Automated analysis device

Abstract

The present application provides an automatic analysis device for estimating a cause of variation in a measured value of a precision management substance. The present application is an automatic analysis device for analyzing a test object, characterized by comprising: an acquisition unit that acquires a variation amount of a measured value of a precision management substance used for precision management; a calculation unit that calculates a variation prediction value based on a difference value before and after a batch change of a concentration value of a calibration solution used for calibration; and an estimation unit that estimates a cause of variation occurring in the measured value of the precision management substance based on a comparison result of the variation amount and the variation prediction value.

Description

Technical Field

[0001] This invention relates to an automated analysis device for analyzing samples. Background Technology

[0002] Automated analytical instruments are used to determine the concentration of specific components in samples such as blood and urine. More specifically, they measure the absorbance of the reaction solution after the sample and reagents react, and the potential of the electrolyte solution after diluting the sample. The absorbance, potential, and other measurement results are then converted into the concentration of the specific component using a pre-prepared calibration curve. Furthermore, the calibration curve is generated by performing calibrations that include measurements of absorbance, potential, etc., using multiple standard solutions and calibration solutions with known concentrations. In addition, to manage the accuracy of the automated analytical instrument, it is necessary to periodically verify whether the measured values ​​of precision-managed substances with known concentrations are within the accuracy management range. Calibration is recommended based on the results of accuracy management and other factors, with appropriate implementation details and intervals.

[0003] Patent Document 1 discloses an automatic analysis device that, based on a comparison of stored variation patterns with measured variation patterns, notifies the content and duration of calibration based on a combination of accuracy management and calibration results.

[0004] Existing technical documents

[0005] Patent documents

[0006] Patent Document 1: Japanese Patent Application Publication No. 2012-026815 Summary of the Invention

[0007] The technical problem that the invention aims to solve

[0008] However, Patent Document 1 does not disclose any content that assists in analyzing the causes of variations in the measured values ​​of precision-managed substances. When the measured values ​​of precision-managed substances change, it is desirable to be able to quickly analyze the causes of the changes. For example, if it can be deduced whether the change in the measured values ​​of precision-managed substances is due to a batch change in the calibration solution used in calibration, subsequent responses become easier.

[0009] Therefore, the object of the present invention is to provide an automatic analysis device for estimating the cause of variation in the measured values ​​of a substance to manage accuracy.

[0010] Technical solutions adopted to solve technical problems

[0011] To achieve the above objectives, the present invention is an automated analysis device for analyzing samples, characterized in that it includes: an acquisition unit for acquiring the amount of variation in the measured value of a precision management substance for precision management; a calculation unit for calculating the predicted amount of variation based on the difference between the concentration values ​​of a calibration solution before and after a batch change; and an estimation unit for estimating the cause of the variation in the measured value of the precision management substance based on a comparison result of the amount of variation and the predicted amount of variation.

[0012] Invention Effects

[0013] According to the present invention, an automatic analysis device is capable of providing the reasons for variations in the measured values ​​of substances with estimated accuracy management. Attached Figure Description

[0014] Figure 1 This is a diagram illustrating an example of the structure of an automatic analysis device.

[0015] Figure 2 A diagram showing an example of the structure of an electrolyte measurement unit is provided.

[0016] Figure 3 This is an example graph showing the daily variation of the results of periodic measurements of a substance used for precision management.

[0017] Figure 4 This is an example graph showing the daily variation of the measured values ​​of precision management substances due to batch changes in calibration solutions.

[0018] Figure 5 This is a diagram illustrating an example of the processing flow of Embodiment 1.

[0019] Figure 6 This is a diagram illustrating an example of a presumed process for determining the cause of a change.

[0020] Figure 7 This is a diagram illustrating an example of a situation where the measured value of a precision management substance changes due to a batch change in the calibration solution.

