JPH0599930A - Automatic chemical analyzing apparatus - Google Patents

Abstract

PURPOSE:To judge a specimen in need of re-examination quickly and to improve analyzing efficiency by providing a reaction-liquid adjusting part, an optical measuring part, a memory part, an operating part and two re-examination controlling parts for controlling the reaction- liquid adjusting part and the optical measuring part. CONSTITUTION:A re-examination controlling part 6 individually compares an absorbance Ai, which is measured at every constant time, with a limit value Ah and sends a control signal into a driver 7 so as to execute the re-examination for a specimen, whose amount is decreased when Ai>Ah. Even in the case of Ai<=Ah, the computation of an anticipated value and the comparison of the anticipated value and the limit value Ah at this point are performed based on the data of a memory part 9 and a specified expression of relation. When the anticipated value is higher than Ah, a control part 6A starts the re-examination of the reduced amount by the same way. When the result of the comparison is not applicable to any of the above described cases, the anticipated value of the measured concentration is roughly computed in a control part 6B. When the value exceeds a threshold value, the control signal is sent into the driver 7 so as to perform the ordinary re-examination. For the specimen, which does not require the re-examination for the reduced amount, an operating part 5 determines the quantity based on a specified calibration curve.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an automatic chemical analyzer. More specifically, it relates to an automatic analyzer useful for quantifying a predetermined component in a biochemical sample containing multiple components such as serum, plasma, urine and lymph.

[0002]

2. Description of the Related Art Conventionally, as a method of analyzing a predetermined component in a biochemical sample (specimen) as described above, one kind or two kinds of specimens are used.
A method of mixing predetermined reaction reagents of at least one kind and reacting them, and quantifying a predetermined component based on a change in the optical density value (absorbance value, fluorescence value, etc.) of the reaction solution caused by this reaction and the rate of change during the reaction Is known as a so-called end point method or rate method, and is applied to various automatic biochemical analyzers.

And, in these concrete analyzes,
The change or the rate of change of the optical density value is measured with the optical density value Ab of the reaction reagent blank solution (a solution containing no sample component and containing the same reaction reagent) as a baseline, and the measurement sensitivity. From the point of performing proper quantification, it is performed uniformly within a range of optical density up to a certain fixed optical density value Ah (optical density limit value).

For example, in the end point method, the optical density at the end of the reaction and the optical density A of the reagent blank are
Quantification is performed based on the difference from b, and the optical density limit value Ah for obtaining this difference is, for example, in the vicinity of the optical density value before reaction saturation regulated by the amount of the substrate etc. in a reaction reagent using an enzyme. It had been.

On the other hand, in the rate method, a plurality of optical densities during the reaction from the start of the reaction to the time t at which the reaction ends are measured over time, and the rate of change in the optical density is determined from the relationship between the series of actually measured optical densities and time. Although it is required, this change rate was similarly determined within the range of the optical density limit value Ah.

At the end of the reaction, a sample exceeding the optical density limit value Ah, that is, a sample having an extremely high value, was judged to be unquantifiable or unsuitable, and another measurement (retest) was carried out with the sample amount reduced.

On the other hand, regarding a quantifiable sample that does not exceed the optical density limit value Ah, for example, for a high-value sample that exceeds the normal value range (threshold value Ch), the quantitative value of the quantitative value is more important than that of the normal value range sample. High measurement accuracy is required. Therefore, such a quantifiable high-value sample was literally retested without changing the sample amount.

An automatic chemical analyzer for performing quantitative determination by automatically controlling the determination of suitability for quantification based on the optical density limit value Ah, the retesting operation and the retesting operation based on the threshold value Ch is also known. ..

[0009]

However, in the conventional automatic chemical analyzer, the determination as to whether the above-mentioned weight loss retest or normal retest is necessary is made at the end of the reaction of each reaction solution. Therefore, it takes a time about the same as the quantification time for a normal sample just to determine the necessity of the sample requiring retesting, which is an obstacle to speeding up the whole analysis.

