JPS6315163A - Immunological analyzer - Google Patents

Abstract

PURPOSE:To fully automate an analytical process and to treat a plurality of processes simultaneously in parallel, by providing a main body, a specimen container holding plate, an arm, a reagent injection nozzle movable in Y-axis and Z-axis direction and a washing unit movable in the Z-axis direction as an analyzer. CONSTITUTION:At the start time of analysis, an arm 5 is stopped at a first row in an X-axis direction and a nozzle support part 6 is made nearest to an apparatus main body. The nozzle support part 6 is allowed to fall in a Z-axis direction to distribute a standard reagent in a No.1 specimen container 4 having a specimen received therein from a first reagent injection nozzle 8 and subsequently raised to be moved in a Y-axis direction and again made to fall to successively distribute a first reagent in No.2-10 specimen containers 4 from the injection nozzle 8 to start primary reaction. Next, the injection nozzle 8 is moved to a second row in an X-axis direction and the first reagent is injected in the specimen container 4 of a second row and, at the same time, beads are successively thrown in the specimen container 4 of a first row from a bead throw-in nozzle 11.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to an immunological analysis device that utilizes antigen-antibody reactions.

[Conventional technology]

BACKGROUND OF THE INVENTION With the recent advances in medical care, the diagnosis of various intractable diseases such as malignant intestines, abnormal hormone secretion diseases, and immune diseases has been carried out by immunological analysis using antigen-antibody reactions.

Various immunological analysis methods have been proposed, but recently, labeled antigens or stray antibodies bound to labeled antigens or antibodies, which have high detection sensitivity, have been proposed. The methods used have become mainstream, and depending on the type of label, radioimmunoassay using radioisotopes, fluorescence immunoassay using fluorescent substances, enzyme immunoassay using enzymes, etc. are known. Among them, enzyme immunoassay (E
Technique A) requires no special equipment or measurement techniques and can be easily performed using a general colorimeter, so it is particularly noteworthy. are collecting.

EIA has two methods: one is to quantify the test substance by directly determining the change in the activity of the labeled enzyme depending on the presence or absence of an immunochemical reaction, and the other is to quantify the test substance by directly determining the change in the activity of the labeled enzyme depending on the presence or absence of an immunochemical reaction. Alternatively, use an antibody and wash the labeled antigen or standard antibody that has reacted with it with the unreacted one.
There is a method of separating and quantifying the test substance by determining the activity of the labeled enzyme after B-F separation. The former method can quantify only low-molecular-weight test substances, but the latter method is becoming popular because it can properly analyze both low-molecular-weight and high-molecular-weight test substances.

Furthermore, as for the latter method of performing B-F separation, the competitive method and the sandwich method are known.

Is the competitive method an antigen-antibody reaction between the test substance in the sample? A labeling reagent that is enzyme-labeled with the same substance as the test substance and is injected into the sample sample, and the antigen or antibody on the beads is immobilized in advance on the antibody or antigen to be tested and labeled with the labeling reagent. Competitive binding, unreacted test substance and labeled reagent are removed by B-F separation by washing operation, and then a coloring reagent containing a substrate that reacts with the labeled enzyme to develop color is added to cause a coloring reaction. After adding a reagent to stop the color reaction, the solution is measured colorimetrically and the test substance is added.

On the other hand, in the sandwich method, antibodies or antigens immobilized on beads are reacted with the test substance, E-F separation is performed to remove unreacted test substances, and the substance that reacts with the test substance and the antigen-antibody is treated with an enzyme. A labeled labeling reagent is added and reacted, B-F separation is performed again to remove unreacted labeling reagent, a coloring reagent is added to cause a coloring reaction, a coloring reaction stopping reagent is added, and the solution is measured colorimetrically. Quantitate the test substance.

Immunological analysis such as EIA has traditionally been performed manually, but automated analysis devices are also used in some cases. For example, most multi-specimen biochemical analyzers use a turntable with multiple sample containers arranged on the same circumference. It is installed in a thermostatic chamber, and while rotating it, the sample container is stopped at each position of the injection nozzle for various reagents, the bead injection nozzle, and the suction nozzle for the sample solution, which are fixed to the main body of the device, and each operation is performed. . In addition, in a microplate-type E-A device, a sample container is movably held in a constant-temperature premises, and various reagent injection nozzles, bead injection nozzles, and Some systems perform analysis operations by sequentially moving sample containers to a sample solution suction nozzle.

However, although some conventional immunological analyzers automate a single process, none automate the entire process, and because each operation is performed in series, the analysis time is long and it is difficult to process multiple samples. took an enormous amount of time. In addition, since the entire process is not automated, it is difficult to manage the reaction time, and there is a problem with analysis accuracy, especially in EIA, which requires strict reaction time management.

