JPH01109264A - Automatic analysis apparatus - Google Patents

Abstract

PURPOSE:To automate analyses by supplying cells for reaction fixed with desired antigens and antibodies on the inside walls selectively to a reaction line. CONSTITUTION:A sampler 1 is equipped with racks 21 loaded with sample vessels 11 in which the samples to be analyzed are housed. The racks 12 are carried successively by a belt conveyor, etc., in the route shown by arrows A and the samples are sucked in the position P1. A dilution unit 2 is disposed adjacently to the sampler 1 and unused plates 21 for dilution are successively carried to the positions P2, P3 where the samples and diluting liquids are respectively dispensed into wells 24. A prescribed volume of the diluted sample liquid is then sucked in the position P4 and is discharged into the desired reaction vessel. The plate 41 for agglutination reaction subjected to the dispensing of the diluted sample receives dispensing of a reagent in the position P5 and the agglutination patterns of the particles formed in the well 40 of the plate 41 are photoelectrically detected in a measuring instrument 48. The cells 51 immobilized with the desired antigens or antibodies are selectively supplied and the assigned immune reaction tests are carried out according to the turning of a turn table 50 in an enzyme immune testing unit 5.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to an automatic analyzer, and particularly to an automatic analyzer suitable for automatically conducting blood transfusion tests.

[Conventional technology]

Conventionally, when performing a blood transfusion, the hospital side uses ABO formula, Rh (D
) blood type tests, antibody screening to identify irregular antibodies, HBs, HBc.

We perform tests for infectious diseases such as ATL, HIV, and syphilis, but tests for infectious diseases are normally only performed upon request from the patient's doctor.

In addition, at the blood center, blood type tests, antibody screenings, and infectious disease tests are performed on blood collected from blood donors.

When performing a blood transfusion, blood type must be the same as the patient's (ABO type; Rh).
In this case, blood cannot be transfused simply because the blood types of the recipient and donor are the same. Sometimes blood must be tested for agglutination and hemolysis before transfusion. This type of test is called a crossmatch test, and consists of a main test in which the recipient's blood cells are mixed with the donor's blood cells, and a subtest in which the recipient's blood cells are mixed with the donor's serum. It is being done.

[Problem that the invention seeks to solve]

As mentioned above, when performing a blood transfusion, the hospital conducts tests for the patient's blood type and antibody screening, and in some cases tests for infectious diseases as well as blood of the same blood type supplied from the blood center. We also conducted cross-matching tests. Conventionally, there are known devices that automatically perform blood type and antibody screening tests on patients.
For example, Japanese Patent Application Laid-open No. 58-105065 related to the applicant's application
It is stated in the No. In addition, at the blood center,
An automatic analyzer that tests for various infectious diseases by enzyme immunoreaction is also known, and is described in Japanese Patent Application Laid-Open No. 147067/1983, which is also filed by the applicant.

However, cross-matching tests are performed manually in hospitals and cannot be processed efficiently. In addition, there has been a strong desire to develop an analysis device that can automatically perform cross-matching tests in order to reduce the labor force of inspectors and eliminate human errors. However, even if an analyzer that can automatically perform such cross-matching tests is developed, there is still a desire for hospitals to install analyzers that can also automatically perform blood type tests and antibody screening. In some cases, the disadvantage is that the equipment costs a lot of money and requires a lot of space. In particular, when two automatic analyzers are used, the sample must be divided into two, and it is also troublesome to integrate the analysis results.

Furthermore, even if there were devices that automatically performed the agglutination tests, enzyme immunoassays, and antibody screenings mentioned above,
Depending on the scale of the hospital, it may not be necessary to perform all of these tests; for example, if you want to perform an infectious disease test using an agglutination test and an enzyme immunoreaction, or if you only want to perform an infectious disease test using an enzyme immunoreaction. In such cases, the analyzer is not used effectively, and some parts are wasted.

The purpose of the present invention is to eliminate the above-mentioned drawbacks, to be able to automatically perform tests for various blood types and infectious diseases, as well as to automatically perform cross-matching tests, and to meet the needs of users. The purpose of this invention is to provide an automatic analyzer that allows only the desired tests to be performed.

[Means and effects for solving the problem] The automatic analyzer according to the present invention sequentially transports a large number of sample containers each containing a sample to be analyzed through a sample suction position, and also transports the sample at the sample suction position to a destination. A dilution plate transport line includes a sample dispensing means for aspirating a fixed amount and discharging it at a predetermined position, and a large number of dilution plates each having a plurality of wells that receive a predetermined amount of sample aspirated and discharged by the sample dispensing means. A dilution means for dispensing the diluted sample by dispensing the diluted solution into the well along the well, and a reaction vessel or slope with a predetermined antigen or antibody immobilized on the inner wall. A reaction container having a bottom surface is selectively supplied to the reaction line according to the analysis item and transported sequentially, and a diluted sample is dispensed from the diluting means into the reaction container to examine the presence or absence of infection or agglutination due to enzyme immunoreaction. It is characterized by comprising means for.

According to the automatic analyzer of the present invention, by supplying reaction containers corresponding to test items to the reaction line, it is possible to selectively determine blood type based on the presence or absence of agglutination and test for various infectious diseases using enzyme immunoreaction. Furthermore, by cross-dispensing diluted samples of blood recipients and donors into agglutination reaction containers, cross-matching tests can be performed using the physiological saline method and the enzymatic method. In this way, it is possible to easily construct an automatic analyzer that meets the needs of each individual user, and it is also very easy to add or change test items in accordance with the user's needs.

〔Example〕

FIG. 1 is a diagrammatic plan view showing the overall configuration of an embodiment of an automatic analyzer according to the present invention. In this example, an agglutination test line and an immunological test line are provided separately. The sampler 1 includes a sample rack 12 loaded with ten sample containers 11 containing samples to be analyzed.
These racks are sequentially transported along a rectangular path as shown by arrow A. For clarity of the drawing, not all racks 12 are loaded with sample containers 11 in FIG. The rack 12 is intermittently sent to position the sample containers 11 in sequence at the sample suction position indicated by point P1, and the bar code and rack provided on the sample containers 11 positioned at the sample suction position P1 are A barcode provided at 12 is read by a barcode reader 13.

This barcode consists of an ID mark that identifies each sample and a mark that identifies analysis items, etc. By reading this barcode, you can check the sample and analysis results and perform the necessary analysis operations. Each part is controlled.

