JP3419142B2 - Enzyme immunoassay analyzer - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a reagent / sample tray, and more particularly to a reagent / sample tray used in an enzyme immunoassay measuring apparatus.

[0002]

2. Description of the Related Art Conventionally, regarding enzyme immunoreactions in clinical tests, reagent makers have been developing various techniques and various reagents used therefor as a technique for accurately grasping the immune reaction. There is.

In the measurement of this enzyme immunoreaction, conventionally, as a pre-process, a sample and a reagent are dispensed, vibration and temperature control for accelerating the reaction, and a next reagent dispensing process are performed. For this purpose, the washing (the reaction portion of the reagent with respect to the sample remains on the wall surface even after washing) and the like are repeatedly performed by changing the reagent variously.

[0004]

In the above-mentioned conventional example, the dispensing of the specimen and the reagent, the vibration and temperature control for promoting the reaction, and the washing for entering the next dispensing step of the reagent, etc. Each of these was done by different equipment by different workers. That is, the dispensing of the sample and the reagent was performed by the dispenser, and the vibration, temperature adjustment, and cleaning were performed by the shaker, the temperature adjuster, and the cleaning device, respectively.

Among the above-mentioned operations, particularly with respect to the dispensing operation, other operations are omitted due to the complexity of the operation. For example, this dispensing work may be accompanied by a diluting work of a reagent, a sample, etc. In such a case, a dispensing work of a reagent or the like to be diluted and a liquid for diluting the same is added, and further. However, in order to maintain the accuracy of these operations, it is necessary to dispense an accurate amount of liquid, and due to the recent increasing complexity of tests, a wide variety of reagents and specimens have been prepared. In addition, it is necessary to replace part of the equipment used for each reagent and sample from the viewpoint of preventing confusion of reagents and samples and hygiene. Due to such factors, dispensing work becomes complicated and complicated. Since the amount of work and the work time have doubled and increased, conventional dispensers are far from solving these difficulties, and when moving to the next work after dispensing is completed. Also, the process leading to the reaction measurement due to human intervention Latency of each sample is increased, also sometimes mistaken like arrangement position of the sample is also prone, Therefore, measurement of enzymatic immune response takes time,
At the same time, it was always accompanied by the inconvenience of requiring a lot of labor for workers.

[0006]

It is an object of the present invention to improve the disadvantages of the conventional example, and particularly in the pre-step of measuring the enzyme immunoreaction, the diluting work or the number of reagents, which makes the dispensing work complicated, Provided is an enzyme-immunoreaction measuring device which can effectively cope with an increase in the number of samples and can be performed continuously and in a short time without the work such as loading and unloading and transferring of samples and the like performed by workers on the way. That is the purpose.

[0007]

According to the present invention as set forth in claim 1, a reagent / sample tray in which the positions where one or more reagents and samples are arranged are specified in advance, and the reagent / sample tray is provided side by side with the reagent / sample tray. And a microplate transfer means for urging a force for transferring a microplate having a plurality of reaction recesses in which a reaction of a sample is performed to an immune reaction measurement site, and a dispensing nozzle for sucking a predetermined amount of a sample or a reagent A reagent / sample dispensing mechanism that has a section and conveys the dispensing nozzle section to the entire area of the reagent / sample tray and each reaction recess of the microplate, and the reagent / sample tray is arranged with reagents and samples. In the area excluding the position, at least two or more disposable chip stocker areas for mounting a disposable chip stocker on which a plurality of disposable chips are detachably mounted on the tip of the dispensing mechanism are mounted. Has, in the respective disposable chips stocker region adopts a dilution plate having a plurality of recesses are formed freely sized detachable to the disposable chips stocker region, a structure that is equipped with a disposable chips stocker.

In the case of the present invention according to claim 2,
The dilution plate has a microplate and a mounting portion on which the microplate is detachably mounted,
An insertion member formed to have a detachable size in a region on which the disposable chip stocker is placed, and the other parts have the same structure as that of the present invention.

The present invention is intended to achieve the above-mentioned object by each of the above-mentioned configurations.

[0010]

In the configuration of the present invention described in claim 1 above, first, the reagent and the sample are arranged at a specific position on the reagent / sample tray, and the region except the specific position of the reagent and the sample is first arranged. In one or more of the provided disposable chip stocker areas, one dilution plate having a plurality of recesses is first arranged, and in each of the remaining disposable chip stocker areas, a plurality of disposable chip stockers are stored. Are stored one by one.

