Automatic analysis device and anomaly detection method

Abstract

The present disclosure proposes a technique for an operation that facilitates an operator's investigation of the cause of an abnormal situation. For example, an automatic analysis device is disclosed, which includes: a reagent dispensing unit that aspirates a reagent from a reagent container storing the reagent and discharges the reagent into a reaction container storing a reaction solution containing a sample; a storage unit that stores concentration correlation information associated with the type of the sample and the concentration of a measurement target component contained in the sample determined according to the type of the sample; a detection unit that detects the concentration of the measurement target component contained in the reaction solution, i.e., the measurement concentration; and a determination unit that determines whether an abnormality has occurred in the reagent container based on the concentration correlation information and the measurement concentration.

Description

Technical Field

[0001] The present invention relates to an automatic analysis device and an abnormality detection method. Background Art

[0002] In an automatic analysis device for analyzing biological samples such as blood and urine, analysis is performed using different reagents for each analysis item. These reagents are stored in reagent containers in a certain amount according to the type of reagent, and are usually mounted in a reagent storage of the automatic analysis device.

[0003] In an automatic analysis device, accuracy management is performed to confirm that the analysis performance of the device is normal. In accuracy management, a calibration substance (control sample) is measured at regular time intervals or at intervals of a certain number of samples during the measurement of patient samples, and it is studied whether the measurement results are within the management range associated with the control sample, or the within-day variation or day-to-day variation, to determine whether the precision is within the range.

[0004] When the measurement result of the accuracy management is outside the range, the operator investigates the cause based on the state of the automatic analysis device, the reagent, and the sample. There are various causes such as contamination of the automatic analysis device, bubbles in the reagent container, and bubbles in the sample. When the operator determines that there is some problem with the reagent container, it is necessary to remove the reagent container from the automatic analysis device and check the container.

[0005] As a technique for detecting the cause of some problems occurring in a reagent container, for example, there is bubble detection in the reagent container. As a technique for detecting bubbles in the reagent container, there is a method of detecting bubbles based on the change in the liquid level height (for example, refer to Patent Document 1). In addition, there are also a method of detecting bubbles based on the movement amount during dispensing by a reagent probe, a method of recording the change in the liquid level height from the first dispensing (for the latter, for example, refer to Patent Document 2), and the like.

[0006] Prior Art Documents

[0007] Patent Documents

[0008] Patent Document 1: Japanese Patent Application Laid-Open No. 2007-303937

[0009] Patent Document 2: Japanese Patent Application Laid-Open No. 2004-170279 Summary of the Invention

[0010] Problems to be Solved by the Invention

[0011] When a problem occurs in precision management, it is necessary to detect whether there is a problem with the reagent (for example, generation of bubbles, reagent deterioration, etc.), and discharge the reagent container. Thus, it is easy for the operator to conduct a cause investigation operation. In addition, it is necessary to prevent deterioration caused by temperature changes of the reagent discharged due to bubble detection.

[0012] However, in the above method of detecting bubbles based on the liquid level height at the time of dispensing, when bubbles in the reagent container continuously remain since the previous dispensing, the liquid level height does not change, so bubbles may not be detected. Therefore, it is necessary to confirm the bubble risk even after dispensing and eliminate the reagent with a risk.

[0013] In view of such a situation, the present disclosure proposes a technique that facilitates the operator's operation of investigating the cause of a malfunction.

[0014] Means for Solving the Problem

[0015] To solve the above problem, the present disclosure provides an automatic analysis device including: a reagent dispensing unit that aspirates a reagent from a reagent container storing the reagent and discharges the reagent into a reaction container storing a reaction solution containing a sample; a storage unit that stores concentration correlation information associated with the type of the sample and the concentration of a measurement target component contained in the sample determined according to the type of the sample; a detection unit that detects the concentration of the measurement target component contained in the reaction solution, that is, the measurement concentration; and a determination unit that determines whether an abnormality has occurred in the reagent container based on the concentration correlation information and the measurement concentration.

[0016] According to the description and drawings of the present specification, other features associated with the present disclosure become clear. In addition, the embodiments of the present disclosure are achieved by combinations of elements and multiple elements, and by the following detailed description and the appended claims.

[0017] It should be understood that the description in this specification is merely a typical example and does not limit the claims or application examples in any sense.

[0018] Effects of the Invention

[0019] According to the technique of the present disclosure, it is easy for the operator to conduct an operation of investigating the cause of a malfunction in the automatic analysis device. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 is a block diagram showing the overall configuration of the automatic analysis device.

[0021] Figure 2 is a diagram showing an example of the configuration of the analysis module.

[0022] Figure 3 is a diagram showing an example of the configuration of the moving unit in the analysis module.

[0023] Figure 4 is a diagram showing a structural example of a measurement concentration data table that represents the measurement concentration obtained from the measurement unit.

[0024] Figure 5 is a diagram showing a structural example of a control sample allocation data table that stores information allocated to each control sample.

[0025] Figure 6 is a diagram showing a structural example of a warning data table that stores various warnings of the device detected by the abnormality detection unit or a bubble generation warning detected by the judgment unit.

[0026] Figure 7 is a flowchart for explaining the details of the accuracy management process of the analysis module performed by the judgment unit.

[0027] Figure 8 is shown in Figure 7 a diagram showing a structural example of a screen that represents the range of the measurement results confirmed in step 702.

[0028] Figure 9 is a diagram showing a structural example of a reagent discharge setting screen 900 for setting whether to automatically discharge the bubbles in the reagent container when it is determined that "bubbles are generated" in the target reagent container.

[0029] Figure 10 is a diagram showing a structural example of a reagent discharge selection screen 1000 for asking the operator whether to discharge the bubbles in the reagent container determined to have "bubbles generated".

[0030] Figure 11 is a diagram showing a structural example of a reagent container internal cause threshold table 1100 that stores reagent deterioration thresholds and bubble presence thresholds for groups allocated to each control sample and measurement item.

[0031] Figure 12 is a flowchart for explaining the details of the process of determining whether the abnormality in the reagent container determined to be abnormal is caused by bubbles in the reagent container or by reagent deterioration.

