JPH04329362A - Automatic analyzer - Google Patents

Abstract

PURPOSE:To judge whether a reagent separate injecting action is normally performed or not by directly monitoring a reagent separately injected into a reaction container. CONSTITUTION:A comparison/judgment section 42 which compares the measured value of the absorption wavelength light of water in the near infrared region while water or an aqueous solution is filled in the reaction container and the measured value of the absorption wavelength light of water while a sample and an analysis reagent are separately injected into the reaction container within the measured values of a spectrometer 40 illuminating the light to the solution in the reaction container to measure the light absorption in the near infrared region and judges whether the liquid quantity is at the normal liquid quantity state for quantifying the sample constituent or not is provided.

Description

[Detailed description of the invention]

0001

[Industrial Application Field] The present invention is a reaction vessel direct photometry method in which a sample and an analytical reagent are mixed at a predetermined ratio in a reaction vessel, reacted under certain conditions, and the sample components are quantified based on the optical changes. This invention relates to an automatic analyzer. Such automatic analyzers are used, for example, as automatic biochemical analyzers that perform biochemical tests on samples such as blood and urine.

0002

[Background Art] In order to dispense an analytical reagent into a reaction container into which a specimen has been dispensed, an automatic analyzer uses a reagent suction/dispensing probe to aspirate the reagent in a reagent bottle and dispense it into the reaction container. . In this case, the liquid level of the reagent in the reagent bottle is detected before dispensing. However, the reagent dispensing operation was not directly confirmed. The present inventor has already proposed a method for determining whether or not reagent dispensing was normal by holding the dispensing nozzle above the reagent liquid surface after reagent dispensing and detecting the presence or absence of the reagent liquid surface. (Unexamined Japanese Patent Publication No. 2-405
(See Publication No. 62).

0003

[Problems to be Solved by the Invention] The method proposed by the present inventor requires the dispensing nozzle to be kept below the reagent liquid level, so it is difficult to insert the dispensing nozzle into the reaction vessel. This applies to automatic analyzers that can. Therefore, it cannot be applied to high-speed reagent dispensing type automatic analyzers that perform reagent dispensing above the opening of the reaction vessel, or closed type automatic analyzers that perform reagent dispensing through a liquid supply line directly connected to the reaction vessel. I can't. SUMMARY OF THE INVENTION An object of the present invention is to directly monitor the reagent dispensed into a reaction container to determine whether the reagent dispensing operation is performed normally.

0004

[Means for Solving the Problems] As shown in FIG. 1, the present invention provides a solution among the measured values of a spectrometer 40 that irradiates a solution in a reaction container with light and measures light absorption in the near-infrared region. , Measured values of absorption wavelength light of water in the near-infrared region when the reaction container is filled with water or aqueous solution, and absorption of water in the near-infrared region when the sample and analytical reagent are dispensed into the reaction container. A comparison determination section 42 is provided that compares the measured value of the wavelength light and determines whether the liquid volume is in a normal liquid volume state for quantifying sample components.

[0005]

[Function] Measured value when the reaction container is irradiated with water absorption wavelength light in the near-infrared region, and the absorption value of water at the preset optical path length of the reaction container (thickness of the solution in the reaction container). Alternatively, if the reaction container is in a water bath, it is determined whether the amount of reagent liquid in the reaction container is sufficient by comparing the absorption value of water corresponding to the thickness of water in the water bath. It is determined whether the amount of reagent liquid is sufficient before and after reagent dispensing, and it is determined whether reagent dispensing has been executed normally. If there is an abnormality in reagent dispensing, measures can be taken such as re-inspecting only that portion if it occurs once, or issuing an alarm indicating that the dispenser is abnormal if it occurs continuously. .

