JPS6385429A - Method and device for centrifugal type continuous analysis - Google Patents

Abstract

PURPOSE:To easily detect the abnormality of the discharge of liquid from cuvettes, the dispensation of cleaning liquid, etc., by detecting whether or not there is liquid in the cuvettes during the rotation of a centrifugal separating rotor from the characteristic absorption wavelength of the liquid at the cleaning stage of the curvettes. CONSTITUTION:The dispensation is performed from a sample tray 13 and a 1st and the 2nd reagent bottle receivers 6 and 7 to the cuvettes 3 on a reaction tray 2 by a pipetter 9 and the 1st and the 2nd reagent dispensers 17 and 23 and a measurement is taken after fast rotation. The tray 2 is fed stepwise after the measuring operation to inject the cleaning water in all cuvettes 3 by a cleaning water dispenser 32, and then the tray 2 is rotated at a high speed to discharge the cleaning water by a siphon phenomenon. A measuring instrument 49 for abnormality detection provided to a measurement part 30 finds the absorbance of detection light 52 passing through the reaction and light measurement part 46 of the cuvette 3 during the water discharging operation and then the absorbance of the reaction and light measurement part 46 which is clean and empty is compared with that of the reaction and light measurement part 46 which is filled with the washing liquid to detect whether or not there is abnormality.

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Industrial Application Field The present invention relates to a centrifugal continuous analysis method and apparatus thereof, and in particular, to a centrifugal continuous analysis method and apparatus for analyzing samples such as blood, plasma, serum, urine, other body fluids, secretions, etc. The present invention relates to a centrifugal continuous analysis method and device for biochemical sample analysis. The present invention also relates to a method and device for detecting clogging of a cuvette discharge path in a centrifugal automatic analyzer, and a method and device for monitoring the operation of a sample dispensing device and a washing liquid dispensing device.

(b) Conventional technology A centrifugal automatic analyzer is equipped with a rotor that includes a sample receiving section, a reagent receiving section, and a reaction/photometry section that communicates with these through or without a passage. By rotating the rotor, the sample injected into the sample receiver and the reagent injected into the reagent receiver are sent to the reaction and photometry section, where they are mixed and reacted and the reaction products are measured, so the measurement time is extremely long. In addition, it is possible to automatically and smoothly introduce trace amounts of samples and reagents into the cuvette.

However, centrifugal automatic analyzers must rotate a rotor containing cuvettes or disks at high speed in order to generate centrifugal force, and during this time, injection of samples, reagents, washing liquid, etc. Because operations cannot be performed, the batch method has to be used.

Therefore, the present applicant has previously proposed a centrifugal automatic analyzer that is equipped with a cuvette in the discharge path such as a siphon tube and is capable of continuous analysis.

(c) Problems to be Solved by the Invention However, in the siphon bone cuvette as described above, since the discharge path portion such as the siphon tube has a small diameter, it may become clogged during repeated use.

If the discharge path is clogged, the reaction solution or washing solution cannot be drained, causing the reaction solution to overflow, or furthermore, making subsequent analysis impossible and wasting valuable samples such as blood. This was a problem.

It is an object of the present invention to solve such problems related to clogging of the cuvette discharge path.

(d) Means for Solving the Problems The present invention provides a centrifugal continuous analysis method and apparatus that can detect clogging in the discharge path of a cuvette during rotation of a rotor.

That is, in the present invention, a sample and a reagent are mixed and reacted in a cuvette under the action of centrifugal force, the reaction product is measured, and then the reaction solution is discharged outside the cuvette, washed, and then continuously. A centrifugal continuous analysis method in which the presence or absence of a liquid in the cuvette is detected by measuring the absorbance of light at a characteristic absorption wavelength of the liquid in the cuvette washing step. Continuous analysis method. Further, the present invention provides a centrifugal continuous automated system comprising a rotor having a cuvette attachment part, a discharge liquid path surrounding the rotor, a sample injector, a reagent injector, a photometer, and a cleaning liquid injector provided around the rotor. A centrifugal type continuous automatic analyzer is characterized in that a light source containing light having a wavelength in a characteristic absorption wavelength region of a liquid and a photometer are provided with a cuvette attachment part in between.

