JP2015010863A - Automatic analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an automatic analyzer capable of effectively using a reagent so as not to cause the dead volume of the reagent to increase as much as possible, even when a portion of the reagent near a liquid surface in a reagent container is deteriorated or a gradient in concentration of the reagent occurs in the reagent container.SOLUTION: An automatic analyzer 1 for analyzing a sample by using a reagent MM in a reagent container 30 (31) includes a measurement information generation unit 55 which, when a pipette 220, i.e., a suction tool for sucking the reagent MM from the reagent container, is lowered and the suction tool penetrates from the reagent liquid surface LL, holds a standard amount of penetration LS of the suction tool and at least one penetration amount L1, L2 for reagent abnormality detection larger than the standard amount of penetration LS. When a measurement request for the accuracy management or calibration of the reagent MM is issued, the measurement information generation unit 55 adds a measurement by dispensation of the reagent MM using the penetration amount L1, L2 for reagent abnormality detection, in addition to a measurement by dispensation of the reagent MM using the standard amount of penetration LS.

Description

  The embodiment of the present invention relates to an automatic analyzer that analyzes a sample by reacting a sample such as blood or urine with a reagent.

  As an example of the automatic analyzer, Patent Document 1 discloses an automatic analyzer. In the automatic analyzer of Patent Document 1, a sample such as a patient specimen and a reagent in a reagent container are dispensed into a reaction container (reaction cell).

JP 2012-26815 A

  However, the automatic analyzer disclosed in Patent Document 1 does not consider the following points.

  When aspirating and dispensing the reagent, in order to reduce the area where the reagent adheres on the outer periphery of the pipette (probe), which is a suction tool, insert the tip of the pipette near the reagent surface in the reagent container. The reagent is aspirated only from the vicinity of the reagent liquid surface.

  By the way, if the reagent in the reagent container is easily affected by contact with the outside air, or if the concentration gradient is likely to occur in the reagent, the reagent in the reagent container is especially over time. The portion near the liquid level is likely to deteriorate. Therefore, if the pipette is used to limit the position where the reagent in the reagent container is sucked to the vicinity of the reagent liquid surface, the deteriorated reagent part in the reagent container is dispensed to the sample side of the reaction container. There is a risk of abnormalities in the data results.

  On the other hand, when aspirating a portion near the reagent liquid surface using a pipette, the pipette entry position is set to a position deeper than the reagent liquid surface instead of the portion near the liquid surface. In this case, a portion in which the reagent in the reagent container cannot be used, that is, a dead volume in which the reagent in the reagent container is not used increases, and the reagent is wasted.

  In addition, if a concentration gradient occurs in the reagent in the reagent container, even if the suction position by the pipette is set to a position deeper than the portion near the reagent liquid surface, there is a concentration gradient of the reagent, so the analysis data There is a risk of abnormal results.

  The present invention has been made in order to solve the above-described problems. The object of the present invention is to prevent a portion near the liquid level of the reagent in the reagent container from deteriorating or a concentration gradient of the reagent from occurring in the reagent container. Another object of the present invention is to provide an automatic analyzer that can effectively use a reagent so that the dead volume of the reagent does not increase as much as possible.

According to a first aspect of the present invention, there is provided an automatic analyzer for analyzing a sample using a reagent in a reagent container, wherein the suction tool is lowered to suck the reagent in the reagent container. And holding a standard penetration amount of the suction tool when the suction tool penetrates from the reagent liquid surface, and at least one reagent abnormality detection penetration amount larger than the standard penetration quantity, When a measurement request for accuracy control or calibration is issued, in addition to measurement by dispensing of the reagent using the standard intrusion amount, by dispensing of the reagent using the intrusion amount for detecting the reagent abnormality A measurement information generation unit for adding measurement is provided.

It is a figure which shows the automatic analyzer of embodiment of this invention. It is a block diagram which shows the example of a connection structure of the element of an automatic analyzer. It is a figure which shows the example of the reagent abnormality detection parameter setting screen displayed on the display apparatus shown in FIG. It is a figure which shows the example of the fall amount of the reagent dispensing pipette corresponding to a reagent abnormality detection parameter. It is a flowchart which shows analysis of the measurement information for abnormality detection of the reagent MM using a reagent abnormality detection parameter. It is a flowchart which judges reagent abnormality using a measurement result. It is a flowchart which shows the control procedure at the time of the measurement request reception of a patient's sample (specimen).

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

  FIG. 1 is a diagram showing an automatic analyzer according to an embodiment of the present invention. The automatic analyzer 1 shown in FIG. 1 reacts a sample (or specimen) such as blood or urine of a patient with a reagent prepared in advance in a reaction tube 70, and this sample for a predetermined analysis item. It is a device that analyzes. In the automatic analyzer 1, a plurality of reaction tubes 70 are arranged in a reaction tank 11 that is, for example, a constant temperature bath.

  The reaction tube 70 includes a sample such as blood and urine, a test reagent in the reagent container 30 held in the first reagent container 10A, or a test reagent in the reagent container 31 held in the second reagent container 10B. The reaction tube 70 contains a reaction solution composed of a sample and a reagent. Then, the automatic analyzer 1 irradiates the reaction solution in the reaction tube 70 with light from the measurement unit 13, and the transmitted light from the reaction solution in the reaction tube 70 is received by the measurement unit 13. The measurement result can be reported by measuring the component concentration of the sample. The automatic analyzer 1 optically or electrically measures the concentration or activity value of a component contained in a sample using a chemical reaction between the sample and a test reagent.

  A preferred structural example of the automatic analyzer 1 will be described with reference to FIG. As shown in FIG. 1, the automatic analyzer 1 includes a user interface 56, a controller 90, an analyzer 104, a data processor 105, and a display device 6.

