JP3258602B2 - Reaction tube stirrer - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for effectively stirring a solution in a reaction tube by rotating a reaction tube (also referred to as a reaction vessel), standing up the reaction tube in a standby state, and homogenizing the solution in the reaction tube during stirring. The present invention relates to a reaction tube stirrer in an automatic analyzer that can stir quickly.

[0002]

2. Related Art As an automatic analyzer according to the present invention, for example, an automatic immunoassay for measuring a specific substance in a sample by an antigen-antibody reaction is known.

[0003] As an immunoassay using the antigen-antibody reaction, a non-competitive sandwich method and a competitive method of a one-step method and a two-step method are known.

A method of measuring the amount of antigen contained in a sample such as blood collected from a patient as a sample by a one-step non-competitive sandwich method will be described. For example, an antibody (solid phase antibody) bound to an insoluble simple substance (solid phase) such as an inner wall or a particle made of a synthetic resin, and an antibody (labeled antibody) bound to a labeling substance such as a radioactive substance, a fluorescent substance, or an enzyme. Is added to the reaction tube to which is added in advance.

Thus, in the reaction tube, the antigen contained in the sample reacts with the solid-phase antibody by an antigen-antibody reaction (immune reaction) to form an antigen-antibody complex, and at the same time, the antigen-antibody complex is labeled. The antibody is also conjugated to form a conjugate in which the three components of solid phase antibody-antigen-labeled antibody are sandwiched. In this way, the label of the labeled antibody is bound to the solid phase using the antigen in the sample as a mediator.

Next, extra labeled antibodies other than the label bound to the solid phase and not binding to the antigen added to the reaction tube, antibody components not involved in the immune reaction, and the like are removed. The separation (B / F separation) operation is performed, and finally, the amount of the label, which is proportional to the amount of the antigen bound to the solid phase, is quantitatively measured by a physical or chemical method utilizing the properties of the label. Determine the antigen concentration in the medium.

On the other hand, in the two-step non-competitive sandwich method, the first reaction is carried out by adding a sample to a reaction tube to which only a solid phase antibody has been previously added, and then a labeled antibody is added. This is a method in which a second reaction is performed by adding a substance to perform measurement.

In addition to these non-competitive sandwich methods, a so-called competitive method in which an antigen (labeled antigen) previously labeled with a labeling substance and an antigen in a sample are competitively reacted with the solid phase antibody described above. Methods are also known.

In such an immunoassay method, it is necessary to stir the solution in the reaction tube in order to sufficiently react the sample with the reagent and to sufficiently perform the washing treatment in the B / F separation.

As means for stirring the solution in the reaction tube,
A method is employed in which a stirring rod is inserted into a reaction tube and stirred. When this stirring rod is used, when the type of the solution in the reaction tube is changed, if the stirring rod is used as it is, contamination with other kinds of solutions (contamination) occurs.
Therefore, it was necessary to wash the stirring bar every time the type of the solution changed. This cleaning process becomes more complicated in the process, and the cleaning mechanism also needs to be automated, and there is a problem that the mechanism becomes complicated.

Therefore, the contents are agitated by applying vibration to the container or rotating the container. When a plurality of such reaction containers are accommodated in a holder in which a plurality of reaction containers are arranged and stirring is performed at the same time, even if vibration or rotation is given to the entire container holder, the liquid in each container is not stirred and the object is not achieved .

The most effective method is the stirring method in which the neck portion of each container is fixed and the bottom is moved in a circular motion. In order to realize such a method, there is known a method in which a neck portion of a container is fixed, and an eccentric vibrating plate is provided below the container.

[0013] However, in the case of the method using such an eccentric circular motion to the oscillation plate is located always eccentric state oscillation plate, would be held in the container is tilted even at a time other than during stirring. Therefore, it is difficult to access the inside of the container with various nozzles for the purpose of dispersing the internal solution or washing the inside of the container without keeping the container in a vertical state during standby other than the stirring. There was a problem.

An automatic analyzer with a stirring mechanism for maintaining a vertical state during standby has also been proposed (Japanese Patent Application Laid-Open No. Hei 8-
However, it has been difficult to reliably maintain an upright state during standby.

