JP4006203B2 - Precision analysis method for automatic analyzer and chemical analysis method - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an analyzer for biological samples such as blood and urine, and more particularly to an automatic analyzer capable of analyzing a large number of samples in a short time.
[0002]
[Prior art]
The automatic analyzer can handle a large number of samples at the same time, and can analyze and process multiple components quickly and with high accuracy. It is used for inspections in various fields such as intoxication tests at institutions. Especially in hospital use, the analysis target is a biological fluid sample such as blood or urine of the patient, and the analysis results determine the diagnosis and treatment policy of the disease. Is always sought. For this reason, management of an apparatus that performs analysis is important, and there is a method of measuring an accuracy control sample having a known concentration as one of methods for confirming whether the apparatus operates normally and measurement is performed correctly. This is because the sample for quality control is measured before and after the measurement of the patient sample or between measurements, and if the measured value of the sample for quality control is within the control, the device is judged to be operating normally, and the measurement of the patient sample is performed. This is a method of guaranteeing the value. Therefore, if the measurement value of the quality control sample is out of control, an error has occurred in the device, and the measurement value of the patient sample cannot be guaranteed. It is necessary to investigate immediately and take countermeasures.
[0003]
In response to this problem, Japanese Patent Laid-Open No. 2000-275252 discloses a technique for observing a change pattern of absorbance of a photometer measured by an automatic analyzer and estimating the presence or absence of an abnormality and the cause of the abnormality. It is disclosed.
[0004]
[Problems to be solved by the invention]
The technique described in Japanese Patent Application Laid-Open No. 2000-275252 compares the change in absorbance at the time of measurement with the change in absorbance at the time of some abnormalities to estimate the presence and cause of the abnormality. The cause of abnormality is not limited to one, and a plurality of causes may be involved. When a plurality of causes are related in this way, it is difficult to identify the cause with the technique described in Japanese Patent Application Laid-Open No. 2000-275252, and eventually the operator needs to identify the cause by looking at measurement data. is there. In this case, if the analysis item indicating abnormal data is a single item or multiple items, or if there are multiple items, whether there is commonality in the operation of the device, what is the absorbance in the reaction process, what is the result of the calibration, periodic exchange When the parts were maintained, the mechanical parts such as the sample probe, reagent probe, agitation mechanism, and washing mechanism worked normally, and there was no dirt or clogging in each part, and there was no problem with the sample or reagent. I have to check various things. Therefore, it takes time to investigate the cause and take countermeasures, and the output of the measurement result of the patient specimen for which a quick result is required is delayed. In addition, the skill level of the user's device is related, and the time that a beginner spends on countermeasures is immeasurable. Conventional automatic analyzers can fully demonstrate their capabilities when they are in a normal state, but once an abnormality occurs, the cause must be investigated and countermeasures taken. However, the investigation of the cause is related to the skill level of the user, and therefore results in a delay in dealing with patient specimens that require quick and accurate result reporting.
[0005]
The object of the present invention is to determine whether there is an abnormality in the measurement of a quality control sample, and the cause of the abnormality, even if there are multiple causes of the abnormality. It is an object of the present invention to provide an automatic analyzer capable of improving the performance.
[0006]
[Means for Solving the Problems]
The configuration of the present invention for achieving the above object is as follows.
(1) A sample container for storing a test sample, a reagent container for storing a reagent to be added to the sample, a reaction container for reacting the sample and the reagent, and the reaction in the reaction container for absorbance of the reaction solution In an automatic analyzer equipped with a photometer that measures the change, the difference in absorbance between the photometry points of the sample for quality control of known concentration, the change in absorbance, the difference in absorbance change between the two sections, the change in absorbance A storage unit that stores in advance at least one absorbance change pattern selected from the ratio of the above, a variation in absorbance calculated from a photometric point in an arbitrary interval, and the reaction process absorbance of the sample for quality control, the change pattern An arithmetic processing unit for comparing changes, and if there is an abnormality in the measurement result of the quality control sample as a result of the comparison, a control unit for controlling the display device to display the cause of the abnormality; and From the control An automatic analyzer having a display device for displaying the cause of the abnormality in accordance with the shown.
