JP2548626B2 - Immune automatic analyzer - Google Patents

Description

TECHNICAL FIELD The present invention relates to an automatic immunoassay device, and more particularly to an automatic immunoassay device suitable for an enzyme immunoassay (EIA method) utilizing an antigen-antibody reaction.

[Conventional technology]

As an immunoassay utilizing the antigen-antibody reaction, the EIA method has been used in recent years because the reaction is extremely sensitive and the measurement accuracy is excellent.

By the way, as a method of this EIA analysis, there are a bead EIA method in which an antibody is immobilized on the surface of a spherical bead, a coating EIA method in which an inner wall surface of a reaction vessel is coated with an antibody, etc. Dispense the solution of
After stirring and discharging the solution, another solution is further dispensed,
Currently, a multi-step treatment process such as stirring and washing is required, and the reaction time at each stage is long, so that it takes a long time for measurement.

One of the inventors of the present invention previously proposed a device for fully automating the immunoassay and significantly shortening the measurement time (Japanese Patent Application No. 1-313363).

This is because instead of coating the antibody on the bead or the inner wall of the container, the antibody is immobilized on the magnetic microparticles and the insolubilized antibody solution containing the microparticles is used to discharge or react various solutions dispensed in the reaction container. The magnetic fine particles can be aggregated by a magnetic force when cleaning the container, and the operation of the apparatus at the stage of liquid discharge and container cleaning is simplified and speeded up.

[Problems to be Solved by the Invention]

In the immuno-automatic analyzer previously proposed by one of the present inventors, a magnet device for collecting and adsorbing the antibody-insoluble magnetic substance on the inner peripheral side wall surface of the reaction container is fixed and disposed at the same height position. Therefore, there is a problem that a part of the antibody-insoluble magnetic material diffused in the solution floats due to the magnetic force without being adsorbed on the inner wall surface of the reaction container.

As a means for solving such a problem, a magnet having a strong magnetic force may be used. However, when the antibody-insoluble magnetic substance is collected by using such a strong magnet, the residual magnetic force is increased during the washing / stirring work in the next step. There is a problem that the antibody-insoluble magnetic substance remains adsorbed on the inner wall surface of the reaction container by the action of.

As a means for solving such a problem, for example, magnets are arranged along the transfer path of the reaction vessel at different heights, or the magnets are moved in the vertical direction so that the antibody-insoluble magnetic substance is removed. Various methods have been proposed in the past for surely adsorbing to the inner wall surface of a reaction container.

By the way, in the magnet used for collecting the antibody insoluble magnetism, as shown in FIG. 3, since the magnetic flux 72 spreads also to the side surface of the magnet 70, the antibody insoluble magnetic material is widely spread on the inner wall surface of the reaction container 80. Since they are aggregated in a distributed state, there is a problem that the measurement transmission optical path is blocked and measurement cannot be performed.

The present invention has been made in view of the present situation, and an object thereof is to prevent the magnetic flux from spreading to the side surface of the magnet when the resistive non-magnetic material in the reaction container is collected by the magnet. With the configuration, it is intended to provide an automatic immunoassay device configured to efficiently collect antibody-insoluble magnetic substances collected on the inner wall surface of the reaction container in a narrow range so that the measurement transmission optical path is not blocked. is there.

[Means for solving the problem]

In order to achieve the above-mentioned object, the automatic immune analyzer according to the present invention comprises means for controlling transfer of a plurality of reaction vessels, and a predetermined sample, antibody-insoluble magnetic substance solution, enzyme-labeled antibody solution and substrate solution for each reaction vessel. A plurality of solution dispensing means for sequentially dispensing to the position, a magnet means arranged along the transfer path of the reaction vessel for collecting the antibody-insoluble magnetic substance on the inner peripheral side wall surface of the reaction vessel, and a reaction in each reaction vessel In the immuno-automatic analyzer comprising an optical measuring means for optically measuring the state, the magnet means has a side surface not facing the reaction vessel, which is covered with a ferromagnetic material so that a part of the magnetic flux is present. It is characterized by being shielded.

[Action]

In the automatic immunoassay device according to the present invention, the antibody-insoluble magnetic material in the reaction vessel that sequentially moves on the transfer path is formed by the inner peripheral side wall surface of the reaction vessel in accordance with the magnetic force lines of the magnet means arranged on the transfer path. It will be gathered and aligned in a state of being adhered to the wall surface. Since a plurality of magnet means are arranged at different height positions, it is easier to set and select the magnet strength as compared with the case where magnetic particles are collected by one strong magnet.
Each magnet means can be arranged by changing the height position with respect to the reaction container, and the antibody-insoluble magnetic material is sequentially arranged according to the height position of the magnet means, and the leakage of magnetic particles is reduced.

