JPH0145581B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a dispensing device, particularly for dispensing blood cell components such as red blood cell types, white blood cell types, platelets, and lymphocyte types and types, as well as various antibodies, antigens, specific proteins, viruses, etc. In devices that analyze blood components such as serum components and foreign substances by agglutination reactions using blood cell particles, latex particles, carbon particles, etc., it is now possible to check whether a sample has been dispensed or not to prevent misjudgments. This relates to an analytical device.

Recently, a device has been developed that automatically detects the types of various components in blood, various antibodies, various proteins, and foreign substances such as viruses by determining the aggregation patterns of blood cells, latex particles, and carbon particles. ing. For example, blood cells obtained by centrifugation using a reaction vessel with a curved bottom like a wine cup are
Make a 5% suspension, dispense a fixed amount of this into a wine cup-shaped reaction container, dispense a fixed amount of anti-A or anti-B serum into the reaction container, stir both, let stand, and then centrifuge. The reaction container is vibrated violently to shake out the precipitated blood cells, and then vibrated relatively slowly to collect the agglomerated components in the center of the bottom of the container to form an agglutination pattern, which is detected photometrically. A device for automatically determining blood type has been proposed. This blood type determination device separates the precipitated blood cells by shaking the reaction container vigorously after centrifugation, so it can be advantageously applied to determination in cases where the aggregation bond strength is strong, such as in the ABO method. . However, for blood types other than the ABO blood type, such as the Rh blood type, it is necessary to check for the presence or absence of antibodies called irregular antibodies or immune antibodies, and their type. Since the bonding force of is extremely weak, as mentioned above, when the reaction vessel is vibrated, the once bonded blood cell particles will separate, so there is a drawback that this method cannot be applied.

In order to eliminate such drawbacks, the applicant has proposed in Japanese Patent Application Laid-Open No. 146044/1987 that not only blood types based on natural antibodies with strong aggregating forces but also blood types based on irregular antibodies with very weak aggregating forces can be determined with sufficient accuracy. We proposed a method for determining blood type. Such a blood type determination method uses, for example, a reaction container with a conical bottom, dispenses blood corpuscles and a standard antiserum reagent into which the blood type is to be determined, and stirs the resulting mixture for a relatively short period of time. The blood type is determined by detecting the agglutination pattern after the device is allowed to stand (for about 30 minutes). In this method, when the blood cells to be tested react with the antiserum reagent, the aggregated blood cells settle and are deposited thinly like snow on the bottom of the conical shape, but when the blood cells and the antiserum reagent do not react, In this case, the blood cell particles do not aggregate, but settle in a discrete manner, and when they reach the cone base, they roll down the slope and collect in the center of the cone base. Therefore, the blood type can be determined by photoelectrically detecting the difference in the pattern of precipitated blood cells depending on the presence or absence of reaction with the antiserum reagent formed on the bottom of the cone. In addition to determining blood type, this method can also effectively detect various antigens and antibodies such as _HBS antigen and syphilis antibody.

The applicant has also discovered that by performing such analyzes automatically, it is possible to improve analytical efficiency and accuracy, and in particular to perform various immunological analyzes on blood, i.e., on red blood cells, using the same device. Blood cell components such as type, white blood cell type, platelet, lymphocyte type and type, various antibody antigens, specific proteins, components in serum such as viruses, and foreign substances such as blood cell particles, latex particles, carbon particles, etc. We are developing an analytical device based on immunological agglutination reaction that is appropriately configured to enable selective analysis depending on the agglutination reaction used.