[Problem that the invention seeks to solve]

In view of the shortcomings of conventional immunological analyzers, the present invention provides an immunological analysis system that fully automates the analysis process, allows multiple processes to be performed simultaneously, and allows easy management of reaction time. The purpose is to provide equipment.

[Means to solve the problem]

The immunological analyzer of the present invention includes an immunological analyzer main body, an X
A sample container holding board in which sample containers are arranged in multiple rows in the axial and Y-axis directions, and a sample container holding board that protrudes in the Y-axis direction on the sample container holding board and is supported by the device body and can be moved in the X-axis direction on the sample container holding board. an arm, a reagent injection nozzle supported by the arm so as to be movable in the Y-axis direction and a Z-axis direction perpendicular to the horizontal plane, and a cleaning device for B-F separation supported by the arm so as to be movable at least in the Z-axis direction. It is equipped with a unit.

The number of cleaning units is the same as the number of sample containers in one row in the Y-axis direction.
If they are provided in one row in the axial direction, it is not necessary to move in the Y-axis direction, but if the number is less than that, it is necessary to provide them so that they can be moved in the Y-axis direction as well as the Z-axis direction.

In addition to the plurality of reagent injection nozzles and washing unit described above, the arm has a bead injection nozzle for injecting beads immobilized with antibodies or antigens into three sample containers, and a suction nozzle for the sample solution read by the solution concentration measuring device. They can also be supported movably in the Y-axis and X-axis directions, respectively.

In this case, an arm movable in the X-axis direction is provided with a nozzle support part movable in the Y-axis and It can be movably supported.

However, the suction nozzle should be immersed in the sample solution in the sample container.
It is necessary to prevent other nozzles from touching the sample solution, so either the suction nozzle is provided separately from the other nozzles and is movable one step further in the X-axis direction from the arm or nozzle support, or the arm or nozzle is The movement of the support part in two axial directions is made into two stages so that it can be lowered further during suction than during reagent injection.

〔Example〕

An embodiment of the present invention will be described with reference to the drawings.

As shown in FIG. 1, the immunological analyzer of the present invention has an X-axis and a Y-axis that are orthogonal on a horizontal plane to a specimen container holding plate 3 fixed horizontally in a constant temperature bath 2 of an apparatus main body 1. A plurality of sample containers 4 (30 rows in the X-axis direction and 10 in the Y-axis direction) are arranged at equal intervals in each direction, and each line is at the intersection of a straight line parallel to the X-axis and a straight line arranged at equal intervals parallel to the Y-axis. It is located and arranged.

An arm 5, which protrudes in the Y-axis direction on the sample container holding plate 3 and is supported by the apparatus main body 1, is movable on the sample container holding plate 3 in the X-axis direction. The arm 5, which is movable in the X-axis direction, has a nozzle support part 6 supported movably in the Y-axis and Z-movement directions in a through groove 7 extending in the Y-axis direction and penetrating in the X-axis direction. .

This nozzle support part 6 is provided with a first reagent injection nozzle 8, a second reagent injection nozzle 9, and a third reagent injection nozzle 10 in a row in the Y-axis direction as shown in FIG. Or beads with immobilized antigens? The bead injection nozzle 1) for injecting the beads into the sample container 4 from the bead extraction unit 16 provided in the device main body 1 and the suction nozzle 12 for the sample solution connected to the solution concentration measuring device are connected to each reagent injection nozzle 8, 9, and 10 from the rows. They are arranged in a row in the Y-axis direction and shifted by one row of sample containers 4 in the X-axis direction.

A cleaning unit support section 14 is provided on the outer surface of the arm 5 on the side opposite to the nozzle support section 6 with respect to the Y-axis direction, so as to be movable along the support column 13 in the X-axis direction. The cleaning unit support part 14 has sample containers 4 arranged in a row in the Y-axis direction, shifted by three rows of sample containers 4 in the X-axis direction from the row of each reagent injection nozzle 8, 9, and 10. Same number (10 pieces)
The washing unit 15 is provided with washing units 15 for B-F separation, and each washing unit 15 is composed of a physiological saline injection nozzle and its suction/discharge nozzle.

Also, inside the apparatus main body 1, there are a device for driving the arm 5 in the X-axis direction, a device for driving the nozzle support portion 6'E-Y-axis and the X-axis direction, and a device for driving the cleaning unit support portion 14 in two-axis directions. Each device is housed in the device, and each part is driven according to a sequence sent to the control section of the device main body 1, so that analysis operations can be performed automatically.

[Effect]

Enzyme immunoassay using competitive method (E-TechA), all operations are performed in 12 seconds per sample container and 1 time in the Y-axis direction using the above device.
The sequence for one black sample container is shown in FIG. 3 when the reaction is carried out for 2 minutes per 10 rows and the reaction time is 60 minutes.

At the start of analysis, the arm Sf is stopped in the first row in the X-axis direction, and the nozzle support part 6 is stopped closest to the apparatus main body 1.