When the side surface of the magnet means is coated with a ferromagnetic material, a part of the magnetic flux with respect to the reaction vessel can be shielded, and only a narrow area of the inner wall surface of the reaction vessel facing the magnet means can be magnetized. It becomes possible to aggregate body particles.

〔Example〕

 Embodiments of the present invention will be described below with reference to the accompanying drawings.

FIG. 1 is a diagram showing an automatic immune analyzer according to this embodiment. First, the overall configuration will be briefly described. 1 is a reaction vessel, 2 is a reaction table for rotationally driving the reaction vessel 1,
3 is a reagent holder whose rotation is controlled according to a predetermined program, 4 is an antibody-insoluble magnetic substance liquid containing antibody-insoluble magnetic substance fine particles in which antibodies are immobilized on magnetic substance fine particles, and 5 is an enzyme-labeled antibody liquid. Further, 6 is a sample container containing a sample solution, 7 is a sample transport device for linearly transporting the sample container 6, 8 is a table device, and 9 is the table device 8
It is the substrate solution set in.

Then, the respective solutions 4, 5, 6 and 9 are dispensed into the reaction vessel 1 by the corresponding pipette devices 14, 15, 16 and 19 and stirred by the stirring devices 24, 25 and 29.

On the other hand, reference numerals 31, 32, 33 and 34 are drain pipettes for discharging the solution in the reaction container 1, and 41, 42 and 43 are reaction containers 1.
The cleaning liquid supply device supplies the cleaning liquid to the. Further, 51, 52 and 53 are stirring devices for stirring the cleaning liquid.

55 is a pipette device that dispenses the cleaning liquid into the reaction container 1, 56 is a drain pipette for discharging unnecessary solutions, and 57
Is a pipette device for dispensing a reaction terminator, 58 is an optical measuring device for optically measuring the reaction state, and 59 is a washing device for washing the reaction container 1 for which measurement has been completed.

A magnet device for gathering and aligning the antibody-insoluble magnetic material on the inner peripheral surface of the reaction container 1 on the outer peripheral edge of the reaction table 2.
61 to 66 are provided. The magnet devices 61 to 66 are composed of either permanent magnets or electromagnets, and of these magnet devices 61 to 66, face the reaction container 1 of the magnet device 66 arranged at least at the measurement position. No side, for example,
As shown in FIG. 2, the upper side is covered with a ferromagnetic material 71 such as an iron plate to shield a part of the magnetic flux, and the fine particles of the antibody-insoluble magnetic material are on the side surface of the reaction container 1 (also on the side surface not facing the magnet). (Including) is collected and adsorbed in a narrower range, and the measurement transmission light path is not blocked. In this embodiment, the magnet devices 61 to 66 are arranged even if they are arranged at different heights, but the magnet devices 61 to 66 are slidably arranged in the vertical direction of the reaction vessel 1. It may be installed and configured.

As the ferromagnetic material, not only iron but also nickel or the like that can reduce the cost can be used. Further, the coating location of the ferromagnetic material may be appropriately changed depending on the size of the reaction container and the distance from the magnet device to the reaction container.

Next, the operation of this automatic immune analyzer will be described.

When the device is activated, the sample container 6 is intermittently transferred to the sample suction position, and the pipette device 16 sequentially dispenses a fixed amount of sample into the reaction container 1.

At this time, the reaction table 2 is intermittently rotated counterclockwise by one pitch, and the reaction container 1 is also moved by one pitch in the counterclockwise direction.

Next, when the reaction container 1 moves counterclockwise by one pitch, the antibody insoluble magnetic substance liquid is dispensed by the pipette device 14, and the solution is agitated by the agitator 24. Next, when the washing liquid is dispensed from the pipette device 55 into the reaction container 1 and the reaction container 1 moves to the installation position of the magnet device 61, the antibody-insoluble magnetic substance gathers on the inner peripheral side wall of the reaction container 1. The sample solution other than the insoluble magnetic substance is discharged to the outside of the container by the drain pipette 56.

The enzyme-labeled antibody liquid is dispensed from the pipette device 15 into the reaction container 1, then stirred by the stirring device 25, further the cleaning liquid is supplied from the cleaning liquid supply device 41, and the stirring device 51 stirs at the next position. Processing is performed. After that, the sample is transferred to the discarding position, and when the reaction container reaches that position, the antibody-insoluble magnetic material is collectively adsorbed by the inner wall of the reaction container 1 by the magnet device 62, and the sample other than the antibody-insoluble magnetic material is drained with a drain pipette. Discharged by 31.