This analyzer uses a microplate with a large number of reaction vessels arranged in a matrix on a substrate, each of which has a slightly inclined bottom. , in an analyzer that performs immunological analysis of blood type, various antigens, antibodies, etc., based on an agglutination pattern formed on the bottom surface of a reaction container as a result of an antigen-antibody binding reaction of particles that settle due to natural sedimentation, the microplate. means for sequentially supplying blood samples from the inlet side of the reaction line from the inlet side of the reaction line, and means for dispensing a predetermined amount of the blood sample to be analyzed, that is, serum or blood cells, or a suspension thereof, into at least one reaction container of the microplate on the reaction line. a means for dispensing a predetermined amount of a reagent, that is, a particle reagent or a serum reagent, according to the analysis item into the reaction vessel; and a microplate dispensing the blood reagent into such a reaction vessel along the reaction line. a means for transferring the sample and reagent in a substantially stationary state, and a means for causing an antigen-antibody binding reaction to occur while transferring the sample and reagent into the reaction vessel on the reaction line in a substantially stationary state, thereby forming a sample and a reagent on the bottom surface of the reaction vessel; A photometric detection means that photoelectrically detects the aggregation pattern of the particles, a circuit that performs immunological analysis by determining the presence or absence of particle aggregation due to natural sedimentation based on the output signal obtained from this photometry detection means, The apparatus is equipped with means for sequentially discharging microplates that have been analyzed into the reaction vessel from the outlet side of the reaction line.

In this device, a microplate having a large number of reaction vessels is transferred to a sample dispensing means, a reagent dispensing means, and a photometric detection means in an almost stationary state,
After a predetermined period of time has elapsed after the sample and reagent were dispensed, a photometric detection means detects the aggregation pattern on the bottom surface of the reaction container, which is transferred in a substantially stationary state. That is, in the conventional microtimer method, after dispensing the reagent and sample, it is necessary to keep the reaction container completely stationary to allow the particles to settle naturally. Therefore, when automating this process, it is necessary to transfer reagents, sample dispensing means, and agglutination detection means to a stationary reaction container, making the apparatus large and complicated. However, according to experiments conducted by the present inventors, even if the microplate is transported at approximately the same speed as the container in a conventional biochemical analyzer, the amount of vibration and movement caused the formation of aggregation patterns of particles due to natural sedimentation. It was found that a sufficiently clear aggregation pattern was formed without any influence on the Therefore, the container is transported to the extent that it is used in conventional biochemical analyzers, but it can be regarded as almost a stationary state in immunological agglutination reactions. 1 more
Since a large number of reaction vessels are formed in one microplate, the transport mechanism becomes extremely simple and the throughput increases.

In addition, by dispensing each sample into a plurality of reaction containers to create a plurality of aggregation patterns and comprehensively determining these patterns, extremely highly accurate analysis can be performed. Generally, this device is used in blood transfusion centers, for example, to quickly process large amounts of blood samples, so making a mistake can immediately lead to a serious accident, so it is important to improve processing capacity and analytical accuracy. is very important.

In such a blood analyzer, whole blood collected from a subject is centrifuged to separate a blood sample and a blood cell sample, and a predetermined amount of each sample is diluted and dispensed to prepare a test solution. Dispensing of this internal blood cell sample can be carried out in various ways, including aspirating a predetermined amount with a dispensing nozzle, discharging it into a reaction vessel, and subsequently dispensing the diluted liquid through the same nozzle, or dispensing it into a reaction vessel. Generally, a predetermined amount of diluent is dispensed in advance and the blood cell sample is discharged into it. However, in the former method, when a blood cell sample is discharged into an empty reaction container, scattered blood cells adhere to the inner wall of the container. Even if the amount of this adhesion is small, the total amount of blood cell sample is small, resulting in a relatively large error, which has the drawback of lowering the accuracy of analysis. In addition, in the latter dispensing method, the diluent is stored in the reaction container in advance, which reduces the number of blood cells adhering to the inner wall, but the blood cells are not well dispersed in the diluent. Therefore, after dispensing the blood cells, it is necessary to stir the reaction container by vibration or other operations to uniformly disperse the blood cells in the diluent.