(2) In (1), the reaction process absorbance and the absorbance change pattern calculated from the reaction process absorbance in the accuracy control sample of the known concentration are stored for both normal and abnormal operation of the apparatus. A memory unit that stores the details of malfunctions at the time, an arithmetic processing unit that determines the compatibility with the reaction process absorbance of the quality control sample, and displays whether the measurement of the quality control sample is normal or abnormal after the determination. And a control unit that controls to display the content of the defect and the treatment method.
(3) In (2), when the absorbance pattern of the quality control sample does not match the stored absorbance pattern, a storage unit that newly registers and stores the reaction process absorbance pattern and the contents of the defect Automatic analyzer equipped with.
(4) In any one of (1) to (3), when the reaction process absorbance of the quality control sample is determined to be abnormal, a control unit is provided to control to stop the measurement of the corresponding analysis item. Automatic analyzer.
(5) In the accuracy management method of the chemical analysis method in which the sample and the reagent are mixed and the reaction between the sample and the reagent is measured by the change in absorbance of the reaction solution, an arbitrary photometry point of the photometry point of the sample for accuracy control at a known concentration At least one absorbance change pattern selected from the difference in absorbance between them, the change in absorbance, the difference in absorbance change between the two sections, the ratio of the absorbance change, and the variation in absorbance calculated from the photometric point in any section An accuracy management method of a chemical analysis method for comparing the change in absorbance of the reaction process of the accuracy control sample and determining whether there is an abnormality in the measurement result of the accuracy control sample.
[0007]
DETAILED DESCRIPTION OF THE INVENTION
The automatic analyzer to which the present invention is applied has a measurement unit that reacts a target component in a sample with a reagent, optically measures a reaction liquid, and measures the reaction process absorbance at multiple points, and inputs and outputs information through a screen. Alternatively, an operation unit capable of setting conditions is provided.
[0008]
In the present invention, a storage unit for storing a reaction process absorbance Ai (i is a photometric start point to a photometric end point) as a reference for a quality control sample having a known concentration, and an allowable absorbance Li (i is a photometric start point to It includes a display unit that displays a registration screen for setting the metering end point, and also sets the abnormal reaction process absorbance change pattern at the time of failure, and the failure content for that absorbance change pattern, and stores each A storage unit, and a display unit for determining an abnormal part by an arithmetic processing unit for determining compatibility between the reaction process absorbance as the reference and the reaction process absorbance at the time of the defect, and displaying the content of the defect according to the determination content It is characterized by.
[0009]
Here, the change pattern of the reaction process absorbance for determining the content of the defect is the content of the following 1) to 4).
[0010]
1) Absorbance difference before and after reagent addition 2) Absorbance change amount in arbitrarily set range after reagent addition 3) Difference or ratio of absorbance change in two arbitrarily set sections 4) Absorbance variation The variation in absorbance is represented by a numerical value calculated by statistical processing such as standard deviation (SD) and standard residual (Syx) from the absorbance at each photometric point in an arbitrarily set range.
[0011]
Since the above shows a specific pattern depending on the content of the defect, applying it to the reaction process absorbance of a quality control sample that is measured periodically or arbitrarily makes it easy to identify the defective part at the time of abnormality, and promptly Treatment and recovery are possible.