In addition, in the conventional stirring method, the stirring is often non-uniform, which is one of the causes of the generation of bubbles in the reaction liquid during stirring, which is one of the causes of a decrease in measurement accuracy.

[0016]

SUMMARY OF THE INVENTION The present invention has been made in consideration of the above-mentioned problems, and has been made in consideration of the above problems. It is an object of the present invention to provide a reaction tube stirring device capable of uniformly stirring the liquid in each reaction vessel.

[0017]

[MEANS FOR SOLVING THE PROBLEMS]
In addition, the reaction tube stirring device of the present invention comprises a rotatable reaction tube turret that locks the upper portion of the reaction tube and swingably supports the lower portion, and a reaction tube turret located below the reaction tube turret. A stirring plate that has an insertion hole that penetrates the lower portion, is coaxially rotated with the reaction tube turret, and is mounted so as to swing sideways; an annular stirring base that is mounted on the lower surface of the stirring plate; An eccentric plate having an agitating roller circumferentially in contact with the inner peripheral surface of the agitating base and having an arc-shaped eccentric hole formed therein, and an agitating pin loosely inserted into the arc-shaped eccentric hole protruded from the upper surface peripheral portion. When the stirring boss is rotated, the stirring pin is located at an eccentric position of the eccentric hole and rotates the eccentric plate in an eccentric state, whereby the stirring base is rotated by the eccentric plate. Eccentric rotation through the stirring roller By the stirring plate rotates eccentrically together with the record, it rotates the lower part of the reaction tube, characterized in that a solution of the reaction tube was set to be stirred.

In the reaction tube stirring device of the present invention, the solution in the reaction tube is stirred by rotating the lower portion of the reaction tube supported by the reaction tube turret with the upper portion locked and the lower portion free. Therefore, stirring can be performed effectively and uniformly, and foaming during stirring of the reaction solution is prevented,
Even if the solution is changed, there is no risk of mixing other types of solutions.

Further, when the reaction tube is not rocked, the reaction tube is securely supported in a vertical state, so that no trouble occurs in the work of injecting and sucking out the solution.

[0020]

DESCRIPTION OF THE PREFERRED EMBODIMENTS One embodiment of the present invention will be described below with reference to the accompanying drawings.

FIG. 1 is a top view showing an example of the automatic analyzer. FIG. 2 is a side view of FIG. FIG. 3 is a top view showing one embodiment of the reaction tube stirring device of the present invention in which a part of the reaction tube turret is cut away. FIG. 4 is a longitudinal sectional view of FIG. FIG. 5 is a perspective view showing the stirring base and the eccentric plate. FIGS. 6A and 6B are explanatory diagrams showing the relationship between the eccentric plate and the reaction tube during standby. FIG. 6A shows a state where the eccentric plate is not eccentric, and FIG. 6B shows a state where the reaction tube is upright. 7A and 7B are explanatory diagrams showing the relationship between the eccentric plate and the reaction tube at the time of stirring. FIG. 7A shows a state in which the eccentric plate is eccentric, and FIGS. 7B and 7C show a state in which the reaction tube performs uniform stirring. Show. FIG. 8 is an explanatory diagram showing the motion trajectory of the inner peripheral surface of the stirring base.

In FIG. 1, reference numeral 12 denotes an automatic analyzer to which the reaction tube stirring device of the present invention is applied, specifically, an automatic immunoassay device, which has a reaction tube turret 14 which rotates intermittently at a predetermined speed. ing. At the periphery of the upper surface of the reaction tube turret 14, there is formed a reaction tube holding portion 18 in which a plurality of reaction tube holders 16 are arranged in two rows, an inner row and an outer row. The number of the reaction tube holders 16 provided on the upper surface of the reaction tube turret 14 may be appropriately set according to the mode of the reaction, but in the example of FIG. An example in which a reaction tube holder 14 is installed is shown.