[0032] Figure 13 is a diagram showing a structural example of a reagent container internal liquid level table 1300 that maintains the liquid level height in each reagent container.

[0033] Figure 14 is a flowchart for explaining the process that combines a structure for detecting bubbles based on changes in the reagent liquid level and a structure for judging reagent deterioration based on the reagent deterioration threshold. Detailed implementation mode

[0034] Hereinafter, embodiments of the present disclosure will be described with reference to the accompanying drawings. In the drawings, functionally identical elements may sometimes be denoted by the same reference numerals. In addition, the drawings illustrate specific embodiments and installation examples that follow the principles of the present disclosure, but these are for understanding the present disclosure and are not used to limitatively interpret the present disclosure.

[0035] In the present embodiment, those skilled in the art have described it in sufficient detail for implementing the present disclosure. However, it should be understood that other installations and forms are also possible, and structural and constructional changes and replacement of various elements can be made without departing from the scope and spirit of the technical idea of the present disclosure. Therefore, the following description should not be construed as being limited thereto.

[0036] Moreover, the embodiments of the present disclosure can be implemented either by software running on a general-purpose computer or by dedicated hardware or a combination of software and hardware.

[0037] In addition, in the following description, the various information of the present disclosure is described in the form of "tables", but these information may not necessarily be represented by a data structure based on a table, and may also be represented by data structures such as lists, databases (DBs), queues, or others. Therefore, in order to indicate independence from the data structure, "tables", "lists", "DBs", "queues", etc. are sometimes simply referred to as "information".

[0038] <Overall structural example of the automatic analysis device>

[0039] Figure 1 It is a system block diagram showing an overall structural example of the automatic analysis device 1.

[0040] The automatic analysis device 1 includes an overall management computer 10 and an analysis module 20. The overall management computer 10 includes the structural elements of a general computer, for example, having: a processor, a memory, a storage device, a communication device, a display device (display unit), and an input device, etc. For example, Figure 1 the determination unit 11 in [] is constituted by a processor, and the storage unit 12 is constituted by a memory and a storage device. In addition, the determination unit 11 determines the possibility of bubble generation, and the storage unit 12 stores information related to the measurement concentration obtained from the analysis module 20 (the content of the table described later in Figures 4 to 6 .

[0041] The analysis module 20 includes: a detection unit 21 for detecting the measurement concentration, a moving unit 22 for moving the reagent container, a reagent dispensing unit 23 for sucking the reagent stored in the reagent container and discharging the reagent into a reaction container for generating a reaction solution composed of the reagent and the sample, and an abnormality detection unit 24 for detecting an abnormality of the analysis module. The abnormality detection unit 24 is provided, for example, inside the analysis module 20 and includes a sample bubble detection camera 218 (refer toFigure 2 ), in addition, it is composed of various sensors that can be actuated by the detection mechanism, various abnormalities in the detection information processing, and various software for abnormalities in the analysis results.

[0042] <Example of the structure of the analysis module>

[0043] Figure 2 It is a diagram showing an overall structural example of the analysis module 20. The analysis module 20 includes: a transport rack 201, a sample dispensing nozzle 203, an incubator (reaction plate) 204, a sample dispensing pipette and a reaction vessel transport mechanism 206, a sample dispensing pipette and a reaction vessel holding member 207, a reaction vessel stirring mechanism 208, a sample dispensing pipette and a reaction vessel waste hole 209, a rack transport line 216, a reagent tray 211, a reagent tray cover 212, a reagent dispensing nozzle 213, a reaction solution suction nozzle 214, a detection unit 215, and a sample bubble detection camera 218.

[0044] A sample container 202 for holding a sample is installed on the transport rack 201 of the analysis module 20 and is moved to a sample dispensing position near the sample dispensing nozzle 203 through the rack transport line 216. Above the rack transport line 216, there is a sample bubble detection camera 218. The sample bubble detection camera 218 confirms whether there are bubbles in the sample, and in the case of having bubbles, it notifies the overall management computer 10 as an abnormality.

[0045] In the incubator 204, a plurality of reaction vessels 205 can be set, and a rotational movement for moving the reaction vessels 205 arranged in the circumferential direction to specified positions can be realized.

[0046] The sample dispensing pipette and the reaction vessel transport mechanism 206 can move in three directions of the X-axis, Y-axis, and Z-axis, and move within the ranges of the sample dispensing pipette and the reaction vessel holding member 207, the reaction vessel stirring mechanism 208, the sample dispensing pipette and the reaction vessel waste hole 209, the sample dispensing pipette installation position 210, and the specified parts of the incubator 204 to transport the sample dispensing pipette and the reaction vessel.

[0047] A plurality of unused reaction vessels and sample dispensing pipettes are provided in the sample dispensing pipette and the reaction vessel holding member 207. The sample dispensing pipette and the reaction vessel transport mechanism 206 moves above the sample dispensing pipette and the reaction vessel holding member 207, descends to hold the unused reaction vessel and then ascends, and then moves above the specified position of the incubator 204 and descends to set the reaction vessel.

[0048] Next, the sample dispensing pipette and the reaction vessel transport mechanism 206 move above the sample dispensing pipette and reaction vessel holding member 207, lower to hold an unused sample dispensing pipette, then rise, move above the sample dispensing pipette mounting position 210, and lower to set the sample dispensing pipette there.

[0049] The sample dispensing nozzle 203 can rotate and move up and down. After rotating and moving above the sample dispensing pipette mounting position 210, it lowers, presses the sample dispensing pipette into the end of the sample dispensing nozzle 203 and installs it. The sample dispensing nozzle 203 with the sample dispensing pipette installed moves above the sample container 202 placed on the transport rack 201 and then lowers to aspirate a specified amount of the sample held in the sample container 202. The sample dispensing nozzle 203 with the aspirated sample moves above the incubator 204 and then lowers to dispense the sample into an unused reaction vessel 205 held in the incubator 204. When the sample dispensing is completed, the sample dispensing nozzle 203 moves above the sample dispensing pipette and reaction vessel discard hole 209 and discards the used sample dispensing pipette through the discard hole.