In the present invention, the absorbance of the cuvette is measured for the cuvette during the reaction solution discharging stage and the washing solution discharging stage. The wavelength of light at which the absorbance of the cuvette is measured is selected from among the characteristic absorption wavelengths of the reaction solution or washing solution. Therefore, the wavelength of light used for measurement may be different wavelengths for the reaction solution or for the cleaning solution, but if light with a common characteristic absorption wavelength is used, abnormalities in the cuvette can be detected. This is preferable because it simplifies the photometric process for measuring absorbance. These common characteristic absorption wavelengths are:
A characteristic absorption wavelength of a solvent, such as water, such as 1470 nm or 1200 nm in the near-infrared region.

It is preferable to select light of a wavelength different from the measurement wavelength band for analysis, such as 970 nm. For this purpose, for example, the light source is provided with a filter for a specific wavelength.

In the present invention, absorbance measurement for detecting an abnormality in the cuvette discharge path is performed while the rotor is rotating.

Therefore, the measuring device should be positioned at least as long as the light source and photometer are placed across the reaction and photometry section of the cuvette, and the length of the optical path passing through the reaction and photometry section of the cuvette is constant during photometry. , can be provided at an appropriate cylindrical location around the rotor.

Detection of an abnormality in the cuvette discharge path, etc. according to the present invention is performed by comparing the measured value of absorbance with a blank value, but when an abnormality is detected, for example, by means such as an alarm or a signal light, This can be notified to the work tool.

(E) Effect In the present invention, the absorbance of light having the characteristic absorption wavelength of these liquids is measured in the cuvette at the reaction liquid discharge stage or washing liquid discharge stage, for example, immediately after the reaction liquid or washing liquid has been discharged. By comparing this measured value (D) with the measured value (B) of the absorbance of light at the relevant wavelength for an empty cuvette at the time of cleaning, an abnormality in the cuvette discharge path can be detected.

That is, if B=D, it means that there is no reaction solution or washing solution in the cuvette during the discharge step,
This indicates that there is no abnormality in the cuvette discharge path, that is, it is not clogged.

If B << D, it means that the liquid remains without being drained from the cuvette during the draining stage, indicating that an abnormality has occurred in the cuvette drain path.

In addition, in the present invention, the absorbance of light having a characteristic absorption wavelength of the liquid is measured for the cuvette from the reaction solution discharging stage to the washing stage, and the absorbance during washing with the washing solution is measured. Value (C
) and the absorbance (D) at the time of draining the washing liquid, the measured value (B) of the absorbance for light at the characteristic absorption wavelength of the empty cuvette at the time of cleaning, and the absorbance (B) of the empty cuvette at the time of cleaning, and the absorbance of the cuvela T at the time of washing with a washing liquid, e.g., water. By comparing the measured value (B) of the absorbance for light at the absorption wavelength, it is possible to detect abnormalities in the discharge path of the cuvette and in the operating state of each dispenser.

That is, if B=D and B=C, the cleaning liquid was introduced into the reaction/photometering section of the cuvette during the washing step with the washing liquid, and the washing solution was not introduced into the reaction/photometering section of the cuvette during the washing liquid discharge step. This means that the cuvette has been drained and is empty, indicating that there is no abnormality in the cuvette discharge path and that the washing liquid dispenser is also operating normally.

However, even if B=D, if B=C, it means that the cleaning liquid is not introduced into the reaction/photometering section of the cuvette during the cleaning stage with the cleaning liquid, so the operation of the cleaning liquid dispenser will be affected. It is defective and indicates that an abnormality has occurred.

If B=C, it means that some liquid remains in the reaction and photometry part of the cuvette during the cleaning liquid discharge stage, indicating that the cuvette discharge path is defective and an abnormality has occurred. There is.

As described above, according to the present invention, abnormalities such as a discharge failure in the cuvette discharge path or a dispensing failure in each dispenser can be immediately detected, and the cuvette in a centrifugal continuous automatic analyzer can be detected immediately. And the operating status of each dispenser can be monitored.

(F) EXAMPLES Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings, but the present invention is not limited in any way by the following explanations and examples.

FIG. 1 is a plan view of an example of a centrifugal automatic analyzer according to an embodiment of the present invention. FIG. 2 is a schematic cross-sectional view mainly showing the abnormality detection measuring section of the embodiment shown in FIG. 1. FIG.

The centrifugal automatic chemical analyzer 1 is connected to an electric motor (not shown) that is controlled to enable high-speed rotation and intermittent feeding via a gear or other motion transmission mechanism (not shown). The reaction tray 2 is equipped with a plurality of cuvettes 3. A reagent tray 4 is provided juxtaposed to the reaction tray 2, and is connected to an electric motor via a motion transmission mechanism to enable high-speed rotation and intermittent feeding, similar to the reaction tray. The tray 4 is provided with two concentric rows of reagent bottle holders for disposing the reagent bottles 5. The outer reagent bottle holder 6 is for the first reagent bottle, and the inner reagent bottle holder 7 is for the second reagent bottle, and they are provided so as to be moved independently.