Reference numeral 20 denotes a reaction tube rack, and a plurality of receiving portions 21
Is held in the reaction tube T. 22 is a reaction tube transfer means. The reaction tube transfer means 22 transfers the reaction tubes T held in the receiving portion 21 of the reaction tube rack 20 to the reaction tube holder 16, and sets a desired number of the reaction tubes held in one reaction tube holder 16. The operation of skipping one reaction tube holder 16 and transferring it to another reaction tube holder 16 is performed.

In this case, the reaction tubes T held in the inner or outer rows of the reaction tube holders 16 can be transferred to the reaction tube holders 16 of the same circumference, or the reaction tubes of other circumferences can be transferred. 16 can also be transferred. The reaction tube transfer unit 22 includes a reaction tube supply unit that supplies the reaction tube T to the reaction tube holding unit 18 and a reaction tube disposal unit that takes out the measured reaction tube T from the reaction tube holding unit 18 and discards the reaction tube T. Have.

Reference numeral 26 denotes particle supply means for supplying particles to the reaction tube T, and a particle nozzle 26a is provided below the particle supply means. Reference numeral 28 denotes a reagent dispensing means for dispensing the labeling reagent into the reaction tube T, and a reagent nozzle 28a is provided below the reagent dispensing means. Reference numeral 30 denotes a cleaning unit for performing B / F separation. Reference numeral 32 denotes a measuring reagent dispensing means for dispensing the measuring reagent into the reaction tube T. Reference numeral 34 denotes a measuring means for measuring the amount of the label in the reaction solution after the reaction in the reaction tube T.

A reagent table mechanism 86 has a reagent table 87. The reagent table 87 has a mounting hole 8
7a, 87a are drilled, and the mounting holes 87a, 87
Reagent holders 88, 88 are detachably attached via a. A particle bin 90 and a labeled reagent bin 92 are detachably attached to the reagent holders 88, 88, respectively.

In FIG. 4, reference numeral 35 denotes a substrate.
On the upper side, a rotating shaft 36 is supported and supported by a column 36a. The rotating shaft 36 rotatably supports the reaction tube turret 14 via a connecting shaft 37. A pulley 38 is fixed to the rotating shaft 36. A rotary motor 40 has a drive shaft 42 to which a motor pulley 44 is attached. The motor pulley 44 is connected to the pulley 38 via a timing belt 45,
The rotation of the motor pulley 44 is transmitted to the pulley 38, and the reaction tube turret 14 intermittently rotates via the rotation shaft 36 and the connection shaft 37.

The reaction tube holder 16 of the reaction tube turret 14 locks the upper portion of the reaction tube T, makes the lower portion a free end, and applies a force from the side so that the reaction tube T swings about the upper portion as a fulcrum. Move.

Reference numeral 46 denotes a stirring plate, which is located below the reaction tube turret 14 and has a play insertion hole 48 for loosely inserting the lower portion of the reaction tube T. Reference numeral 50 denotes an annular stirring base provided below the stirring plate 46. The overall shape of the stirring base 50 is well shown in FIG.
The connecting shaft 37 has a play hole 37 a formed in the stirring plate 46 and a play hole 5 formed in the stirring base 50.
1, the lower surface of the reaction tube turret 14 and the upper surface of the upper plate 36a of the rotating shaft 36 are connected. The reaction tube turret 14, the stirring plate 46 and the stirring base 50
Are connected by an anti-vibration rubber 52. Reference numeral 53 denotes a mounting hole formed in the stirring base 50 for mounting the vibration isolating rubber 52.

An eccentric plate 54 has a center hole 55 formed in the center thereof. The eccentric plate 54 is slidably mounted on the upper surface of the stirring boss 56 by the holding plate 58 and the screw 60 through the center hole 55. Reference numeral 62 denotes a stirring roller provided on the upper surface of the peripheral portion of the eccentric plate.

A stirring shaft 64 rotatably supports the stirring boss 56 and is rotatably provided in a hollow portion 66 formed inside the rotary shaft 36. A stirring pulley 68 is fixed to the lower end of the stirring shaft 64. A stirring motor 70 has a drive shaft 72 to which a motor pulley 74 is attached. The motor pulley 74
Is connected to the stirring pulley 68 via a timing belt 76, the rotation of the motor pulley 74 is transmitted to the stirring pulley 68, and the stirring boss 56 rotates via the stirring shaft 64.