[0050] A plurality of reagent containers 217 are provided in the reagent tray (reagent setting mechanism) 211. A reagent tray cover 212 is provided on the upper part of the reagent tray 211, and the inside of the reagent tray 211 is kept at a specified temperature. In addition, an opening (reagent tray cover opening) can be provided in a part of the reagent tray cover 212.

[0051] The reagent dispensing nozzle 213 can rotate and move up and down. After rotating and moving above the opening of the reagent tray cover 212, it lowers, immerses the end of the reagent dispensing nozzle 213 in the reagent in a specified reagent container, and aspirates a specified amount of the reagent. In order to reduce the amount of liquid adhering to the outer wall of the nozzle, the reagent dispensing nozzle 213 detects the liquid level in the reagent container, stops the lowering movement of the nozzle when the end of the nozzle reaches a position slightly below the liquid level, and aspirates a specified amount of the reagent. After the reagent dispensing nozzle 213 rises, it rotates and moves above a specified position of the incubator 204 and dispenses the reagent into the reaction vessel 205.

[0052] The reaction vessel 205 holding the dispensed sample and reagent is moved to a specified position by the rotation of the incubator 204 and transported to the reaction vessel stirring mechanism 208 by the sample dispensing pipette and reaction vessel transport mechanism 206. The reaction vessel stirring mechanism 208 stirs and mixes the sample and reagent in the reaction vessel by applying a rotational motion to the reaction vessel. The reaction vessel after stirring is returned to a specified position in the incubator 204 by the sample dispensing pipette and reaction vessel transport mechanism 206.

[0053] The reaction solution suction nozzle 214 can rotate and move up and down, dispense samples and reagents. After the stirring is completed, it moves above the reaction vessel 205 that has undergone a specified reaction time in the incubator 204, descends, and sucks the reaction solution in the reaction vessel 205. The reaction solution sucked by the reaction solution suction nozzle 214 is analyzed by the detection unit 215.

[0054] The reaction vessel 205 with the sucked reaction solution is moved to a specified position by the rotation of the incubator 204, and is moved from the incubator 204 to above the sample dispensing pipette and the reaction vessel disposal hole 209 by the sample dispensing pipette and the reaction vessel transport mechanism 206, and is discarded from the disposal hole.

[0055] Figure 3 It is a diagram showing an overall structural example of the moving unit 22. The moving unit 22 constitutes a part of the analysis module 20 and includes: a rotary reagent setting mechanism (reagent tray) 211, a reagent dispensing nozzle 213, a reagent stirring mechanism (magnetic particle stirring mechanism) 219, a reagent loader 220, and a reagent information reading mechanism 221. A plurality of reagent containers 217 are provided in the reagent setting mechanism 211 and the reagent loader 220. For example, a set of three liquid reagents required for measuring one test item is provided in the reagent container 217. One of them is a reagent added with magnetic particles. The reagent information reading mechanism 221 is provided adjacent to the reagent loader 220. Reagent information is given to the reagent container 217, and the reagent information reading mechanism 221 can obtain the reagent information on the reagent loader 220.

[0056] The operator sets the reagent container 217 in a specified position of the reagent loader 220 to load the reagent. In addition, the operator operates the reagent loader 220 using the overall management computer 10 to discharge the reagent container 217 to the reagent discharge preparation position of the reagent loader 220. In addition, usually, the reagent loader 220 is refrigerated.

[0057] <Example of the Structure of the Measurement Concentration Data Table>

[0058] Figure 4 It is a diagram showing an example of the structure of the measurement concentration data table 400 that stores the concentration measured by the detection unit 21 of the analysis module 20.

[0059] In the measurement concentration data table 400, the constituent items include: the measurement time 401, the sample 402 indicating the type of the measured control sample, the information 403 of the reagent container used for the measurement, the measurement item 404, the measurement concentration 405, and the influence of bubbles 406. Here, in the column of the influence of bubbles 406, "Yes" is stored when the determination unit 11 determines that there is an influence of bubbles.

[0060] For example, the measured concentration data 407 indicates that when measuring the measurement item DDD for the control sample d using the reagent in the reagent container D, the measured concentration is 201, and there is an influence of bubbles.

[0061] <Example of the structure of the control sample allocation information table>

[0062] Figure 5 It is a diagram showing an example of the structure of the control sample allocation data table 500 that stores information allocated to each control sample.

[0063] In the control sample allocation information table 500, the constituent items include: the control sample 501 indicating the type of the control sample, the measurement item 502, the known concentration 503 indicating the correct concentration of the corresponding control sample, the allowable lower limit value 504 of the measured concentration, and the allowable upper limit value 505 of the measured concentration.

[0064] For the analysis module 20, precision management processing is performed to measure each control sample at a specified interval (for example, once a day, etc.) to confirm the measurement accuracy of the device. In such precision management processing, it is confirmed whether the analysis module 20 is normal by checking whether the measurement result (precision management result) is within the management range. For example, in the precision management processing, when measuring the measurement item AAA of the "control sample a", the allowable lower limit value 504 is set to "35", and the allowable upper limit value 505 is set to "65". Therefore, if the measured concentration of the control sample a is within the range of 35 or more and 65 or less, it is determined that the operation of the analysis module 20 is normal, and if not, it is determined that there is some problem.

[0065] <Example of the structure of the warning data table>

[0066] Figure 6 It is a warning (hereinafter referred to as an alarm) of various abnormalities of the device detected by the abnormality detection unit 24 (refer to Figure 1 )). Or it is a diagram showing an example of the structure of the warning data table 600 that stores the bubble generation warning detected by the determination unit 11.

[0067] In the warning data table 600, the constituent items include: the generation date and time 601 of the alarm, the alarm code 602, and the alarm content 603. Here, the alarms include types such as abnormalities during information processing, abnormalities during mechanism operation, and abnormalities in analysis results.