In order to eliminate such drawbacks, the applicant has
No. 55-187554, we proposed a method for dispensing particle samples such as blood cells so that they do not adhere to the inner wall of a reaction vessel and are uniformly dispersed in a diluent. In the sequential analysis steps using this particle sample dispensing method, for example, in blood type determination, whole blood collected from a subject is first centrifuged to separate serum and blood cell particles. Next, the serum and blood cell particles are dispensed into separate test tubes using separate dispensers such as microsyringes. In accordance with the dispensing of the serum or blood cell sample, a predetermined amount of the diluent is dispensed into each test tube using separate dispensers at a predetermined timing to obtain a diluted serum solution and a blood cell suspension, respectively. Next, a predetermined amount of diluted serum is collected into a plurality of reaction containers using a dispenser, and a test solution is obtained by adding an A blood cell reagent and a B blood cell reagent to each of the reaction containers. Further, a predetermined amount of the blood cell suspension is collected into a plurality of reaction containers using a dispenser, and a test solution is obtained by dispensing anti-A serum reagent and anti-B serum reagent into each of the reaction containers. These reaction vessels have conical bottoms. Next, after stirring each reaction container containing these test solutions, the blood cells are allowed to settle naturally by avoiding violent vibrations in the reaction container to create an accumulation pattern, and this accumulation pattern is photoelectrically analyzed. The blood type is determined by detecting the

In addition, when dispensing a particle sample and a diluent at a predetermined timing, when diluting and dispensing a particle sample such as blood cell particles, a first dispenser that aspirates and discharges a predetermined amount of the particle sample and a predetermined amount of diluent are used. After the second reactor starts discharging the diluted liquid, the first dispenser discharges the particle sample, and the diluted liquid continues to flow until after discharging the particle sample. By continuously dispensing the sample and dispensing while mixing the particle sample and the diluent, it is possible to prevent the particle sample such as blood cells from adhering to the inner wall of the reaction vessel and to ensure that it is evenly dispersed in the diluent. ing.

However, in such particle agglutination reaction measurements, if the sample is not dispensed properly, and if it is not possible to determine that the sample has not been dispensed, erroneous judgments may occur, leading to a very serious accident. If serum or plasma is used for the sample, e.g. H _B
In analyzes such as antigen detection, if a sample positive for H _B antigen is not dispensed into the reaction container for some reason, H _B
A false positive result will be made.

Therefore, in the particle agglutination reaction measurement described above, whole blood collected from a subject is dispensed into a test tube, the test tube is centrifuged using a centrifuge, and the whole blood is separated into serum and blood cell particles. , aliquoting when transferring serum to another test tube to obtain a diluted serum solution, and further dispensing when transferring this diluted serum solution to a designated reaction container to obtain a test solution containing A blood cell reagent and B blood cell reagent. It is desirable to check whether the specified amount of each sample has been dispensed by checking the notes.

On the other hand, when dispensing samples using a mechanical dispensing device, the causes of trouble with the dispensing device are (1) when the amount of sample to be dispensed is too small to be aspirated by the pump; (2) when the amount of sample to be dispensed is too small to be aspirated by the pump; Clogged dispensing nozzle caused by Pei et al. (Feublin) (3) Pressure from the pump system leaks due to the tube coming off or punctured, (4) Mechanical trouble in the pump system and nozzle drive system, (5) There are many causes of trouble, such as malfunction of the pump system and nozzle drive system due to malfunction of electrical signals, and it is difficult to confirm whether a predetermined amount of sample has been dispensed into a predetermined container.

This kind of confirmation can be done by measuring the weight of the container such as a test tube or reaction container in advance and comparing it with the weight of the container after dispensing the sample. Since the sample volume is small with this type of analyzer,
It is not practical due to the influence of variations in container weight and sample amount. Another option is to measure the liquid level in the storage container to confirm whether sufficient sample has been dispensed, but in general, such analyzers only use a single block to improve throughput. Because a microplate with a large number of reaction vessels formed in a matrix is used, measuring the liquid level of each individual reaction vessel requires a complicated device and is also prone to problems such as the inclination of the reaction vessels, variations in the amount of sample dispensed, etc. This method is not practical due to the influence of the inclination of the sample surface on the amount to be dispensed.

SUMMARY OF THE INVENTION An object of the present invention is to eliminate the above-mentioned drawbacks and provide an appropriately configured analyzer that can accurately confirm the presence or absence of sample dispensation with a simple configuration and prevent erroneous judgments.

