagent disk, 108…Reagent container, 109…Reagent heating mechanism, 110…Reagent syringe pump, 111…Reaction vessel stock section, 112…Reaction vessel transfer mechanism, 113…Detection unit, 114…Reaction vessel installation section, 115…Light source, 116…Light receiving section, 117…Reaction vessel disposal section, 118…Input / output section, 118a…Mouse, 118b…Keyboard, 118c…Display, 119…Storage section, 120…Control section, 120a…Analysis operation control section, 120b…Coagulation time calculation section, 120c…Graph creation section, 121…A / D converter, 122…Interface, 123…Printer, 124…Incubator

Claims

1. Dispensing a plurality of empty specimen containers with the test plasma and / or normal plasma added to correct the clotting time of the test plasma, and dispensing a prepared specimen containing only the test plasma, only the normal plasma, or a mixed plasma in which the test plasma and the normal plasma are mixed, from the specimen container to a reaction container; a specimen dispensing mechanism, A reagent dispensing mechanism for dispensing a reagent into the reaction container; A measuring unit that irradiates the prepared specimen with the reagent added in the reaction container with light from a light source and measures the light intensity of the scattered light or transmitted light obtained; An analysis operation control unit that controls the operations of the specimen dispensing mechanism, the reagent dispensing mechanism, and the measuring unit; A clotting time calculation unit that calculates the clotting time based on the light intensity measured by the measuring unit; A graph creation unit that creates a graph regarding the clotting time of each prepared specimen calculated by the clotting time calculation unit; In an automatic analyzer comprising a display unit that displays the graph created by the graph creation unit, When there is a prepared specimen for which the clotting time cannot be calculated, the graph creation unit, An automatic analyzer characterized in that a graph is created using at least one of the clotting time calculated by the clotting time calculation unit for a prepared specimen prepared outside the automatic analyzer and the clotting time estimated by the clotting time calculation unit based on the light intensity measured by the measuring unit.

2. In the automatic analyzer according to Claim 1, The display unit makes a display prompting deletion of the prepared specimen for which the clotting time could not be calculated from the graph creation target by the graph creation unit, When deletion is selected, the graph creation unit creates a graph using only the prepared specimens for which the clotting time could be calculated. An automatic analyzer characterized by this.

3. In the automatic analyzer according to Claim 1, The clotting time calculation unit calculates a reference intensity difference, which is the intensity difference between the light intensity at the start level of the clotting reaction and the light intensity at the end level of the clotting reaction, and calculates the time until the intensity difference from the start level of the clotting reaction reaches a predetermined ratio with respect to the reference intensity difference as the clotting time. When there is a prepared specimen for which the measurement of the light intensity has ended before reaching the end level of the clotting reaction, The clotting time calculation unit estimates the clotting time of the prepared specimen by estimating the reference intensity difference of the prepared specimen using the reference intensity differences of other prepared specimens. ​ The graph creation unit creates a graph using, for the prepared specimen, the estimated coagulation time, and for other prepared specimens, the calculated coagulation time, respectively. An automatic analyzer characterized by this.

4. In the automatic analyzer according to claim 3, the display unit displays the estimated coagulation time separately from the calculated coagulation time. An automatic analyzer characterized by this.

5. In the automatic analyzer according to claim 3, the coagulation reaction start level and the coagulation reaction end level are determined based on the second derivative value of the light intensity. An automatic analyzer characterized by this.

6. In the automatic analyzer according to claim 3, when there is a prepared specimen for which the measurement of the light intensity was ended before reaching the predetermined ratio with respect to the estimated reference intensity difference, the coagulation time calculation unit estimates, as the coagulation time, the time until the first derivative value of the light intensity peaks after the coagulation reaction start level, the graph creation unit creates a graph using the estimated coagulation time for all prepared specimens. An automatic analyzer characterized by this.

7. In the automatic analyzer according to claim 1, the display unit displays a prompt for switching at least to the percentile method or the first derivative method as the method for calculating the coagulation time by the coagulation time calculation unit, when the percentile method is selected, the coagulation time calculation unit calculates a reference intensity difference, which is the intensity difference between the light intensity at the coagulation reaction start level and the light intensity at the coagulation reaction end level, and calculates, as the coagulation time, the time until the intensity difference from the coagulation reaction start level reaches a predetermined ratio with respect to the reference intensity difference, when the first derivative method is selected, the coagulation time calculation unit calculates, as the coagulation time, the time until the first derivative value of the light intensity peaks after the coagulation reaction start level. An automatic analyzer characterized by this.

8. In the automatic analyzer according to claim 1, the coagulation time calculation unit calculates a reference intensity difference, which is the intensity difference between the light intensity at the coagulation reaction start level and the light intensity at the coagulation reaction end level, and calculates, as the coagulation time, the time until the intensity difference from the coagulation reaction start level reaches a predetermined ratio with respect to the reference intensity difference, when there is a prepared specimen for which the coagulation time cannot be calculated, the coagulation time calculation unit estimates the coagulation time of the prepared specimen by estimating the coagulation reaction curve using the second derivative value of the light intensity measured by the measurement unit. The graph creation unit creates a graph using the estimated coagulation time for the prepared specimen and the calculated coagulation time for other prepared specimens, respectively, in an automatic analyzer.