[0068] <Details of the precision management processing>

[0069] Figure 7It is a flowchart for explaining the details of the accuracy management process of the analysis module 20 performed by the judgment unit 11. This accuracy management process can be executed by the judgment unit 11, for example, at the moment when the measurement of one item of one control sample is completed. The judgment unit 11 judges the possibility of bubble generation in the reagent container based on the information in the measurement concentration data table 400, the control sample allocation information table 500, and the warning data table 600 stored in the storage unit 12. In the present embodiment, the accuracy management process will be described by taking the case where the measurement of the measurement item "XXX" of the "control sample X" using the "reagent container X" is completed and the information 408 is stored in the measurement concentration data table 400 as an example. In addition, since the accuracy management process can be implemented by a computer program, the judgment unit 11 corresponding to the processor is the action subject of each step. However, the processing of each step or the processing of multiple steps can also be modularized, and the corresponding module can be used as the action subject. Here, as an example of an abnormality in the reagent container, the presence or absence of bubbles in the reagent container is described. However, the deterioration of the reagent, etc. can also be set as an abnormality in the reagent container.

[0070] (i) Step 701

[0071] The judgment unit 11 obtains the measurement concentration "20" of the measurement item "XXX" of the "control sample X" from the measurement concentration 405 of the measurement concentration data table 400. Then, the judgment unit 11 confirms whether the obtained measurement concentration (concentration value 20) is within the allowable range defined by the allowable lower limit value 504 and the allowable upper limit value 505 of the control sample allocation information table 500. If the measurement concentration is within the allowable range (if it is in step 701), it is judged as "no abnormality", and the accuracy management process ends. On the other hand, if the measurement concentration is outside the allowable range (if it is no in step 701), the process transfers to step 702. For example, in the control sample allocation information table 500, the allowable lower limit value 504 of the measurement item "XXX" of the "control sample X" is "90", and the allowable upper limit value 505 is "100". Therefore, the measurement concentration "20" is outside the allowable range. Therefore, the judgment unit 11 executes step 702.

[0072] (ii) Step 702

[0073] The determination unit 11 confirms whether the measurement concentration of the control sample using a reagent container other than the "reagent container X" is normal in order to confirm whether there is a problem with the detection unit 21, that is, whether the measurement concentration of each control sample is within the allowable range set by the control sample distribution information table 500. At this time, the control sample with the influence of bubbles 406 being "yes" in the measurement concentration data table 400 is excluded from the confirmation target. In this case, it is a problem with the reagent container, rather than the detection unit 21. In addition, regarding the range to which confirmation is made (for example, the measurement concentration up to 1 day ago or the measurement concentration up to 2 days ago), the user can use Figure 8 the confirmation range setting screen 800 to set. In Figure 8 , an example is shown in which the operator has set the measurement concentration up to 2 days ago for confirmation.

[0074] When it is determined that the measurement concentration of the control sample using another reagent container (for example, a reagent container other than the "reagent container X") is normal (when it is "yes" in step 702), the process proceeds to step 703. When it is determined that the measurement concentration of the control sample using another reagent container (for example, a reagent container other than the "reagent container X") is abnormal (when it is "no" in step 702), the process proceeds to step 705. In addition, when there is no measurement result of the confirmation target, the process also proceeds to step 705.

[0075] In the present embodiment, since the measurement concentrations of all the confirmation targets in the measurement concentration data table 400 are within the allowable range, the process proceeds to step 703.

[0076] In addition, by performing the processes of step 702 and step 703, it is confirmed that no abnormality has occurred outside the reagent container X.

[0077] (iii) Step 703

[0078] The determination unit 11 refers to the warning data table 600 and confirms whether an abnormality has occurred in the analysis module 20 since the date and time when normal measurement was possible. However, the alarm for detecting bubbles in the reagent container is excluded from the confirmation target. This is because when an alarm such as the detection of bubbles in a specific reagent container is used as the confirmation target, it is impossible to distinguish it from other abnormalities (such as abnormalities in the device itself, such as sensor abnormalities), and even when bubbles are generated, the process proceeds to step 705. That is, this is because when bubbles are generated, it is necessary to perform detection separately from problems for other reasons.

[0079] When it is determined based on the date and time that can be measured normally that an abnormality has occurred in the analysis module 20 (when the answer is yes in step 703), the process proceeds to step 705. When it is determined based on the date and time that can be measured normally that no abnormality has occurred in the analysis module 20 (when the answer is no in step 703), the process proceeds to step 704.

[0080] In addition, in the present embodiment, in the measurement concentration data table 400, the last date and time that can be measured normally is 12:00 on January 3, 2019. Also, in the warning data table 600, the last alert other than the bubble detection occurred at 9:30 on January 1, 2019. The determination unit 11 determines that no abnormality has occurred in the analysis module 20 based on the date and time that can be measured thereafter, and causes the process to proceed to step 704.

[0081] (iv) Step 704

[0082] The determination unit 11 determines that there is no problem in the analysis module 20, and bubbles may be generated in the target reagent container, and discharges the reagent container to the discharge preparation position. That is, in the case of the above example, the determination unit 11 determines that there is no abnormality in the analysis module 20, and bubbles may be generated in the "reagent container X", and discharges the reagent container X to the discharge preparation position (the refrigerated reagent loader 220). In addition, the determination unit 11 stores the information of "bubbles" in the influence of bubbles 406 of the measurement concentration data table 400 for the measurement results determined to be likely to have bubbles.

[0083] (v) Step 705

[0084] In the case where there is an abnormality in other measurement concentrations, the abnormality may be caused by factors other than the generation of bubbles in the reagent container X. Therefore, the determination unit 11 notifies the operator of the abnormality of the measured value (measurement concentration). In addition, the notification can be performed by using a method of displaying an alarm on the screen of the display unit or a method of using an alarm sound such as a buzzer.

[0085] <Reagent discharge setting>

[0086] (i) Figure 9 This is a structural example diagram of a bubble reagent discharge setting screen 900 that sets whether to automatically discharge the reagent container when it is determined that "bubbles are generated" in the target reagent container.

[0087] The operator can automatically discharge the reagent container determined to "have bubbles generated" by checking the check item box 901 and pressing the OK button 902. That is, when the determination unit 11 determines that "bubbles are generated" in the target reagent container, it automatically discharges the reagent container in response to the check in the check box 901.