[0021] Figure 8 This is a diagram showing an example of a display guided by input values. Detailed Implementation

[0022] Preferred embodiments of the automatic analysis apparatus of the present invention will now be described with reference to the accompanying drawings. Furthermore, in the following description and drawings, repeated descriptions are omitted by using the same reference numerals to denote components having the same functional structure. Additionally, sometimes the drawings schematically illustrate embodiments, simplifying the representation of the actual object.

[0023] Example 1

[0024] use Figure 1 An example illustrating the structure of the automated analysis device 1 is provided. The automated analysis device 1 includes a sample tray 2, a reagent tray 4, a reaction vessel 5, a reagent dispensing unit 6, a sample dispensing unit 7, an electrolyte measurement unit 8, an interface 9, a computer 10, an input unit 11, an output unit 12, and a photometer 13.

[0025] The specimen tray 2 holds specimen cups 3, which contain patient-provided blood, urine, and other specimens, as well as standard specimens used for calibration and accuracy management, arranged side-by-side in a concentric circle. Alternatively, the specimen cups 3 may not be mounted on the specimen tray 2, but rather on a specimen rack arranged in a straight line.

[0026] In addition, the standard samples used in calibration include standard solutions and calibration solutions with known concentrations of specific components. The standard solution is a solution containing specific components and has a concentration near both the upper and lower limits of the measurement range of the automated analyzer 1. That is, at least two standard solutions are used. The calibration solution is a solution that simulates a sample provided by a patient.

[0027] The reagent tray 4 contains reagents that react with the sample. In the reaction vessel 5, reagents are dispensed from the reagent tray 4 via the reagent dispensing section 6, and samples are dispensed from the sample cup 3 via the sample dispensing section 7. The reagents and samples dispensed into the reaction vessel 5 react and develop color while maintaining a specified temperature. The absorbance of the resulting liquid is measured by the photometer 13. Furthermore, the reagent tray 4, reaction vessel 5, and photometer 13 involved in the absorbance measurement are collectively referred to as the colorimetric unit.

[0028] Electrolyte assay unit 8 is used to measure the potential of electrolyte solutions diluted with the sample or standard sample, and will be used later. Figure 2 Describe it.

[0029] Computer 10 controls the various components connected via interface 9 and calculates the concentration value of a specific component based on the results measured by the colorimetric unit and electrolyte measurement unit 8, and outputs the concentration value to output unit 12. Output unit 12 is, for example, an LCD monitor, touch panel, or printer, which displays or prints the concentration value of the specific component output from computer 10. Measurement conditions in the colorimetric unit and electrolyte measurement unit 8 can be input from input unit 11. Input unit 11 is, for example, a keyboard or mouse, and when output unit 12 is a touch panel, a GUI (Graphical User Interface) displayed on the touch panel serves as input unit 11.

[0030] use Figure 2Here is an example illustrating the structure of the electrolyte measurement unit 8. The electrolyte measurement unit 8 is a unit for measuring the concentration of ions contained in a sample or standard sample, and includes an electrolyte concentration calculation unit 14, a potentiometer 15, a dilution tank 18, a Cl electrode 19, a K electrode 20, a Na electrode 21, a pressure valve 22, and a comparison electrode 23.

[0031] In the dilution tank 18, the sample or standard sample dispensed from the sample cup 3 by the sample dispensing unit 7 is diluted to a suitable concentration for measurement by the diluent 17. The diluted sample or standard sample passes through the Cl electrode 19, K electrode 20, and Na electrode 21 by the action of the pressure valve 22. Potentials corresponding to the concentrations of Cl, K, and Na ions contained in the solution are generated at the Cl electrode 19, K electrode 20, and Na electrode 21, respectively. Furthermore, since a potential corresponding to the concentration of the comparison electrode solution 24 is also generated at the comparison electrode 23, the potential difference between the Cl electrode 19, K electrode 20, Na electrode 21 and the comparison electrode 23 is measured by the potentiometer 15. Additionally, before measuring the potential difference of the diluted sample or standard sample, the potential difference between the internal standard solution 16 and the comparison electrode solution 24 is measured as the reference potential of the electrolyte measurement unit 8. The potential difference measured by the potentiometer 15 is transmitted to the electrolyte concentration calculation unit 14.