The present invention provides a means for transporting a reaction container along a predetermined reaction line, a means for preparing a test solution by dispensing a predetermined amount of a sample or reagent into the reaction container, and a means for dispensing a predetermined amount of a sample or reagent into the reaction container. a means for measuring the reaction by the measuring means; a means for determining the type of the sample or the presence or absence of a specific foreign substance from the measurement results by the measuring means;
a dispensing means for dispensing a coloring reagent that reacts with the sample into the reaction container after the determination by the determination means in the reaction line; and an optical system for optically measuring the reaction in the reaction container into which the coloring reagent has been dispensed. The present invention is characterized in that it prevents erroneous determination by the determination means that occurs when a predetermined amount of the sample is not dispensed based on the amount of color developed by the optical measurement means and the optical measurement means.

The present invention will be described in detail below with reference to the drawings.

FIG. 1 is a plan view diagrammatically showing the configuration of an example of an analysis device according to the present invention. Reference numeral 1 designates the sampler as a whole, in which a rack cassette 2 is loaded with a number of racks 3, and each rack is equipped with a number of sample containers 4. These sample containers 4 are arranged in a row 3
Each rack 3 is equipped with 12 rows of sample containers. Sample containers 4-1-1, 4 at the bottom of each row
-2-1, 4-3-1... contain centrifuged sample blood (whole blood), and the remaining two sample containers 4-1-2, 4-1-3; -2-2,
4-2-3; Leave blank. The rack 3 with the rows of sample containers is transported at a predetermined pitch in the direction indicated by arrow A and onto the extension of the sample guide line 5. When one rack 3 has entered the sample guide line 5, the rack 3 moves one pitch in the direction of arrow A. The sample guide line 5 is provided with a pair of endless belts 6-1 and 6-2, which are constantly rotated at a relatively high speed in the direction of arrow B, so that the rack 3 entering the line 5 is sent to the left. . This rack 3 is indexed to the sample dilution position C by the stopper 7-1, and, for example, blood cells and serum samples contained in the sample container 4-1-1 are collected by the dispensing device 8, and the empty sample container 4- A predetermined amount is discharged to 1-2 and 4-1-3. This dispensing device 8 has two dispensing nozzles 8-1 and 8-2, which are connected to arms 8-3 and 8-4, respectively. The dispensing nozzles 8-1 and 8-2 are moved horizontally from the standby position shown in FIG. Reaction container 4- containing the blood obtained by centrifuging the tip of 8-2
1-1 to different depths and aspiration is performed to aspirate blood cells and serum, respectively. Next, after pulling up the nozzle, move it horizontally and position it above the empty sample containers 4-1-2 and 4-1-3, respectively, and place the previously aspirated blood cells and serum into the respective sample containers. Exhale. At the same time, a predetermined amount of physiological saline contained in the diluent container 9 is discharged from the two nozzles 10-1 and 10-2 of the diluent dispenser 10, and a 1.5% blood cell suspension and a 25% serum Prepare a predetermined amount of diluent. Finally, the nozzles 8-1 and 8-2 are immersed in the cleaning tank 8-5 to be cleaned.

When the above-described dispensing and dilution operation for the samples in the first row in the rack 3 is completed, the stopper 7-1 is driven, and the sample containers in the next row are indexed to the dilution position C.
Perform a similar aliquot dilution. In this example, the pitch of sequential movement of the sample container rows is 15 seconds. Therefore 15×
The dispensing and dilution of all the samples stored in one rack 3 is completed in 12=180 seconds=3 minutes. This rack 3 is further sent in the direction B by the belts 6-1 and 6-2, and reaches the sample dispensing position D. A stopper 7-2 is also provided at this position so that successive rows of sample containers can be indexed at intervals of 15 seconds. This sample dispensing position D has 4
A sample dispensing device 12 having a regular dispensing nozzle is provided.

A reaction line 13 is provided parallel to the sample guide line 5, in which three reaction line passages 13-1 to 13-3 are arranged parallel to each other. Therefore, the reaction vessels are transferred in a zigzag pattern along these three reaction line passages. The left end of the first reaction line passage 13-1 is the entrance of the reaction line, from which microplates 15 in which a large number of reaction vessels 14 are arranged in a matrix are sequentially supplied either as they are or in a frame-shaped cassette. do.
For convenience of explanation, a combination of a microplate and a cassette will also be simply referred to as a microplate. Various types of autoloading mechanisms can be adopted for this microplate autoloading mechanism, but in this example, an elevator-type autoloader is used, and a large number of microplates 15 are stacked vertically and stored, and the reaction lines are sequentially loaded starting from the upper microplate. 13. Therefore, in FIG.
The microplate on the left side of 3-1 has not yet been placed on the reaction line. A pair of endless belts 16-1, 16-2 in each passage 13-1, 13-2 and 13-3 of the reaction line;
17-1, 17-2; 18-1, 18-2 are provided, and everything except the belt 17 always rotates at a relatively high speed in the direction indicated by the arrow.

