JPH085562A - Automatic analytic method - Google Patents

Abstract

PURPOSE:To obtain an automatic analytic method in which the presence of a disturbance in a cuvette can be determined by measuring the variation of absorbance of a reaction liquid in the cuvette with time at each period of a cuvette wheel. CONSTITUTION:Every time when a cuvette 1, dispensed 9-11 with a sample from a sample cup 3 and reagents from reagent containers 5, 7, passes a position A (every period), a lamp 12 projects a white light containing a plurality of wavelengths which are not absorbed by a reaction liquid. The light transmitted through the cuvette 1 is passed through a diffraction grating 13 and received by a photodiode array 14. At the end of 8 periods, a cleaning unit 15 discharges the reaction liquid to clean the cuvette 1 thus ending the measurement of absorbance. Presence of a disturbance in the cuvette 1 is then determined based on the measurement results. A normal cuvette 1 is reused but an abnormal cuvette is affixed with display or printer comment information, for example. The cuvette 1. affixed with comment information is replaced, cleaned again, or not used for next analysis.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an automatic analysis method for automatically identifying and / or quantifying various components in blood.

[0002]

2. Description of the Related Art In recent years, a sample and a reagent are quantitatively collected in a reaction container, and the sample and the reagent are reacted to prepare a reaction solution.
An analyzer that is capable of irradiating the reaction container with light and measuring the absorbance of the reaction solution in the reaction container a number of times over time is widely used. In such an analyzer, the reaction solution in the reaction container is usually discharged after the measurement is completed, and the reaction container is washed and reused.

Of such analyzers, a reaction vessel after cleaning is filled with a liquid such as pure water, the absorbance of the liquid is measured, and the suitability of using the reaction vessel after cleaning is determined from the measured value. Is proposed in Japanese Patent Laid-Open No. 53-10480. According to JP-A-53-10480, the state of dirt accumulated during repeated use after cleaning the reaction container
It can be determined by detecting an increase in the absorbance of the reaction container. Further, the reaction container determined not to be reusable can be controlled so as to be repeatedly washed until it becomes clean, and to suspend the use during that period.

[0004]

However, in the above-mentioned JP-A-53-10480, the overall stain on the inner surface of the reaction vessel is determined by detecting the increase in absorbance, and the inner surface of the reaction vessel is judged by a strong alkaline reagent. Minute scratches generated on the surface of the reaction vessel, small dust adhering to the outer surface of the reaction vessel, spot-like stains caused by scattered reagents generated during sampling, bubbles adhering to the inside of the reaction vessel during analysis, so-called soaking the reaction vessel in a constant temperature liquid. In the water bath method, no consideration is given to a disturbance factor that occurs suddenly and randomly such as bubbles adhering to the outer surface of the reaction vessel.

An object of the present invention is to provide an automatic analysis method capable of determining the presence or absence of disturbance occurring in a reaction container.

[0006]

The automatic analysis method of the present invention is designed to automatically determine a desired component in a reaction solution by measuring the change in the absorbance of the reaction solution in the reaction vessel or the absorbance at the end point of the reaction solution. In the analysis, the presence or absence of disturbance associated with the photometric part of the reaction container is determined based on the change in the absorbance of the reaction solution over time, and comment information is added to the measurement result based on the determination result. It is a thing.

The time-dependent absorbance change of the reaction solution is measured using light of a plurality of wavelengths, and the photometric unit of the reaction vessel is based on the measured value of light having a wavelength that is not absorbed by the reaction solution according to the analysis item. It is preferable to determine the presence / absence of a disturbance related to (3) because it becomes extremely easy to determine the presence / absence of a disturbance.

In determining the presence or absence of a disturbance related to the photometry section of the reaction container, the analysis allowable limit of each analysis item is
By using the reference value of the value obtained by dividing the measured absorbance corresponding to each analysis item by the coefficient that converts it into a concentration value, the criteria for abnormality can be set by a simple theory according to the required analysis accuracy and data reliability. Therefore, it is possible to execute suitable quality control for individual data.