In this example, the reaction tray 2 rotates in the same direction as the clock rotation direction.

Around the reaction tray 2, there are sample and first reagent dispensing positions 8.
A pipettor 9 is provided for dispensing the sample into a cuvette located in the chamber. Pipetters 9 are 120° from the axis of rotation.
Three arm members 10 extending outwardly at a distance and rotating counterclockwise.
, 11 and 12, and each arm member is provided with a suction nozzle (not shown). This pipetter 9 aspirates the sample from the sample container 15 located at the sample suction position 14 of the sample tray 13, and then rotates counterclockwise to aspirate the aspirated sample into the cuvette 3 at the sample and first reagent dispensing position 8. Dispense and dispense the sample.

Next, in order to clean the nozzle of the pipetter 9, a container 16 containing a cleaning liquid is provided.
The nozzle tip of the pipetter 9 is immersed in the cleaning liquid inside, and the cleaning liquid is suctioned and discharged to clean the nozzle.

A first reagent dispenser 17 is provided in front of the pipetter 9 in the direction of rotation of the reaction tray 2, that is, in the direction of rotation of the rotor. This reagent dispenser 17 has a nozzle (not shown) like the pipettor 9, and three arm members 18 extending outward from the rotation axis at 120° intervals,
19 and 20, this arm member 18.19 and 2
0 rotates clockwise in the opposite direction to the pipettor 9. This first reagent dispenser 17 sucks the first reagent from the reagent bottle located at the first reagent suction position 21 of the first reagent bottle holder 6, rotates clockwise, and rotates the sample and first reagent dispensing position 8. The aspirated first reagent is discharged into the cuvette 3, and the first reagent is dispensed. Next, in order to clean the nozzle of the first reagent dispenser 17,
A container 22 containing a cleaning liquid is provided, and the nozzle tip of the first reagent dispenser 17 is immersed in the cleaning liquid in the container 22 to suction and discharge the cleaning liquid to clean the nozzle.

A second reagent dispenser 23 is provided in front of the first reagent dispenser in the rotational direction of the reaction tray 2 . This second reagent dispenser 23 has a nozzle (not shown) similarly to the first reagent dispenser, and has a nozzle (not shown) that is arranged at a distance of 120 mm from the rotation axis.
Three arm members 24, 25 and 26 extending outwardly at ° intervals
However, the arm members 24, 25 and 26 rotate counterclockwise in the opposite direction to the first reagent dispenser 17. This second reagent dispenser 23 is located at a second reagent suction position 27 of the second reagent bottle receiver 7.
Aspirate the second reagent from the reagent bottle located at Dispense reagents. Next, in order to clean the nozzle of the second reagent dispenser 23, a container 29 containing a cleaning liquid is provided, and the nozzle tip of the second reagent dispenser 23 is immersed in the cleaning liquid in this container 29. to suction and discharge the cleaning liquid,
Clean the nozzle.