On the other hand, on the other hand, on the microplate transfer means, a microplate having a plurality of reaction recesses in which a reagent and a sample are reacted is placed.

The flat plate surface of the reagent / sample tray is
Since it is located within the movement range of the sample dispensing mechanism,
Various reagents and samples required for measurement are sucked by the dispensing nozzle portion of the reagent / sample dispensing mechanism and moved to each reaction recess of the microplate for dispensing. At this time, the dispensing nozzle portion of the reagent / sample dispensing mechanism replaces the tip of each of the reagent and the sample with a plurality of disposable chips stored in the disposable chip stocker for the dispensing work.

The microplate transfer means guides the microplate on which the reagent and the sample have been dispensed to the immunoreaction measurement site, and the immunoreaction measurement is performed for each reaction recess of the microplate.

When it is necessary to dilute the reagent or sample, the dispensing nozzle section aspirates the reagent or sample to be diluted, in the same manner as described above, and makes a plurality of recesses in the dilution plate. Dispensing is performed in the required number of recesses in the container.

Furthermore, when the number of specimens or reagents used in the immunoreaction measurement is large and the number of disposable chips is expected to be insufficient, the dilution plate in the disposable chip stocker area is removed and replaced. A disposable chip stocker is placed on. That is, the disposable chip stockers are all placed in the plurality of disposable chip stocker areas.

In the case of the configuration of the present invention according to claim 2,
In one of the plurality of disposable chip stocker areas, instead of the plate for dilution, an insertion member is placed in a state in which a microplate having a plurality of reaction recesses is placed on the placement part, and the microplate is The dilution plate functions similarly to the above-described dilution plate, and the other configurations perform the same operation as in the case of claim 1.

[0017]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A first embodiment of the present invention will be described below with reference to FIGS.
It will be described based on. 1 and 2 show the configuration of the whole enzyme immunoassay measuring apparatus.

The enzyme immunoassay measuring apparatus shown in FIGS. 1 and 2 immunoreacts with a reagent / sample tray 1 and a microplate 2 provided in parallel with the reagent / sample tray 1 and having a plurality of reaction recesses 2A. The microplate guide mechanism 3 that guides the measurement point 100 and the belt conveyor mechanism 4 that is installed in the microplate guide mechanism 3 and applies a predetermined traveling force to the microplate 2 are provided. In this belt conveyor mechanism 4, a stepped belt is used.
The belt conveyor mechanism 4 and the microplate guide mechanism 3 described above constitute a microplate transfer means.

Then, along the microplate guide mechanism 3, an immune reaction measurement site 100 and a vibrating mechanism 5 for vibrating the microplate 2 into which the reagent and the sample are injected,
A microplate cleaning mechanism 6 for individually cleaning each reaction recess 2A of the microplate 2 after completion of the immune reaction is provided.

Further, a reagent / sample dispensing mechanism 8 as a dispensing mechanism having a dispensing nozzle portion 7 (described in detail later) for sucking a predetermined amount of the sample or reagent is located above the microplate guiding mechanism 3. The microplate guide mechanism 3 and the reagent / sample tray 1 are arranged so as to straddle them. The reagent / specimen dispensing mechanism 8 has a function of transporting and injecting the specimen or the reagent sucked by the dispensing nozzle portion 7 to the predetermined concave portion 2A of the one microplate 2 described above.

At one end of the microplate guide mechanism 3 (upper side in FIG. 1), there is a thermostat mechanism 9 for maintaining the microplate 2 in which the reagent and the sample are injected at a predetermined reaction temperature for a certain time. It is arranged. Reference numeral 10 indicates a main body case.

Each part of the above-mentioned enzyme immunoassay measuring device will be described in detail below.

First, as shown in FIG. 3, the reagent / sample tray 1 includes a reagent stocker area 13 for detachably storing reagent stockers 11 and 12 equipped with a plurality of reagents corresponding to an inspection method, and a plurality of samples. It has a flat plate surface 1A provided with a sample stocker area 15 for storing a sample stocker 14 having a plurality of sample storage sections 14A for individually storing.