[0009]

In the automatic analysis method of the present invention, when the change in the absorbance of the reaction solution in the reaction vessel or the absorbance at the end point of the reaction solution is measured to automatically analyze the desired component in the reaction solution, The presence or absence of a disturbance associated with the photometric part of the reaction container is determined based on the temporal change in absorbance, and comment information is added to the measurement result based on the determination result. Therefore, when the desired component in the reaction container is automatically analyzed, the presence or absence of the disturbance of the reaction container can be determined from the comment information based on the temporal change in the absorbance of the reaction solution.

[0010]

Embodiments of the automatic analysis method of the present invention will be described in detail with reference to the drawings. FIG. 1 is a schematic configuration diagram of an analyzer that performs the automatic analysis method of the present invention. In this example, this analyzer is an automatic chemical analyzer that collects a sample and a reagent in a reaction container and measures the absorbance of the reaction solution through the reaction container to quantify the concentration of components in the sample. This analyzer comprises a cuvette wheel 2 having a plurality (15 in this example) of cuvettes 1 as a reaction container, a sampler 4 having a plurality of sample cups 3, and a first reagent container 5 having a plurality of first reagent containers 5. The reagent table 6, the second reagent table 8 having a plurality of second reagent containers 7, the sample in the sample cup, the first reagent in the first reagent container 5 and the second reagent in the second reagent container 7 are respectively Dispensers 9, 10 and 11 for sampling and discharging a fixed amount into the cuvette 1, a lamp 12 for irradiating the cuvette 1 with white light, a diffraction grating 13 for separating the white light transmitted through the cuvette 1, and the separated light. A photodiode array 14 for receiving the light and a cleaning device 15 for cleaning the cuvette 1 for which measurement has been completed are provided.

The cuvettes 1 are arranged on the circumference of a cuvette wheel 2 at equal intervals, and the cuvette wheel 2 is rotated and stopped in the counterclockwise direction by 360 ° + 1 cuvette by a drive system and a control system not shown. It operates to repeat. That is, the cuvette 1 in which the sample in the sample cup 3 is injected is 360 ° in one cycle.
Rotate stepwise counterclockwise by +1 cuvette. The sampler 4 is used as a table in which the sample cups 3 containing the sample are intermittently stopped one cup at a time. First
The reagent table 6 and the second reagent table 8 are selectively used for the first reagent container 5 and the second reagent container 7 depending on the analysis item.
Is stopped at the suction position and is controlled to rotate or rotate. The dispenser 9 performs one-to-one or one-to-many dispensing, and the sample in one sample cup 3 is 1 or 2
Dispense into cuvette 1 above. The dispensers 10 and 11 perform one-to-one dispensing, and one cuvette 1 has a first reagent container 5 and a second reagent container 7 each having a first reagent and a second reagent. Dispense reagents.

In this analyzer, the measurement with a plurality of wavelengths of light is performed by irradiating the cuvette 1 at the position A with white light including a wavelength that is not absorbed by the reaction solution from the lamp 12 whose irradiation direction is constant. This is performed by a method in which the transmitted white light is dispersed by the diffraction grating 13 and the dispersed light is received by the photodiode array 14. This measurement is performed every time the cuvette 1 passes the position A, that is, every one cycle. The absorbance data for each cuvette 1 measured by this method is accumulated in a data processing device (not shown),
The accumulated data can be output to a display or a printer (not shown) as needed.

The operation of this example will be described. The sample in one or more sample cups 3 of the plurality of sample cups 3 is sampled by the dispenser 9, and the cuvette 1 at the position B is sampled.
Dispense in fixed quantity. The cuvette 1 at the position B stops at the position C after one cycle. When the cuvette 1 is stopped at the position C, one first reagent corresponding to a desired analysis item in the first reagent container 5 is sampled by the dispenser 10 and is quantitatively discharged to the cuvette 1. After that, the sample and the first reagent in the cuvette 1 are mixed by a stirring device (not shown), preheated, and preliminarily reacted until the sample and the first reagent stop at position D after four cycles. When the cuvette 1 stops at the position D, the second reagent, which is the reaction trigger, is sampled by the dispenser 10 from one of the second reagent containers 7 corresponding to the analysis item, and is quantitatively discharged to the cuvette 1. Then this cuvette 1
The sample, the first reagent and the second reagent therein are mixed by a stirrer to form a reaction solution.