[0088] On the other hand, when the checkbox 901 is not selected, the determination unit 11 will display the Figure 10 screen exemplified below on the display screen and wait for the operator's instruction input.

[0089] (ii) Figure 10 is a diagram showing a structural example of the bubble reagent discharge selection screen 1000 for asking the operator whether to discharge the reagent container determined to "generate bubbles". As described above, the bubble reagent discharge selection screen 1000 is a screen displayed when it is detected by the determination unit 11 that bubbles may be generated in the target reagent container and the checkbox 901 is not selected.

[0090] When the bubble reagent discharge selection screen 1000 is displayed, if the operator presses the OK button 1001, the reagent container determined by the determination unit 11 to "possibly generate bubbles" is discharged. On the other hand, if the operator presses the Cancel button 1002, the reagent container determined by the oil determination unit 11 to "possibly generate bubbles" is not discharged and remains unchanged in the reagent tray 211.

[0091] <Difference between reagent deterioration and bubble generation by comparison of the last measured concentration>

[0092] In addition, by adding the Figure 11 reagent container internal cause threshold table 1100 and replacing step 704 with the Figure 12 processing, the accuracy of bubble detection can be further improved.

[0093] <Structural example of the reagent container internal cause threshold table>

[0094] Figure 11 is a diagram showing a structural example of the reagent container internal cause threshold table 1100 that stores the reagent deterioration threshold and the bubble threshold for each control sample and measurement item group.

[0095] In the reagent container internal cause threshold table 1100, the constituent items include: the control sample 1101 indicating the type of the control sample, the measurement item 1102, the reagent deterioration threshold 1103 for identifying whether the cause of the abnormal measurement concentration is reagent deterioration, the bubble threshold 1104 for identifying whether the cause of the abnormal measurement concentration is bubble generation, and the effective last measured value 1105.

[0096] By whether the difference between the last and this measured concentrations exceeds the thresholds of the reagent deterioration threshold 1103 and the bubble threshold 1104, the cause of the abnormal measurement concentration is judged. When the difference between the this and last measured concentrations does not exceed the reagent deterioration threshold 1103, the determination unit 11 considers that there is not enough difference for discrimination and judges that there may be both reagent deterioration and bubbles.

[0097] For example, the reagent deterioration threshold 1103 for the measurement item "AAA" of "control sample a" is set to "previous measurement value ± 25", and the bubble threshold is set to "previous measurement value ± 30". Therefore, if -25 ≤ (current measurement concentration - previous measurement concentration) ≤ 25, it is considered that there is no difference sufficient for discrimination, and it is judged that there may be both reagent deterioration and bubbles. In addition, if -30 ≤ (current measurement concentration - previous measurement concentration) < -25 or 25 < (current measurement concentration - previous measurement concentration) ≤ 30, it is judged that there may be reagent deterioration. In addition, if -30 > (current measurement concentration - previous measurement concentration) or 30 < (current measurement concentration - previous measurement concentration), it is judged that bubbles are generated in the reagent container.

[0098] In this embodiment, the influence of the measurement concentration has a greater impact on the generation of bubbles than reagent deterioration, resulting in a relationship where the reagent deterioration threshold 1103 is nested within the bubble threshold 1104. In the case where the reagent deteriorates severely due to long-term exposure of the reagent to normal temperature, etc., the influence of reagent deterioration on the measurement concentration is greater than the influence of bubble generation, and this nested relationship may collapse. Therefore, an effective previous measurement value 1105 is set. It is considered that the nested relationship of the measurement values during the period exceeding the effective previous measurement value 1105 may collapse and is not used.

[0099] For example, when judging reagent deterioration and bubble generation for "measurement item CCC" of "control sample c" measured at 12:00 on January 3, 2019 in the measurement concentration data table 400, the effective previous measurement value 1105 for "measurement item CCC" of "control sample c" is up to 1 day ago. Therefore, the previous value up to 12:00 on January 2, 2019 is used.

[0100] <Details of the determination process of reagent deterioration and bubble generation by comparison with the previous measurement concentration>

[0101] Figure 12 This is a flowchart for explaining the details of the process of determining whether the abnormality of a reagent container judged to be abnormal is caused by bubbles in the reagent container or reagent deterioration. This process judges the possibility of bubble generation and reagent deterioration in the reagent container based on the information in the measurement concentration data table 400 and the reagent container internal cause threshold table 1100 stored in the storage unit 12.

[0102] (i) Step 1201

[0103] The determination unit 11 determines whether there has been a measured concentration of the measurement item for the specimen in the past. In order to use past measurement values for differentiating reagent deterioration and bubble generation, if there is none, the differentiation between bubbles and reagent deterioration cannot be performed, and the process proceeds to step 1207. If there is, the process proceeds to step 1202.

[0104] In the present embodiment, the determination unit 11 determines whether the measurement item "xxx" has been measured in the "control specimen x" in the past. First, the determination unit 11 obtains the valid previous measurement value 1105 "until 12 hours ago" of the measurement item "xxx" of the "control specimen x" from the reagent container internal cause threshold table 1100. Therefore, the determination unit 11 obtains past measurement values within the range from 12 hours ago until the current measurement date and time, i.e., 13:00 on January 4, 2019. There is a measured concentration "98" corresponding to 10:00 on January 4, 2019 in the measurement concentration data table 400, so the process proceeds to step 1202. If there is no past measured concentration, the threshold is not calculated, so the process proceeds to step 1207.

[0105] (ii) Step 1202

[0106] The determination unit 11 obtains the thresholds for differentiating reagent deterioration and bubble generation from the reagent container internal cause threshold table 1100. If there is no combination of a matching control specimen and measurement item in the reagent container internal cause threshold table 1100, the threshold cannot be obtained, so the differentiation between bubbles and reagent deterioration cannot be performed, and the process proceeds to step 1207.

[0107] In the present embodiment, the reagent deterioration threshold 1103 and the bubble threshold 1104 of the measurement item "xxx" of the "control specimen x" are obtained from the reagent container internal cause threshold table 1100. The reagent deterioration threshold 1103 of the measurement item "xxx" of the "control specimen x" can be obtained as ±15 of the previous value, and the bubble threshold 1104 can be obtained as ±20 of the previous value, so the process proceeds to step 1203.