[0032] The electrolyte concentration calculation unit 14 is a calculator that converts the potential difference measured on the sample into the concentrations of Cl ions, K ions, and Na ions contained in the sample. It is typically composed of a CPU (Central Processing Unit) and memory. Alternatively, the computer 10 can function as the electrolyte concentration calculation unit 14. When converting the measured potential difference into the concentration of a specific component, a straight line representing the relationship between potential difference and concentration, i.e., a calibration curve, is used. The calibration curve is generated by performing calibration that involves measuring the potential difference using multiple standard solutions and calibration solutions with known concentrations.

[0033] Specifically, the slope of the calibration curve is calculated using the potential difference measured against the low-concentration standard solution and the potential difference measured against the high-concentration standard solution as the vertical axis, and the concentrations of the two standard solutions as the horizontal axis. Furthermore, the intercept of the calibration curve, with the calculated slope, is calculated based on the potential difference measured relative to the calibration solution and the concentration of the calibration solution. The calibration curve generated through calibration is stored in the electrolyte concentration calculation unit 14 and is read out and used when calculating the concentrations of the sample and the precision management substance.

[0034] use Figure 3 Explanation of accuracy management. For the accuracy management of the automatic analysis device 1, the measured values ​​of the accuracy-managed substances with known concentrations are periodically checked using a daily variation chart to confirm whether they are within the accuracy management range. Figure 3This is an example of a daily variation graph. The vertical axis represents the measured value of the precision-managed substance with a known Na concentration, and the horizontal axis represents the measurement day. Each day, the measured value of the precision-managed substance's concentration is confirmed to be between the upper and lower limits. Upper and lower limits are set for each precision-managed substance. For example, the range of precision management can be (average - 2 × standard deviation) to (average + 2 × standard deviation) based on the average and standard deviation of multiple measurements of the same precision-managed substance.

[0035] use Figure 4 Explain the variation in the measured values ​​of substances subject to precision management. Figure 4 This is an example of a daily variation graph showing changes in the measured values ​​of precision-managed substances, specifically the case where the calibration solution batch changed on January 14, 2020. In creating the calibration curve used to calculate the concentration of precision-managed substances, the concentration value of the calibration solution provided by the reagent manufacturer and the potential difference measured for that calibration solution are used. The concentration value of the calibration solution provided by the reagent manufacturer is then referred to as the displayed value. The displayed value is input by the operator into the automatic analyzer via input unit 11. If the displayed value of the calibration solution is, for example, represented as an integer 140, the actual concentration of the calibration solution ranges from 139.5 to 140.4. That is, even for the same calibration solution with a displayed value of 140, the actual concentration value can differ by a maximum of 0.9 between different batches. Using different calibration curves based on the difference in actual concentration values ​​can sometimes lead to changes in the measured values ​​of precision-managed substances. Furthermore, the reasons for changes in the measured values ​​of precision-managed substances are not limited to batch changes of the calibration solution; if the operator misinterprets the cause of the change, it will take a long time to respond.

[0036] Therefore, in this embodiment, the cause of the change in the measured value of the precision management substance is inferred by comparing the predicted change calculated based on the difference between the concentration values ​​of the calibration solution used in the calibration and the measured change of the precision management substance.

[0037] use Figure 5 An example of the processing flow of this embodiment is explained step by step.

[0038] (S501)

[0039] Computer 10 causes the colorimetric unit or electrolyte measurement unit 8 to measure the standard solution and calibration solution, and performs calibration. Specifically, the slope of the calibration curve is calculated based on the absorbance or potential difference measurements of the low-concentration and high-concentration standard solutions and the concentrations of the two standard solutions. The intercept of the calibration curve with the calculated slope is calculated based on the absorbance or potential difference measurements of the calibration solution and the displayed concentration of the calibration solution.