[0006] When measuring the absorption of water using air as a control,
When the thickness of water is 1 cm, the absorbance is 0.23 Abs at the measurement wavelength of 975 nm and 0.034 Abs at 1070 nm.
, 0.524 Abs at 1200 nm and 0.443 Abs at 1260 nm. As shown in FIGS. 2(A) and 2(B), in the case of a reaction vessel immersion type automatic analyzer in which the reaction vessel 46 is a water bath, the absorbance when the reaction vessel 44 is empty is the same as that when the reaction vessel 46 is filled. Due to the thickness of the water, the reaction vessel 4
It is the value obtained by subtracting the length equivalent to 4. 45 and 47 are window plates. Usually, glass, acrylic resin, etc. used for reaction vessels do not have a large absorption band in the vicinity of 900 to 1300 nm. On the other hand, as shown in FIG. 2(A), the reaction vessel 4
When the aqueous solution 48 is filled in the reaction tank 4, the absorbance when the entire measurement light beam 50 passes through the aqueous solution 48 is approximately equal to that of the reaction tank 4.
This corresponds to the thickness of water of 6. Of course, the absorbance decreases by the thickness of the wall of the reaction vessel 44. Therefore, as shown in FIG. 2(C), the absorbance of the light beam at the absorption wavelength of the water irradiated onto the reaction vessel 44 in the reaction tank 46 is determined from Awo when the reaction vessel 44 is empty, so that there is no problem in measurement. It shows the absorbance up to the absorbance Awf when the liquid level reaches the height.

In applying the present invention, the absorbance when the reaction vessel is empty (Awo) and the absorbance when the liquid level is sufficient to reach a height that does not interfere with measurement (Awf) are input. Either set the absorbance Av1 at that time by dispensing water (reagents may be used) with liquid volumes V1 and V2 into the reaction container.
, Av2 to determine the relationship between liquid volume and absorbance.

In actual analysis, following the first analytical reagent (R1), the second analytical reagent (R2) is often additionally dispensed after a certain period of time, so the absorbance after dispensing R1 and before dispensing R2 From the relationship shown in FIG. 2(C) regarding the absorbance A2 after dispensing A1 and R2, it is determined whether the sample reaction solution has been correctly prepared (whether or not the predetermined amounts of R1 and R2 have been dispensed correctly). . As an example of judgment, when determining whether the liquid volume can be measured normally, if A1 (A2) ≧ Awo, it is normal; if A1 < Awo, R1 is a dispensing error (one reagent method);
In the case of the reagent method, the amount of liquid R1 is determined from A1, and the amount of liquid R2 is determined from A2, and a dispensing error in R1 and R2 is determined.

In the case of an automatic analyzer in which the reaction vessel is an air bath, air does not exhibit absorption in the near-infrared region, so the absorbance when the reaction vessel is empty is considered from the relationship shown in Figure 2 (C). Since it can be considered that Awo=absorbance 0, the relationship between liquid volume and absorbance is as shown in FIG. 2(D). Whether or not the dispensed liquid amount is normal can be determined in the same manner as described above. The measurement wavelengths for determining whether the liquid amount is normal are two wavelengths in the near-infrared region, at least one of which is the absorption wavelength of water, for example, around 975 nm or around 1200 nm. This is because in single-wavelength measurement, if a liquid level or bubbles enter the measurement light beam, the liquid level may not be accurately detected.

0010

Embodiment FIG. 3 is a block diagram of an example of an automatic analyzer. A sample dispensing nozzle mechanism is provided for dispensing the sample into the reaction vessels arranged in the reaction line, and the pipettor pump 44 dispenses the sample using the pipettor.
C from the sampler control unit 46 via the interface 48
It is controlled by PU50. A dispenser is provided to dispense into the reaction container an analytical reagent to be reacted with a sample in the reaction container. It is then controlled by the CPU 50. A reaction section control section 56 is provided to stir the solution in the reaction vessel of the reaction line and to control a cleaning mechanism for cleaning the reaction vessel after the reaction is completed.
6 is also controlled by the CPU 50 via the interface 48. A spectrometer 40 is provided to optically detect the reaction between the sample and the analytical reagent in the reaction container.
The detection output in the ultraviolet-visible range of 0 is taken into the CPU 50 from the concentration calculation section 60 via the interface 48. The spectrometer 40 also measures the absorption wavelength of water in order to determine the amount of liquid in the reaction container, and the measurement signal is taken into the CPU 50 via the interface 48. The comparison and determination section 42 in FIG. 1 is realized by the CPU 50. The interface 48 further includes a printer 62, a keyboard 64, a CRT 66, and a floppy disk drive 6.
8 are connected.