  The user interface 56 is an input device such as a pointing device such as a mouse or a trackball of a computer or a keyboard that accepts the contents of instructions such as various commands and measurement conditions from a user (operator). The control unit 90 controls the operation of each unit of the analysis unit 104 according to the instruction content input by the user via the user interface 56.

  The analysis unit 104 has the structure illustrated in FIG. The analysis unit 104 includes a circular first reagent chamber 10A, a circular second reagent chamber 10B, a ring-shaped reaction tank 11, a circular sample disk 44, a sampling arm 7, a first reagent arm 8, and a second. It has a reagent arm 9 and the like.

  The reaction tank 11 is also referred to as a reaction disk, and the reaction tank 11 holds a plurality of reaction tubes (an example of a reaction vessel) 70 arranged in a circumferential direction so as to be detachable along the circumferential direction. The reaction vessel 11 repeats rotation and stop in a predetermined constant cycle, so that the reaction tube 70 can be indexed by rotating in the circumferential direction. The reaction tube 70 is a container for accommodating a reaction liquid composed of a reagent and a sample and causing a chemical reaction inside. As will be described later, the reaction tube 70 is made of, for example, glass and has, for example, a side portion having a rectangular cross section and a bottom portion, but the upper end portion is an opening.

  The sample disk 44 is disposed beside the reaction tank 11. The sample disk 44 holds a plurality of sample containers 45 that store samples (samples). The sample disk 44 rotates so that a specific sample container 45 can be positioned at a predetermined sample suction position.

  The first reagent storage 10 </ b> A is arranged concentrically with the reaction tank 11, and the first reagent storage 10 </ b> A is inside the reaction tank 11. The first reagent storage 10A holds a plurality of reagent containers 30 in which a first reagent that selectively reacts with each measurement item of a sample is accommodated. The first reagent storage 10A rotates so that a specific reagent container 30 can be positioned at a predetermined first reagent suction position.

  The second reagent storage 10 </ b> B is disposed on the side of the reaction tank 11. The second reagent storage 10B holds a plurality of reagent containers 31 in which a second reagent that selectively reacts with each measurement item of the sample is accommodated. The second reagent storage 10B rotates so that the specific reagent container 31 can be positioned at a predetermined second reagent suction position. The reagent container 30 contains a first reagent that reacts with the components of the test item included in each sample of the standard sample and the test sample, and the reagent container 31 is the test item included in each sample of the standard sample and the test sample. A second reagent that reacts with the other components.

  As shown in FIG. 1, the sampling arm 7 is disposed between the reaction vessel 11 and the sample disk 44. A sampling probe 17 is attached to the tip of the sampling arm 7. The sampling arm 7 places the sampling probe 17 at the sample suction position on the sample disk 44, lowers the sampling probe 17, and causes the sampling probe 17 to suck a sample in the sample container 45 placed at the sample suction position. . When the sample is sucked, the sampling arm 7 raises the sampling probe 17 and rotates to supply the sample into a predetermined reaction tube 70 of the reaction tank 11. The sample container 45 accommodates each test sample such as a standard sample and urine, whole blood, and serum or plasma separated from the whole blood.

  As shown in FIG. 1, the 1st reagent arm 8 is arrange | positioned on the outer side of the reaction tank 11, and the 2nd reagent arm 9 is arrange | positioned on the outer side of the 2nd reagent storage 10B. The first reagent arm 8 has a first reagent probe 18, and the second reagent arm 9 has a second reagent probe 19.

  The first reagent arm 8 places the first reagent probe 18 at the first reagent inhalation position on the first reagent storage 10A and lowers the first reagent probe 18 so that the first reagent probe 18 is in the reagent container 30 at the first reagent inhalation position. The first reagent is inhaled by a predetermined amount. When the first reagent is inhaled, the first reagent arm 8 raises the first reagent probe 18 and rotates the first reagent probe 18 to supply the first reagent into a predetermined reaction tube 70 of the reaction tank 11. It is supposed to be.

Similarly, the second reagent arm 9 is located at the second reagent inhaling position by placing the second reagent probe 19 at the second reagent inhaling position on the second reagent storage 10B and lowering the second reagent probe 19. A predetermined amount of the second reagent in the reagent container 31 is aspirated. When the second reagent is inhaled, the second reagent arm 9 raises the second reagent probe 19 and rotates the second reagent probe 19 to supply the second reagent into a predetermined reaction tube 70 of the reaction tank 11. It is supposed to be. The first reagent probe 18 and the second reagent probe 19 constitute a reagent dispensing control mechanism unit 80.

  Next, the stirrer (stirring arm) 12, the measuring unit 13, and the reaction tube cleaning mechanism unit 15 arranged around the reaction tank 11 shown in FIG. 1 will be described.

  The stirrer 12 has a stirring bar at the tip, and stirs the test solution in the reaction tube 70. The measurement unit 13 performs photometry of the test container in the reaction tube 70. The measurement unit 13 includes an irradiation unit 13A and a detection unit 13B. The irradiation unit 13A irradiates the reaction tube 70 passing through the photometric position of the reaction tank 11 with a photometric beam. The detection unit 13B detects the photometric beam irradiated by the irradiation unit 13A and passed through the test solution via the reaction tube 70 for each wavelength of the inspection item. The detector 13B sends the intensity data of the photometric beam to the data processor 105. The data processing unit 105 generates standard data and test data represented by absorbance data, for example, based on the intensity data of the photometric beam, and generates calibration data and analysis data. These data can be displayed on the display device 6. The reaction tube cleaning mechanism 15 has a function of cleaning the reaction tube 70.

  Next, with reference to FIG. 2, an example of the electrical connection configuration of the components of the automatic analyzer 1 will be described. FIG. 2 is a block diagram illustrating a connection configuration example of elements of the automatic analyzer 1.