[0040] Additionally, when the calibration solution is changed to a different batch, the displayed value C is based on the concentration of the new batch of calibration solution after the batch change.N A calibration curve is generated using the measured values ​​of the new batch of calibration solution, and this curve is stored along with information indicating that the batch of calibration solution has been changed. Furthermore, unlike the generated calibration curve, the concentration value C of the old batch of calibration solution (the calibration solution used before the batch change) is displayed. O The displayed value C of the new batch of calibration solution N They are stored together. In addition, the absorbance or potential difference measurements for the old and new batches of calibration solution are also stored. If the batch of calibration solution remains unchanged, the displayed value C is based on the old batch of calibration solution. O Generate and store calibration curves based on the measured values ​​of the old batch of calibration solution.

[0041] (S502)

[0042] Computer 10 causes the colorimetric unit or electrolyte measurement unit 8 to measure the concentration values ​​of at least two precision-managed substances. Specifically, based on the calibration curve calculated in S501, the measured values ​​of absorbance or potential difference of each precision-managed substance are converted into the concentration values ​​of each precision-managed substance. The calculated concentration values ​​can also be displayed on the daily variation graph.

[0043] (S503)

[0044] Computer 10 determines whether there has been a change in the concentration values ​​of each precision-controlled substance measured in S502. For example, it determines whether there has been a change by comparing the average value ±2 standard deviation of past measurements with the measurement value in S502. Figure 4 The measured value of 120.9 on January 14, 2020, falls outside the range of 119.8 to 120.2 determined based on the average value of 120.0 and standard deviation of 0.1 for measurements from January 1 to January 13, 2020, and is therefore considered to have changed. If the concentration value of the precision-managed substance has changed, the process proceeds to S504; if the concentration value of the precision-managed substance has not changed, the process proceeds to S505. Furthermore, the difference between the average value of past measurements and the measurement value in S502 is obtained as the amount of change in the measured value of the precision-managed substance. In other words, the computer 10 functions as a unit for obtaining the amount of change in the measured value of the precision-managed substance.

[0045] (S504)

[0046] The computer estimates the reasons for the variation in the measured concentration of the substance.

[0047] use Figure 6 Here is an example illustrating the processing flow for this step.

[0048] (S601)

[0049] Computer 10 determines whether the batch of the calibration solution has changed. If the batch has changed, the process proceeds to S602; otherwise, the process proceeds to S608.

[0050] (S602)

[0051] Computer 10 determines whether the measured values ​​of each precision-managed substance meet specified conditions. Specified conditions include, for example, that the number of measurements for each precision-managed substance exceeds a specified number, the coefficient of variation (CV) of the measured values ​​for each precision-managed substance is below a set value, and the deviation of the measured values ​​for each precision-managed substance relative to the displayed value is within a set value. The specified number of measurements is, for example, 3 times; the set value for the coefficient of variation (CV) is, for example, 3%; and the set value relative to the displayed value is, for example, 3%. If the specified conditions are met, the process proceeds to S603; if the specified conditions are not met, the process proceeds to S608.

[0052] (S603)

[0053] Computer 10 calculates the concentration values ​​of the old and new batches of the calibration solution as unknown samples. Specifically, based on the calibration curve generated in S501, the measured values ​​of absorbance or potential difference for the old and new batches of calibration solution stored in S501 are converted into the concentration value C' of the old batch of calibration solution. O The concentration value C' of the new batch of calibration solution N .

[0054] (S604)

[0055] Computer 10 determines whether the measured values ​​of each precision-managed substance and the concentration values ​​of the calibration solution change in the same direction between batches. Specifically, it determines whether the sign of the change obtained in S503 is the same as the concentration value C' calculated in S603. O and C' N The difference (C') N –C' O The signs of the numbers are the same. If the direction of change is the same, proceed to S605; if the direction of change is different, proceed to S608.