FIG. 2 shows a transport mechanism for the sample rack 12 in the sampler 1. In FIG. 2, transport in the lateral direction is performed by endless bells Ha and 1b, and transport in the vertical direction is performed by pushers lc and ld. Belts la and lb are rotated in one direction by rollers and motors (not shown). In this case, sample rack 12 and belt la.

In order to ensure the engagement with 1b, a bottle may be set up on the belt and engaged with a groove formed on the bottom surface of the rack. Further, the bushings lc and ld engage the racks le and if with the pinions Ig and lh, and the pinions are reversibly rotated by a motor to cause reciprocating movement.

The dilution unit 2 located adjacent to the sampler 1 has a dilution plate stocker 22 that holds unused dilution plates 21 stacked vertically and sequentially discharges them from the lowest dilution plate to the dilution plate transport line. have. The dilution plate conveyance line is constituted by an endless belt 23, and the dilution plates 21 discharged from the stocker 22 are placed on this endless belt and conveyed in a stepwise manner. The dilution plate 21 has a large number of wells 2 containing diluted samples.
4) Form an IJ hook shape. A sample suction and discharge device 25, a diluted liquid dispensing device 26, and a diluted sample suction and discharge device 27 are further provided along the dilution plate conveyance line. Furthermore, a stocker 28 for storing used dilution plates 21 in a stack is provided at the end position of the dilution plate conveyance line.

3A to 3C show the structure of the stocker 22 of the dilution plate 21. The stocker 22 has two sets of claws 22a,
22b, 22C, and 22d, which are driven to fall in order from the lowest plate 21 onto the belt 23 constituting the conveyance line. That is, in the state shown in FIG. 3A, all the claws 22a to 22d protrude inward, and the lowest plate has claws 22a, 22.
b, and the other plates are held by claws 22c, 22
It is held by d. Next, as shown in FIG. 3, the lower claws 22a, 22b are opened outward, and the lowermost plate is caused to fall onto the belt 23 by the action of gravity. Next, as shown in FIG. 3C, the claw 22a.

After returning the claw 22b to the inwardly protruding position, the claw 22c.

22d is opened outward and the plate stack is dropped by the thickness of one plate. By repeating such operations, the dilution plates 21 can be fed onto the belt 23 one by one.

Figure 4 shows the used dilution plate 21 in the stocker 28.
This shows the mechanism for storing data in the . The stocker 28 has claws 28a that support the dilution plate 21 in the lowermost layer.

28b, a button 28c, and a drive mechanism 28d for vertically moving the button. As shown in FIG. 4A, the plate stack is supported by claws 28a and 28b,
With the bushing 28c at the lowest position, the belt 23 is driven to move the dilution plate 21 above the bushing 28C. Next, as shown in Figure 4, the claws 28a, 28
With b open outward, pushbutton 28c is raised,
The lowest plate is placed above the level of the claws 28a, 28b. Next, after supporting the plate stack by protruding the claws 28a and 28b inward, the pusher 2
Lower 8C to the lowest position. By repeating such operations, the used dilution plates 21 can be sequentially stored in the stocker 28.

FIG. 5 shows the configuration of the sample suction and discharge device 25. As shown in FIG. The sample suction and discharge device 25 includes a guide member 25a that moves up and down, a syringe head 25b that reciprocates horizontally along the guide member, and a nozzle 25C provided at the tip of the syringe head.

As schematically shown in FIG.
b and the nozzle 25C are positioned at the sample suction position A1, the eight sample discharge positions B, ~B, and the cleaning position C, which correspond to the eight wells 24 in the first row of the dilution plate 210, and at the position A. and C, it is moved up and down.

Next, the sample dispensing operation will be explained. First, the syringe head 25b and nozzle 25c are positioned at the sample suction position A and then lowered, the nozzle is immersed in the sample in the sample container 11 held in the sample rack 12, and the syringe assembled in the syringe head 25b is operated. to aspirate a predetermined amount of sample into the nozzle. Next, the syringe head 25b is raised to the sample discharge position B,...
B, . After discharging, the syringe head 25b is positioned at the nozzle cleaning position C, and the nozzle 25C is allowed to enter the cleaning tank 29, and the cleaning liquid is sucked and discharged through the nozzle to clean the inner and outer walls of the nozzle. Next, the nozzle is raised and repositioned to the sample suction position A in preparation for dispensing the next sample. As described above, after one sample is dispensed into one row of eight wells 24 of the dilution plate 21 located at the sample discharge position P2, the sample rack 12 is advanced one pitch and the dilution plate 21 is also moves forward one pitch, and moves the next sample forward one pitch.
Dispense into rows of 8 wells 24. In this way, successive samples can be dispensed into successive rows of wells in the dilution plate.

FIG. 6 shows well 2 of dilution plate 21 as described above.
4 shows the configuration of a diluent dispensing device 26 that dispenses a diluent at a diluent dispensing position P to the sample dispensed in FIG. The diluent is stored in a tank 26a, and is discharged into the well 24 through a tube 26b1, a pump 26c1, a valve 26d, and a diluent discharge nozzle 26e. In this example, in order to further stir the sample and the diluent, an air pump 26f is provided to blow pressurized air into the well 24 through the tube 26g1 valve 26h and the air discharge nozzle 26i. This allows the sample and diluent to be stirred well without contact.

A diluted sample is formed in the wells 24 of the dilution plate 21 as described above.Next, the diluted sample suction and discharge device 27 for selectively dispensing the diluted sample into the agglutination reaction container and the enzyme immunoreaction container will be explained. do. In this example, a custom nozzle is used to eliminate carryover between diluted samples.

That is, a nozzle conveyance line 3 is provided in parallel to the dilution plate conveyance line of the dilution unit 2, and a large number of nozzles 3
1 to the nozzle stocker 33.
The samples are fed one by one onto the endless belt 34 and transported to the diluted sample dispensing position P.

FIG. 7 shows the configuration of the nozzle 31 and nozzle cassette 32. The nozzle 31 is integrally formed with a large-diameter cup portion 31a and a tapered probe portion 31b, and the nozzle cassette 32 is a box with a large number of holes 32a, into which the probe portion 31b is inserted. to hold the nozzle.