The microplate 15 supplied to the reaction line 13 is conveyed by belts 16-1 and 16-2, and is moved to the first reagent dispensing position E by a stopper 7-3 before reaching the sample dispensing position D mentioned above. It will be indexed. The microplate 15 of this example is formed with 8×12 reaction vessels 14, so that eight analyzes can be performed on each sample. There are various types of these analyses, but in this example, ABO blood type determination on the front and back sides, Rh blood type, and antibody screening will be performed. That is, the first and second reaction vessels 14-
1-1 and 14-1-2, Rh formula determination is performed using the third and fourth reaction vessels 14-1-3 and 14-1-4, and the fifth and sixth reaction vessels Reaction vessels 14-1-5 and 14
-1-6 to perform antibody screening,
Seventh and eighth reaction vessels 14-1-7 and 1
4-1-8 shall be used to determine tails in ABO style. For this purpose, a first reagent dispensing device 19 is provided at the first reagent dispensing position E, and its eight dispensing nozzles 19-1 to 19-8 are selectively operated to remove the reagent container 20-1. Dispense a predetermined amount of the required reagents in ~20-8. That is, in this example, the first to fifth reagent containers 20-1 to 20-5 each contain 12.5% anti-A serum (diluted with physiological saline), 12.5% anti-B serum (diluted with physiological saline), Contains 12.5% anti-D serum (diluted with phosphate buffer), phosphate buffer and bromelin, respectively. First, the arm supporting the dispensing nozzle is retracted to position the nozzles 19-1 to 19-8 above the reagent containers 20-1 to 20-8, and then the nozzles are lowered and the nozzles 19-1 to 19-5 are placed inside the nozzles 19-1 to 19-5. Aspirate 25μ of the anti-A serum and anti-B serum, 12.5μ of the anti-D serum and phosphate buffer, and bromelin in predetermined amounts. Next, after raising the nozzles, the arm is maneuvered and the nozzles 19-1 to 19-8
The eight reaction vessels 1 located on the first reagent dispensing position E
4-1-1 to 14-1-8, and discharges the reagent to reaction vessels 14-1-1 to 14-1-5. When the reagent dispensing to the reaction container is completed, the stopper 7-3 operates and the microplate 1
5 is moved by one pitch, and the same operation is performed thereafter. When the reagent dispensing operation for all the reaction container rows is completed, the microplate 15 is moved to the belt 16-1, 16-1.
6-2 sends it to the right and the next stopper 7-4
The above-mentioned sample dispensing position D is indexed by this. A sample dispensing device 12 is provided at this position.
The four nozzles 12-1 to 12-4 suck the blood cell suspension and diluted serum from the sample containers 4-1-2 and 4-1-3, and the reaction containers 14-1-
1 to 14-1-8. Nozzles 12-1 and 12-2 are connected to arms 12-5 and 1, respectively.
2-6, and nozzles 12-3 and 12-4
are connected to arms 12-7 and 12-8, respectively. In this example, arms 12-5 to 12-8 are
Moving horizontally from the standby position shown in the figure, the nozzles 12-1 and 12-2 are placed above the sample container 4-1-2, and the nozzles 12-3 and 12-4 are placed above the sample container 4-1.
-3, respectively, and then lowered the nozzles 12-1 and 12-2 to enter the sample container 4-1-2 to aspirate the blood cell suspension.
3, 12-4 into the sample container 4-1-3 and aspirate the diluted serum solution. Next, after pulling up the nozzles, the arms 12-5 to 12-8 are moved appropriately in the horizontal direction, and the nozzles 12-1 to 12-4 are moved to the reaction vessels 14-1-1, 14-1-3, 14-1, respectively. 1-5
and located above 14-1-7. Here, the syringe of the dispensing device 12 is operated, and the reaction vessel 1 is
Dispense 25μ of 1.5% blood cell suspension into reaction vessels 14-1-1 and 14-1-3, and transfer to reaction vessels 14-1-5.
and 25μ of 25% serum dilution to 14-1-7.
Dispense in portions. Next, the arms 12-5 to 12-8 are moved appropriately in the horizontal direction, and the nozzles 12-1 to 12 are
-4 to reaction vessels 14-1-2, 14-1-4, 1
4-1-6 and 14-1-8 respectively, and operate the syringe of the dispensing device 12 again to fill the reaction vessels 14-1-2 and 14-1-4.
Dispense 25μ of blood cell suspension into reaction container 14-1-
Dispense 25% serum dilution into cells 6 and 14-1-8. After dispensing, move the arms 12-5 to 12-8 and move the nozzles 12-1 to 12-4 into the cleaning tank 12-9.
After cleaning the nozzle, move it to the standby position.