[0056] (S605)

[0057] Computer 10 calculates the predicted change in the concentration value of the precision management substance due to a batch change in the calibration solution. In other words, computer 10 functions as a calculation unit to calculate the predicted change. The predicted change is based on the old batch display value C of the calibration solution. O And the new batch display value C N The difference between (C) N–C O ) and the concentration value C' calculated in S603 O and C' N The difference between (C') N –C' O It is calculated from the difference value of ). More specifically, the difference value (C') is calculated. N –C' O ) and difference (C N –C O The difference between {(C') N –C' O )-(C N –C O The ± setpoint is used as the predicted change. For example, a setpoint of 50% is used.

[0058] (S606)

[0059] Computer 10 determines whether the variation in the measured value of each precision-managed substance is within the predicted variation range. If it is within the predicted variation range, the process proceeds to S607; otherwise, the process proceeds to S608.

[0060] (S607)

[0061] The computer-presumed accuracy management system determines that the variation in measured values ​​is due to batch changes in the calibration solution. The estimated cause of the variation could also be, for example,... Figure 7 As shown in the daily variation chart. Figure 7 In the daily variation graph, areas where the measured Na concentration changes are indicated by different markers than other areas. Warning signs and explanations of the reasons for the changes are also displayed. Specifically, other areas are marked with black circles, while areas with changes in measured values ​​are marked with white diamonds. Furthermore, an exclamation mark (!) is displayed as a warning, and the explanation "Concentration change due to batch change of calibration solution" is provided as an explanation of the reason for the change.

[0062] (S608)

[0063] The computer-presumed accuracy management system indicates that the change in the measured value of the substance is not due to a batch change in the calibration solution. The presumed cause of the change can also be displayed as a note in the daily variation chart. Alternatively, the difference (C') between the measured concentration values ​​of the calibration solution before and after a batch change can also be displayed. N -C' O () is displayed as a reference instead of a note explaining the reason for the change.

[0064] Based on the above processing procedure, the cause of the variation in the measured concentration of the substance under precision management is estimated. That is, the computer 10 functions as an estimation unit to determine the cause of the variation in the measured value of the substance under precision management. Furthermore, the operator can respond based on the estimated cause of the variation.

[0065] Back Figure 5 Explanation.

[0066] (S505)

[0067] Computer 10 determines whether the concentration value of the precision-managed substance is within the precision management range. If it is within the precision management range, the process proceeds to S506; otherwise, the process returns to S501.

[0068] (S506)

[0069] Computer 10 enables the colorimetric unit or electrolyte measurement unit 8 to measure the specimen provided by the patient. The measurement results are output to output unit 12.

[0070] According to the processing procedure described above, when the measured value of the precision-managed substance changes, the cause of the change is deduced. The operator can take appropriate measures based on the cause of the change deduced by the automatic analysis device 1, thus ensuring the smooth execution of subsequent sample measurements and maintaining the accuracy of the sample measurements.

[0071] Example 2

[0072] In Example 1, the reasons for variations in the measured values ​​of the estimated accuracy-managed substance were explained. The operator preferably takes measures corresponding to the estimated reasons for the variations, and for example, can change the concentration value of the calibration solution input via input unit 11 within the range of the displayed values ​​provided by the reagent manufacturer. In this example, a suggestion for a more suitable input value is explained.

[0073] The calibration solutions provided by reagent manufacturers typically display values ​​within a range of input values; for example, the display value for Na is labeled "140 ± 1". Therefore, in this embodiment, when the value reaches... Figure 6 In step S607, the computer 10 calculates a more appropriate input value and outputs that input value to the output unit 12. For example, the predicted change calculated in S605 is calculated to be the minimum displayed value C within the range of the displayed values ​​provided by the reagent manufacturer. N And output it as a more appropriate input value.