FIG. 4 shows the basic reaction steps of the automatic analyzer. The washed reaction vessel is filled with water, and Awf is measured at the absorption measurement wavelength of water (900 to 1200 nm region), and two wavelengths (λs, λr) of the absorption wavelength in the ultraviolet-visible region are used to quantify the reaction components. Cell blank Acb is measured. The water is then drained and the Awo measured. After that, the sample is dispensed into the reaction container, and the first reagent R1 is dispensed. Water absorption measurement A1 before the second reagent R2 is dispensed
and the measurement Af in the quantitative range of the reaction component is measured. After that, the second reagent R2 is dispensed, and at the end of the reaction water absorption measurement A
2 and the reaction components are quantitatively measured Ab. Water measurement Aw
f and Awo may be measured for each reaction vessel, or may be measured in advance and stored in a storage device.

When the reaction components are quantified using the end point method and the reagent blank correction method as shown in FIG.
}-(Arb-Acb)] (1). Here K
is a concentration conversion coefficient, fv is a liquid volume correction coefficient, and Ard is a reagent blank.

FIG. 5 shows the operation for checking the amount of reaction liquid. From the measured values obtained in the basic reaction steps shown in Figure 4, A1 is compared with Awf±α (α is the tolerance range) in the one-reagent method, and A2 is compared with Awf±α in the two-reagent method. Then, when each condition is satisfied, the concentration C is calculated and output. If the amount of liquid is insufficient, the measurement is performed again, and if the amount of reagent liquid is not normal in the remeasurement, an alarm is issued and the measurement is interrupted. In calculating the concentration C, when using the one-reagent method, use the following formula C=K {(Ab-Acb)-(Arb-Acb)}
It is calculated by (2), and in the case of the two-reagent method, it is calculated by equation (1).

A specific example of an automatic analyzer to which the present invention is applied is shown in FIG. A sample such as blood is placed in a sample container, and a sample rack 2 in which a plurality of sample containers are arranged is moved along a belt conveyor type transport path 4. The transport path 4 consists of an outgoing path 4a for transporting the sample rack 2 from left to right in the figure, and a return path 4b for transporting the sample rack from right to left. In the figure, a sample rack supply section 6 for feeding the sample rack 2 to the outward path 4a is provided at the left end of the outward path 4a, and a storage section 8 for storing the sample rack 2 after measurement is provided at the left end of the return path 4b.
is provided. In the figure, the right end portion of the conveyance path 4 shows the outgoing path 4.
The sample rack 2 that was sent a is temporarily stored, and the return trip 4b
A rack standby section 10 is provided for sending out racks. While the sample rack 2 is being transported on the outbound route 4a, the analysis units 26a, 26
The analysis unit 26a is stopped at the sample dispensing position b.
, 26b. On the return trip 4b, the outbound trip 4a
According to the measurement results of the sample dispensed and measured, the sample that needs to be retested is re-dispensed.

Two analysis units 12 are installed along the transport path 4.
a and 12b are arranged. Both have the same structure. In each analysis unit, a reaction disk 14 in which a reaction container 15 that also serves as a cuvette is arranged is placed near the transport path 4, and a reaction disk 14 is placed in the transport paths 4a and 4b.
A stopping device (not shown) is provided to stop the sample rack 2 at a sample dispensing position near the sample rack 4 . Conveyance path 4a or 4
A pipettor 16 equipped with a nozzle is disposed to dispense a sample from the sample rack 2 stopped on the sample rack 2 into the reaction container 15. Two turntable-type reagent stores 18a, 18b are arranged in each analysis unit 12a, 12b for dispensing reagents into the reaction container 15. Dispensers 20a and 20b are provided for dispensing. A cleaning mechanism 22 is provided to clean the reaction container after analysis is completed using the reaction disk 14. The reaction disk 14 is provided with an optical analysis section for measuring the reaction in the reaction container 15 containing the sample and reagent, but it is not shown.

The sample rack supply section 6 and storage section 8 are provided with an interface and a CPU 24, and each analysis unit 12a and 12b is also provided with an interface and a CPU 24, respectively.
PUs 26a and 26b are provided, and the standby section 10 is also provided with an interface and a CPU 28. Those CPUs 24, 26a, 26b, 28 are main CPUs
It is connected to 30. The main CPU 30 also has C
An RT 32, a keyboard 34 and a printer 36 are connected.