  As shown in FIG. 2, the computer 5 includes a control unit (CPU) 90, a storage unit (database) 91, and a data processing unit 105. The computer 5 includes a display device 6, a measurement information generation unit 55, a user interface 56, a stirrer 12, a measurement unit 13, a reaction tube cleaning mechanism unit 15, a reagent dispensing control mechanism unit 80, and a notification unit 100. Electrically connected.

  The user interface 56 is, for example, a keyboard, and input information such as measurement information necessary for the control unit 90 of the computer 5 can be input by a user operation. When the measurement information generation unit 55 receives, from the input information by the user, for example, that the measurement request for the quality control sample or the calibration sample is issued from the control unit 90, the measurement information generation unit 55 analyzes the measurement information. Etc. are to be performed.

  The control unit 90 of the computer 5 includes a display operation of necessary items on the display device 6, an operation control of the stirrer 12, an operation control of the measurement unit 13, an operation control of the reaction tube cleaning mechanism unit 15, and a measurement information generation unit 55. The analysis of the measurement information and the like, the operation control of the reagent dispensing control mechanism unit 80, and the operation control of the notification means 100 can be performed. The notification unit 100 is, for example, a buzzer, a speaker, or the like. When necessary, for example, when a reagent liquid level deterioration or a reagent concentration gradient abnormality is obtained by an instruction from the control unit 90, an alarm is generated by sound or voice guidance. Occurs and notifies the user to that effect.

  FIG. 3 shows an example of the reagent abnormality detection parameter setting screen 110 displayed on the display device 6 shown in FIG. The display device 6 is, for example, a touch panel type liquid crystal display device, and the user can input necessary information to the reagent abnormality detection parameter setting screen 110 when the user directly touches the touch device with, for example, a touch pen or a finger.

  When the user (or operator) sets parameters necessary for reagent abnormality detection, the reagent abnormality detection parameter setting screen 110 shown in FIG. 3 is displayed on the display device 6. The reagent abnormality detection parameter is set for each reagent and is stored and held in the storage unit 91.

As shown in FIG. 3, the reagent abnormality detection parameter setting screen 110 includes an abnormality detection presence / absence setting unit 1.
20, a detection pipette intrusion amount setting unit 130, a pipette intrusion amount display unit 140 at the time of reagent liquid level deterioration, a parameter setting update acceptance button “OK” 150, and a parameter setting update cancel button “Cancel” 160. doing. This pipette is part of the probe and is an example of a suction tool.

  The abnormality detection presence / absence setting unit 120 shown in FIG. 3 includes an “valid” button 121 for executing the abnormality detection process and an “invalid” button 122 for invalidating the abnormality detection process. When the user clicks the “valid” button 121, the control unit 90 of the computer 5 can perform the reagent abnormality detection process for the target reagent under the conditions set on the reagent abnormality detection parameter setting screen 110. If the user clicks the “invalid” button 122, the control unit 90 of the computer 5 does not perform the reagent abnormality detection process for the target reagent under the conditions set on the reagent abnormality detection parameter setting screen 110. Disable processing.

  The detection pipette intrusion amount setting unit 130 shown in FIG. 3 has a plurality of numerical value input windows 131 and 132 and an additional setting permission button 138. The detection pipette intrusion amount setting unit 130 for detecting a reagent abnormality detection state is a specified pipette intrusion amount used for reagent abnormality detection, and a pipette for detecting a reagent abnormality deeper than a normal standard pipette intrusion amount. The amount of intrusion can be specified. The normal standard pipette penetration amount will be described later with reference to FIG. 4, and is, for example, 10 mm downward from the liquid level LL of the reagent in the reagent container.

  In the numerical input windows 131 and 132 shown in FIG. 3, for example, for detecting a reagent abnormality that is deeper than the normal standard pipette penetration amount of 10 mm for entering a detection pipette from the reagent liquid surface of the reagent container. You can set the pipette penetration amount. For example, the numerical value input windows 131 and 132 can be set to 20 mm, 30 mm, or the like. When the user presses the additional setting permission button 138, a numerical value input window (edit box) is added as shown in FIG. 3, and is added to the numerical value input windows 131 and 132, for example, to input a third numerical value. Since it is possible to add and display the window 133, the fourth numerical value input window 134, etc., the user can set the pipette intrusion amount for deeper reagent abnormality detection, for example, 40mm, in addition to 20mm, 30mm, etc. It can also be set to 50 mm or the like.

  The pipette intrusion amount display unit 140 at the time of reagent liquid level deterioration has a numerical value display window part 141. For example, the numerical value display window part 141 has, for example, a pipette intrusion amount at the time of reagent liquid level deterioration of 20 mm. Can be displayed. When the control unit 90 shown in FIGS. 2 and 3 determines that the reagent liquid level in the reagent containers 30 and 31 has deteriorated due to detection of a reagent abnormality described later, The amount of pipette penetration (for example, 20 mm) when the actual reagent used in the measurement of the sample (specimen) is deteriorated can be set in the numerical value display window 141.

  Finally, in FIG. 3, when the user executes the reagent abnormality detection parameter setting update, the target reagent is set on the reagent abnormality detection parameter setting screen 110 by clicking the “valid” button 121. A reagent abnormality detection process can be performed under certain conditions. In addition, when the user does not execute the parameter setting update, by clicking the “invalid” button 122, the reagent abnormality detection process is performed for the target reagent under the conditions set in the reagent abnormality detection parameter setting screen 110. Absent.

  Next, referring to FIG. 4, the intrusion of the pipette 220 for dispensing the first reagent probe 18 (or the second reagent probe 19) of the reagent dispensing control mechanism 80 and the example of the reagent container 30 (31). An example of the amount (down amount) will be described. FIG. 4 shows an example of the penetration amount (falling amount) of the reagent dispensing pipette corresponding to the reagent abnormality detection parameter. The pipette 220 is a thin metal tube, for example.