Reference numeral 78 denotes a stirring pin protruding from the upper surface of the stirring boss 56. An arc-shaped eccentric hole 80 is formed at an intermediate portion between the center hole 55 and the peripheral edge of the eccentric plate 54. The stirring pin 78 is inserted through the arc-shaped eccentric hole 80. When the stirring pin 78 is located at the base end portion 80a, the center of the eccentric plate 54 and the center of the stirring boss 56 are aligned (FIG. 6A).
When the stirring pin 78 is located at position b, the center of the eccentric plate 54 does not coincide with the center of the stirring boss 56, that is, the eccentric plate 54 is eccentric (FIG. 7A).

Therefore, when the stirring boss 56 rotates and the stirring pin 78 rotates, the stirring pin 78 moves from the base end portion 80a of the arc-shaped eccentric hole 80 to the tip end portion 80b and reaches the tip end portion 80b. , And engages with the eccentric plate 54 to rotate integrally. As shown in FIG.
When the stirring pin 78 is located at the tip end portion 80b of the arc-shaped eccentric hole 80, the eccentric plate 54 rotates in an eccentric state. At the same time, the stirring roller 62 attached to the eccentric plate 54 is
The stirring boss 50 rotates eccentrically by the pressing force of the stirring roller 62. The stirring boss 50
8 rotates eccentrically, as shown in FIG. 8, showing the trajectories X, Y, and Z of the inner peripheral surface 50a, and the stirring plate 46 rotates eccentrically therewith.

Therefore, the reaction tube T whose upper portion is supported by the reaction tube holder 16 of the reaction tube turret 14 and whose lower portion is loosely inserted into the play insertion hole 48 of the stirring plate 46 is shown in FIG.
(B) As shown in (c), the upper part is supported and the lower part is rotated obliquely, that is, a so-called miso-suri motion is performed to stir the reaction solution and the like inside.

With the above configuration, in the standby state,
The rotation motor 40 and the stirring motor 70 rotate in synchronization. The rotation of the rotary motor 40 causes the eccentric plate 54 to rotate integrally with the reaction tube turret 14, the stirring plate 46, the stirring base 50, and the stirring roller 62 via the rotating shaft 36 and the connecting shaft 37. The rotation of the stirring motor 70 rotates the stirring pin 78 via the stirring shaft 64 and the stirring boss 56. At this time, since the eccentric plate 54 and the stirring pin 78 rotate synchronously,
The stirring pin 78 located at the base end portion 80a of the eccentric hole 80 of the eccentric plate 54 keeps rotating without being moved toward the tip end portion while being positioned at the base end portion 80a (FIG. 6A). In this state, the reaction tube holder 1 of the reaction tube turret 14 is
6 and the play insertion hole 48 of the stirring plate 46 are in a straight state with each other. Therefore, the reaction tube T inserted and held in the reaction tube holder 16 of the reaction tube turret 14 and the play insertion hole 48 of the stirring plate 46 is upright. Maintain the state [Fig.
(B)].

At the time of stirring the reaction tube T, the reaction tube turret 14 stands still, and the stirring boss 56 and the stirring pin 78 are rotated by the rotational driving force from the stirring motor 70. The stirring pin 78 is connected to the base end 8 of the eccentric hole 80 of the eccentric plate 54.
Then, the eccentric plate 54 is moved from the position 0a to the tip portion 80b, and the position of the eccentric plate 54 is restricted to the eccentric position by the stirring pin 78 (FIG. 7A). In this state, the stirring motor 70
8, the eccentric rotational force of the eccentric plate 54 is transmitted to the stirring base 50 and the stirring plate 46 via the stirring roller 62 as described above. As described above, the agitating plate 46 also performs eccentric movement, and as a result, the lower part of the reaction tube T whose upper end is held by the reaction tube holder 16 of the reaction tube turret 14 performs so-called miso-suri motion. And the reaction solution in the reaction tube T is uniformly stirred [FIGS. 7 (b) and 7 (c)].