8 to 10 show the structure of the diluted sample suction and discharge device 27. FIG. Eight nozzle heads 27a are installed in a line on plate 27b, and solenoids 27c and 27 are attached to both ends of this plate via angle members.
d, and a button 27e is attached to the tip of the plunger of these solenoids. A nozzle receiver 27f is formed at the lower end of the nozzle head 27a to be inserted into a hole formed in the large diameter portion 31a of the nozzle 310.

Further, each nozzle head 27a is connected to a syringe through a tube 27g. The nut block 2? is attached to the plate 27b via the L carving tool 27h. i, and a screw 27j is screwed into this nut block. This screw 27
] is rotatably supported by a frame 27k and has one end connected to a motor 27J. Further, the frame 27 is connected to the tip of a rod 27n of a vertical movement device 27m.

With this configuration, the plungers 27c and 27d
By driving the motor 27β, the button plate 27e can be moved up and down as shown by arrow A, and by driving the motor 27β, the nut block 27i,
Therefore, the nozzle head 27a can be moved left and right as shown by arrow B, and the whole can be moved up and down as shown by arrow C by driving the vertical movement device 27m. As clearly shown in FIGS. 9 and 10, a substantially semicircular notch 27p is formed at one side edge of the bushing plate 27e. The diameter of this notch 27p is slightly larger than the diameter of the nozzle receiver 27f, but the large diameter portion 3
It shall be smaller than the diameter of 1a.

Next, the diluted sample suction and discharge operation will be explained. First, the motor 271 is driven to position the nozzle receiver 21f of the nozzle head 27a above the nozzle 31 at the diluted sample dispensing position P, and then the vertical movement device 27m is driven to lower the nozzle head. The nozzle receivers of the book are simultaneously inserted into the holes formed in the large diameter portions 31a of the eight nozzles 31, respectively. In this case, Butshapley) 27e
is in the raised position, and the nozzle large diameter portion 3 of the nozzle receiver 27f
Make sure not to obstruct the insertion into 1a. Next, the vertical movement device 27m is driven to raise the nozzle 31 together with the nozzle head 27a to remove the nozzle from the nozzle cassette, and then the motor 211 is driven to position the nozzle head 27a at the diluted sample dispensing position P4. The nozzle probe section 31b is positioned above the well 24 of the dilution plate 21, and the vertical moving device 27m is driven again to lower the nozzle head 27a, so that the nozzle probe section 31b penetrates into the well 24 to a predetermined depth. Next, the syringe connected via the tube 27g is driven to suck a predetermined amount of the diluted sample into the nozzle. In this case, the amount of suction and the dimensions of the nozzle are determined so that the diluted sample is not suctioned up to the nozzle receiver 27f. Next, the vertical movement mechanism 27m is driven again to raise the nozzle head 27a and the nozzle 31 that sucked the diluted sample, and then the motor 2T1 is driven to move the nozzle head and the nozzle to the agglutination reaction line on the agglutination reaction line, which will be described later. The diluted sample drawn into the nozzle is discharged into the well. In addition, when performing an enzyme immunoreaction, the solution is discharged into an enzyme immunoreaction container to be described later. After discharging the diluted sample into the desired reaction container in this way, the motor 2
7I! to drive the nozzle head 27a and the nozzle 31.
is positioned above the nozzle cassette 32, and then the vertical moving device 27m is driven to lower the nozzle head 27a and the nozzle 31, and the probe section 31b is inserted into the hole 32a of the nozzle cassette. Next, the solenoids 27c, 27
d to lower the button (buttonshape) 27e.

27e is nozzle 3
Since the nozzle 31 comes into contact with the large diameter portion 31a of No. 1 and presses it down, the nozzle 31 falls out of the nozzle receiver 27f and is stored in the nozzle cassette 32. By repeating the above-described operations, successive diluted samples can be selectively dispensed into the agglutination reaction container and the immune reaction container.

Next, returning to FIG. 1, the aggregation reaction unit 4 will be explained. The agglutination reaction unit 4 of this example uses the agglutination reaction plate 41, but the agglutination reaction plate 41 of this example includes:
A large number of wells 40-1-1 to 40-4 as shown in FIG. 11A.
0-1-12; 40-2-1 to 40-2-12
... 40-8-1 to 40-8-12 are formed in a matrix, and 12 wells are arranged in one row. Each well 40 has a conical inclined bottom surface 40a as shown in FIG. 11B, and fine steps are formed on this bottom surface so that a stable particle base layer is formed by the aggregation reaction.

The aggregation reaction plates 41 are intermittently conveyed onto the conveying endless belt 43 sequentially from the bottom layer of the stocker 42 along the aggregation reaction line.

After a predetermined amount of the diluted sample accommodated in the well 24 of the dilution plate 21 is sucked by the diluted sample suction/discharge device 27 and the nozzle 31, the agglutination reaction plate 41
0 to a predetermined well 40.

The agglutination reaction plate 41 that has received the diluted sample is transported stepwise along the agglutination reaction line by a transport means shown as an endless belt 43, and positioned at a reagent dispensing position P. A reagent dispensing device 44 is provided at this reagent dispensing position P.

This reagent dispensing device 44 includes eight reagent dispensing probes,
These probes are placed between the reagent container 45 and the dispensing position P.

A mechanism for moving the probe between the two probes and a microsyringe mechanism for sucking and discharging the reagent from the probe are provided so that desired reagents can be simultaneously dispensed into the wells 40 of the plate 41. The plate 41 to which the reagent has been dispensed is further transported and sent to the elevator section 46. As shown in FIG. 12, the elevator section 46 includes a pair of endless bells).
46a and 46b are arranged facing each other, and a locking claw 46c is attached to these endless belts at a constant interval.
46d, the agglutination reaction plate 41 is held in a hanging manner and slowly moved from top to bottom. In addition, the entire elevator section is housed in an air bath-type thermostatic chamber, and the reaction solution is kept at 25
I try to keep it at room temperature above ℃. By using the elevator section 46 having such a configuration, a long reaction time can be obtained with a minimum space.

The aggregation reaction plate 41 that has been conveyed to the lowest part by the elevator section 46 is placed on an endless belt 47, and is thereby fed into a photometry device 48.

The measuring device 48 photoelectrically detects the particle aggregation pattern formed on the bottom surface 40a of the well 40 of the plate 41.