  As shown in FIG. 4, the reagent container 30 (31) is a plastic container, for example, and has an opening 30M (31M) at the top. In the reagent container 30 (31), the reagent MM is accommodated up to the level of the reagent liquid level LL. The pipette 220 is held downward by the first reagent probe 18 and the second reagent probe 19 of the reagent dispensing control mechanism unit 80 shown in FIG. 2 and enters the reagent MM. The pipette 220 can be inserted into the reagent container 30 (31) through the mouth 30M (31M) of the reagent container 30 (31).

  In FIG. 4, three reagent containers 30 (31) are shown, and the reagent liquid level LL is indicated by broken lines in the three reagent containers 30 (31). In FIG. 4, the left reagent container 30 (31) shows a standard pipette penetration amount LS, the intermediate reagent container 30 (31) shows a pipette penetration amount L1 for reagent abnormality detection, and the right side. The reagent container 30 (31) shows a pipette penetration amount L2 for detecting a deeper reagent abnormality.

  The standard pipette penetration amount LS is set to, for example, 10 mm, the abnormality detection pipette penetration amount L1 is set to, for example, 20 mm, and the deeper abnormality detection pipette penetration amount L2 is set to, for example, 30 mm. The standard pipette penetration amount LS corresponds to the standard penetration amount of the pipette 220 as a suction tool, and the pipette penetration quantities L1 and L2 for detection of reagent abnormality are used for reagent abnormality detection of the pipette 220 as suction tool. Corresponds to the amount of intrusion.

  Next, measurement control for detecting abnormality of the reagent MM using the reagent abnormality detection parameter described above will be described with reference to FIG. FIG. 5 shows a flow showing analysis of measurement information for detecting an abnormality of the reagent MM using the reagent abnormality detection parameter.

  In step S1 of FIG. 5, first, the user issues a measurement request for accuracy management of the reagent MM or calibration (calibration) to the measurement information generation unit 55 using the user interface 56 shown in FIG. In response to this, the measurement information generation unit 55 analyzes the measurement request.

  The loop for all measurement items in step S2 in FIG. 5 starts, and the process proceeds to step S3. In the determination of necessity / unnecessity of reagent abnormality detection in step S3, the measurement information generation unit 55 sets the reagent abnormality detection function for these reagents to “valid”, that is, reagent abnormality detection for all reagents used in response to the measurement request. It is determined whether it is necessary or “invalid”, that is, whether reagent abnormality detection is unnecessary. Since all the reagents have one reagent abnormality detection parameter that is associated in advance, the subsequent steps depend on whether the “presence or absence of reagent abnormality detection” in the reagent abnormality detection parameter is valid or invalid. It is determined whether or not the processing from S5 to S7 is performed.

  In the determination of necessity / unnecessity of reagent abnormality detection in step S3 in FIG. 5, if the “invalid” button 122 of the abnormality detection presence / absence setting unit 120 is clicked in FIG. 3, the presence / absence of abnormality detection of the reagent is invalid (unnecessary). Therefore, the reagent abnormality detection process is not performed, and the process proceeds to step S4. In step S4, it is determined whether or not there are remaining measurement items. If there are remaining measurement items, the process returns to step S2.

  In the determination of necessity / unnecessity of reagent abnormality detection in step S3 of FIG. 5, the user designates the reagent abnormality detection processing by clicking the “valid” button 121 shown in FIG. If the reagent is not used for the measurement for a certain period or longer, the presence / absence of abnormality detection of the reagent is valid (necessary), so it is determined to be valid (necessary), and the process proceeds to step S5. The process after step S5 is performed.

In step S5, the measurement information generation unit 55 verifies the number of times of multiple measurement for the measurement information of the item using the reagent for which it is determined that the reagent abnormality detection process is effective by the above-described procedure. Here, multiplex measurement is a predetermined number of times in order to confirm whether the dispersion of measurement results falls within a certain range by dispensing the same sample and the same reagent multiple times in the same amount and measuring. This is a repeated measurement.

That is, in step S5, the measurement information generation unit 55 in FIG. 2 has a relationship between the designated number of detection pipette intrusions and (multiple measurement times-1).
Specified number of detection pipette penetrations ≤ (Number of multiple measurements-1)
It is determined whether or not.

  The number of times of multiple measurement is a value specified in accuracy management setting (request) or calibration setting (request). If the number of multiple measurements is the specified number of intrusion amount settings specified as the detection pipette intrusion amount in the reagent abnormality detection parameter 110 of FIG. 3 (a plurality of numerical value input windows 131 (for example, 20 mm) shown in FIG. When the number is smaller than the number of input windows 132 (e.g., 30 mm) (corresponding to two), the specified number of intrusion amount settings is used as the number of times of multiplex measurement. In this way, the measurement request is changed.

  That is, when the relational condition between the designated number of detection pipette intrusions and the number of multiple measurements shown in step S5 is satisfied, the process proceeds to step S7, and FIG. 4 used for the reagent aspiration for each of the multiple measurements. The pipette 220 penetration amount of the pipette 220 to the reagent liquid surface LL shown is assigned and set. That is, with respect to the reagent liquid level LL, the standard pipette penetration amount LS is 10 mm, for example, the abnormality detection pipette penetration amount L1 is 20 mm, and the deeper abnormality detection pipette penetration amount L2 is 30 mm, for example. set.