[0108] (iii) Step 1203

[0109] The determination unit 11 determines whether reagent deterioration and bubbles can be differentiated based on the current measurement value. If the reagent deterioration threshold 1103 is not exceeded, that is, if the difference between the current and previous measured concentrations does not exceed the reagent deterioration threshold, it is considered that there is no difference in the measured concentration sufficient to differentiate reagent deterioration and bubbles, and the process proceeds to step 1207. If the reagent deterioration threshold is exceeded, it is considered that there is a difference in the measured concentration sufficient to differentiate reagent deterioration and bubbles, and the process proceeds to step 1204.

[0110] In this embodiment, the measured concentration this time is "20", and the measured concentration last time was "98". When the difference between the measured concentration this time and last time is "-78", it exceeds the reagent deterioration threshold 1103 of "-15". Therefore, it is considered that the measured concentration has a difference sufficient to distinguish between reagent deterioration and bubbles, and the process proceeds to step 1204.

[0111] (iv) Step 1204

[0112] The determination unit 11 determines whether the abnormality of the measured concentration this time is caused by reagent deterioration or the generation of bubbles based on the threshold obtained in step 1202. If the difference between the measured concentration this time and last time exceeds the reagent deterioration threshold 1103 and does not exceed the bubble generation threshold 1104, it is determined that there may be reagent deterioration, and the process proceeds to step 1205. If the difference between the measured concentration this time and last time exceeds the bubble generation threshold 1104, it is determined that there may be bubbles generated in the reagent container, and the process proceeds to step 1206.

[0113] In this embodiment, when the difference between the measured concentration this time and last time is "-78", it exceeds the bubble threshold 1104. Therefore, it is determined that there may be bubbles generated, and the process proceeds to step 1206.

[0114] (v) Step 1205

[0115] If it is determined in step 1204 that there may be reagent deterioration, the determination unit 11 notifies the operator of the possibility of reagent deterioration.

[0116] (vi) Step 1206

[0117] If it is determined in step 1204 that there may be bubbles generated in the reagent container, the determination unit 11 notifies the operator of the possibility of bubble generation.

[0118] (vii) Step 1207

[0119] If the threshold cannot be obtained in step 1202, or if it is determined in step 1203 that it is impossible to distinguish between reagent deterioration and bubbles, the operator is notified that there may be reagent deterioration or bubble generation. In addition, it is also possible to notify which step has been entered, and inform the operator that there is no registered threshold or no significant difference has occurred.

[0120] In addition, the notifications in step 1205, step 1206, and step 1207 can be made by using the method of displaying an alarm on the screen of the display unit, or by using the method of an alarm sound such as a buzzer.

[0121] (viii) Step 1208

[0122] The determination unit 11 determines that there is no problem in the analysis module 20, but there is a problem with the reagent container of interest, and discharges the reagent container to the discharge preparation position.

[0123] <Example of detection of bubbles based on changes in the reagent liquid level position>

[0124] In addition, by adding the reagent container liquid level gauge 1300, steps 1230, 1204, 1205, and 1206 are replaced with Figure 14 processing, and a structure for detecting bubbles based on changes in the reagent liquid level height can be incorporated.

[0125] <Example of the structure of the reagent container liquid level gauge>

[0126] Figure 13 It is a diagram showing an example of the structure of the reagent container liquid level gauge 1300 that holds the liquid level height in each reagent container.

[0127] In the reagent container liquid level gauge 1300, the reagent container 1301 and the current reagent liquid level height 1302 of the reagent container are included as constituent items.

[0128] The liquid level height 1302 is obtained based on the descent amount of the reagent dispensing nozzle 213 during reagent suction, the suction amount at this time, and the bottle size.

[0129] By comparing the liquid level heights, the generation of bubbles can be detected. For example, when detecting the liquid level of bubbles during reagent suction, the descent amount of the reagent dispensing nozzle 213 becomes smaller, and the calculated liquid level height is higher than the previous liquid level height. At this time, it can be determined that bubbles are generated.

[0130] In addition, by comparing the liquid level heights, the disappearance of bubbles can also be detected. For example, when calculating the previous liquid level height in a state with bubbles, and the bubbles disappear during the current reagent dispensing, the liquid level height is lower than expected.

[0131] The threshold value for identifying the change in the liquid level height of bubble generation or bubble disappearance can be set by the operator from the overall management computer 10, or a fixed value can be set in advance in the storage unit 12 by the product designer.

[0132] <Details of the bubble detection process based on changes in the reagent liquid level position>

[0133] Figure 14This is a flowchart for explaining the process that combines the structure for detecting bubbles based on the change in the liquid level of a reagent and the structure for determining reagent deterioration based on the threshold of reagent deterioration. This process determines the possibility of bubble generation or disappearance and the possibility of reagent deterioration in the reagent container based on the information in the reagent container cause threshold table 1100 and the reagent container liquid level height table 1300 stored in the storage unit 12.

[0134] (i) Step 1401

[0135] The determination unit 11 calculates the liquid level height based on the amount by which the reagent dispensing nozzle 213 descends during the current reagent aspiration and the shape of the reagent container. The calculated liquid level height is compared with the previous liquid level height 1302 recorded in the reagent container liquid level height table 1300. As a result of the comparison, if the currently calculated liquid level height is greater than the previously calculated liquid level height, it is determined that bubbles may have been generated, and the process proceeds to step 1402. If the currently calculated liquid level height is less than the previously calculated liquid level height, it is determined that bubbles may have disappeared, and the process proceeds to step 1403. If there is no difference between the currently calculated liquid level height and the previously calculated liquid level height, it is determined that there is no possibility of bubble generation or disappearance, and the process proceeds to step 1404.

[0136] In this embodiment, when the threshold for the change in the liquid level height for identifying bubble generation is set to "2 mm" and the threshold for the change in the liquid level height for identifying bubble disappearance is set to "-4 mm", if the liquid level height of "reagent container X" calculated this time is greater than "2 mm" compared to the previous liquid level height, it is determined that bubbles have been generated. If it is less than "-4 mm", it is determined that bubbles have disappeared. If it is between "-4 mm" and "2 mm", it is determined that there is no possibility of bubble generation or disappearance.