A blood cell suspension and a diluted serum solution contained in a row of sample containers 4-1-2 and 4-1-3 are transferred to a row of reaction containers 14-1-1 to 15 on a microplate 15.
After dispensing to 14-1-8, the stoppers 7-2 and 7-4 are driven to move the rack 3 containing the sample containers one pitch to the left and move the microplate 15 containing the reaction containers one pitch to the right. Move it in a pinch. Both of these movement periods are 15 seconds, but the movement amounts are different. In this way, the dispensing operation for the samples is performed sequentially, and when the dispensing of all the samples for one rack 3 is completed, the rack 3 is moved to the left by the belts 6-1 and 6-2 and stored in the rack. It is stored in a cassette 22. The cassette 22 containing the rack 3 is transported in the direction indicated by arrow F at a predetermined pitch. On the other hand, the microplate 15, which has received the samples dispensed into all the reaction vessels, is then indexed to the second reagent dispensing position G by the stopper 7-5. At this second reagent dispensing position G, a second reagent dispensing device 23 having exactly the same configuration as the first reagent dispensing device 19 is provided. 8 nozzles 23-1
8 reagent containers 24-1 corresponding to ~23-8~
24-8, third to eighth reagent containers 24-3
~24-8 contains 0.44% bromelain (diluted in phosphate buffer), 0.44% bromelain (diluted in phosphate buffer), O blood cell reagent, O blood cell reagent, 1.2% A blood cell reagent (diluted in physiological saline). and 1.2% B blood cell reagent (diluted with physiological saline). 12.5μ of bromelain by nozzle 23-3
Dispense into reaction container 14-1-3 and use nozzle 23-
Transfer bromelin to a 12.5μ reaction vessel by 14-
1-4, and nozzles 23-5 and 23-6.
A predetermined amount of O blood cell reagent is added to the reaction container 14-1.
-5 and 14-1-6, and nozzle 23-
7, add the A blood cell reagent to a 25μ reaction container 14-1-
7 and the B blood cell reagent through nozzle 23-8.
Dispense into 25μ reaction vessel 14-1-8.

This second reagent dispensing position G is the reaction start position,
From this point on, the binding and aggregation reaction is carried out by leaving the mixture almost stationary for 30 minutes. A fixed stopper is provided at the right end of the first passage 13-1 of the reaction line 13, and after the microplate 15 reaches this position, the second passage 13-2 is moved by the microplate transport device 25 at a predetermined timing. moved to the right edge. This conveyance device 25 has a plate-shaped arm 25-1 that freely passes between belts 16-1 and 16-2,
In FIG. 1, it is designed to be able to reciprocate in the vertical direction. That is, the arm 25-1 is located below the first passage 13-1, and the arm 25-1 is located below the first passage 13-1, and
5, it rises, supporting the microplate 15 in this process and lifting it above the belts 16-1 and 16-2. Next, as shown by the imaginary line, the microplate 15 is moved downward in FIG. 1 and transported above the second passage 13-2.