[0012]
Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 shows a schematic configuration of an automatic analyzer to which the present invention is applied. 1 includes a sample disk 2 on which a plurality of sample cups 1 can be installed, a sampling mechanism 4 having a sample probe 3 for collecting a predetermined amount of sample, a reagent pipetting mechanism 5a, 5b for dispensing a plurality of reagents, and a reagent. Central processing unit for controlling the disks 6a and 6b, the reaction disk 8 holding a plurality of reaction vessels 7 for direct photometry, the stirring mechanisms 9a and 9b, the reaction vessel cleaning mechanism 10, the photometer 11, and the entire mechanism system ( Microcomputer) 12 and the like are mainly configured. The reaction disk 8 holding a plurality of reaction vessels controls the operation of rotating and temporarily stopping the half rotation + 1 reaction vessel every cycle. That is, at the time of stopping every cycle, the reaction vessel 7 of the reaction disk 8 stops in the form of proceeding by one reaction vessel in the counterclockwise direction. As the photometer 11, a multi-wavelength photometer having a plurality of detectors is used. When the reaction disk 8 is in a rotating state as opposed to the light source lamp 13, the row of reaction vessels 7 passes the light beam 14 from the light source lamp 13. Is configured to do. A reaction container cleaning mechanism 10 is disposed between the position of the light beam 14 and the sample discharge position 15. Further, it comprises a multiplexer 16 for selecting a wavelength, a logarithmic conversion amplifier 17, an A / D converter 18, a printer 19, a CRT 20, a reagent dispensing mechanism drive circuit 21, etc., all of which are connected to the central processing unit 12 via an interface 22. It is connected. This central processing unit performs control of the entire device including control of the entire mechanical system and data processing such as calculation of concentration or enzyme activity value. The operation principle in the above configuration will be described below. When the start switch on the operation panel 23 is pressed, the reaction vessel 7 starts to be washed by the reaction vessel washing mechanism 10, and the water blank is further measured. This value is a reference for the absorbance measured in the reaction vessel 7 thereafter. When the reaction disk 8 advances to the sample discharge position 15 by repeating the operation of one cycle of the reaction disk 8, that is, the operation of temporarily stopping the counter-rotation + 1 reaction container, the sample cup 1 moves to the sampling position. Similarly, the two reagent disks 6a and 6b are also moved to the reagent pipetting position. During this time, the sampling mechanism 4 operates, and the sample amount of, for example, the analysis item A is sucked from the sample cup 1 by the sample probe 3 and then discharged to the reaction container 7. On the other hand, in the reagent pipetting mechanism, when the sampling mechanism is discharging the sample to the reaction vessel 7, the reagent pipetting mechanism 5a starts operating, and the first reagent of the analysis item A constructed on the reagent disk 6a is moved by the reagent probe 24a. Suction. Next, the reagent probe 24a moves onto the reaction vessel 7 and discharges the sucked reagent, and then the inner wall and outer wall of the probe are washed in the probe washing tank to prepare for the first reagent dispensing of the next analysis item B. Photometry is started after the first reagent is added. Photometry is performed when the reaction vessel 7 crosses the light beam 14 when the reaction disk 8 rotates. When the reaction disk rotates twice by two reaction containers after the first reagent is added, the stirring mechanism 9a is activated to stir the sample and the reagent. When the reaction container 7 moves from the sample dispensing position to the position rotated by 25 rotations + 25 reaction containers, that is, to the second reagent dispensing position, the second reagent is added from the reagent probe 24b and then stirred by the stirring mechanism 9b. By the reaction disk 8, the reaction vessel 7 successively traverses the luminous flux 14, and the absorbance is measured each time. These absorbances are measured 34 times in total for a reaction time of 10 minutes. After completion of photometry, the reaction vessel 7 is washed by the reaction vessel washing mechanism 10 to prepare for the next sample analysis. The measured absorbance is converted into a concentration or enzyme activity value by the central processing unit 12 and the analysis result is output from the printer 19.
[0013]
Next, one specific example of the present invention applied to the analyzer of FIG. 1 will be described. First, an accuracy control sample with a known concentration is multiplexed n times in a normal state of the operation of the apparatus, and each photometric point i (i: 1 to 34) is obtained from the reaction process absorbance according to the following equations (1) and (2). ) Average absorbance XAi and standard deviation SDi of each photometric point.
[0014]
XAi = 1 / n (A1 + A2 + ... + An) (1)
SDi = (Σ (A−XAi) ² / (n−1)) ^1/2 (2)
Next, the obtained average absorbance XAi is set as a reference absorbance, and from the standard deviation SDi, ± 2SDi is stored in the storage unit as an allowable range with respect to the reference absorbance XAi at each photometric point as shown in FIG. The reference absorbance and allowable range of each photometric point are displayed on the reaction process monitor screen 25 as shown in FIG. 3 to facilitate confirmation of the reference reaction process absorbance and allowable range, Setting is also possible.