  As the order of assigning and setting the pipette penetration amount of the pipette 220 to the reagent liquid level LL, the largest pipette penetration amount is assigned to the reagent container to be dispensed at the end of the measurement, and the second from the end. The reagent container dispensed is assigned the value described in the reagent abnormality detection parameter as the detection pipette penetration amount in the form of the second largest pipette penetration amount. Then, after the values described in the reagent abnormality detection parameters are assigned, all the remaining values are assigned the standard pipette penetration amount LS shown in FIG. For example, if the number of multiple measurements is set to 5 according to the user's instruction, the largest pipette penetration amount of 30 mm is assigned to the reagent container to be dispensed at the end of the measurement, and the reagent container is dispensed second from the end. The second largest pipette penetration 20 mm is assigned to the reagent container to be poured, and the standard pipette penetration LS shown in FIG. 4 is allotted to the remaining three reagent containers.

  If the condition shown in step S5 of FIG. 5 is not satisfied, the process proceeds to step S6. In step S6, the number of times of multiple measurements is set to “specified number of detection pipette intrusions + 1” and is increased, and the process proceeds to step S7. Thus, the same sample and the same reagent are dispensed and measured a plurality of times in the same amount, and variations in measurement results are obtained.

  When the setting of the pipette penetration amount is completed in step S7, the process proceeds to step S4. In step S4, it is determined whether there are remaining measurement items. If there are remaining measurement items, the process returns to step S2.

  As described above, after the measurement request analysis by the measurement information generation unit 55 is completed, as illustrated in FIG. 4, measurement for the measurement request is started.

The first reagent probe 18 (second reagent probe 19) of the reagent dispensing control mechanism unit 80 shown in FIG. 2 responds to each of the multiplexed measurement requests described above with the corresponding reagent container 30 (31). Dispensing the reagent MM inside. Among these, in the scene where the reagent MM is aspirated, various types of motors (not shown) are controlled so that the pipette 220 for dispensing enters the reagent liquid surface LL in the same manner as the pipette penetration amount described in the measurement request. It has become. Thereafter, the dispensing pipette 220 sucks the reagent MM in the reagent container 30 (31), and discharges the reagent MM to the reaction container 70 shown in FIG.

  Next, a procedure for detecting a reagent abnormality using the above-described measurement result will be described with reference to FIG. FIG. 6 is a flowchart for detecting a reagent abnormality using a measurement result and determining a reagent abnormality.

  As a premise for determining a reagent abnormality, when the measurement of an item using a reagent for which it is effective to perform a reagent abnormality detection process, the amount of pipette entering the reagent liquid surface LL differs according to the procedure shown in FIG. (Standard pipette penetration amount LS: 10 mm, abnormality detection pipette penetration amount L1: 20 mm, abnormality detection pipette penetration amount L2: 30 mm) Two or more multiple measurement results (absorbance) are obtained. Therefore, when the number of these multiple measurement results is “2” and “3” or more, the reagent abnormality detection process is branched.

  As shown in FIG. 6, when the reagent abnormality detection is started, in step R0, the multiplex measurement result (absorbance) is waited, and the process proceeds to step R1.

  First, in step R1 in FIG. 6, when the number of multiple measurement results (absorbance) is “2”, the process proceeds to step R2. In step R2, when the difference between the two multiplex measurement results is equal to or greater than a separately set threshold value, the process proceeds to step R3. In step R3 of FIG. 6, since the difference between the two multiplex measurement results is equal to or greater than a separately set threshold value, it is determined that “the reagent liquid level LL has deteriorated”, and “the reagent liquid level LL is If it is “degraded”, the target reagent state is updated and the process ends.

  As described above, when the measurement information generation unit 55 in FIG. 2 determines that the reagent liquid level LL of the reagent MM in the reagent container 30 (31) has deteriorated, the control unit 90 causes the notification unit 100 to By driving, for example, an alarm with a sound from a buzzer is generated, or an alarm is issued by voice guidance through a speaker, thereby notifying the user of a warning about the deterioration of the reagent liquid level LL. Thereby, the user can surely know the deterioration of the reagent liquid level LL by sound or voice guidance. In addition, the display device 6 shown in FIG. 2 can display display contents for notifying the deterioration of the reagent liquid level LL. Therefore, the user can surely know the deterioration of the reagent liquid level LL visually.

  Otherwise, if the difference between the two multiple measurement results in step R2 of FIG. 6 is less than a separately set threshold, the process moves to step R8. In Step R8, the difference between the two multiplex measurement results is less than a separately set threshold value, so that “the reagent is not abnormal” is determined, and “the reagent liquid level LL is not deteriorated”. Then, the target reagent state is updated and the process ends.

  Subsequently, in step R1 in FIG. 6, when the number of multiple measurement results (absorbance) is “3” or more, the process proceeds to step R4. In step R4, the multiple measurement results are grouped by the pipette penetration amount used in each measurement. For example, as shown in FIG. 3, when a detection pipette penetration amount L1 (20 mm) and a detection pipette penetration amount L2 (30 mm) having different values are set as the detection pipette penetration amount, The measurement result is divided into three groups: a measurement result having an amount of 30 mm, a measurement result having a pipette penetration amount of 20 mm, and a measurement result using a standard pipette penetration amount LS (10 mm).

In step R4, measurement information is generated for each measurement result in which the pipette penetration amount L2 is 30 mm, the measurement result in which the pipette penetration amount L1 is 20 mm, and the measurement result using the standard pipette penetration amount LS (10 mm). The unit 55 calculates an average value of the measurement result values, calculates a variance value as an element thereof as an evaluation value, and proceeds to Step R5.

  If, in step R5, these variance values are equal to or greater than a separately provided threshold value, the process proceeds to step R7. In step R7, the measurement information generating unit 55 estimates that the reagent state has changed despite the deep position away from the reagent liquid level LL. It is determined that a large concentration gradient is generated in the reagent MM, and the target reagent state is updated when “the concentration gradient of the reagent in the target is abnormal”.