[0074] In addition, the output can have multiple input values, such as Figure 8 As shown, the daily variation chart generated using various input values ​​can be displayed as a guide to the input values. According to... Figure 8Guided by the input value, the operator can quickly determine which input value is better to use.

[0075] Example 3

[0076] In Example 1, the reasons for variations in the measured values ​​of the estimated precision-managed substance were explained. When the cause of variation is clear, the measured values ​​of the precision-managed substance can also be corrected based on the cause of variation. Therefore, in this example, in... Figure 6 When S607 is reached, the measured value of the precision management substance is corrected based on the change caused by the batch change of the calibration solution. Specifically, the difference in concentration between the old and new batches of the calibration solution (C') is subtracted from the measured value of the precision management substance. N -C' O The difference between the displayed value and the actual value (C) N -C O The deviation of {(C')} N -C' O )-(C N -C O This is used for correction. Furthermore, whether the measured values ​​of precision-managed substances can be corrected is selected by the operator's settings.

[0077] Several embodiments of the present invention have been described above. The present invention is not limited to the above embodiments, and modifications can be made to the structural elements without departing from the spirit of the invention. Furthermore, the various structural elements disclosed in the above embodiments can be appropriately combined. Moreover, several structural elements can be deleted from all the structural elements shown in the above embodiments.

[0078] Label Explanation

[0079] 1: Automatic analysis device; 2: Specimen tray; 3: Specimen cup; 4: Reagent tray; 5: Reaction container; 6: Reagent dispensing unit; 7: Specimen dispensing unit; 8: Electrolyte determination unit; 9: Interface; 10: Computer; 11: Input unit; 12: Output unit; 13: Photometer; 14: Electrolyte concentration calculation unit; 15: Potentiometer; 16: Internal standard solution; 17: Diluent; 18: Diluent tank; 19: Cl electrode; 20: K electrode; 21: Na electrode; 22: Pressure valve; 23: Comparison electrode; 24: Comparison electrode solution.

Claims

1. An automatic analysis device, characterized in that, include: A unit for acquiring the variation in measured values ​​of precision management substances used for precision management; The calculation unit calculates the predicted change based on the difference in concentration values ​​of the calibration solution used for calibration before and after the batch change. as well as Based on the comparison between the change amount and the predicted change amount, a presumption section is used to estimate the cause of the change in the measured value of the precision-managed substance.

2. The automatic analysis device as described in claim 1, characterized in that, The calculation unit calculates the predicted change based on the difference between the displayed concentration of the calibration solution and the measured concentration of the calibration solution before and after the batch change (i.e., the display difference value) and the measured concentration difference of the calibration solution before and after the batch change (i.e., the measured difference value). When the amount of change is within the range of the predicted amount of change, the estimation unit estimates that the batch change of the correction fluid is the cause of the change.

3. The automatic analysis device as described in claim 2, characterized in that, When the measured value of the precision management substance and the measured value of the concentration of the calibration solution change in different directions, the estimation unit presumes that the batch change of the calibration solution is not the cause of the change.

4. The automatic analysis device as described in claim 2, characterized in that, When the estimation unit estimates that the batch change of the correction solution is the cause of the change, it displays the input value of the concentration of the correction solution calculated based on the change prediction.

5. The automatic analysis device as described in claim 4, characterized in that, The input value is displayed in a daily variation graph representing the change in the measured value of the precision-managed substance.

6. The automatic analysis device as described in claim 2, characterized in that, When the estimation unit estimates that the batch change of the calibration solution is the cause of the change, the measured value of the precision management substance is corrected based on the displayed difference value and the measured difference value.

7. The automatic analysis device as described in claim 2, characterized in that, When the estimation unit determines that the batch change of the calibration solution is not the cause of the change, the measurement difference value is displayed in the daily variation graph representing the change in the measured value of the precision management substance.

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