9. In the automatic analyzer according to claim 8, when the coagulation time calculation unit cannot estimate the coagulation reaction curve, it estimates the time until the first derivative value of the light intensity peaks after the coagulation reaction start level as the coagulation time, and the graph creation unit creates a graph using the estimated coagulation time for all prepared specimens, in an automatic analyzer.

10. In the automatic analyzer according to claim 1, when there is a prepared specimen for which the coagulation time cannot be calculated, the graph creation unit creates a graph using the coagulation time estimated by the coagulation time calculation unit, in an automatic analyzer.

11. In the automatic analyzer according to claim 1, the coagulation time of each prepared specimen used for creating the graph is managed by one test ID, in an automatic analyzer.

12. An automatic analysis method using an automatic analyzer having a specimen dispensing mechanism, a reagent dispensing mechanism, a measurement unit, a coagulation time calculation unit, a graph creation unit, and a display unit, wherein the specimen dispensing mechanism dispenses the test plasma and / or normal plasma added to correct the coagulation time of the test plasma into a plurality of empty specimen containers, and dispenses a prepared specimen containing only the test plasma, only the normal plasma, or a mixed plasma in which the test plasma and the normal plasma are mixed from the specimen container into a reaction container; the reagent dispensing mechanism dispenses a reagent into the reaction container; the measurement unit irradiates the prepared specimen with the reagent added in the reaction container with light from a light source and measures the light intensity of the scattered light or transmitted light obtained; the coagulation time calculation unit calculates the coagulation time based on the light intensity measured by the measurement unit; the graph creation unit creates a graph regarding the coagulation time of each prepared specimen calculated by the coagulation time calculation unit; and the display unit displays the graph created by the graph creation unit, and includes when there is a prepared specimen for which the coagulation time cannot be calculated, The step of the graph creation unit creating a graph using at least one of the coagulation time calculated for a prepared specimen prepared outside the automatic analyzer and the coagulation time estimated by the coagulation time calculation unit based on the light intensity measured using another prepared specimen. An automatic analysis method characterized by further comprising this.

13. In the automatic analysis method according to claim 12, The step of the display unit making a display prompting deletion of a prepared specimen for which the coagulation time could not be calculated from the objects for which the graph creation unit creates a graph; The step of, when deletion is selected, the graph creation unit creating a graph using only the prepared specimens for which the coagulation time could be calculated. An automatic analysis method characterized by further comprising this.

14. In the automatic analysis method according to claim 12, The coagulation time calculation unit calculates a reference intensity difference that is the intensity difference between the light intensity at the start level of the coagulation reaction and the light intensity at the end level of the coagulation reaction, and calculates the time until the intensity difference from the start level of the coagulation reaction reaches a predetermined ratio with respect to the reference intensity difference as the coagulation time. When there is a prepared specimen for which the measurement of the light intensity ended before reaching the end level of the coagulation reaction, The step of the coagulation time calculation unit estimating the coagulation time of the prepared specimen by estimating the reference intensity difference of the prepared specimen using the reference intensity differences of other prepared specimens; The step of the graph creation unit creating a graph using the estimated coagulation time for the prepared specimen and the calculated coagulation time for other prepared specimens, respectively. An automatic analysis method characterized by further comprising this.

15. In the automatic analysis method according to claim 12, The step of the display unit making a display prompting switching to at least the percentile method or the first derivative method as the method for calculating the coagulation time by the coagulation time calculation unit; When the percentile method is selected, the coagulation time calculation unit calculates a reference intensity difference that is the intensity difference between the light intensity at the start level of the coagulation reaction and the light intensity at the end level of the coagulation reaction, and calculates the time until the intensity difference from the start level of the coagulation reaction reaches a predetermined ratio with respect to the reference intensity difference as the coagulation time. When the first derivative method is selected, the solidification time calculation unit further includes a step of calculating, as the solidification time, the time until the first derivative value of the light intensity reaches a peak after the solidification reaction start level. An automatic analysis method characterized by this.

16. In the automatic analysis method according to claim 12, The solidification time calculation unit calculates a reference intensity difference, which is the intensity difference between the light intensity at the solidification reaction start level and the light intensity at the solidification reaction end level, and calculates, as the solidification time, the time until the intensity difference from the solidification reaction start level reaches a predetermined ratio with respect to the reference intensity difference. When there is a prepared specimen for which the solidification time cannot be calculated, The solidification time calculation unit estimates the solidification time of the prepared specimen by estimating the solidification reaction curve using the second derivative value of the light intensity measured by the measurement unit. The graph creation unit further includes a step of creating a graph using the estimated solidification time for the prepared specimen and the calculated solidification time for other prepared specimens, respectively. An automatic analysis method characterized by this.

17. In the automatic analysis method according to claim 12, An automatic analysis method characterized in that the solidification time of each prepared specimen used for graph creation is managed by one test ID.

Images