  As described above, when the measurement information generation unit 55 in FIG. 2 determines that a large concentration gradient is generated in the reagent MM in the reagent container 30 (31) and the concentration gradient is abnormal, the control unit 90 Then, the notification unit 100 is driven to generate an alarm with a sound from a buzzer, for example, or to give an alarm by voice guidance through a speaker, thereby notifying the user of a reagent abnormality warning. Thereby, the user can surely know the abnormality of the concentration gradient of the reagent MM by sound or voice. Further, the display device 6 shown in FIG. 2 can display the display contents for notifying the abnormality of the concentration gradient of the reagent MM. As a result, the user can surely visually recognize that a large abnormal concentration gradient is generated in the reagent MM.

  Otherwise, if the evaluation value is less than the threshold value in step R5 of FIG. 6, the process proceeds to step R6. In Step R6, the average value of the measurement results based on the detection pipette penetration amounts L1 (20 mm) and L2 (30 mm) is compared with the measurement result value based on the standard pipette penetration amount LS (10 mm), and the comparison is made. If the result (difference) is equal to or greater than a separately set threshold, the process proceeds to step R3. The measurement information generation unit 55 in FIG. 2 determines that “the reagent liquid level LL has deteriorated” in the reagent container 30 (31), and the “reagent liquid level LL has deteriorated” indicates that the target The reagent state is updated and the process ends.

  As described above, when the measurement information generation unit 55 in FIG. 2 determines that the reagent liquid level LL of the reagent MM in the reagent container 30 (31) has deteriorated, the control unit 90 causes the notification unit 100 to By driving, for example, an alarm with a sound from a buzzer is generated, or an alarm is issued by voice guidance through a speaker, thereby notifying the user of a warning about the deterioration of the reagent liquid level LL. Therefore, the user can surely know the deterioration of the reagent liquid level LL by sound or sound guidance. In addition, the display device 6 shown in FIG. 2 can display display contents for notifying the deterioration of the reagent liquid level LL. Thus, the user can surely know the deterioration of the reagent liquid level LL visually.

  In step R6, the average value of the measurement results based on the detection pipette penetration amount L1 (20 mm) and L2 (30 mm) is compared with the measurement result value based on the standard pipette penetration amount LS (10 mm). If the comparison result (difference) is less than a separately set threshold, the process proceeds to step R8. In step R8, it is determined that the reagent liquid level LL is not deteriorated and there is no abnormality, and “the reagent liquid level LL is not deteriorated” is determined. Update after completing.

  Even if the reagent is determined to be abnormal by detecting the abnormality of the reagent as described above, after the problem is solved by the user (for example, the reagent is stirred by manually shaking the reagent container), Accuracy control or calibration using the same reagent is performed again. In addition, when it is determined that the reagent is normal, the reagent is aspirated using the standard pipette penetration amount (depth) thereafter.

  Next, with reference to FIG. 7, the control at the time of receiving a measurement request for a patient sample (specimen) performed after the reagent abnormality test is completed will be described. FIG. 7 is a flowchart showing a control procedure when receiving a measurement request for a sample (specimen) of a patient.

  First, in response to the user issuing a measurement request for a specimen sample of a patient to the measurement information generation unit 55 through the user interface 56 of FIG. 2, the measurement information generation unit 55 analyzes the measurement request. . During these measurement requests, the process proceeds from the loop for all measurement items in step T0 shown in FIG. 7 to the reagent state confirmation step T1. In this step T1, the reagent state is confirmed, and when the reagent liquid level LL shown in FIG. 4 is deteriorated, measurement items using the reagent MM determined to be deteriorated are included. In the case, the process proceeds to step T2.

  In this step T2, the pipette intrusion amount adopted when the reagent MM of that item is aspirated is “pipette intrusion amount at the time of liquid level deterioration (for example, 20 mm) of the pipette intrusion amount display portion 140 at the time of liquid level deterioration shown in FIG. The measurement request is changed to use the value “)”, and a flag indicating the deterioration of the reagent liquid level LL is set in the measurement result in step T3. Thereafter, if there are remaining measurement items in step T8, the process returns to step T0, but if not, the process ends.

  In Step T1 of FIG. 7, when the reagent state is confirmed and the reagent MM includes a measurement item using the reagent MM in which a large concentration gradient (abnormal concentration gradient) is generated, Step T4 is performed. Move on. In step T4, the measurement is canceled (skip) without measuring the target item. That is, when there is an abnormality in the concentration gradient of the reagent in this way, the target item for the reagent MM is not measured. Thereafter, if there are remaining measurement items in step T8, the process returns to step T0, but if not, the process ends.

  Further, in step T1 in FIG. 7, the reagent state is confirmed and the reagent state is normal and normal, but in step T5, the reagent MM is a reagent abnormality detection target and has been used for measurement for a certain period or more. If a measurement item using a non-reagent MM is included, the process proceeds to step T6. In step T6, a reagent blank calibration using the reagent MM is added so as to be performed prior to the measurement item. As a result, if the reagent MM has not been used for a certain period of time or longer, the reagent MM is automatically subjected to reagent blank calibration, so that the current state of the reagent MM can be reliably grasped. The reagent blank calibration refers to measuring the absorbance of a standard sample whose concentration is known in advance, such as water.

  In this calibration, a reagent abnormality detection process is performed. If it is determined that the reagent MM is abnormal, the result of the patient measurement using the reagent MM is Set the error flag.

  In step 7, when the used reagent MM is normal, the pipette penetration amount is changed to the standard pipette penetration amount LS shown in FIG. If the used reagent MM is not a reagent abnormality detection target in step T5, the process proceeds to step T7, and the pipette penetration amount is changed to the standard pipette penetration amount LS. After step T7, if there are remaining measurement items in step T8, the process returns to step T0, but if not, the process ends.