The cuvette 1 at the position D is at the position E after eight cycles.
After that, the reaction liquid is discharged by the cleaning device 15, and then the cleaning is performed. Thus, the measurement of the absorbance is completed, and the presence or absence of the disturbance of the cuvette 1 is determined based on the measurement result. When it is determined that there is an abnormality by the method described later, comment information is added to the display or printer, for example. It is preferable that the reaction container with such comment information is exchanged, washed repeatedly, not used in the next analysis, and the like, and the same sample is re-analyzed as necessary. On the other hand, when it is determined that there is no abnormality, the comment information is not added and the cuvette 1 is reused.

A method for determining the presence or absence of disturbance associated with the photometric section of the reaction container based on the change in absorbance over time will be described below. After the absorbance is measured using light of a plurality of wavelengths including a wavelength that is not absorbed by the reaction solution, the variation in the measurement data obtained a plurality of times by the light of the wavelength that is not absorbed by the reaction solution is determined according to the analysis item. As the variation, the difference between the maximum measurement value and the minimum measurement value, the standard deviation, or the like is used.

Next, the degree of variation and the reference value are compared. In this example, as the reference value, a value obtained by dividing the analysis accuracy allowable limit of each analysis item by a coefficient for converting the absorbance corresponding to each analysis item into a concentration value is used. Therefore, if P is the reference value, SD is the allowable limit of analytical accuracy, and C is the coefficient for converting the absorbance of each analytical item into a concentration value,

## EQU1 ## P = SD / C.

Such a reference value is proposed by Tonks (1963). In this case, the allowable limit of analysis accuracy is 1/4 of the normal range width, but the reference value is a standard of ± 2 times the analysis error. Since it can be interpreted as a range of deviation, 1/2 of this value may be used. Therefore, if SD is the analytical accuracy allowable limit and Δ is the normal range width, the analytical accuracy allowable limit is

## EQU2 ## SD = Δ / 8. If the absorbance of each analysis item is I and the concentration value is a,

## EQU00003 ## It can be expressed as a = CI.

When the degree of variation exceeds the reference value, the comment information of the abnormality is added to the display or printer as described above.

FIG. 2A shows the change in absorbance over time when there is no disturbance in the photometric portion of the reaction vessel, and FIG. 2B shows the change in absorbance over time when there is disturbance in the photometric portion of the reaction container. Two-wavelength measurement in which a wavelength λ ₁ close to the absorption maximum wavelength of the reaction solution and a wavelength λ ₂ without absorption of the reaction solution are set will be described with reference to FIG.

When there is no disturbance associated with the photometric part of the cuvette 1 (FIG. 1), the wavelength λ ₁ close to the absorption maximum wavelength of the reaction solution becomes a smooth curve as shown in FIG. The non-wavelength λ ₂ becomes a flat straight line.

On the other hand, when there is disturbance, the wavelength λ ₁ close to the absorption maximum wavelength of the reaction solution is not smooth and the wavelength λ ₂ without absorption of the reaction solution is not flat, as shown in FIG. 2B. Here, at the wavelength λ ₁ close to the maximum absorption wavelength of the reaction solution, it is difficult to determine the presence or absence of disturbance from the change in absorbance due to the reaction in the portion where the reaction overlaps with that in FIG. 2A. In the case of the wavelength λ ₂ where the reaction solution is not absorbed, there is little overlap with the case of the flat straight line in FIG. Therefore, when determining the presence or absence of disturbance that affects the measurement, it is effective to select the wavelength that does not absorb the reaction solution and use it for the measurement while checking the wavelength used according to each analysis item. Is.

According to this example, when the absorbance of the reaction solution was measured using the cuvette, the presence or absence of the disturbance generated in the cuvette was determined, so that the accuracy control of individual data can be performed quickly and efficiently, and the absorbance From the comment information added to the data, it is possible to determine whether or not the analysis measurement result is affected by a disturbance such as scratches, stains, or air bubbles on the reaction container. Further, it is preferable that the same cuvette in which the above-mentioned abnormality is continuously detected is appropriately replaced or cleaned (including the outer wall).