[0137] (ii) Step 1402

[0138] When it is determined in step 1401 that bubbles may have been generated, the determination unit 11 notifies the operator of the possibility of reagent deterioration, and the process proceeds to step 1407.

[0139] (i) Step 1403

[0140] When it is determined in step 1401 that there is a possibility of bubble disappearance, the determination unit 11 notifies the operator of the possibility of bubble disappearance, and the process proceeds to step 1407.

[0141] In addition, when it is determined that there is a possibility of bubble disappearance, the previous measurement results using this reagent container can also be notified to the operator.

[0142] (i) Step 1404

[0143] When the determination unit 11 determines in step 1401 that there may be no bubble generation or the bubbles have disappeared, it confirms whether the difference between the previous and current measured concentrations exceeds the threshold for reagent deterioration. If it exceeds the threshold for reagent deterioration, it proceeds to step 1405. If it is smaller than the threshold for reagent deterioration, it is considered that it is impossible to determine whether the abnormality of the measured concentration is caused by bubbles or reagent deterioration within the set threshold, and it proceeds to step 1406.

[0144] (i) Step 1405

[0145] When the determination unit 11 determines in step 1404 that the reagent may have deteriorated, it notifies the operator that the reagent container of the notified object may have reagent deterioration.

[0146] (i) Step 1406

[0147] In step 1404, when the difference between the previous and current measured concentrations is smaller than the threshold for reagent deterioration, the determination unit 11 notifies the operator that it is impossible to determine whether the abnormality of the measured concentration is caused by bubbles or reagent deterioration.

[0148] (i) Step 1407

[0149] The determination unit 11 determines that there is no problem in the analysis module 20 and there is a problem in the reagent container of the object, and discharges the reagent container to the discharge preparation position.

[0150] In addition, the notifications in step 1402, step 1403, step 1405, and step 1406 can use the method of performing an alarm display on the screen of the display unit, or can also use the method of an alarm sound such as a buzzer.

[0151] <Summary>

[0152] (i) According to the present embodiment, in the automatic analyzer, based on the concentration correlation information associated with the type of the specimen (for example, various control specimens) and the concentration of the measurement target component contained in the specimen determined according to the type of the specimen, and the concentration of the measurement target component contained in the reaction solution (by comparing these two pieces of information), it is determined whether an abnormality has occurred in the reagent container (generation of bubbles in the reagent container, deterioration of the reagent itself contained in the reagent container). In this way, when an abnormality occurs in the measurement result of precision management, it is detected whether the reagent is problematic, and by automatically discharging the problematic reagent, the operator can easily perform the cause investigation work.

[0153] Specifically, the above concentration correlation information represents the allowable range of the concentration of the component to be measured determined for judging whether there are air bubbles in the reagent container. And, the judgment unit (processor) judges whether air bubbles are generated in the reagent container and whether there is deterioration of the reagent based on the comparison result of whether the measured concentration is included in the allowable range. Thus, in the present embodiment, it is possible to detect the possibility of abnormality of the reagent only by judging whether the measured concentration is within an appropriate range. That is, it is possible to detect the possibility of abnormality in the reagent by a relatively simple process.

[0154] In addition, when it is judged that an abnormality has occurred in the reagent container, the judgment unit responds to an instruction (an instruction for automatic discharge by the operator or an instruction for each discharge), and controls the moving unit to move the reagent container to the discharge preparation position (the position where the reagent container is refrigerated). Thus, by discharging the reagent container judged to be abnormal to the position where it is refrigerated, the deterioration of the reagent caused by temperature change disappears, and the operator can confirm the discharged reagent container at a preferred time. In addition, when the abnormality is the generation of air bubbles in the reagent container, by discharging the reagent container with a high possibility of air bubbles, the concern about improper results caused by air bubbles can be reduced, and the reliability of the measurement result can be improved.

[0155] In addition, by comparing the previous measured concentration with the measured concentration exceeding the allowable range, it is judged whether the abnormality in the reagent container is caused by air bubbles in the reagent container or deterioration of the reagent itself contained in the reagent container. Thus, by more detailedly judging the cause of the abnormality in the reagent container, it is easy for the operator to perform the cause investigation operation.

[0156] In addition, the present invention can also more detailedly judge the cause of the abnormality in the reagent container by combining with the detection of air bubbles based on the change of the reagent liquid level in the reagent container.

[0157] (ii) The functions of the embodiment can also be implemented by a program code of software. In this case, a storage medium recording the program code is provided to the system or device, and a computer (or CPU, MPU) of the system or device reads the program code stored in the storage medium. In this case, the program code itself read from the storage medium implements the functions of the above embodiment, and the program code itself and the storage medium storing the program code constitute the present disclosure. As a storage medium for supplying such a program code, for example, a floppy disk, a CD-ROM, a DVD-ROM, a hard disk, an optical disc, an optical disk, a CD-R, a magnetic tape, a non-volatile memory card, a ROM, etc. are used.

[0158] In addition, an OS (operating system) running on a computer or the like can also perform part or all of the actual processing according to the instructions of the program code, and the functions of the above-described embodiments can be implemented through this processing. Further, after the program code read from the storage medium is written into the memory of the computer, the CPU or the like of the computer can perform part or all of the actual processing according to the instructions of the program code, and the functions of the above-described embodiments can be implemented through this processing.

[0159] Moreover, the program code of the software that implements the functions of the embodiments can also be distributed via a network. Thus, it is stored in a storage unit such as a hard disk or a memory of a system or a device, or a storage medium such as a CD-RW or a CD-R. When in use, a computer (or a CPU or an MPU) of the system or the device reads and executes the program code stored in the storage unit or the storage medium.

[0160] The processes and techniques described herein are not inherently associated with any particular apparatus. Additionally, various types of general-purpose devices can be used in accordance with the description of the present disclosure. Furthermore, it is beneficial to construct a dedicated apparatus based on the implementation of the technology of the present disclosure.