  In a normal automatic analyzer, since the reagent liquid level in the reagent container is always in contact with the outside air, the deterioration of the reagent progresses rapidly near the reagent liquid level. When attempting to aspirate the reagent from a position deeper than the reagent liquid surface, the area of the outer wall of the pipette (also referred to as a probe) in contact with the reagent increases, and the area of the outer wall of the pipette that becomes dirty increases. For this reason, the washing | cleaning cost for removing a reagent from a pipette will increase.

  However, in the above-described automatic analyzer 1 of the embodiment of the present invention, when a specific condition is satisfied, the measurement of the requested item is multiplexed, and when the reagent MM is dispensed to the added amount, The reagent can be aspirated by lowering the pipette to a position deeper than usual. For this reason, it is possible to detect the deterioration of the reagent liquid level LL while suppressing the cleaning cost for removing the outer wall dirt of the pipette (probe).

  Compare the measurement result by dispensing the reagent MM at the normal lowering position of the pipette with the measurement result by dispensing at a deeper position, and if the difference is more than a certain value, near the reagent liquid level LL It is determined that the reagent MM is deteriorated, and the reagent container can be manually stirred by the user.

  Specific conditions described above include a case where a certain time or more has passed since the previous measurement and a state where a certain amount of time has passed without the reagent storage being rotated.

  With respect to the reagent MM that is known to have a remarkable deterioration of the reagent liquid level LL due to the outside air, it is possible to always set the pipette to enter the reagent MMM with a descending amount deeper than usual to dispense the reagent MM.

  If it is determined that the deterioration near the reagent liquid level LL is significant as described above, the pipette is always allowed to enter the reagent MMM with a descending amount deeper than usual with respect to the reagent MM. The setting for dispensing the reagent MM can be automatically enabled.

  Abnormality in the measurement result due to the deterioration of the reagent liquid level LL and the concentration gradient of the reagent MM can be detected early. Since the amount of penetration of the pipette is increased only when the reagent liquid level LL is deteriorated, an increase in reagent dead volume can be reduced as much as possible.

  The automatic analyzer 1 according to the embodiment of the present invention is an apparatus that analyzes a sample using the reagent MM in the reagent container 30 (31). This automatic analyzer 1 lowers the suction tool (for example, pipette 220) to suck the reagent MM in the reagent container 30 (31), and the standard penetration amount of the suction tool when the suction tool enters from the reagent liquid level LL. LS and at least one reagent intrusion amount L1, L2 for detecting reagent abnormality larger than the standard intrusion amount LS are held, and when a measurement request for accuracy management or calibration of the reagent MM is issued, the standard In addition to the measurement by dispensing the reagent MM using the intrusion amount LS, a measurement information generating unit 55 that adds measurement by dispensing the reagent MM using the intrusion amounts L1 and L2 for detecting reagent abnormality is provided.

  As a result, the reagent is effectively used so that the dead volume of the reagent is not increased as much as possible even if the portion near the liquid surface of the reagent in the reagent container deteriorates or a concentration gradient of the reagent occurs in the reagent container. be able to. In addition, it is possible to prevent the portion of the deteriorated reagent MM in the reagent container from being dispensed to the sample side of the reaction container, and to prevent abnormalities in the results of the analysis data.

In this automatic analyzer 1, the amount of intrusion from the reagent liquid level LL of the suction tool when the reagent liquid level LL is deteriorated is retained, and measurement is performed by dispensing the reagent MM using the standard intrusion amount LS. When the result is compared with the measurement result by dispensing the reagent using one reagent abnormality detection intrusion amount, and it is determined that there is a deviation of a certain value or more in the comparison result, In the measurement of the sample using the reagent MM, the penetration amount of the suction tool is set using the penetration amount when the reagent liquid level is deteriorated. As a result, although the reagent liquid level LL is deteriorated, the reagent part below the reagent liquid level LL can be used, and the intrusion amount of the suction tool is set using the intrusion amount at the time of the reagent liquid level deterioration. By doing so, it is possible to avoid sucking and dispensing the deteriorated portion of the reagent liquid level LL. Accordingly, it is possible to prevent the portion of the deteriorated reagent MM in the reagent container from being dispensed to the sample side of the reaction container, and to prevent an abnormality in the analysis data result.

  Further, in the automatic analyzer 1, the measurement result by the reagent dispensing using the standard intrusion amount LS and the reagent dispensing using the reagent intrusion amounts L1 and L2 for detecting at least two different values are set. Between the measurement result obtained by dispensing the reagent using the standard intrusion amount LS and the measurement result obtained by dispensing the reagent using the intrusion amounts L1 and L2 for reagent abnormality detection. When the values differ, but there is no discrepancy between the measurement results of reagent dispensing using the reagent intrusion amounts L1 and L2 for detecting reagent abnormality with at least two different values. In the subsequent measurement of the sample using the reagent, the amount of penetration of the suction tool is set using the amount of penetration when the reagent liquid level deteriorates. As a result, although the reagent liquid level is deteriorated, it is assumed that there is no abnormality in the concentration gradient of the reagent part below the reagent liquid level LL. Part can be used. For this reason, by setting the amount of penetration of the suction tool using the amount of penetration when the reagent liquid level deteriorates, it is possible to avoid sucking and dispensing the portion of the reagent liquid level LL that has deteriorated. Accordingly, it is possible to prevent the portion of the deteriorated reagent MM in the reagent container from being dispensed to the sample side of the reaction container, and to prevent an abnormality in the analysis data result.