The influence of the disturbance on the measured value differs for each analysis item, but in this example, the abnormality detection standard can be set by a simple theory according to the required analysis accuracy, data reliability, and the like. .

The present invention is not limited to the above-mentioned embodiment, and various modifications can be made. For example, as a method for obtaining the absorbance, one or a plurality of filters that selectively pass light of a desired wavelength may be installed before projecting light onto the reaction container. Further, there are also a photometric method for reducing the amount of movement of the cuvette by guiding a plurality of wavelengths to a plurality of photometric positions by a light guide after analyzing white light with a diffraction grating, and a method for rotating a photometric unit. Further, the type of reagent used in the reaction and the number of times of dispensing may be arbitrarily changed according to the analysis item. In addition, as the reference value for determining the variation, To
Other than the one proposed by nks (1963), one that defines other tolerances may be appropriately selected. Further, as a method of obtaining the measurement result of a plurality of times, it can be performed by appropriately changing the rotation angle of 360 ° + 1 cuvette, for example, 360 ° + n cuvette (n ≧ 2), or twice or several times. You may set so that it may go around once when stopping.

[0025]

As described above, according to the automatic analysis method of the present invention, the change in the absorbance of the reaction solution in the reaction vessel or the absorbance at the end point of the reaction solution is measured to determine the desired component in the reaction solution. At the time of automatic analysis, the presence or absence of disturbance associated with the photometric part of the reaction container is determined based on the temporal absorbance change of the reaction solution, and comment information is added to the measurement result based on the determination result. Therefore, it is possible to determine from the comment information whether or not the analysis measurement result is affected by the disturbance such as scratches, stains, and air bubble adhesion on the reaction container based on the change in the absorbance of the reaction solution over time.

Further, in the automatic analysis method of the present invention, a simple method can be used without adding a new mechanism when measuring the time-dependent absorbance change of the reaction solution in the reaction container or the absorbance at the end point of the reaction solution. It is possible to directly determine the presence or absence of disturbance factors such as scratches, stains, and air bubble adhesion on the reaction container.

Further, in the automatic analysis method of the present invention, the presence or absence of disturbance associated with the photometric section of the reaction container is determined based on the temporal change in absorbance of the reaction liquid in the reaction container. That is,
Since the absorbance of the reaction solution in the reaction vessel to be washed and reused is directly used, it can be used as a method for confirming the measurement result.

[Brief description of drawings]

FIG. 1 is a schematic configuration diagram of an analyzer that performs an automatic analysis method of the present invention.

FIG. 2A is a temporal absorbance change when there is no disturbance in the photometric portion of the reaction container, and B is a temporal absorbance change when there is a disturbance in the photometric portion of the reaction container.

[Explanation of symbols]

1 cuvette 2 cuvette wheel 3 sample cup 4 sampler 5 first reagent container 6 first reagent table 7 second reagent container 8 second reagent table 9, 10, 11 dispenser 12 lamp 13 diffraction grating 14 photodiode array 15 washing device λ ₁ Wavelength close to absorption maximum wavelength of reaction solution λ ₂ Wavelength without absorption of reaction solution A, B, C, D, E position

Claims (3)

[Claims] 1. A method for measuring the absorbance of a reaction solution in a reaction vessel over time or for measuring the end point absorbance of the reaction solution to automatically analyze a desired component in the reaction solution. The presence or absence of disturbance related to the photometric part of the reaction vessel is determined based on the above, and comment information is added to the measurement result based on the determination result. 2. The time-dependent change in absorbance of the reaction solution is measured using light of a plurality of wavelengths, and is related to the photometric section of the reaction container based on a measurement value of light having a wavelength that is not absorbed by the reaction solution. The automatic analysis method according to claim 1, wherein the presence or absence of disturbance is determined. 3. A value obtained by dividing the analysis allowable limit of each analytical item by a coefficient for converting the measured absorbance corresponding to each analytical item into a concentration value in determining the presence or absence of disturbance related to the photometric section of the reaction container. 3. The automatic analysis method according to claim 1, wherein is used as a reference value.