In the same manner, the cleaning liquid is supplied to the reaction container 1 by the cleaning supply device 42, stirred by the stirring device 52 at the next position, and then transferred to the sample discarding position, and the magnet device 63.
As a result, the antibody-insoluble magnetic material is collectively adsorbed on the inner wall surface of the reaction container 1. For samples other than the antibody-insoluble magnetic substance, use the drain pipette 32.
Is drained. The cleaning liquid supply device 43, the stirring device 53, the magnet devices 64 and 65, and the drainage pipettes 33 and 34 operate in the same manner.

After that, the substrate liquid 9 is supplied to the reaction container 1 by the pipette device 19, is stirred by the stirring device 29, and then the reaction stop solution is dispensed by the pipette device 57.

The reaction container 1 in which the enzymatic reaction has stopped due to the reaction stop solution is transferred to the optical measurement unit 1, but in this case as well, the magnet device 66 collects and adsorbs the antibody-insoluble magnetic substance on the inner wall surface of the container. Since it is necessary not to block the measurement optical path of the optical measuring device 58 at this position, the magnet device 66 is arranged near the bottom surface of the reaction container 1 so that the antibody-insoluble magnetic substance is attracted to the lower part of the inner wall of the reaction container 1. In addition, the upper side of the magnet device 66 not facing the reaction vessel 1 is covered with a ferromagnetic material 71 such as an iron plate to shield a part of the magnetic flux, and the Since the fine particles are configured to be collected and adsorbed in a narrower range on the side surface of the reaction container 1, there is no possibility that the fine particles of the antibody-insoluble magnetic substance will intervene in the measurement transmission optical path, and with higher accuracy. It is possible to obtain stable measurement data.

The data thus measured by the optical measuring device 58 is processed according to a predetermined program, and the data is stored in a recording means such as a magnetic recording card or an IC card.

The reaction container 1 after the optical measurement work is transferred to the cleaning device 59, all the sample in the reaction container 1 is drained by the cleaning device 59, and the inside of the reaction container 1 can be reused by the cleaning water. It is washed in multiple stages until it becomes, and the measurement process is completed.

In this way, since the antibody-insoluble magnetic substance is collectively adsorbed on the inner peripheral side wall surface of the reaction container 1 in each treatment stage by the magnet devices 61 to 66, the treatment such as drainage and washing is simplified and the treatment time is shortened. To be done. In this case, since the height positions of the magnet device are set to be different from each other, it is possible to efficiently adsorb the magnetic fine particles in each stage, and even if a permanent magnet or the like having a not so strong magnet strength is used. Since it can be implemented, the cost can be reduced.

〔The invention's effect〕

As described above, in the automatic immune analyzer according to the present invention, when the antibody-insoluble magnetic material in the reaction container is collected by the magnet, the magnetic flux is shielded so that part of the magnetic flux does not spread to the side surface of the magnet. As a result, it is possible to collect magnetic particles only in a narrow area of the inner wall surface of the reaction container that faces the magnet means, and it is possible to reduce the trouble of collecting the magnetic particles after the measurement. Produce the effect.

[Brief description of drawings]

FIG. 1 is an explanatory view showing the overall structure of an automatic immune analyzer according to an embodiment of the present invention, and FIG. 2 is an explanatory view showing the structure of a magnet device arranged at the measurement position of the automatic immune analyzer. FIG. 3 is an explanatory view showing the spread of magnetic flux when a ferromagnetic material is not provided in the magnet means. [Explanation of reference symbols] 1 ... reaction container, 2 ... reaction table 3 ... reagent holder, 4 ... antibody-insoluble magnetic substance liquid, 5 ... enzyme-labeled antibody liquid, 6 ... sample container, 9 ... substrate liquid 14,15 , 16,19,55 …… Pipette device 24,25,29,51,52,53 …… Stirring device 31,32,33,34,56 …… Drainage pipette 41,42,43 …… Cleaning liquid supply device 59 …… Cleaning device 61 to 66 …… Magnet device 71 …… Ferromagnetic material

Claims (1)

(57) [Claims] 1. A means for controlling transfer of a plurality of reaction vessels, and a plurality of solution dispensers for sequentially dispensing a sample, an antibody-insoluble magnetic substance solution, an enzyme-labeled antibody solution and a substrate solution to each reaction vessel at predetermined positions. Means, magnet means arranged along the transfer path of the reaction vessel for collecting the antibody-insoluble magnetic substance on the inner peripheral side wall surface of the reaction vessel, and optical measuring means for optically measuring the reaction state in each reaction vessel In the immuno-automatic analyzer comprising the following, the magnet means is configured such that a side surface not facing the reaction container is covered with a ferromagnetic material and a part of magnetic flux is shielded. Automatic immune analyzer.