13 and 14 show the configuration of the photometric device 48. FIG. The aggregation reaction plate 41 conveyed by the belt 47 is further conveyed intermittently by a pair of belts 48a and 48b. The photometer 48 is further provided with a light source unit (48c) and a light receiver unit (48d) so as to sandwich the plate 41 therebetween, and these units are constructed so as to be able to reciprocate as an integral unit as shown by arrow A in FIG. As shown in FIG. 14, the light source unit 48C is provided with a light source lamp 48e1, an aperture 48f, and a lens 48g, so that a light beam enters the agglutination reaction plate 41 from the bottom surface thereof. The light receiver unit 48d includes a lens 48h that collects the light transmitted through the agglutination reaction plate 41, and a photoelectric conversion element 481 that receives the light collected by this lens.
and. In this manner, the photometric device 48 scans the bottom surface 40a of the well 40 of the agglutination reaction plate 41 with a light beam, and detects the particle aggregation pattern formed on this bottom surface. The photometer 48 is further provided with a lift, and the agglutination reaction plate 41 that has completed photometry is immediately lifted up and transported to a visual observation device placed above the photometer, where the agglutination pattern can be visually observed. do. For this reason, the visual observation device is provided with a uniform illumination light source and a transparent window for observation, but a detailed explanation of its configuration will be omitted. The plates 41 that have been visually observed are further sent to a used agglutination reaction plate stocker 49 and loaded from the bottom layer. These measured agglutination reaction plates 41 are later taken out all at once.

Next, the enzyme immunoassay test unit 5 will be explained. In this example, as shown in FIG. 1, a turntable 50 that rotates intermittently in the direction indicated by arrow F is provided, and a reaction container, that is, a cell 51 in which a desired antigen or antibody is immobilized, is selected on this turntable. supply to the public. The cells 51 are loaded into a cell pack 52, and a cell supply device 53 selectively positions a large number of cells stored in a plurality of cell bags at a cell supply position so that they can be loaded onto the turntable 50. Along the rotation path of the turn tape>b50, the antigen or antibody immobilized on the cell 51, the bound antibody or antigen, and the unbound antibody or antigen are separated (this separation is performed in B- A first B-F separation device 54 that performs cleaning for (referred to as F separation), a first reagent dispensing device 55 that dispenses the first reagent into the cell, a second B-F separation device 56, a second reagent dispensing device 57, a reaction stopper dispensing device 58 for stopping the coloring reaction caused by the enzyme substrate;
A colorimetric photometer 59 and a cell disposal device 60 for removing cells from the turntable are sequentially provided. Next, the configuration and operation of each of these devices will be explained.

FIG. 15A shows a cell pack 52 that stores a large number of cells 51.
FIG. 15B is a perspective view showing the configuration of the device, and FIG. 15B is a sectional view of a portion thereof. The cell bag 52 is made of a plate-like member as a whole, and ten holes 52a are formed therein, and guide grooves 52b are formed in the holes so as to communicate with the holes. For example, 10 cells 51 are stored in each hole 52a, stacked vertically. As shown in FIG. 15, an elastic locking claw 52C is integrally formed at the lower end of the guard hole 52a to prevent the cell 51 stored in the hole from falling due to gravity. Further, a groove 52d is formed in the rear portion of the top surface of the cell pack 520.

As will be described later, a claw for vertically feeding the cell pack is engaged with this groove 52d to position the cell pack at the cell supply position.

FIG. 16 shows the configuration of the cell supply device 53.

As described above, the cell packs 52 each storing a large number of cells 51 are arranged side by side on the cell back stand 53a. This cell back stand 53a is slidably supported by a pair of guide shafts 53b and 53c, and is configured to be reciprocated in the lateral direction as shown by arrow A by an endless belt 53d and a motor 53e. The cell back stand 53a is housed in a case 53f, and the case has an opening through which the cell pack 52 can pass. The motor 53e is driven so that any one of the five cell packs can be positioned with respect to this opening. A screw 53g is rotatably attached to the case 53f, and the screw is configured to be reversibly rotated by a motor 53h. Further, a vertical feed pawl 53j is screwed onto the screw 53g via a nut 531, so that the pawl can be reciprocated in the vertical direction as shown by arrow B by a motor 53h. This claw 53j can be inserted into a guide groove 52d formed in the cell pack 52. Therefore, the cell pack storing desired cells is moved to the case 53 by driving the motor 53e.
After positioning the motor 53 at a position facing the opening of
h can be driven to transport the cell bag to the outside of the case through the opening. A screw 53k is further rotatably attached to the case 53f, and this screw can be reversibly rotated by a motor 531. A cell sending pawl 53n is screwed onto this screw 53k via a nut 53m, and the pawl can be moved up and down as shown by arrow C by driving this motor 53Il. The tip of the claw 53n enters the hole 52a through the groove 52b formed in the cell pack 52, and engages with the seven flange of the cell 51.

Therefore, by driving the motor 531, the cells 51 stored in the predetermined holes 52a of the cell pack 52 are sequentially dropped from the lowest layer, and the cell receiver formed on the turntable 50 can be stored in the holes 50a.

In this example, since any cell 51 can be stored in the cell pack 52, cells corresponding to the measurement items desired by the user are stored in advance in the hole 52a of the cell pack in a predetermined order. is preferable.

For example, when testing each sample for three types of infectious diseases, A, B, and C, three types of cells with antigens or antibodies used for each immune reaction immobilized on their inner walls are stacked one on top of the other. The packs 52 are loaded into the holes 52, and they are sequentially dropped into the holes 50a of the turntable 50.

In addition, if a specific sample is to be tested for infectious diseases, it should be loaded into a cell pack consisting of cells immobilized with antigens or antibodies against the infectious disease, and this cell pack should be placed at the cell supply position. The cell is taken out and dropped into the hole 50a of the turntable 50. In this manner, by selectively positioning any one of the plurality of cell packs at the cell supply position, a designated immune reaction test can be performed on each sample.

FIG. 17 is a sectional view showing the detailed structure of the turntable 50. A turntable 50 having a hole 50a for accommodating a cell 51 is rotatably supported by a shaft 50c via a bearing 50b, and a flange 50d with teeth cut on the inner edge is integrally formed. The turntable 50 can be rotated by rotating the gear 50e that meshes with the teeth of the flange 50d using the motor 50f. A heater block 50 is provided below the turntable 50.
A lid 50h is placed above the cell 51 to maintain the temperature of the liquid contained in the cell 51 at 37°C. A hole 501 is formed in the heater block 50g at a position facing the cell 51, and the test liquid in the cell can be colorimetrically measured through this hole. In addition, turntable 50
The holes 50a into which the cells 51 are loaded are arranged in a staggered manner to increase the number of cells that can be loaded. Further, in this example, a heater block of 50 g is used to keep the temperature of the reaction solution constant, but a water bath or an air bath can also be used.