Next, arm 25-1 is attached to belts 17-1, 17-
2 and place the microplate 15 on the belt. In this way, the first passage 13
The microplate 15 can be moved from the end point of -1 to the start point of the second passage 13-2 in a substantially stationary state. In this example, it is assumed that this movement also requires 3 minutes. In the second passage 13-2, the microplate 15 is moved to the left by the belts 17-1 and 17-2, but since no dispensing is performed in this passage, the speed is set very slowly, for example, about 10 mm/ Move in 15 seconds. A fixed stopper is also provided near the end of the second passage 13-2, and when the microplate 15 comes to this position, a microplate conveyance device 26 having the same configuration as the microplate conveyance device 25 described above moves the microplate 15 to the third passage 13-2. −
Moved to the starting point of 3. The microplate 15 transferred to the third passage 13-3 is transferred to the right by belts 18-1 and 18-2 moving at a relatively high speed, and at the pattern detection position H, the microplate 15 is moved to the right by the belts 18-1 and 18-2 moving at a relatively high speed.
The position is determined by At this detection position H, the pattern detection device 27 photoelectrically detects the pattern formed on the bottom surface of the reaction container. Since it takes 30 minutes for the microplate 15 to come from the reaction start position G to the detection position H, the reaction time is 30 minutes. The pattern-detected signal is supplied to a determination circuit 28, where various determinations are made, and the results are displayed on a display device 29. At the pattern detection position H, the reaction containers 14 in the microplate 15 are processed one row at a time.

The microplate 15, on which patterns have been determined for all the reaction vessels 14, is further transferred to the right and stopped at the photographing position I by the stopper 7-7. At this photographing position I, an illumination lamp is placed above the microplate 15 and a camera is placed below so that the patterns of all reaction vessels 14 on the microplate 15 can be photographed at once from the back side of the plate. . The photographed microplate 15 is then placed at the stopper 7.
-8, the visual observation position J is indexed. At this position, the operator can visually observe the pattern formed on the bottom surface of the reaction vessel. In this viewing section, an illumination lamp is installed below the microplate. Next, the microplate is further moved to the right and positioned at the coloring reagent dispensing position K by the stopper 7-9. At this position, the microplate 15 is intermittently fed, and the coloring reagent 31 contained in the coloring reagent container 30 is dispensed into each reaction container 14 by the pump section 32 and the coloring reagent dispensing section 33. The microplate 15 in which the coloring reagent has been dispensed into all the reaction vessels 14 is further transferred to the right, and is moved to the absorbance photometry position L of the photometry section 34.
The position is determined by the stopper 7-10. The photometry section 34 intermittently feeds the microplate and measures the absorbance of the coloring reagent dispensed in the previous step as it reacts with the serum sample in the test solution, and dispenses the serum sample into the reaction container. Determine whether or not it was done. The microplates 15 that have reached the right end of the reaction line passageway 13-3 are discharged from there and stored in the microplate storage device 30 in a stacked manner. For this purpose, the storage device 35 is provided with a plate 36 that moves up and down. Pump part 3 in Fig. 1
2 may be constituted by a tube pump 38 as shown in FIG. 2, or may be constituted by a syringe pump 39 as shown in FIG.

Furthermore, as shown in FIG. 4, the reagents 31 contained in the reagent containers 30 are once guided to the pump section 32 through the tubes 45, and then the reagents 31 contained in the reagent containers 30 are introduced into the pump section 32 in a manner corresponding to each of the reaction containers 14-1-1 to 14-1-8 of the microplate 15. Eight dispensing tubes 46-1 to 46-8 are provided. Three-way valves 47-1 to 47-8 are arranged between these dispensing tubes 46-1 to 46-8 and the pump section, respectively, and the respective branch tubes 48-1 to 48-8 are connected to reagent containers. Try to get it back within 30. According to the dispensing device with such a configuration, by selectively operating the three-way valve by means (such as an electric circuit) not shown while the pump unit 32 is operating, the dispensing device can dispense only into desired reaction vessels on the microplate. Reagents can be selectively dispensed. Reagents that are not dispensed into the reaction vessel return to the reagent vessel through the branch tube.