  Furthermore, in the automatic analyzer 1, the measurement result by dispensing of the reagent using the standard intrusion amount LL and the dispensing of the reagent using the intrusion amounts L1 and L2 for reagent abnormality detection in which at least two different values are set. When there is a discrepancy of a certain value or more in all of the measurement results by reagent dispensing using the intrusion amount for reagent abnormality detection in which at least two different values are set. In this case, the target reagent MM is not used. Thereby, when there is a deviation of a certain value or more between the measurement results by the reagent dispensing using the reagent intrusion amounts L1 and L2 for detecting reagent abnormality in which at least two different values are set, that is, the reagent liquid level Since there is an abnormality in the concentration gradient of the reagent portion below the LL portion, the reagent liquid surface LL portion and the reagent MM portion below the reagent liquid surface LL portion cannot be used. For this reason, it is determined that the reagent MM cannot be used in an abnormal state, and the use of the abnormal reagent is stopped. In this case, the user can remove the abnormality in the concentration gradient in the portion of the reagent below the portion of the reagent liquid level LL by shaking the reagent container by hand.

  In the automatic analyzer 1, the addition / change of measurement information for detecting a reagent abnormality is performed when a reagent that has not been used for a certain period of time is used, or when an instruction is given through an operation by a user. As a result, if a certain time has passed or the user instructs, measurement information for detecting reagent abnormality can be added / changed.

  The automatic analyzer 1 retains reagent information indicating whether the reagent is a reagent subject to reagent abnormality detection processing, and performs sample measurement when the reagent has not been used for a certain period of time or more when performing sample measurement of a patient using the reagent. Before performing the above, calibration by the reagent blank by the reagent is automatically added. As a result, when the reagent has not been used for a certain period of time or longer, the current state of the reagent can be reliably grasped by automatically performing calibration with the reagent blank of the reagent.

  The automatic analyzer 1 has a notification means for generating an alarm when the liquid level deterioration of the reagent MM or the concentration gradient abnormality of the reagent MM is obtained. Thereby, when there is a liquid level deterioration of the reagent MM or a concentration gradient abnormality of the reagent MM, the notification means can reliably notify the user to that effect.

Although an embodiment of the present invention has been described, this embodiment is presented as an example and is not intended to limit the scope of the invention. This embodiment can be implemented in various other forms, and various omissions, replacements, and changes can be made without departing from the spirit of the invention. This embodiment and its modifications are included in the scope and gist of the invention, and are included in the invention described in the claims and the equivalents thereof.

  In the illustrated embodiment of the present invention, two reagent abnormality detection intrusions L1, L2 are set, but three or more reagent abnormality detection intrusions L1, L2,... good.

DESCRIPTION OF SYMBOLS 1 Automatic analyzer 8 1st reagent arm 9 2nd reagent arm 15 Reaction tube washing | cleaning mechanism part 18 1st reagent probe 19 2nd reagent probe 30 Reagent container 31 Reagent container 70 Reaction tube 80 Reagent dispensing control mechanism part 220 Pipette (aspiration) Example of ingredients)
MM Reagent LS Standard pipette penetration (standard penetration of suction tool)
L1, L2 Pipette intrusion amount for reagent abnormality detection (invasion amount for reagent abnormality detection of aspirator)

Claims (7)

An automatic analyzer for analyzing a sample using a reagent in a reagent container,
A standard entry amount of the suction tool when the suction tool is lowered to suck the reagent in the reagent container and the suction tool enters from the reagent liquid surface;
Holding at least one reagent abnormality intrusion amount larger than the standard intrusion amount,
When a measurement request for accuracy control or calibration of the reagent is issued, in addition to measurement by dispensing the reagent using the standard intrusion amount, the reagent using the intrusion amount for detecting the reagent abnormality is used. An automatic analyzer comprising a measurement information generation unit for adding measurement by dispensing. The amount of penetration of the suction tool from the reagent liquid level when the reagent liquid level is deteriorated is retained, the measurement result by dispensing the reagent using the standard penetration amount, and the one Compared with the measurement result by dispensing of the reagent using the amount of invasion for reagent abnormality detection, if it is determined that there is a deviation of a certain value or more in the comparison result,
2. The automatic analyzer according to claim 1, wherein in the subsequent measurement of the sample using the reagent, the amount of penetration of the suction tool is set using the amount of penetration when the reagent liquid level deteriorates. Comparing the measurement result obtained by dispensing the reagent using the standard penetration amount with the measurement result obtained by dispensing the reagent using the penetration amount for detecting the abnormality of the reagent in which at least two different values are set do it,
There is a difference between the measurement result obtained by dispensing the reagent using the standard penetration amount and the measurement result obtained by dispensing the reagent using the penetration amount for detecting reagent abnormality, but at least 2 In the case where there is no divergence of a certain value or more between the measurement results by the reagent dispensing using the reagent abnormality detection intrusion amount in which two different values are set,
3. The automatic analyzer according to claim 2, wherein in the subsequent measurement of the sample using the reagent, the amount of penetration of the suction tool is set using the amount of penetration when the reagent liquid level deteriorates. The measurement result by dispensing the reagent using the standard penetration amount is compared with the measurement result by dispensing the reagent using the penetration amount for detecting the abnormality of the reagent in which at least two different values are set. And
When a difference of a certain value or more is found in all of the measurement results by the reagent dispensing using the intrusion amount for detecting the reagent abnormality in which at least two different values are set, the target reagent The automatic analyzer according to claim 1, wherein the automatic analyzer is not used.   The addition / change of the measurement information for detecting the reagent abnormality is performed when the reagent that has not been used for a certain period of time is used or when instructed through an operation by a user. The automatic analyzer described. Reagent information indicating whether the reagent abnormality detection processing target reagent is retained,
When performing the sample measurement of a patient using the reagent, when the reagent has not been used for a certain period of time or longer, calibration with a reagent blank by the reagent is automatically added before the sample measurement is performed. The automatic analyzer according to claim 3 or 4.   The automatic analyzer according to any one of claims 1 to 6, further comprising a notification means for generating an alarm when the reagent level deterioration or the reagent concentration gradient abnormality is obtained. .

Images