The present invention has been made under such circumstances, and it is intended to provide an automatic analyzer capable of increasing the efficiency of the whole biochemical analysis by making the judgment more promptly for the specimens requiring retesting. It is what

[0011]

Thus, according to the present invention, (a) a reaction solution preparing section for preparing a test reaction solution by mixing a predetermined amount of a sample and a reaction reagent, and (b) a test reaction solution The optical density of the standard reaction solution in which the optical density of the reference reaction solution in which the standard sample and the reaction sample are mixed is measured from the start of the reaction to the end of the reaction (time t) at fixed intervals, and after the end of the reaction. A storage unit for storing the optical density for each constant time until (time t) and the concentration of a predetermined component in this standard sample, and (d) the final optical density At of the reaction liquid to be tested at time t is a predetermined optical density. For a sample that falls within the range of the limit value Ah, a computing unit that quantifies a predetermined component in the sample based on the At value, and (e)
Final optical density At of the reaction liquid to be tested at the time t
Whether or not exceeds the optical density limit value Ah based on the optical density value during the reaction, and for samples judged to exceed Ah, re-examination is performed under the condition that the sample amount is decreased. A first re-examination control unit for controlling the reaction solution preparation unit and the optical measurement unit, and (f) whether or not the concentration of a predetermined component in the sample exceeds a predetermined threshold value Ch. It is determined in advance based on the ratio of the optical density on the way and the corresponding optical density in the storage unit.
There is provided an automatic chemical analyzer comprising a reaction liquid preparation unit and a second re-examination control unit that controls the optical measurement unit so as to re-examine a sample that is determined to exceed the above.

Further, according to the present invention, (a) a reaction solution preparing section for preparing a test reaction solution by mixing a predetermined amount of a sample and a reaction reagent, and (b) an optical density of the test reaction solution From the start to the end of the reaction (time t), an optical measuring unit capable of measuring at regular intervals, and (c) from the start of the reaction to the end of the reaction (time t) for the reference reaction liquid in which the standard sample and the reaction reagent are mixed. A storage unit for storing the optical density at regular time intervals and the concentration of a predetermined component in this standard sample, and (d) the optical density of a predetermined optical concentration limit value Ah of the optical densities of the test reaction liquid obtained over time.
An arithmetic unit for quantifying a predetermined component in the sample based on a plurality of change rates of the optical density belonging to the range, and (e) the optical density of the test reaction solution measured during the reaction is the optical density limit value Ah. The reaction solution preparation unit is configured to judge whether or not the above is exceeded, and to re-examine a sample having an optical density value of less than 3 points that belongs to the Ah range when it exceeds Ah under the condition that the amount of the sample is reduced. And a first re-examination control unit that controls the optical measurement unit, and (f) whether or not the concentration of a predetermined component in the sample exceeds a predetermined threshold Ch, and an optical concentration during the reaction of the test reaction liquid, A second re-examination control unit that controls the reaction solution preparation unit and the optical measurement unit to perform a re-examination for a sample that is previously determined based on the ratio of the corresponding optical densities in the storage unit and is determined to exceed Ch. Provided automatic chemical analysis equipment It is.

According to the present invention, the necessity of re-examination for weight reduction and normal re-examination is judged in real time based on the optical density value in the optical density fluctuation region until the reaction is completed, and the instruction of these re-examination operations is made by the judgment. It is configured so that the reaction can be performed before the end of the reaction.

The first aspect of the present invention relates to an automatic chemical analyzer using the end point method. The determination of whether the final optical density At exceeds Ah in the first re-examination control unit is performed by using a microcomputer, comparing the measured optical density Ai with Ah for each measured optical density Ai during the reaction, and this Ai is A
If it is less than h, a plurality of optical densities A _{i -1} , A _i -2 up to A _i
It is suitable to carry out by a step of approximately predicting the optical density At at the end of the reaction from ..., and comparing the predicted value with the above Ah. Here, when Ai exceeds Ah, the re-examination control unit determines that At exceeds Ah, and the re-examination is performed on the condition that the amount of the sample is reduced, regardless of the reactivity of the reaction solution at that time. The reaction solution preparation section and the optical measurement section are driven in this manner. Even when Ai does not exceed Ah, if the above-described predicted value of At is determined to exceed Ah, the re-examination control unit similarly causes re-examination to be performed. If neither exceeds Ah, no re-examination will be conducted,
The quantification is performed in the calculation unit based on the actual final optical density At.

Here, the above-mentioned prediction value is calculated in three or more ways.
A regression equation is calculated from the relationship between the optical density value above the point and the reaction time, and the regression equation is used to calculate At at the end of the reaction t (for example, the least squares method based on the quadratic regression or cubic regression equation). Although it can be performed, it can be calculated more easily by using the ratio with the optical density data of the standard sample in the storage unit.

That is, at time i, the proportional relationship between the predetermined component concentration and the optical concentration of the reaction solution is in principle expressed by the following equation (1): (Ai-Ab) .Cst = (Ai.st-Ab). Cs ... (1) [wherein Ai is the optical density of the test reaction solution at time i,
Ai · st is the optical density of the reference reaction liquid (using a standard sample) at time i, Ab is the optical density of the reagent blank, and Cs
t represents the concentration (or activity value) of the predetermined component of the standard sample, and Cs represents the concentration (or activity value) of the predetermined component of the test sample].