A measurement section 30 is provided at a measurement position in front of the second reagent dispenser 23 in the rotational direction of the reaction tray 2. Alternatively, a photometer is provided for optically measuring the cuvette 3 present at the measurement position. In addition, the measuring section 3
0, a cleaning water injector 32 is provided at a cleaning water injecting position 31 in front of the reaction tray 2 in the rotational direction, corresponding to this cleaning water injecting device 31 . This cleaning water dispenser 3
2 is designed to insert a nozzle into the washing water container 33, suck up the washing water, turn counterclockwise, and discharge the washing water into the cuvette located in the washing water injection device 31. The water container 33 and the cleaning water injection position 31 can be opened and reciprocated. Moreover, for this cleaning water injector 32,
At the detergent dispensing position 34 at the front of the reaction tray 2 in the rotational direction,
A detergent dispenser 35 is provided corresponding to the detergent dispensing position 34. This detergent dispenser 35 inserts a nozzle into a detergent container 36, sucks in detergent, rotates counterclockwise, and discharges and dispenses the detergent into a cuvette located at a detergent dispensing position 34. It is capable of reciprocating between the detergent container 36 and the detergent dispensing position 34. With respect to the detergent dispenser 35 , a cleaning water dispenser 38 is provided at a cleaning water dispenser 37 in front of the reaction tray 2 in the rotational direction, corresponding to the cleaning water dispenser 37 . This washing water injector 38 inserts nozzles into three washing water containers, sucks out the washing water, rotates counterclockwise, and discharges the washing water into the cuvette located at the washing water injection position. , can reciprocate between the cleaning water injection position 37 and the cleaning water container 39. In contrast to the cleaning water injector 38, a pure water injector 41 is provided corresponding to a pure water injecting position 40 in front of the reaction tray 2 in the rotational direction. The pure water injector 41 inserts a nozzle into a pure water container 42, sucks in pure water, rotates counterclockwise, and discharges and dispenses the pure water into the cuvette 3 located at the pure water injection position 40. It is capable of reciprocating between the pure water injection position 40 and the pure water container 42. Also, it is located between the pure water injector 41 and the pipetter 9, and is located at a washing water injecting position 43 of the rotor.
A washing water injector 44 provided corresponding to the washing water container 45 inserts a nozzle into the washing water container 45, sucks out washing water, rotates counterclockwise, and fills the cuvette 3 located at the washing water injection position 43.
．． The washing water injection position 43 and the opening of the washing water container 45 can be moved back and forth.

The reaction tray 2 of this example has a rotor (not shown).
It is attached to the rotor and rotates with the rotor. Cuvettes 3 are formed radially around the outer periphery of this reaction tray. The cuvette 3 includes a sample receiving section 43 and a sample receiving section 44, with a second reagent amount section 45 formed therebetween. A reaction/photometering section 46 is located at the end in the direction in which centrifugal force acts.
is provided, and a siphon pipe 47 is formed at the end thereof. In the cuvette of this example, the photometric window 48 is formed near the end so that even a small amount of cleaning liquid remaining can be detected.

In this example, the abnormality detection measuring device 49 has a light source and a detection section (both not shown) arranged in the direction in which the photometric window section 48 of the cuvette is lined up, and the light from the light source is semitransparent. A negative portion of the light is reflected by the mirror 50 and becomes the reference light 51, and the remaining portion is transmitted and becomes the detection light 52.

Since the centrifugal automatic chemical analyzer of this example is roughly configured as described above, the reaction tray is fed intermittently, that is, step fed, and at this stage, the cuvettes in reaction tray 2 are sequentially loaded with the sample and the first reagent. Here, the sample and first reagent are respectively poured into all of these cuvettes from the sample tray 13 by the pipetter 9 and from the first reagent bottle receiver 6 by the first reagent dispenser 17. The sample receiver is sequentially dispensed into the section 43 and the first reagent amount is dispensed into the section 44.

When the sample and the first reagent have been dispensed into all of these cuvettes, the reaction tray 2 is rotated at high speed, and the sample and the first reagent are moved to the reaction/photometry s46 and mixed.
Measurement is performed using a photometer for measurement. Next, reaction tray 2
is fed in steps, and the second reagent is dispensed into the cuvette 3 by the second reagent dispenser 23. When the dispensing of the second reagent is completed, the reaction tray 2 is rotated at high speed, and a measurement is performed using a photometer for measurement, and an analysis value is obtained by combining the measurement value with the value measured during high speed rotation in the previous stage.

When the measurement is finished, the reaction tray 2 is moved in steps, and the washing water injector 32 injects washing water into the first reagent portion 44 . After washing water has been poured into all of the cuvettes 3, the reaction tray 2 is rotated at high speed. The amount of washing water dispensed is determined by the reaction and photometry section 46 of the cuvette 3.
During high-speed rotation, the liquid level is higher than the bending point of the siphon tube, so the siphon phenomenon causes the liquid to be discharged. During and after this discharge, the measuring section 30 checks the presence or absence of the cleaning liquid in the reaction/photometering section 46.
The measurement is performed using an abnormality detection measuring device 49 provided in the.

The light projected from the light source side has a wavelength of 1470 nm, and part of it becomes reference light 51 reflected by the semi-transparent mirror 50 and is sent to a comparison section (not shown). on the other hand,
Detection light 52 that passes through the semi-transparent mirror 50 and passes through the photometry window 48 of the cuvette 3 and the reaction and photometry section 46 of the cuvette 3 is sent to the detection section.