[0015]
The method of determination and treatment with reference absorbance when measurement of a quality control sample is started periodically or arbitrarily after setting will be described with reference to the flowchart of FIG. First, when measurement of a quality control sample is started (S1), the measured absorbance Bi at each photometric point is measured (S2). Next, it is determined whether or not the measured absorbance Bi at each photometry point is within the allowable range of the reference absorbance, that is, within the range of the following equation (3) (S3).
[0016]
(XAi + 2SDi)>Bi> (XAi-2SDi) (3)
As a result of this determination, if the measured absorbance Bi is within the allowable range of the reference absorbance, it is determined to be normal, and the fact that it has been measured normally is displayed on the screen (S4). If it is outside the allowable range, it is determined as abnormal, and the abnormality is displayed on the screen (S5), and the user is notified by an alarm or the like (S6).
[0017]
Subsequently, for pre-registered device normality and abnormalities of known concentration accuracy control sample reaction process absorbance, absorbance change pattern calculated from reaction process absorbance, and periodically or arbitrarily measured accuracy control The following is an example of determining the compatibility with the reaction process absorbance of the sample, and displaying the details of the failure and the treatment method when it matches the reaction process absorbance at the time of abnormality and the absorbance change pattern calculated from the reaction process absorbance. Shown in
[0018]
First, FIG. 5 shows the absorbance of the reaction process during normal and abnormal apparatus operation of LD (lactate dehydrogenase), which is a component in a biological sample. In the analysis of LD, in the presence of the coenzyme NADH (β-nicotinamide adenine dinucleotide reduced form), LD catalyzes the reaction of converting the substrate pyruvic acid into lactic acid, and simultaneously absorbs NADH at a wavelength of 340 nm. Is oxidized and converted to NAD (β-nicotinamide adenine dinucleotide oxidation type) having no absorption at a wavelength of 340 nm, and the rate of decrease at this time is measured at a wavelength of 340 nm to determine the activity value of LD. . Usually, the analysis reagent is a two-reagent system, and the first reagent contains coenzyme NADH and the second reagent contains the substrate pyruvic acid.
[0019]
Therefore, the reaction process absorbance in the quality control sample of known concentration when the apparatus is operating normally, as shown in the normal state of FIG. 5, when the specimen is dispensed and subsequently the first reagent is added, Absorption of the coenzyme NADH itself in the first reagent results in an absorbance of about 1000 (Abs. × 10 ⁴ ). Next, the absorbance is reduced by the reaction with endogenous pyruvic acid, which is an interfering component in the specimen, and then pyrubin is removed to make the absorbance constant. Next, when the substrate pyruvic acid is added with the second reagent, the absorbance immediately after the addition decreases to around 7000 (Abs. × 10 ⁴ ) because the coenzyme NADH is diluted with the second reagent, Next, the substrate pyruvic acid changes to lactic acid with the LD activity value of the quality control sample, NADH is converted to NAD, and the absorbance decreases at a constant rate.
[0020]
However, when the state of the apparatus is abnormal, for example, the reaction process absorbance at the time of clogging of the sample probe in FIG. 5 is that the sample is not dispensed, so there is no reaction due to endogenous substances in the sample, and the absorbance immediately after the addition of the first reagent is Only the absorption of NADH in the reagent only shows a constant absorbance without change. Furthermore, since the absorption due to the color of the sample itself such as the chyle of the sample is also eliminated, the absorbance tends to be lower than that when the sample is normally dispensed. In the case of clogging with the first reagent probe, since the amount of the reaction solution necessary for photometry is not reached, light passes through the air layer, and the absorbance becomes a value near zero. Furthermore, in the case of clogging with the second reagent probe, since the coenzyme NADH is not diluted by the addition of the second reagent, the absorbance does not decrease, and further, since no substrate pyruvic acid is added, no reaction occurs and the absorbance decreases. There is no reaction.
[0021]
In addition, if there is a problem in photometry such as deterioration of the light source lamp or contamination of the optical cell, the absorbance at all or some of the photometry points in the reaction process varies, and the reaction proceeds linearly or smoothly. Tend to not. Therefore, as shown in FIG.