On the other hand, 2 of the standard reaction solution for the standard sample
For the optical densities Ai.st and Aj.st at two times i and j, the following equation (2): (Ai.st-Ab) / (Aj
-St-Ab) = (Ai-Ab) / (Aj-Ab) = k
(Constant) [wherein Ai and Aj are optical densities of the test reaction liquids at time points i and j].

Therefore, from these equations (1) and (2), the following equation (3): Aj = Ab + (Ai-Ab). (Aj.st-Ab) /
(Ai.st-Ab) ... (3) is derived, and the known data Ai.st, Aj.st and the reagent blank value of the reference reaction solution and the optical density A of the test reaction solution in the middle of the reaction are thereby derived.
The predicted value (Aj) of the optical density after that can be easily estimated from i, and the final absorbance At when j = t can be predicted and compared with Ah.

On the other hand, the second re-examination control unit is further provided with a test reaction liquid whose final optical density At does not exceed Ah in the first re-examination control unit, that is, a quantifiable test reaction liquid, during the reaction. It is predicted whether or not the concentration of the test component exceeds the upper limit (threshold value Ch) of the normal value, and when it exceeds, control is performed so that a normal retest is performed on the sample.

Prediction of the concentration is based on the above equation (1), and the following equation (4): Cs = Cst. (Ai-Ab) /
(Ai.st-Ab) ... (4) can be calculated.

On the other hand, the second invention relates to an automatic chemical analysis device to which the rate method is applied. Also in this apparatus, the first re-examination control unit compares each measured chemical concentration Ai during the reaction with Ah. However, for samples exceeding Ah, the number of optical density samples belonging to the range of Ah is further checked, and the weight loss retest is performed only when the number of samples is less than 3.

Further, in this case, further, with respect to the reaction liquid of the sample that can be quantified by the rate reaction in the second re-examination control unit, the concentration of the test component is higher than the normal value (threshold value) based on the data of the reference reaction liquid. It is roughly estimated whether or not Ch) is exceeded, and when it exceeds, control is performed so that a normal retest is performed for the sample. The prediction is performed based on the equation (4) as in the above.

In any case, since the optical density of the baseline before the reaction may differ for each sample, the optical density limit value Ah is corrected (Ah ') for each sample correspondingly. Processing may be done. This Ah
Is corrected by calculating the optical density at the start of the reaction, that is, at the time of adjusting the reaction solution (t = 0) based on a plurality of actually measured optical density values at the initial stage of the reaction, and adding or subtracting the calculated optical density to Ah. (See FIG. 6).

[0024]

By the time the end of the reaction in which the quantification is performed in the computing unit is reached, the necessity or non-necessity of the re-examination for weight reduction and normal re-examination is determined for each sample, and the execution of each re-examination is controlled accordingly. Therefore, it is possible to start the retesting for the required sample by the end of the reaction, and the analysis time can be shortened.

[0025]

Embodiments of the present invention will be described below with reference to the accompanying drawings. [FIG. 1] shows an automatic chemical analyzer 1 of an example. This automatic chemical analyzer 1
Consists of a dual-mode multi-item analysis configuration that is configured to allow selective selection of endpoint and rate measurements. Then, basically, the sample sampling table 2 for dispensing the sample in the sample container 22 into the reaction container 41 by the dispenser 21, and the reagent container 3
The predetermined reaction reagent in 2 is supplied to the reaction container 4 by the dispenser 31.
Reagent dispensing table 3 for dispensing into 1 (above, reaction solution preparing section), optical measuring section 4, computing section 5, and retest control section 6
(First re-examination control unit 6A and second re-examination control unit 6B) and a storage unit 9 are provided. In addition, 7 is a driver for the reaction solution preparing section and the optical measuring section 4, and 8 is a display section.

The above-mentioned optical measuring section 4 comprises a large number of reaction vessels 41.
And a rotation absorption optical system 42 and a washing section 43, which are arranged in a fixed cycle to arrange a sample, a sample dispensed at the dispensing position B, and a reaction reagent dispensed at the dispensing position A. With respect to the mixed solution (reaction solution), the absorbance can be monitored at regular intervals by a preset reaction end time t.

Then, the storage unit 9 stores the absorbance of the reference reaction liquid obtained by mixing the standard sample and the reaction reagent for the test item at a constant time interval from the reaction start to the reaction end (time t).
The concentration of the predetermined component in this standard sample is stored in advance as data. In addition, the calculation unit 5 and the re-examination control unit 6 are programmed so as to perform quick determination and start of re-examination and quantitative calculation, respectively, corresponding to the measurement mode.