Since the first and second reagent dispensing devices 55 and 57 have the same configuration, they will be described together. A plurality of reagents are stored in reagent tanks 55a and 57a, and these reagent tanks are set on turntables 55b and 57b,
This turntable is configured to be reversibly rotated as shown by arrows G and H to position a desired reagent tank at a reagent dispensing position. Each reagent tank has an opening 55c;
57c, and through this opening, probes 55d,
57d can be inserted and removed. This probe 55d,
57d is attached to the tip of the arms 55e and 57e (D, and is configured to move this arm up and down as well as rotate it. Also, cleaning tanks 55f and 57f are provided between the turntable 50 and the reagent tank 55a, and the probe 55d ,
57d. Since such reagent dispensing devices 55 and 57 are the same as those provided in general chemical analysis devices, further detailed explanation will be omitted.

FIG. 18 shows the configuration of the colorimetric photometer 59.
The collimator lens 5 emits light emitted from the white light source 59a.
9b, the light is passed through a rotating filter 59c as a parallel light beam.

The rotary filter 59C is provided with a filter that transmits wavelengths λ1 to λ6 depending on the analysis item, and the motor 59
d, a desired filter according to the analysis item can be selectively inserted into the optical path. The light transmitted through the filter is passed through the lens 59e1, the mirror 59f, and the L/lens 59.
g and the bottom surface of the cell 51 through an opening 501 made in the turntable 50g. The light transmitted through the cell is collected by a lens 59h, and is further incident on a detector 59j through a slit 59i. The optical system portion 59 from the mirror 59f to the detector 59j is movable back and forth as shown by arrow A. In this way, the test liquids in the cell 51 loaded on the turntable 50 can be colorimetrically measured one after another.

FIG. 20 shows a detailed configuration of the cell discard device 60. One end of the tube 60b is passed through the fitting part 60a inserted into the cell 51 loaded into the hole 50a of the turntable 50, and this tube is connected to the waste liquid tank 60d via the three-way valve 60C. This waste liquid tank 60d is further connected to a vacuum pump 60f via a tube 60e. Further, the fitting part 60a is connected to an arm 60g, and this arm is connected to the arrow A
It is configured to be able to move up and down as shown by arrow B, and also to be able to reciprocate in the horizontal direction as shown by arrow B.

First, the arm 60g is lowered at position I, and the fitting part 60 is placed inside the cell 51 that accommodates the test liquid colorimetrically measured by the colorimetric photometer 59.
A is inserted, the three-way valve 60c is driven so that passages a and b communicate with each other, and the test liquid is sucked from the cell through the tube 60b and disposed of in the waste liquid tank 60d. Next, the fitting part 60a is further lowered to come into close contact with the bottom surface of the cell, thereby sucking the cell. Next, raise the arm 6h and place the cell 51 on the turntable 5.
After escaping from 0, move the arm to position ■.

Next, the three-way valve 60C is switched so that the passages a to c communicate with each other, and the cell is dropped from the fitting part 60a into the used cell storage box 60h. In this way, the test liquid and the cell can be separated and disposed of.

Hereinafter, operations when performing various analyzes using the above-mentioned automatic analyzer will be explained. The automatic analyzer of this example is configured as a blood transfusion testing device, and is used to determine various blood types, test for various infectious diseases, and perform cross-matching tests. Regarding blood types, in addition to ABO blood type, Rh blood type, M
NSS blood type, P blood type, Kel1 blood type, Le
There are blood types such as the Wis blood type, the Doffy blood type, the Kidd blood type, and the Diego blood type, and these blood types are determined by irregular antibody suffix IJ+. In addition, Rh blood types include Rh (D) type,
Rh (d) formula, Rh (C) formula, Rh (c) formula, R
There are h(E) formula, Rh(e) formula, etc. In the apparatus of the present invention, these blood types are determined by an agglutination reaction. In addition, infectious diseases include HBs antigen, ■8. antibody,
Typical examples include H. H. antibody, syphilis antibody, ATL antibody, and old V antibody. These infectious diseases are tested by enzyme immunoreaction, but they can also be tested by antigen-antibody reaction. In this case, blood type and infectious disease can be analyzed simultaneously for each sample. The cross-matching test consists of a main test in which blood recipient serum and donor blood cells are mixed to check for agglutination or hemolysis, and a test in which blood recipient blood cells and donor serum are mixed to check for agglutination or hemolysis. There are sub-tests to investigate the presence or absence of blood cells. After washing by centrifugation, Coombs serum or bromelin is added, followed by further centrifugation to check for the presence of agglutination using the indirect Coombs method, but the physiological saline method and enzyme method are performed in this apparatus.

Determination of Blood Type and Testing for Infectious Diseases When determining the blood type and testing for infectious diseases, samples are set in the sample rack 3 as shown in FIGS. 20A and 20B. That is, in FIG. 20A, the serum of each sample is placed in one sample container 11-1-1.1.
Plasma and blood cells accommodated in 1-2-1---11-5-1 and centrifuged are placed in sample containers 11-, respectively.
1-2.11-2-2---11-5-2.

Serum samples are primarily used for irregular antibody screening and infectious disease testing, and plasma and blood cells are primarily used for ABO and Rh blood group determination. In this way, blood samples for five people are set in one rack 12. In addition, in the case shown in FIG. 20, each sample container 11-1 to 11-1
0 contains the centrifuged plasma and blood cells of each sample, and in this case, tests for infectious diseases and ABO and R
This is for H type blood type determination, and blood samples from 10 people are set. In the following explanation, the 20th
As shown in Figure A, serum, plasma, and blood cells of each sample are stored in two sample containers.