In this state, the nozzle support part 6 is lowered in the zFqh direction and the first reagent injection nozzle 8 is inserted into the AI sample container 4 containing the sample.
Dispense the labeled reagent from 2 to 10, then raise the nozzle support part 6, move it in the Y-axis direction, and lower it again.
Dispense the first reagent from the injection nozzle 8 into the sample container 4 of -
Start the next reaction. After starting the injection of the first reagent into the sample containers 4 in the first row (10 bottles), the injection nozzle 8 moves in two minutes to the first reagent in the second row in the X-axis direction.

The nozzle support part 6 is lowered to sequentially inject one sample mulberry into the second row of sample containers 4 as described above, and at the same time beads are sequentially introduced into the first row of sample containers 4 from the bead injection nozzle 1).

The 60-minute primary reaction was made to end when beads were added to the sample container 4 for 30 minutes in the X-axis direction and the arm 5 was returned to its initial position so that the washing unit 15 was placed above the first row. Therefore, lower the cleaning unit support part 14 and
0 cleaning units 15310 (cIff sample containers 4
For 12 seconds per container, wash the sample container sequentially in the Y-axis direction, and repeat the washing operation one row at a time while moving the arm 5 in the X-axis direction one after another.
B-F separation of all sample containers 4 up to column 0 is attempted. The cleaning unit 15 moves in the X-axis direction by 3 rows in 6 minutes and
When the cleaning operation for the fourth column is completed, the nozzle support 6 is simultaneously moved in the Y-axis and X-axis directions starting from the cleaning operation for the fourth column, and the A1 sample container 4 is sequentially moved from the second reagent injection nozzle 9 to the second reagent injection nozzle 9. A secondary reaction is caused by dispensing the coloring reagent.

The second reagent injection operation also ends for all sample containers 4 60 minutes after the start of the second reagent injection, and the arm 5 returns to its original position again.

When the secondary reaction is completed, the arm 5 and nozzle support 6 are operated in the same manner as in the case of the first reagent injection, and the reaction stop solution is dispensed from the third reagent injection nozzle 10 in order from the A1 sample container. From the reagent injection in the second row (761), the nozzle support 6 is lowered to the position where the suction nozzle 12 touches the sample solution, and the suction nozzle 12 is simultaneously injected with the third reagent into the sample container 4 (j≦1). 1. The sample solution in the sample container 4 is aspirated and sent to the concentration measuring device, where the absorbance is measured. In this way, 130 minutes after the start of the operation, including the return time of the arm 5, data output for the No.K1 sample is started.

In this embodiment, the cleaning unit 15 was provided in the same number as the specimen containers 4 in one row in the EY axis direction.
It is also possible to support the cleaning unit support part 14 so as to be movable in the Y-axis direction.

〔Effect of the invention〕

According to the present invention, the entire analysis process of an immunological analyzer can be fully automated and the entire apparatus can be made compact. Also, reagent injection - bead injection, reagent injection - washing, reagent injection -
Since the suction steps can be performed simultaneously and in parallel, analysis time can be shortened.

Furthermore, full automation makes it easier to manage the reaction time and is expected to improve analysis accuracy.

[Brief explanation of drawings]

FIG. 1 is a perspective view of a specific example of the device of the present invention, and FIG. 2 is a plan view of an arm portion of the device of FIG. FIG. 3 is a diagram showing the sequence of analysis operations using this apparatus. 1. Equipment body 2. Constant temperature chamber 3. Sample container holding board 4. Sample container 5. Arm
6... Nozzle support part 8... First reagent injection nozzle 9... Second reagent injection nozzle 10... Third reagent injection nozzle 1)... Bead injection nozzle 12... Suction nozzle 14... Cleaning unit support part 15・Cleaning unit diagram 2

Claims (3)

[Claims] (1) An immunological analyzer main body, a sample container holding board that is placed in a thermostatic chamber of the device main body and has sample containers arranged in multiple rows in each of the X-axis and Y-axis directions orthogonal on a horizontal plane, and sample containers. An arm that protrudes in the Y-axis direction on the holding plate and is supported by the apparatus main body and is movable on the sample container holding plate in the X-axis direction, and an arm that is supported movably in the Y-axis direction and the Z-axis direction perpendicular to the horizontal plane. An immunological analyzer comprising: a reagent injection nozzle; and a washing unit for B-F separation supported on an arm so as to be movable at least in the Z-axis direction. (2) The immunological system according to claim (1), wherein the arm movably supports a bead injection nozzle for introducing beads immobilized with antibodies or antigens into a sample container in the Y-axis and Z-axis directions. Analysis equipment. (3) The immunological analyzer according to claim (1), wherein the arm supports a sample solution suction nozzle connected to the solution concentration measuring device so as to be movable in the Y-axis and Z-axis directions.