First, FIG. 2 shows a program of the first re-examination control section 6A which is set when the endpoint mode is selected. As shown in this flow chart,
The re-examination control unit 6 first compares the optical density (absorbance) Ai measured at regular time intervals with the limit value Ah, and when Ai> Ah, executes the weight loss re-examination in which the sample amount is reduced. A control signal is sent to the driver 7 so that Here, Ai and Ah mean the absolute value of the difference from the reagent blank, respectively. As a result, the reaction solution preparation section prepares the reaction solution under the condition that the sample dispensing amount is reduced (in this embodiment, it is reduced to about 1/2), and the optical measurement section prepares the reaction solution for the reaction solution. A re-examination will be conducted. On the other hand, Ai ≦ Ah
In this case, the predicted value of At is calculated based on the relationship between the data in the storage unit 9 and the equation (3), and the predicted value and A
When h is compared and the predicted value becomes Ah or more, the first re-examination control unit 6A starts the weight reduction re-examination in the same manner as above. If none of the above applies, the second re-examination control unit 6
In B, the storage unit 9 corresponding to the absorbance Ai at that time
The estimated value (Cs) of the measured concentration is roughly calculated based on the equation (4) using the absorbance Ai · st of
Compared with h (upper limit of normal value range of the subject item), Ch
When it exceeds, a control signal is sent to the driver 7 so as to perform a normal retest (retest under the same conditions for the same sample amount).

After the above determination, for the reaction solution satisfying At≤Ah, the next absorbance measurement is performed and the same determination is repeated in real time until just before time t. Then, with respect to the sample that does not require the weight loss retest, the calculation unit 5 performs the quantification on the basis of the predetermined calibration curve based on the absorbance At at that time. It should be noted that the capacity may be corrected during the quantification of the retest.

According to the re-examination control, for example, as shown in FIG. 4, for the ultrahigh-value sample S2 whose final absorbance (time t11) in the absorbance increasing reaction exceeds Ah, the change in the absorbance at the time ts or the absorbance up to t4. Whether or not a weight loss re-examination is necessary is started based on the
For samples that do not exceed the threshold, determination and start of necessity of retesting are usually performed for high-value samples in which the concentration of the predetermined component exceeds Ch. Therefore, it is possible to carry out an early retest operation without waiting for the end of the reaction. Then, the normal sample S1 is quantified as in the conventional case.

On the other hand, a program when the rate mode is selected is shown in FIG. The first re-examination control unit 6 as described above compares each absorbance Ai with the limit value Ah in the same manner as described above. Then, in the case of Ai> Ah, the number of samples (the number of actually measured values) belonging to the range of Ah is counted, and when this number is 2 or less, the retesting with the reduced sample amount is started as described above. Here, Ai and Ah mean absolute values of the difference from the reagent blank. Then, when the number of samples is 3 or more and when Ai ≦ Ah, the second re-examination control unit is based on the absorbance Ai · st of the storage unit 9 and the equation (4) corresponding to the absorbance Ai at that point in the same manner as described above. The estimated value (Cs) of the measured concentration is roughly estimated, this is compared with a predetermined threshold value Ch, and if it exceeds Ch, a control signal is sent to the driver 7 so that a normal retest is performed.

After the above determination, the same determination is made at the time t for the reaction liquid of the sample other than that the weight loss retest is performed.
After being repeated in real time until immediately before, at time t, quantification is performed based on a predetermined calibration curve based on the change rates of the plurality of absorbances included in the Ah range. Also in the case of the rate mode, the capacity correction may be performed at the time of quantification of the retest.

According to such re-examination control, it is possible to judge in real time whether or not the re-examination of weight reduction is necessary and to start the ultra-high value sample which exceeds the absorbance Ah and cannot measure the rate of change in absorbance in a short time. For example, as shown in [FIG. 5], the number of samples belonging to the Ah range is 1 for the ultrahigh sample S _3.
Since it is a point, it is judged that re-examination is necessary at the time of t ₂ , and a rapid weight reduction re-examination operation is performed. On the other hand, with respect to the sample S ₂ whose final absorbance exceeds Ah, if the number of samples belonging to Ah is 3 or more, the change rate can be appropriately measured, and therefore the retest is not performed, and the calculation unit The quantification is performed based on the rate of change of the absorbance in Ah as in the normal sample S1.

Furthermore, for samples requiring weight loss retest,
For a high-value sample that exceeds the threshold value Ch, it is determined in real time whether or not a normal retest is necessary and its start.