[0037]

As described above, according to the present invention, during standby, the container is securely placed in an upright state to facilitate access to the bottom surface inside the container, and the stirring state is set to an evenly inclined system so that the liquid in each reaction container is inclined. This achieves the effect that uniform stirring can be achieved.

[Brief description of the drawings]

FIG. 1 is a top view showing an example of an automatic analyzer.

FIG. 2 is a side view of FIG.

FIG. 3 is a top view showing one embodiment of the reaction tube stirring device of the present invention in which a part of the reaction tube turret is cut away.

FIG. 4 is a longitudinal sectional view of FIG.

FIG. 5 is a perspective view showing a stirring base and an eccentric plate.

FIGS. 6A and 6B are explanatory diagrams showing the relationship between the eccentric plate and the reaction tube during standby, wherein FIG. 6A shows a state where the eccentric plate is not eccentric, and FIG. 6B shows a state where the reaction tube is upright.

FIG. 7 is an explanatory diagram showing a relationship between an eccentric plate and a reaction tube at the time of stirring, wherein (a) shows a state in which the eccentric plate is eccentric;
(B) and (c) show a state where the reaction tube is performing uniform stirring.

FIG. 8 is an explanatory diagram showing a movement trajectory of the inner peripheral surface of the stirring base.

[Explanation of symbols]

12 automatic analyzer, 14 reaction tube turret, 16
Reaction tube holder, 18 reaction tube holding unit, 20 reaction tube rack, 21 receiving unit, 22 reaction tube transfer means, 25 reagent table, 26 particle supply means, 26a particle nozzle, 28 reagent dispensing means, 28a reagent nozzle, 30 Washing means, 32 reagent dispensing means for measurement,
34 measuring means, 36 rotation axis, 36a upper plate, 37 connecting shaft, 37a, 51 play hole, 38
Pulley, 40 rotation motor, 42 drive shaft, 44 motor pulley, 45 timing belt, 46 stir plate, 48 play insertion hole, 50 stir base, 52 anti-vibration rubber, 53 mounting hole, 54 eccentric plate, 55 center hole, 56 stir Boss, 58 Pressed plate, 60 Screw, 62
Stirring roller, 64 stirring shaft, 66 hollow part, 6
8 Stirring pulley, 70 Stirring motor, 72 drive shaft,
74 motor pulley, 76 timing belt, 78
Stirring pin, 80 arc-shaped eccentric hole, 80a base end, 8
0b tip, 86 reagent table mechanism, 87 reagent table, 87a mounting hole, 88 reagent holder, 90
Particle bottle, 92 Stirred reagent bottle, T reaction tube

──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Yusaburo Namba, Koshiro, 672-250, Koshiro, Tsukuba, Ibaraki Prefecture (72) Inventor, Masaharu Nakazawa 1603-2, Kinoshita, Inzai City, Chiba Prefecture , A) (58) Field surveyed (Int. Cl. ⁷ , DB name) G01N 35/02 G01N 33/543 515 G01N 33/543 531 G01N 1/36

Claims (1)

(57) [Claims] 1. A rotatable reaction tube turret which locks an upper portion of a reaction tube and swingably supports a lower portion thereof, and an insertion hole located below the reaction tube turret and inserted through a lower portion of the reaction tube. A stir plate that is coaxially rotated with the reaction tube turret and is attached to be swingable sideways;
An annular stirring base attached to the lower surface of the stirring plate, an eccentric plate provided with a stirring roller circumferentially in contact with the inner peripheral surface of the stirring base at the periphery of the upper surface, and having an arc-shaped eccentric hole; A rotatable stirring boss having a stirring pin inserted into the hole protruding from a peripheral portion of the upper surface. When the stirring boss is rotated, the stirring pin is located at an eccentric position of the eccentric hole and the eccentricity is increased. The plate is rotated eccentrically, whereby the agitating base is eccentrically rotated via the agitating roller, and the agitating plate is eccentrically rotated, thereby rotating the lower part of the reaction tube, and rotating the solution in the reaction tube. A reaction tube stirrer, characterized in that the reaction tube is stirred.