As described above, for each sample, the serum sample and the centrifuged plasma and blood cell samples are placed in two sample containers 11-1-1 to 11-5-1 and 11-1-2 to 1.
The rack 12 accommodated in 1-5-2 is moved to the sample suction position P.
.

position. First, the serum sample contained in the sample container 11-1-1 is transferred to the sample dispensing probe 25.
Aspirate a predetermined amount by c. This dispensing amount is set according to the number of items to be analyzed. The serum sample thus aspirated into the probe 25C is dispensed into one or more wells 24 of the dilution plate 21 positioned at the sample discharge position P2. After dispensing, the inner and outer walls of the probe are washed in a washing tank 29. During this time, sample rack 12
is advanced by one pitch, the second sample container 11-1-2 containing the plasma and blood cell samples is positioned at the sample suction position P1, and the plasma sample and the blood cell sample are aspirated into the probe 25C. The plasma sample aspirated in this manner is transferred to the well 2 of the same row of the dilution plate 21.
At the same time, the blood cell sample is discharged into one or more wells of a dilution plate. In this way, a predetermined amount of one sample of serum, plasma, and blood cell sample is dispensed into the wells 24 in the first row of the dilution plate 21, and then the probe 25C is washed. This operation is repeated while sequentially moving the sample rack 12 and the dilution plate 21,
Sequential samples of serum, plasma and blood cell samples are dispensed into the wells 24 of each column of the dilution plate 21.

Next, the dilution plate 21 is positioned at a diluent dispensing position P3, where the diluent dispensing device 26 dispenses a predetermined amount of a predetermined diluent. Physiological saline is usually used as the diluent, but other diluents can also be used. In addition, the dilution ratio is set according to each reaction. in this case,
In order to thoroughly mix the sample and diluent, the diluent dispensing probe can be immersed in the solution and sucked and drained repeatedly, but in this case, the diluent dispensing probe must be cleaned. Since it is necessary to prevent carryover between samples, in this example, air is used for stirring as shown in FIG. After creating a desired diluted sample in this manner, the dilution plate 21 is positioned at the diluted sample suction position P4. In this position, eight disposable nozzles 31 are used to collect diluted serum samples, diluted plasma samples,
Place the diluted blood cell sample in well 4 of the agglutination reaction plate 41.
0 right and enzyme immunoreaction cell 51. That is, the diluted serum sample is dispensed in predetermined amounts into the enzyme immunoreaction cell 51, and the diluted plasma sample and the diluted blood cell sample are dispensed in predetermined amounts into one row of wells 40 in the agglutination reaction plate 41. In addition, the agglutination reaction plate 41
There are 8 wells 40 in one row, and ABO with 4 channels.
Determine the front and back sides of the blood type of the formula, and check Rh in channel 1.
The blood type will be determined, and the remaining 3 channels will be used to screen for irregular antibodies for other blood types. Therefore, diluted blood cell samples are dispensed into the two wells of the agglutination reaction plate 410, and diluted plasma samples are dispensed into the remaining six wells.

In this case, a serum sample may be used instead of a plasma sample, so the diluted serum sample is placed on the agglutination reaction plate 4.
It is also possible to dispense into one well.

As described above, since a predetermined antigen or antibody is immobilized on the inner wall of the enzyme immunoreaction cell 51, an immune reaction is started upon dispensing a diluted serum sample. On the other hand, in the agglutination reaction plate 41, the reaction does not occur only by dispensing the diluted plasma sample and the diluted blood cell sample, but the agglutination reaction starts after the reagent is dispensed at the reagent dispensing position P. As reagents for this agglutination reaction, 14 types of reagents, including 12 types of first reagents and two types of second reagents, are prepared.

For determination of ABO blood type, predetermined amounts of anti-A serum reagent and anti-B serum reagent are dispensed into two diluted blood cell samples, and A blood cell reagent and B blood cell reagent are respectively dispensed into two diluted plasma samples. Dispense in fixed amounts. Also, R
To determine the H blood type, a predetermined amount of serum reagent is dispensed onto one diluted blood cell sample. In determining the Rh blood type, an enzyme such as bromelin may be dispensed as a second reagent to promote the reaction. When determining other blood types, a predetermined blood cell reagent is dispensed into each diluted plasma sample.

In these agglutination reactions, when the antigen-antibody reaction occurs, the blood cells aggregate with each other, and as shown in FIG. When no reaction occurs, the blood cell particles do not aggregate, and the particles that settle on the sloped bottom roll down the slope and are collected at the center of the conical bottom 40a, forming an accumulation pattern, as shown in FIG. Ru.

The aggregation reaction plate 41 on which the aggregation pattern has been formed in this way is sent to the photometer 48, where the light is measured. The agglutination reaction time can be selected from 30 minutes, 45 minutes, 60 minutes, and 90 minutes, and when performing an enzyme immunoreaction as in this example, select 45 minutes, which is equal to the reaction time. However, these reaction times do not necessarily have to be equal.

When determining the aggregation pattern, as shown in FIG. 14, the bottom surface 40a of the well 40 is scanned with a white light beam having a diameter of 0.4 mm, and the transmitted light is detected by the detector 48i.
The output signal is processed to determine the agglomeration pattern shown in FIG. 21A and the accumulation pattern shown in FIG. 21B. In this case, since it may not be possible to clearly distinguish by photometry whether it is an agglomerated pattern or an accumulated pattern, a visual observation device is provided to enable visual determination. When measuring visually in this way, inputting the visual judgment result or correcting the photometric judgment result is performed by operating the keyboard while looking at the display screen.

The diluted serum sample S dispensed into the enzyme immunoreaction cell 51 reacts with the antigen or antibody A immobilized on the inner wall of the cell, as shown in FIG. 22A, and the antibody or antigen in the sample is immobilized on the solid phase. binds to antigen or antibody. Next, the cleaning device 5
4, the cell 51 is washed, B-F separation is performed, and the enzyme-labeled reagent is further dispensed using the first reagent dispensing device 55. This enzyme-labeled reagent R binds to the antibody or antigen S in the sample as shown in FIG. 22B. Next, the second cleaning device 56
After washing again and performing B-F separation, the second reagent dispensing device 57 receives the dispensing of the enzyme coloring reagent. This enzyme coloring reagent causes a coloring reaction in the presence of a labeled enzyme, causing the test solution to develop color. Next, the reaction stop liquid dispensing device 5
Step 8: Dispense the reaction stop solution to stop the coloring reaction. The cell 51 subjected to the enzyme immunoreaction in this manner is further sent to a photometer 59 for colorimetric measurement. Photometry with this photometer 59 is performed using a rotating filter 59 as shown in FIG.
A filter section with a predetermined wavelength of C is inserted into the optical path, and the diameter is, for example, 3 ml! A monochromatic light beam of 1 is made incident on the test liquid in the cell 51, and the transmitted light is received by the data filter 59j to perform colorimetric measurement.