FIG. 5 is a diagram showing the configuration of an example of the photometric section shown in FIG. 1. A light source 51 is provided below a reaction container 50 into which a test solution consisting of a sample and a reagent is dispensed,
The light beam emitted from the light source 51 is transmitted through the test liquid, and is received by the light receiving element 53 via the filter 52. The output of this light receiving element 53 is supplied to one input terminal of a comparator 54, and a reference voltage is applied from a DC power supply 55 to the other input terminal. This reference voltage is set to be the output value obtained by the light receiving element 53 when the reaction container contains only the coloring reagent and is measured. A reagent that develops color by reacting with serum or plasma, such as Biuret, is used as the coloring reagent. According to the photometry section with such a configuration, the coloring reagent develops color depending on the dispensed and undispensed test solutions of serum or plasma samples.
The absorbance of the test solution changes as it drips.
A binary signal is therefore obtained at the output terminal 56 of the comparator 54, by means of which it is possible to ascertain the presence or absence of a serum or plasma sample in each reaction vessel. Note that when it is determined that the sample has not been dispensed as a result of the determination, this may be displayed on the display device 29.

As shown in Figure 6 for Biuret's reagent, the absorbance change depending on the photometric wavelength of the dispensed test solution of the coloring reagent is the absorbance (blank value) when only the coloring reagent or the coloring reagent and serum are contained in the reaction container. (as shown by curve A), the change in absorbance becomes larger as shown by curves B and C as the proportion of the coloring reagent is increased. Therefore, the photometric wavelength used for the light source 51 may be selected as necessary so as to maximize the difference in absorbance. Note that curve D shows standard serum.

As is clear from the above explanation, according to the analyzer according to the present invention, after a predetermined analysis, a coloring reagent is added to a test solution consisting of a sample and a reagent, and the presence or absence of a sample in a reaction container can be confirmed by the change in absorbance. This has the effect of reliably preventing erroneous determinations due to the sample not being dispensed without affecting the predetermined analysis in any way. Furthermore, since the configuration is simple, it is possible to check a plurality of reaction vessels at one place at a time, and it also has the effect of easily responding to increases and decreases in the number of reaction vessels.

Note that the present invention is not limited to the above-mentioned example, and can be modified or changed in many ways. For example, the analyzer according to the present invention can be used not only in an analyzer based on a particle agglutination reaction but also in a general biochemical analyzer.

[Brief explanation of drawings]

FIG. 1 is a plan view diagrammatically showing the configuration of an example of the analyzer according to the present invention, FIG. 2 is a diagram showing the configuration of an example of the color reagent dispensing device shown in FIG. FIG. 4 is a diagram showing the configuration of another example of the coloring reagent dispensing device shown in FIG. 1; FIG. 4 is a diagram showing the configuration of still another example of the coloring reagent dispensing device shown in FIG. 1; FIG. 1 is a diagram showing the configuration of an example of the photometric section shown in FIG. 1, and FIG. 6 is a characteristic diagram of a Biuret sample. 1... Sampler, 2... Rack cassette, 3...
... Rack, 4 ... Sample container, 5 ... Sample guide line, 8 ... Dispensing device, 10 ... Diluent dispenser, 1
2... Sample dispensing device, 13-1 to 13-3... Reaction line passage, 14... Reaction container, 15... Microplate, 19... First reagent dispensing device, 2
2... Rack storage cassette, 23... Second reagent dispensing device, 25, 26... Microplate transport device, 27... Pattern detection device, 28... Judgment circuit, 29... Display circuit, 31... Coloring reagent, 3
2...Pump part, 33...Coloring reagent dispensing part, 34
...Photometering section, 35...Microplate storage device, 51...Light source, 52...Filter, 53...
Light receiving element, 54... comparator.

Claims (1)

[Claims] 1 A means for transporting a reaction container along a predetermined reaction line, a means for preparing a test solution by dispensing a predetermined amount of a sample or reagent into the reaction container, and a means for causing a reaction between the sample and reagent in the reaction container. a means for determining the type of the sample or the presence or absence of a specific foreign substance based on the measurement results obtained by the measuring means; a dispensing means for dispensing the coloring reagent into the reaction vessel; an optical measuring means for optically measuring the reaction in the reaction vessel into which the coloring reagent is dispensed; An analyzer characterized in that it is configured to prevent erroneous determination by the determination means that occurs when a predetermined amount is not dispensed.