The reagent stocker area 13 is provided on the left side portion in FIG. 3 on the flat plate surface 1A, and is set to have an area for accommodating two reagent stockers. Regarding the area of the reagent stocker region 13, if the flat plate surface 1A is larger, the area may be further expanded. As a result, a large number of reagent stockers can be stored, and thus the enzyme immunoassay measuring device can support more tests. In addition, the reagent stocker area 13
If the area is reduced to one reagent stocker, the enzyme immunoassay measuring apparatus can be downsized.

In the lower right portion of the flat plate surface 1A in FIG.
Sample stocker area 15 adjacent to reagent stocker area 13
Is provided. The sample stocker area 15 is set to have substantially the same size as the sample stocker 14.

The sample stocker area 15 shown in FIG.
Two disposable chip stocker areas 18 are provided adjacent to each other above. The disposable chip stocker 16 is stored in one of the disposable chip stocker areas 18, and the dilution plate 17 is stored in the other.
The disposable chip stocker area 18 is formed with a concave recess according to the sizes of the bottom surfaces of the disposable chip stocker 16 and the dilution plate 17, and the disposable chip stocker area 18 is affected by vibrations and the like due to the operation of each part of the enzyme immunoassay measuring apparatus. 16 and the dilution plate 17 are housed with their bottom surfaces fitted so that they do not shift.

In the present embodiment, the disposable tip stocker 16 accommodates a liquid suction auxiliary pipe 7D (disposable tip) which is detachably attached to the tip of a dispensing nozzle portion 7 of a reagent / sample dispensing mechanism 8 to be described later. It is a container. On the upper surface of the disposable chip stocker 16, there are a total of 96 storage holes for storing the liquid suction auxiliary pipe 7D, 8 in the horizontal direction and 12 in the vertical direction.
It is provided in some places. Also, disposable chip stocker 1
In the state where the liquid suction auxiliary pipe 7D is accommodated, the upper end portion of the liquid suction auxiliary pipe 7D is a reagent stocker 1 to be described later.
The height of the disposable chip stocker 16 is set so as to be almost the same as the upper end portion of the reagent bottles stored in the reagent bottles 1 and 12, whereby the reagent bottles and the sample bottle dispensing mechanism 8 are operated at the time of operation. It has a function of preventing collision with the liquid suction auxiliary pipe 7D.

Here, the liquid suction auxiliary pipe 7D is replaced every time a reagent or a sample is sucked, in order to prevent the reagent or sample attached to the tip from mixing with other reagents or samples. Therefore, it is necessary to supply the liquid suction auxiliary pipe 7D in accordance with the number of reagents and samples, and in consideration of hygiene problems, when the liquid suction auxiliary pipe 7D is disposable, the liquid consumption auxiliary pipe 7D is consumed. Since the amount is enormous, it is desirable that a large number of disposable chip stockers 16 be stored on the reagent / sample tray 1. Therefore, in this embodiment, the disposable chip stocker areas 18 are provided at two locations,
The reagent / sample tray 1 may be provided at a larger number of places within the allowable range of the flat plate surface 1A.

The diluting plate 17 has the same size as the above-mentioned disposable chip stocker 16 and the bottom surface thereof, and the top surface thereof has a width of 8 and a length of 12 in total. 96 recesses are provided. These recesses are for diluting the sample or reagent by dispensing a sample or reagent to be diluted and a predetermined amount of dilution liquid into the recess by the reagent / sample dispensing mechanism 8. It is a thing. The dilution plate 17 may be set to have substantially the same height as the upper ends of the reagent bottles stored in the reagent stockers 11 and 12 for the same purpose as that of the disposable chip stocker 16 described above. In this case, the reagent / sample dispensing mechanism 8
At the same time, the vertical movement of the dispensing nozzle unit 7 is omitted or reduced, so that the dilution operation can be performed in a short time.

Since different reagent stockers are required for the reagent stockers 11 and 12 depending on the inspection method, the identification means 1 for setting the identification information corresponding to the inspection method.
It is equipped with 1A and 12A. This identification means 11A,
In the present embodiment, 12A is four circular ultrasonic reflecting surfaces 11A ₁ , 11A ₂ , 11A having different heights set in a line at the left end of each reagent stocker 11, 12 as shown in FIG.
₃ , 11A ₄ ; 12A ₁ , 12A ₂ , 12A ₃ , 12A
₄ (see FIG. 3). This difference in height is sequentially detected by the ultrasonic sensor 10A provided in the reagent / specimen dispensing mechanism 8 and is identified by the control means (not shown), whereby each constituent part described later has the predetermined inspection method. It is designed to work along.