If the antigen or antibody to be tested is present in the diluted serum sample, the enzyme labeling reagent is bound to the cell 51;
A coloring reaction is performed, but if a specific antigen or antibody is not present, the enzyme labeling reagent is washed away by B-F separation, so no coloring reaction occurs. Therefore, by colorimetrically measuring the color development, HBs antigen, HB, antibody,
The presence of HBc antibodies, syphilis antibodies, ATL antibodies, old V antibodies, etc. can be tested.

Cross-matching test As described above, three cross-matching tests are normally performed: the physiological saline method, the enzyme method, and the indirect Coombs method, but in this example, only the physiological saline method and the enzyme method are performed. First, when performing cross-matching inspection, the rack 12
As shown in FIG. 23, the first sample container 11 is
-2 stores the recipient's plasma and blood cell samples, and the remaining nine sample containers 11-2 to 11-10 store the donor's centrifuged plasma and blood cell samples. Of course, the donor's blood sample is of the same blood type as the recipient. First, the sample container 11-1 containing the recipient's sample is positioned at the sample suction position P1, and a predetermined amount of plasma and blood cells are poured into the first row of the dilution plate 21 shown in FIG. 24 using the nozzle 25c. Two eye wells 2
Dispense into 4-1-1.24-1-2. Next, nozzle 25
The rack 12 is advanced one pitch, and the dilution plate 21 is also advanced one pitch, and the plasma and blood cell samples of the first donor housed in the sample container 11-2 are transferred to the dilution plate. 21 into wells 24-2-1 and 24-2-2 of the second row, respectively. Thereafter, similar operations are performed to dilute plasma and blood cell samples from nine donors from wells 24-2-1 and 24-2-2 in the second row to well 24-24 in the tenth row of the dilution plate 21. Dispense by 10-1 and 24-10-2. That is, in the case of a cross-matching test, the sample is diluted using only two rows of wells among the eight rows of wells in the dilution plate 21.

Next, the dilution plate 21 is transferred to the diluent dispensing position P3, and the two wells 24-1-1 and 24-
1-2, a predetermined amount of diluent, ie, physiological saline, is dispensed.

Thereafter, while moving the dilution plate 21 step by step, the two wells 24-2-1, 24-2-2. -1-.

24-10-1. Dispense physiological saline to 24-10-2. After dispensing a predetermined amount of saline in this way,
The diluted sample is positioned at the suction position and dispensed onto the agglutination reaction plate 41 using the diluted sample dispensing device 27. In this dispensing process, the recipient's diluted plasma sample is placed in nine wells 4 in the first row of the agglutination reaction plate 41 shown in FIG. 11A.
0-1-1 to 40-1-9 in sequence, and the diluted blood cell sample was placed in wells 40-2-1 to 40-2=9 in the second row.
Dispense sequentially. Next, the dilution plate 21 is advanced one pitch, and the diluted blood cell sample of the first donor is placed in the first well 40- of the first column of the agglutination reaction plate 41.
1-1, and the diluted plasma sample is dispensed into the first well 40-2-1 of the second column. Next, the dilution plate 21 is further advanced one pitch to dispense the diluted blood cell sample of the second donor into the second well 40-1-2 in the first row of the agglutination reaction plate 41, and dilute it. Dispense the plasma sample into the second well 40-2-2 of the second column. In this way, in the nine wells 40-1-1 to 40-1-9 in the first row of the agglutination reaction plate 41, blood plasma of the recipient and blood cells of nine donors are cross-mixed. The test solution for the main test was prepared and placed in nine wells 40-2 of the second row.
-1 to 40-2-9, the detection will be adjusted for a subtest in which blood cells from the recipient were cross-mixed with plasma from nine donors.

In the case of the physiological saline method, no other reagents are added, so no reagents are dispensed at the reagent dispensing position P, but in the case of the enzyme method, bromelin and papain are dispensed at the reagent dispensing position P5. Dispense a predetermined amount of an enzyme such as , ficin, etc. When the recipient's blood and the donor's blood are compatible, no agglutination reaction occurs, so the bottom surface 4 of the well 40 of the agglutination reaction plate 41
An accumulation pattern as shown in FIG. 21A is formed on the bottom surface 40a of the well 40 as a result of an aggregation reaction occurring if they are not compatible. be done. Therefore, after a predetermined reaction time, for example 30 minutes, the plate 41 is fed into the photometer 48 and the above-mentioned pattern is photoelectrically detected, thereby allowing a cross-matching test using the saline method and the enzyme method to be performed. In this case as well, the reliability of the analysis can be increased by visually observing the pattern using a visual observation device.

In the above embodiment, the agglutination test unit 4 and the immunity test unit 5 were provided separately, but in the present invention, the agglutination test unit and the immunity test unit can also be integrated.

FIG. 25 is a diagrammatic plan view showing the configuration of another embodiment of the automatic analyzer according to the present invention. In FIG. 25, the same parts as those shown in FIG. 1 are designated by the same reference numerals, and detailed explanations will be omitted. In this example, the configuration in which a sampler 1, a dilution unit 2, and a cassette 32 having a disposable nozzle 31 for dispensing the diluted sample is provided in parallel to the conveyance line of the dilution plate 21 is exactly the same as in the previous example, and The operation of forming diluted samples in the wells of the plate is similar. In this example, an agglutination and immunity test unit 6 is provided, the configuration of which is similar to the previous example.

In this example, in addition to the immune reaction cell 51, the agglutination reaction cell 61
can be selectively mounted on the turntable 50. For this purpose, in addition to the cell pack 52 that stores the immune reaction cells 51, the cell pack 6 stores the agglutination reaction cells 61.
A mixture of 2 is provided.

FIGS. 26A and 26B show the configuration of an agglutination reaction cell 61 and a cell pack 62 that stores it. The aggregation reaction cell 61 has a conical bottom surface 61a, and a large number of fine steps are formed on this bottom surface as shown in FIG. 11, so that a base layer with a stable particle aggregation pattern is formed. so that In addition, a flange 61b is formed on the upper part,
This is made to engage with the turntable 50. The cell pack 62 has the same structure as the cell pack 52 shown in FIG. 15A, but the aggregation reaction cells 61 shown in FIG. 26A are stacked and stored in the holes 62a. 1st
As shown in FIG. 6, by pushing down the cell stack from above using the claw 53m, the lowest aggregation reaction cells 61 can be dropped one by one into the holes 50a of the turntable 50. In this way, the agglutination reaction cell pack 62 and the immunoreaction cell pack 52 are selectively positioned at the cell supply position according to the analysis items specified for each sample, and then the claw 53m is lowered to obtain the desired result. The agglutination reaction cell 61 and the immune reaction cell 51 can be selectively set one after another in the hole 50a of the turntable 50.