1) Absorbance change in arbitrarily set range after addition of reagent 2) Absorbance difference before and after addition of reagent 3) Difference or ratio of absorbance change in two sections set arbitrarily 4) Absorbance variation, etc. FIG. 7 shows various absorbance patterns, check points for calculating the values of the respective patterns, that is, photometry points, absorbances used as references, and allowable ranges. As described above, by setting an absorbance pattern for each defect factor, the absorbance pattern is calculated from the reaction process absorbance of the measured quality control sample, that is, the actually measured absorbance Bi, and compared with the set normality and malfunction absorbance patterns. By doing so, it becomes possible to determine the cause of the failure and display the content on the screen.
[0022]
For example, in the example of FIG. 5, the absorbance pattern when the sample probe is clogged is as follows.
Pattern 1
1000 ABS (× 10 ⁴ )> (B1-B5) at measurement points 1 to 5 (4)
Pattern 2
At measurement points 6 to 16, 11000 ABS (× 10 ⁴ ) <Bi (5)
(Bi is the measured absorbance)
Pattern 3
At measurement points 17 to 34, Ai + 200 ABS (× 10 ⁴ ) <Bi (6)
(Ai is the standard absorbance, Bi is the measured absorbance)
Pattern 4
80 ABS / min (× 10 ⁴ )> | ΔB | at the measurement points 20 to 34 (7)
(ΔB is the amount of change in absorbance)
The absorbance pattern when the first reagent probe is clogged is:
Pattern 1
200 ABS (× 10 ⁴ )> Bi at measurement points 1 to 16 (8)
(Bi is the measured absorbance)
Pattern 2
At measurement points 17 to 34, Bi <6000 ABS (× 10 ⁴ ) (9)
(Bi is the measured absorbance)
Pattern 3
80 ABS / min (× 10 ⁴ )> | ΔB | at the measurement points 20 to 34 (10)
(ΔB is the amount of change in absorbance)
Furthermore, the absorbance pattern when the second reagent probe is clogged is
Pattern 1
At measurement points 1 to 16, Ai−200 <Bi <Ai + 200 ABS (× 10 ⁴ ) (11)
(Ai is the standard absorbance, Bi is the measured absorbance)
Pattern 2
At measurement points 17 to 34, Ai + 200 ABS (× 10 ⁴ ) <Bi (12)
(Ai is the standard absorbance, Bi is the measured absorbance)
Pattern 3
80 ABS / min (× 10 ⁴ )> | ΔB | at the measurement points 20 to 34 (13)
(ΔB is the amount of change in absorbance)
Pattern 4
In the absorbance difference between the measurement points 16 and 17, 800 ABS (× 10 ⁴ )> | B16−B17 | (14)
(B is measured absorbance)
As described above, by setting various absorbance patterns for each failure factor and registering them in advance, the absorbance pattern calculated in the same way from the reaction process absorbance of the quality control sample measured periodically or arbitrarily, and the contents of each defect It is possible to display the cause of the failure and how to deal with it as shown in the example of FIG. In addition, after the above determination, if it does not match any absorbance pattern, so that the cause of the abnormality can be estimated to the user, the display of the location where there was no problem, the measurement point outside the normal absorbance tolerance range, The deviation difference in absorbance is displayed, and the absorbance pattern at that time is stored so that it can be used for the next cause estimation.
[0023]
The above embodiment will be described with reference to the flowchart of FIG.
[0024]
First, when the measurement of the quality control sample is started by the user's instruction (S11), the absorbance pattern is calculated from the absorbance at each photometric point (S12), and then the response at the time of normal registration and various malfunctions registered in advance. It is determined whether or not the absorbance pattern matches with the process absorbance pattern (S13). After the determination, if the absorbance pattern matches, it is determined whether the absorbance pattern is normal or abnormal (S14). If the absorbance pattern matches the normal absorbance pattern, it is displayed that the absorbance pattern is normal (S15). If it matches the absorbance pattern, the corresponding defect content is displayed to inform the user (S16). In addition, when it does not match any of the absorbance patterns of the reaction process registered in advance, a means for determining whether or not the user registers the absorbance pattern of the reaction process is provided (S17). The user inputs a defect content and a reaction process absorbance pattern (S18). Thereby, the apparatus stores the defect content and the reaction process absorbance pattern (S19).