FIG. 5 shows a perspective view of one reagent stocker 11. Each reagent stocker 11, 12 is equipped with a plurality of reagents for achieving the inspection method specified for each reagent stocker 11, 12. That is, in this embodiment, six reagent storage portions 11e and 12e having different sizes are provided at the center of each reagent stocker 11 and 12, and the reagent storage portions 11e and 12e are provided with a reagent bottle 11E as a reagent storage container. , 12E (see FIG. 4) are stored. In addition, the right side of the reagent stockers 11 and 12 in FIG.
Reagent storage sections 11f and 12f of the same size are provided, and reagent bottles 11F and 12f are provided in the reagent storage sections 11f and 12f.
12F is stored. Here, the reagent stockers 11, 12
The above is not limited to the reagent storage units 11e and 12e described above, and the size and the number thereof may be changed according to the inspection.

Here, the reagent bottles 11E, 11F, 12E and 12F housed in the reagent stockers 11 and 12, respectively.
Are arranged in a horizontal plane where the positions of their openings are substantially the same. Thereby, each reagent bottle 11E to 11F, 1
It is possible to easily detect the remaining amount of the reagent in 2E to 12F. Further, even if the positions of the reagent stockers 11 and 12 are changed by this, the reagent bottles 11E to 11E
Since F and 12E to 12F are always the same height and there is no particular protruding height, the above-mentioned dispensing nozzle portion 7
Is effectively prevented in advance from colliding with the reagent bottles 11E to 11F and 12E to 12F.

The detection of the remaining amount of this reagent is carried out by actually detecting the ultrasonic sensor 1 attached to the reagent / sample dispensing mechanism 8 mentioned above.
In the case where there is a shortage of reagents (similarly in the case of a shortage of the amount of sample), the fact is externally displayed by a display means (not shown). Further, since the remaining amount of this reagent is captured as liquid level data, the above-mentioned control means, based on such information, determines the descending amount of the dispensing nozzle unit 7 provided in the reagent / sample dispensing mechanism 8. It can be adjusted.

Further, in the lower area of FIG. 3 above each reagent stocker 11, 12, the respective reagent stocker 1 is
Plural kinds of liquid suction auxiliary pipes 7E, 7F having different thicknesses for the dispensing nozzle portion 7 described above are arranged corresponding to the sizes of the openings of the reagent bottles accommodated in 1 and 12, respectively. ing. In FIG. 3, six relatively thick liquid suction auxiliary pipes 7E are prepared for each of the reagent bottles 11E and 12E described above, and a relatively thin liquid suction auxiliary pipe (dispochip) 7F is provided for each of the reagent bottles described above. 10 for each reagent stocker 11 and 12 for 11F and 12F and for sample inhalation
The book is being prepared. As a result, the reagent and the sample can be smoothly and efficiently dispensed into the above-described microplate 2 according to the amount of the reagent used.

A sample stocker 14 disposed on the reagent / sample tray 1 adjacent to the above-mentioned reagent stockers 11 and 12.
Is equipped with a total of 100 sample storage units 14A, each of which stores a plurality of samples individually in the horizontal direction 10 and the vertical direction 10. The sample storage unit 14A is equipped with the reagent stocker 14 so that the upper end of the sample storage unit 14A is at substantially the same height as the upper ends of the reagent bottles stored in the reagent stockers 11 and 12. It has a function of preventing collision with the reagent bottle and the liquid suction auxiliary pipe 7D when the mechanism 8 is operated.

Next, the reagent / sample tray transfer mechanism 21 will be described.

As shown in FIGS. 1 and 6 to 8, the reagent / sample tray 1 supports the reagent / sample tray 1 and the reagent / sample dispensing mechanism 8 described above. A reagent / sample tray transfer mechanism 21 for transferring in a direction substantially orthogonal to the moving direction of the dispensing nozzle unit 7 is provided.

Here, the reagent / sample tray 1 in FIG.
Is 90 degrees counterclockwise as compared to that of FIG.
° It is rotated. 6A shows a state in which the reagent / sample tray 1 is projected from the main body case 10, and FIG. 6B shows an example in a state in which the reagent / sample tray 1 is substantially housed in the main body case 10.