In this embodiment, the dual mode device capable of switching and setting the end point mode and the rate mode has been described, but any one of the modes may be constituted.

[0036]

EFFECT OF THE INVENTION According to the automatic analyzer of the present invention, it is judged whether or not weight reduction retest is necessary for an ultrahigh value sample and the retest is started.
In addition, it is possible to improve the analytical efficiency of the overall chemical analysis of a large number of samples and determine the final results, because the determination of the necessity of retesting for high value samples and the start of retesting are performed in the middle of the reaction until the end of the reaction. It is possible to significantly reduce the time.

[Brief description of drawings]

FIG. 1 is a structural explanatory view showing an automatic chemical analyzer according to an embodiment of the present invention.

FIG. 2 is a flowchart showing the control of the re-examination control unit and the arithmetic unit.

FIG. 3 is a flowchart showing the control of the re-examination control unit and the arithmetic unit.

FIG. 4 is a graph diagram for explaining the operation and effect of the automatic chemical analysis device of the present invention.

FIG. 5 is a graph diagram for explaining the operation and effect of the automatic chemical analysis device of the present invention.

FIG. 6 is a graph diagram for explaining the operation and effect of the automatic chemical analysis device of the present invention.

[Explanation of symbols]

 1 Automatic Chemistry Analyzer 2 Sample Sampling Table 3 Reagent Dispensing Table 4 Optical Measuring Section 5 Computing Section 6 Retest Control Section 6A First Retest Control Section 6B Second Retest Control Section 7 Driver 8 Display Section 9 Storage Section 21 Dispenser 22 Sample container 31 Dispenser 32 Reagent container 41 Reaction container 42 Absorbance measurement optical system 43 Cleaning unit

Claims (2)

[Claims] 1. A reaction solution preparation part for preparing a test reaction solution by mixing a predetermined amount of a sample and a reaction reagent, and (b) an optical density of the test reaction solution after starting the reaction and after finishing the reaction. An optical measuring unit capable of measuring at a constant time up to (time t), and (c) an optical measuring unit at a constant time from the reaction start to the reaction end (time t) for a reference reaction liquid in which a standard sample and a reaction sample are mixed. A storage unit that stores the concentration and the concentration of a predetermined component in the standard sample, and (d) a sample whose final optical density At at the time t of the test reaction liquid is within a predetermined optical density limit value Ah,
An arithmetic unit for quantifying a predetermined component in the sample based on the At value, and (e) whether or not the final optical density At at the time t with respect to the test reaction liquid exceeds the optical density limit value Ah, A judgment is made based on the optical density value during the reaction, and A
For a sample determined to exceed h, a first retest control unit that controls the reaction solution preparation unit and the optical measurement unit to perform a retest under the condition that the amount of the sample is reduced; (f) a predetermined component in the sample Whether or not the concentration exceeds the predetermined threshold value Ch, based on the ratio between the optical density in the course of the reaction of the test reaction liquid and the corresponding optical density in the storage unit. An automatic chemical analyzer comprising a reaction sample preparation section and a second retest control section for controlling the optical measurement section so as to retest the sample to be judged. 2. A reaction solution preparation section for preparing a test reaction solution by mixing (a) a predetermined amount of a sample and a reaction reagent, and (b) an optical density of the test reaction solution from the start of the reaction to the end of the reaction. An optical measurement unit capable of measuring at a constant time up to (time t), and (c) an optical measurement at a constant time from the reaction start to the reaction end (time t) for the reference reaction liquid in which the standard sample and the reaction reagent are mixed. A storage unit for storing the concentration and the concentration of a predetermined component in the standard sample; and (d) a plurality of optical concentrations of the test reaction liquid obtained over time, which belong to a predetermined optical concentration limit value within the Ah range. An arithmetic unit for quantifying a predetermined component in the sample based on the change rate of the optical density, and (e) whether or not the optical density of the test reaction solution measured during the reaction exceeds the optical density limit value Ah. Along with the judgment, the optical density value that falls within the Ah range when Ah is exceeded For samples with less than 3 points, a first re-examination control unit that controls the reaction solution preparation unit and the optical measurement unit so as to perform re-examination under the condition that the amount of the sample is reduced; Whether or not a predetermined threshold value Ch is exceeded is determined in advance based on the ratio between the optical density during the reaction of the test reaction liquid and the corresponding optical density in the storage unit, and the sample determined to exceed Ch Regarding the above, an automatic chemical analysis device comprising the above-mentioned reaction solution preparation unit and a second re-inspection control unit for controlling the optical measurement unit so as to perform re-inspection.