The light beams sent to the comparison section and the detection section are each photometered to determine the absorbance. This absorbance measurement is performed in the first half of the high-speed rotation, that is, when cleaning with the cleaning liquid, and in the second half of the high-speed rotation, that is, when the cleaning liquid is discharged. The absorbance (C) during cleaning and the absorbance (D) during discharge of the cleaning liquid measured in this way are obtained in advance and are set in the comparison circuit, respectively, of the clean and empty reaction/photometer unit 46. Absorbance (
B) and the absorbance (B) of the reaction/photometering section 46 filled with cleaning liquid. In this case, a signal indicating whether there is an abnormality can be obtained by combining the comparison circuits.

That is, if absorbance C=absorbance B, and absorbance D=absorbance B, this indicates that there is no abnormality in dispensing the washing liquid and discharging the cuvette 3. However, even if absorbance D=absorbance B, when absorbance C=absorbance B, the cleaning liquid dispensing operation is defective and becomes abnormal. Also, absorbance D=
Absorbance of 100 indicates poor discharge and is abnormal.

Abnormalities are detected by comparing absorbance in the same way in the detergent washing process, the washing water washing process, and the pure water washing process.

(G) Effects of the Invention The present invention provides a centrifugal analysis method in which the presence or absence of a liquid in the cuvette is determined by absorbing the characteristics of the liquid while the rotor is rotating in the cuvette washing step after the reaction liquid has been discharged outside the cuvette. Because it detects by wavelength, it is easier to detect abnormalities such as the discharge of liquid from Cubela and the dispensing of washing liquid than with conventional methods, ensuring that valuable samples are analyzed without wasting them. be able to.

In addition, by installing absorbance detectors with different characteristic absorption wavelengths in the photometry section of the centrifugal automatic analyzer, we can detect malfunctions in the cuvette discharge path and washing liquid dispenser before abnormal values occur. This makes it possible to eliminate the influence of these failures on analysis results, which was difficult with conventional equipment.
This means that it can be easily prevented with a simple device, and it can also be notified through signal processing.
This contributes to the continuous automation of centrifugal analyzers.

[Brief explanation of the drawing]

FIG. 1 is a plan view of an example of a centrifugal automatic analyzer according to an embodiment of the present invention. FIG. 2 is a schematic cross-sectional view mainly showing the abnormality detection measuring section of the embodiment shown in FIG. 1. FIG. Regarding the symbols in the drawings, 1 is a centrifugal automatic chemical analyzer, 2 is a reaction tray, 3 is a cuvette, 4 is a reagent tray,
5 is a reagent bottle, 6 is a first reagent bottle receiver, 7 is a second reagent bottle receiver, 8 is a sample and first reagent dispensing position, 9 is a pipettor,
10, 11, 12゜18. 19. 20, 24. 25 and 26 are arm members, 13 is a sample tray, 14 is a sample suction position, 15 is a sample container, 16, 22 and 29 are cleaning liquid containers,
17 is the first reagent dispenser, 21 is the first reagent suction position, 23
27 is a second reagent suction position, 28 is a second reagent dispensing position, 30 is a measuring section, 31 and 37 are cleaning water injection positions, 32 and 38 are cleaning water dispensers, 33 and 39
is a washing water container, 34 is a detergent dispensing position, 35 is a detergent dispenser, 36 is a detergent container, 40 is a pure water injection position, 41 is a pure water dispenser, 42 is a pure water container, 43 is a washing water injection position 44 is a washing water dispenser and a reagent receiver, 45 is a washing water dispenser and a second reagent receiver, and 46 is a reaction and photometry section;
7 is a siphon tube, 48 is a photometric window, 49 is a measuring device for abnormality detection, 50 is a semi-transparent mirror, 51 is a reference light, and 52 is a detection light.

Claims (2)

[Claims] (1) Under the action of centrifugal force, the sample and reagent are mixed and reacted in a cuvette, the reaction product is measured, and then the reaction solution is drained out of the cuvette, washed, and analyzed continuously. A continuous centrifugal analysis method in which the presence or absence of a liquid in the cuvette is detected by measuring the absorbance of light at a characteristic absorption wavelength of the liquid in the cuvette washing step. Method. (2) In a centrifugal continuous automatic analyzer equipped with a rotor having a cuvette attachment part, a discharge liquid path surrounding the rotor, a sample injector, a reagent injector, a photometer, and a cleaning liquid injector provided around the rotor. A centrifugal type continuous automatic analyzer, characterized in that a light source containing light with a wavelength in a characteristic absorption wavelength region of a liquid and a photometer are provided with a cuvette attachment part sandwiched therebetween.