Further, FIG. 7 shows a case where the reagent / sample tray 1 is arranged in a deep portion inside the main body case 10, and FIG. 8 shows a right side view of the above-mentioned FIG. 7.

The reagent / sample tray transfer mechanism 21
It is provided on the lower surface side of the sample tray 1 so that each reagent and each reagent on the sample tray 1 and the sample can be smoothly taken in and out. This reagent / sample tray transfer mechanism 21
In FIG. 1, it has a Y-axis direction transfer function for transferring the reagent / sample tray 1 in the vertical direction of FIG.
The sample dispensing mechanism 8 has a function of transferring the dispensing nozzle portion 7 in the left-right direction in FIG. 1, that is, a function of transferring in the X-axis direction. As a result, in the entire area of the reagent / sample tray 1,
Each reagent or specimen can be freely and quickly dispensed from any position to the one microplate 2 described above.

The reagent / sample tray transfer mechanism 21 supports the above-described reagent / sample tray 1 and guide frame body 21A for guiding the reagent / sample tray 1 to move in the vertical direction in FIG. A ball screw mechanism portion 21B arranged along the guide frame 21A for urging a moving force to the reagent / sample tray 1 and a tray drive motor 21C for rotationally driving the screw shaft of the ball screw mechanism portion 21B are provided. There is. Reference numeral 21D indicates a belt mechanism portion that transmits the rotational force of the tray drive motor 21C to the ball screw mechanism portion 21B.

Further, reference numeral 21a indicates a linear guide mounted on the reagent / sample tray 1 corresponding to the guide frame 21A, and reference numeral 21Ba indicates a ball screw mechanism portion 21B.
7 shows a driven member that is driven to be transferred by the screw shaft of FIG. The driven member 21Ba is attached to the back surface of the reagent / sample tray 1, so that the reagent / sample tray 1 is moved to the Y
As it is driven to move in the axial direction, the dispensing operation of each reagent or sample to the microplate 2 becomes possible as described above, and at the same time, the reagent stockers 11 and 12 and the sample stocker 14 described above are shown in FIG. 6 (A). It can be projected from the main body case 10. Therefore, the loading and unloading work of each reagent stocker 11 and 12 and the sample stocker 14
It can be done smoothly and quickly. The reagent / sample tray may be driven by a belt.

Next, the reagent / sample dispensing mechanism 8 will be described.

This is shown in FIGS. 9 to 10. This reagent
The sample dispensing mechanism 8 includes a nozzle portion transfer support 41 (FIG. 1) mounted so as to straddle the microplate guide mechanism 3 and the reagent / sample tray 1 shown in FIGS. 9 to 10, and the nozzle portion. Dispensing nozzle part 7 supported by the transfer support member 41 and capable of transferring along the nozzle part transfer support member 41, and a nozzle part X-axis transfer means for urging a traveling force to the dispensing nozzle part 7. And 43.

The dispensing nozzle section 7 includes two dispensing nozzles 7A and 7B which are vertically movable, and the dispensing nozzle 7
The vertical movement of A and 7B is guided, and the dispensing nozzle 7
Ball screw mechanisms 44A and 44B for individually biasing the vertical movements of A and 7B, and the ball screw mechanisms 44.
Dispensing nozzle lowering drive motors 45A and 45B for individually driving and controlling A and 44B are provided.

Reference numerals 45a and 45b denote couplings made of elastic members for transmitting the rotational force of the dispensing nozzle section lowering drive motors 45A and 45B to the above-mentioned ball screw mechanisms 44A and 44B. Further, reference numeral 46 indicates a nozzle portion frame. The dispensing nozzles 7A and 7B shown in FIGS. 9 and 10 are
One dispensing nozzle 7A is equipped with a relatively thick liquid suction auxiliary pipe 7E, and the other dispensing nozzle 7B is equipped with a relatively thin liquid suction auxiliary pipe 7F.

As a result, in this embodiment, as described above, the size of the reagent bottles 11E, 11F, 12E, 12F, the amount of the reagent to be used, etc. are dealt with.
It is adapted to meet various different conditions.

Further, the nozzle part X-axis transfer means 43 includes a ball screw mechanism 43A for transferring the nozzle part frame 46 equipped with the dispensing nozzle part 7 along the nozzle part transfer support 41,
Nozzle portion X for urging the operation of this ball screw mechanism 43A
And a shaft transfer motor 43B. Reference numeral 43C indicates a belt mechanism portion that transmits the rotational force of the nozzle portion X-axis transfer motor 43B to the ball screw mechanism 43A.