The operation of the automatic analyzer shown in FIG. 6 will be explained. Reagents necessary for measurement of each item are set in reagent storages 18a and 18b of the analysis unit. When the sample racks 2 are arranged in the supply section 6 and the operation is started from the keyboard 34, the reaction container 15 is washed with washing water by the washing mechanism 22. After washing, water is poured into the reaction vessel 15 and a blank measurement is performed. Reaction vessel 1 after blank measurement
When the sample rack 5 moves to the sample dispensing position, the sample rack 2 is sent along the outgoing path 4a of the transport path, is stopped at the sample dispensing position, and the pipetter 1 is moved to the sample dispensing position for the first measurement item to be analyzed.
6, the sample is dispensed into the reaction container 15 in an amount determined for each measurement item. Pipettor 16 after sample dispensing
The nozzle moves to a cleaning pot, which is not shown in the figure, and the inside and outside of the nozzle are cleaned with pure water. Thereafter, the next item of the same sample or the next different sample is sequentially dispensed into other reaction vessels 15. When the reaction container 15 into which the sample has been dispensed with the reaction disk 14 moves to the reagent dispensing position,
A predetermined amount of a predetermined reagent is sucked by the dispenser 20a or 20b and dispensed into the reaction container 15. After dispensing, the probes of the dispensers 20a and 20b are moved to a cleaning position not shown in the figure, and the inside and outside of the probes are cleaned with pure water. Thereafter, the dispensers 20a and 20b move on to the next reagent dispensing operation.

The sample rack 2 travels on the outward path, waits in the standby section 10, waits for the analysis results of the samples, is sent to the return path 4b, and is stored in the storage section 8. While moving on the return path 4b, the sample that needs to be retested is stopped at the sample dispensing position, and sample dispensing is performed again. In the reaction disk 14, the absorbance of a reaction solution containing a sample and a reagent is measured by a measuring section. After the analysis has been completed, the reaction vessel 15 is at a washing position where the reaction liquid is sucked and discharged, washed with water, and the water inside the reaction vessel is drained, thereby preparing it as a reaction vessel for a new sample. If the present invention is applied to an automatic analyzer that has a belt line sample transport system with a forward path and a dual path as shown in Figure 6, even if a reagent dispensing error occurs on the forward path, it will be possible to quickly take measures such as retesting on the dual path. You will be able to do this.

[0019]

According to the present invention, it is possible to judge whether or not the reagent dispensing operation has been carried out normally by directly measuring the amount of liquid in the reaction container. As a result, generation of inaccurate analysis values can be prevented. Reaction liquid in the reaction container immediately after reagent dispensing (reagent accounts for the majority of the total)
The amount can be checked, reagent dispensing abnormalities can be quickly detected, and reanalysis can be performed quickly. If reagent dispensing errors occur consecutively, for example three times in a row, it is possible to interrupt sample collection as a result of an abnormality in the reagent dispenser, thereby preventing wastage of valuable samples. The automatic analyzer of the present invention can be applied to a closed-type reagent feeding and dispensing automatic analyzer, and an open-type high-speed reagent dispensing system that performs reagent dispensing above the opening of the reaction container. It can also be applied to type automatic analyzers.

[Brief explanation of drawings]

FIG. 1 is a block diagram illustrating the present invention.

FIG. 2 is a diagram illustrating the operation of the present invention; (A) shows a case where the reaction vessel is fully filled with liquid, (B) shows a case where the reaction vessel is empty, and (C) shows a case where the reaction vessel is empty. A diagram showing the relationship between the liquid volume and absorbance when the reaction tank is a water bath, and (D) a diagram showing the relationship between the liquid volume and absorbance when the reaction tank is an air bath.

FIG. 3 is a block diagram of an example of an automatic analyzer.

FIG. 4 is a diagram showing basic reaction steps of an automatic analyzer.

FIG. 5 is a flowchart showing an example of operation.

FIG. 6 is a configuration diagram showing a specific example of an automatic analyzer to which the present invention is applied.

[Explanation of symbols]

40 Spectrometer 42 Comparison and judgment section 44 Reaction container 46 Reaction tank 48 Reaction solution 50 Measurement light flux

Claims (1)

[Claims] Claim 1: In an automatic analyzer using a reaction vessel direct photometry method, in which a sample and an analytical reagent are mixed at a predetermined ratio in a reaction vessel, reacted under certain conditions, and the sample components are quantified based on the optical change. , Measured values of absorption wavelength light of water in the near-infrared region when the reaction container is filled with water or aqueous solution, and absorption of water in the near-infrared region when the sample and analytical reagent are dispensed into the reaction container. 1. An automatic analyzer comprising: a comparison/judgment unit that compares a measured value of wavelength light to determine whether a liquid volume is in a normal liquid volume state for quantifying a sample component.