The present invention is not limited to the embodiments described above, and numerous changes and modifications are possible. For example, in the above-described embodiment, the sample dispensing nozzle 25c was cleaned and used repeatedly, but a disposable nozzle that is detachably set at the tip of the suction/discharge pipe may also be used, and in this case, cleaning is not necessary. There isn't. In addition, the rack transport mechanism,
Various known mechanisms can be used as the plate conveyance mechanism and nozzle movement mechanism. Furthermore, the enzyme immunoreaction in the above-mentioned example employed the Sandersch method, in which the same phase of the well and the sample are first reacted, and then the enzyme-labeled reagent is reacted. Laws may also be adopted. In this case, only one washing device is required to dispense the diluted serum sample and the enzyme labeling reagent into the cell at the same time and perform B-F separation. Furthermore, the number of containers set on the rack, the number and arrangement of wells formed on various plates are not limited to the examples described above.

Furthermore, in the embodiment shown in FIG. 25 described above, the agglutination reaction cell and the immune reaction cell may be stored in the same cell pack.

〔Effect of the invention〕

According to the automatic analyzer of the present invention described above, it is possible to determine not only the ABO blood type and Rh blood type necessary for blood transfusion tests, but also other blood types by irregular antibody screening. It is possible to test for various infectious diseases, and the saline method and enzyme method can also perform cross-matching tests required for blood transfusions, so if you have one of these automatic analyzers installed in your hospital, you can , it is possible to sufficiently cope with the situation, and it is possible to reduce equipment costs and labor at hospitals. Furthermore, since the analysis is performed automatically, accidents caused by human error or infection can be almost completely prevented.

In addition, in the automatic analyzer of the present invention, reaction cells with desired antigens and antibodies immobilized on the inner wall are selectively supplied to the reaction line, so that multiple items can be analyzed selectively. The configuration is also simple.

[Brief explanation of the drawing]

FIG. 1 is a diagrammatic plan view showing the overall configuration of an embodiment of an automatic analyzer according to the present invention, FIG. 2 is a plan view showing the configuration of a sampler, and FIGS. 3 A-C are supplying plates for dilution. 4A and B are diagrammatic side views showing the configuration of the storage stocker for diluting plates; FIG. 5 is a diagram showing the operation of the sample suction and discharge device; and FIG. Figure 7 is a line diagram showing the configuration of the diluted liquid dispensing device, Figure 7 is a diagram showing the configuration of the nozzle cassette, Figure 8 is a perspective view showing the configuration of the diluted sample suction and discharge device, and Figure 9 is a diagram showing the configuration of the diluted sample suction and discharge device. Similarly, FIG. 10 is a plan view showing the configuration of a button plate for dropping off the nozzle, and FIGS. 11A and B.
12 is a plan view and a cross-sectional view showing the configuration of the plate for agglutination reaction, FIG. 12 is a diagram showing the configuration of the elevator section that performs the agglutination reaction, FIG. 13 is a perspective view showing the configuration of a photometric device for an agglutination pattern, and FIG. 14 15A and 15B are diagrams showing the configuration of the cell bag for immune reaction, FIG. 16 is a perspective view showing the configuration of the cell supply device, and FIG. 17 is a diagram showing the configuration of the cell supply device. 18 is a diagram showing the configuration of the colorimetric measuring device, FIG. 19 is a diagram showing the configuration of the cell disposal device, and FIGS. 20 A and B are the arrangement of samples on the sample rack. Figure 21 A and B are diagrams showing the particle aggregation pattern;
Figures 2A and B are diagrams showing the enzyme immunoreaction, Figure 23 is a diagram showing how to set the sample container on the sample rack when performing cross-dispensing, and Figure 24 is a plane diagram showing the arrangement of the wells of the dilution plate. 25 is a diagrammatic plan view showing the configuration of another embodiment of the automatic analyzer according to the present invention, and FIGS. 26A and 26B are diagrams showing an agglutination reaction cell and an agglutination reaction cell bag. 1... Sampler 2... Dilution unit 4...
-Agglutination test unit 5...Immune test unit 11...Sample container 12...Sample rack P1...Sample suction position P2...Sample discharge device 21...Dilution plate 25...Sample portion Injection device 26... Diluted liquid dispensing device P3... Diluted liquid dispensing position 27... Diluted sample dispensing device P,... Diluted sample dispensing position 31... Disposable nozzle 32... Nozzle Cassette 41... Agglutination reaction plate 44... Reagent dispensing device P,... Reagent dispensing position 4
6...Elevator part 48...Photometering device 50...
-Turntable 51...immune reaction cell 52...cell bag 53...cell supply device 5
4, 58...Cleaning device 55.57...Reagent dispensing device 58...Reaction stop liquid dispensing device 59...Colorimetric photometer Fig. 3 A B C Fig. 4 A B Fig. 9 Figure 10 4% Figure 12 8c! Figure 8 A (Figure 9 with Figure 21 B Figure 22 Figure 2 Figure 23 Figure 24 f! Figure 5)

Claims (1)

[Claims] 1. Sequentially transporting a large number of sample containers each containing a sample to be analyzed through a sample suction position, aspirating a predetermined amount of sample at the sample suction position, and discharging the sample at a predetermined position. A large number of dilution plates each having a plurality of wells that receive a predetermined amount of sample aspirated and discharged by the sample dispensing means are sequentially transported along a dilution plate transport line, and a diluent is poured into the wells. A dilution means for dispensing the diluted sample, and a reaction vessel with a predetermined antigen or antibody immobilized on the inner wall or a reaction vessel with a sloped bottom surface, depending on the analysis item. It is characterized by comprising means for selectively supplying the sample to a reaction line and conveying it sequentially, dispensing the diluted sample from the diluting means into a reaction container, and inspecting the presence or absence of infection or agglutination due to enzyme immunoreaction. Automatic analyzer.