[0025]
According to the above embodiment, when an abnormality occurs, the user can detect early, and further, by displaying the abnormal part, the subsequent measures can be quickly performed, and the patient sample can be quickly detected. A highly reliable analysis result can be output. In addition, waste of samples and reagents can be eliminated by providing a control unit that stops measurement of the corresponding analysis item when an abnormality is found.
[0026]
【The invention's effect】
According to the present invention, it is not the measurement value whose cause is difficult to be determined by the measurement of the quality control sample of known concentration, but the absorbance before conversion of the measured value that reflects the operating state of the device well, that is, the reaction process absorbance. Since the state is monitored, it leads to early detection when an abnormality occurs, and the cause of the abnormality can be identified, so that quick response and treatment can be performed.
[Brief description of the drawings]
FIG. 1 is a diagram showing a schematic configuration of an automatic analyzer to which the present invention is applied.
FIG. 2 is a diagram showing an example of a reference absorbance and an allowable range in the present invention.
FIG. 3 is a diagram showing an example of a reaction process monitor screen in the present invention.
FIG. 4 is a diagram showing an example of an operation flow according to the first embodiment of the present invention.
FIG. 5 is a diagram showing an example of reaction process absorbance when LD is normal and abnormal in the present invention.
FIG. 6 is a diagram showing an example of checking compatibility with reaction process absorbance in the present invention.
FIG. 7 is a diagram showing an example of a defect content pattern display in the present invention.
FIG. 8 is a diagram showing an example of a quality control state in the present invention.
FIG. 9 is a diagram showing an example of an operation flow according to the second embodiment of the present invention.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 ... Sample cup, 2 ... Sample disk, 3 ... Sample probe, 4 ... Sampling mechanism, 5 ... Reagent pipetting mechanism, 6 ... Reagent disk, 7 ... Reaction container for direct photometry, 8 ... Reaction container, 9 ... Stirring mechanism, DESCRIPTION OF SYMBOLS 10 ... Reaction container washing | cleaning mechanism, 11 ... Photometer, 12 ... Central processing unit, 13 ... Light source lamp, 14 ... Light beam, 15 ... Sample discharge position, 16 ... Multiplexer, 17 ... Logarithmic conversion amplifier, 18 ... A / D converter , 19 ... Printer, 20 ... CRT, 21 ... Reagent dispensing mechanism drive circuit, 22 ... Interface, 23 ... Operation panel, 24a ... First reagent probe, 24b ... Second reagent probe, 25 ... Sample for quality control of known concentration Standard reaction process monitor screen.

Claims (4)

A sample container for storing a test sample, a reagent container for storing a reagent to be added to the sample, a reaction container for reacting the sample with the reagent, and measuring a reaction in the reaction container by a change in absorbance of the reaction solution In an automatic analyzer equipped with a photometer
A calculation means for multiply measuring a sample for quality control at a known concentration in a state where the operation of the apparatus is normal, and calculating an average absorbance for each photometric point from the reaction process absorbance;
A storage unit for storing a plurality of absorbance patterns for each defect factor created based on the average absorbance for each photometric point calculated by the calculation unit;
An arithmetic processing unit that compares the absorbance pattern stored in the storage unit with a reaction process absorbance change pattern of a quality control sample measured periodically or arbitrarily to determine a failure factor;
An automatic analyzer characterized by comprising: The automatic analyzer according to claim 1, wherein
As a result of the determination in the arithmetic processing unit, when there is an abnormality in the measurement result of the quality control sample, a control unit that controls the display device to display the cause of failure;
An automatic analyzer characterized by comprising: The automatic analyzer according to claim 1, wherein
When the absorbance pattern of the quality control sample does not match the absorbance pattern stored in the storage unit, a function of newly storing the reaction process absorbance pattern and its failure factor in the storage unit is provided. An automatic analyzer. In the automatic analyzer in any one of Claims 1-3,
An automatic analyzer comprising a control unit that controls to stop measurement of a corresponding analysis item when a reaction process absorbance of a sample for quality control is determined to be abnormal.

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