[0161] By appropriately combining the multiple structural elements disclosed in this embodiment, various inventions can be formed. For example, several structural elements can also be deleted from all the structural elements shown in this embodiment. Also, the structural elements in different embodiments can be appropriately combined. The technology of the present disclosure has been described in association with the specific example embodiments, but these are not used to limit the technology of the present disclosure, but rather for illustration. Those skilled in the art will recognize that there are multiple combinations of hardware, software, and firmware corresponding to the implementation of the technology of the present disclosure. For example, the described software can be installed using a wide range of programs or scripting languages such as an assembler, C / C++, perl, Shell, PHP, Java (registered trademark), etc.

[0162] Moreover, in the above-described embodiments, the control lines and information lines show the parts considered necessary for explanation, and do not necessarily show all the control lines and information lines on the product. All the structures can also be interconnected.

[0163] Symbol Explanation

[0164] 1 Automatic analysis device

[0165] 11 Judgment unit

[0166] 12 Storage unit

[0167] 10 Overall management computer

[0168] 20 Analysis module

[0169] 21 Detection Unit

[0170] 22 Moving Unit

[0171] 23 Reagent Dispensing Unit

[0172] 24 Abnormality Detection Unit

[0173] 201 Carrier

[0174] 202 Sample Container

[0175] 203 Sample Dispensing Nozzle

[0176] 204 Incubator

[0177] 205 Reaction Vessel

[0178] 206 Sample Dispensing Pipette and Reaction Vessel Transport Mechanism

[0179] 207 Sample Dispensing Pipette and Reaction Vessel Holding Component

[0180] 208 Reaction Vessel Stirring Mechanism

[0181] 209 Sample Dispensing Pipette and Reaction Vessel Waste Hole

[0182] 210 Sample Dispensing Pipette Mounting Position

[0183] 211 Reagent Tray

[0184] 212 Reagent Tray Cover

[0185] 213 Reagent Dispensing Nozzle

[0186] 214 Reaction Liquid Suction Nozzle

[0187] 215 Detection Unit

[0188] 216 Carrier Transport Line

[0189] 217 Reagent Container

[0190] 218 Specimen Bubble Detection Camera

[0191] 219 Reagent Stirring Mechanism (Magnetic Particle Stirring Mechanism)

[0192] 220 Reagent Loader

[0193] 221 Reagent Information Reading Mechanism

Claims

1. An automatic analysis device, characterized in that, it has: a reagent dispensing unit that sucks the reagent from a reagent container storing the reagent and discharges the reagent into a reaction container storing a sample to generate a reaction solution; a storage unit that stores concentration-related information associated with the concentration of a measurement target component contained in the sample determined according to the type of the sample, the concentration-related information indicating an allowable range of the concentration of the measurement target component in the sample, a reagent deterioration threshold, and a bubble threshold for determining whether there is an abnormality in the reagent container; a detection unit that detects the concentration of the measurement target component contained in the reaction solution, i.e., the measurement concentration; and a determination unit that determines whether an abnormality has occurred in the reagent container based on whether the concentration-related information and the current measurement concentration are within the allowable range, the abnormality referring to the generation of bubbles in the reagent container or the possibility of deterioration of the reagent stored in the reagent container, when the absolute value of the difference between the measurement concentration at the previous measurement and the measurement concentration at the current measurement is less than or equal to the reagent deterioration threshold, the determination unit determines that there is a possibility of deterioration of the reagent in the reagent container and a possibility of bubble generation, when the absolute value of the difference between the measurement concentration at the previous measurement and the measurement concentration at the current measurement is greater than the bubble threshold, the determination unit determines that bubbles have been generated in the reagent container, when the absolute value of the difference between the measurement concentration at the previous measurement and the measurement concentration at the current measurement is greater than the reagent deterioration threshold and less than or equal to the bubble threshold, the determination unit determines that there is a possibility of deterioration of the reagent in the reagent container.

2. The automatic analysis device according to claim 1, characterized in that, when the determination unit determines that an abnormality has occurred in the reagent container, in response to an instruction, it controls a moving unit to move the reagent container to a discharge preparation position.

3. The automatic analysis device according to claim 1, characterized in that, when the determination unit determines that an abnormality has occurred in the reagent container, it controls a display device to display a screen on a display screen for selecting whether to move the reagent container to a discharge preparation position.

4. The automatic analysis device according to claim 1, characterized in that, when the determination unit determines that there is a possibility of an abnormality other than the abnormality in the reagent container, it outputs the possibility of the abnormality to the outside.

5. An abnormality detection method, characterized in that, it includes: a reagent dispensing unit sucks the reagent from a reagent container storing the reagent and discharges the reagent into a reaction container storing a sample to generate a reaction solution, a detection unit detects the concentration of the measurement target component contained in the reaction solution, i.e., the measurement concentration; The determination unit obtains from the storage unit concentration correlation information associated with the concentration of the measurement target component contained in the sample determined according to the type of the sample, and the concentration correlation information represents the allowable range of the concentration of the measurement target component in the sample determined for judging whether there is an abnormality in the reagent container, the reagent deterioration threshold, and the bubble threshold; and The determination unit determines whether an abnormality has occurred in the reagent container based on whether the concentration correlation information and the measured concentration in the current measurement are within the allowable range, and the abnormality means that bubbles are generated in the reagent container or there is a possibility that the reagent contained in the reagent container deteriorates, When the absolute value of the difference between the measured concentration at the time of the previous measurement and the measured concentration at the time of the current measurement is less than or equal to the reagent deterioration threshold, the determination unit determines that there is a possibility of reagent deterioration and bubble generation in the reagent container, When the absolute value of the difference between the measured concentration at the time of the previous measurement and the measured concentration at the time of the current measurement is greater than the bubble threshold, the determination unit determines that bubbles have been generated in the reagent container, When the absolute value of the difference between the measured concentration at the time of the previous measurement and the measured concentration at the time of the current measurement is greater than the reagent deterioration threshold and less than or equal to the bubble threshold, the determination unit determines that there is a possibility of reagent deterioration in the reagent container.

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