Therefore, the reagent / sample dispensing mechanism 8 and the reagent / sample tray transfer mechanism 16 described above cooperate with each other so that the plurality of reagents and samples on the reagent / sample tray 1 are connected to the microplate 2 described above. It is possible to perform reagent dispensing and sample dispensing freely, rapidly and with high accuracy in each reaction recess 2A.

As described above, the reagent / sample dispensing mechanism 8
Is a nozzle portion transfer support 4 mounted so as to straddle the microplate guide mechanism 3 and the reagent / sample tray 1.
1, the transfer of reagents and samples between the reagent / sample tray 1 and the microplate guide mechanism 3 and the dispensing are performed. That is, the reagent / sample dispensing mechanism 8 dispenses the reagent and the sample from the reagent / sample tray 1 side to the microplate 2 placed on the microplate guiding mechanism 3.

Here, an example of a plan view of the microplate 2 is shown in FIG. 11 (A), and a sectional view in the front direction is shown in FIG. 11 (B).
Shown in. The microplate 2 is made of transparent plastic having reaction recesses 2A composed of 96 in total, 12 in the horizontal direction and 8 in the vertical direction. Reagents and specimens are individually injected into the reaction recesses 2A. To be done. Here, the microplate 2 is set at 90 ° from the state shown in FIG.
It is mounted on the microplate guide mechanism 3 shown in FIG. 1 in a rotated state.

The microplate guide mechanism 3 has a microplate holder (not shown) which holds the microplate 2 with the reaction recess 2A exposed on the upper surface side. Belt conveyor mechanism 4 for transferring the microplate 2 to each part via the
have. The belt conveyor mechanism 4 applies a moving force in the vertical direction in FIG. 1 to the microplate 2, and a vibrating mechanism 5, a microplate cleaning mechanism 6, and a constant temperature disposed along the microplate guide mechanism 3. A control unit (not shown) controls the microplate 2 to be transferred to the tank mechanism 9 and the immune reaction measurement site 100 in a predetermined order and at a predetermined position.

The vibrating mechanism 5 accelerates the reaction of the sample with respect to the reagent injected into the respective reaction recesses 2A in the microplate 2, and the microplate 2 is placed on the horizontal plane via the above-mentioned microplate holder. It is driven to swing inside.

The microplate washing mechanism 6 is operated when the immune reaction of the sample and the reagent injected into the respective reaction recesses 2A of the microplate 2 is completed, and individually cleans each reaction recess 2A. Then, each reaction recess 2A
Each set is provided with two sets of a cleaning water discharge nozzle and a cleaning water suction nozzle for one horizontal row, and cleaning is performed for each row.

As shown in FIG. 1, the constant temperature bath mechanism 9 is arranged at the upper end of the microplate guide mechanism 3, and a plate insertion opening is provided facing the microplate guide mechanism 3. The microplate 2 is conveyed from the plate insertion port to the internal thermostatic bath, and is maintained at a predetermined temperature inside the thermostatic bath, whereby the reaction of the sample and the reagent in the reaction recess 2A of the microplate 2 is promoted.

At the immune reaction measuring point 100, the vibrating section 5,
The reaction in the reaction recess 2A is measured with respect to the microplate 2 conveyed through the constant temperature bath mechanism 9.

The operation of the enzyme immunoassay measuring apparatus to which the first embodiment is applied will be described below.

First, a predetermined reagent is applied in advance to each reaction recess 2 A of the microplate 2 and placed on the belt conveyor mechanism 4. Next, the belt conveyor mechanism 4 is operated to convey the microplate 2 to a position where the reagent / sample dispensing mechanism 8 can dispense the reagent and the sample.

At this position, the reagent / sample dispensing mechanism 8 is operated to dispense the sample in the sample stocker 14 into each reaction recess 2A of the microplate 2. In the meantime, the reagent / sample dispensing mechanism 8 transfers the dispensing nozzle part 7 to the sample stocker 14 part and controls the descending to suck a predetermined sample, and then ascends again to be transferred to the microplate 2 side. Further, the microplate 2 side is controlled to be lowered to complete the sample dispensing operation. Here, the disposable chip stocker 16 is housed in one of the disposable chip stocker areas 18 provided on the reagent / sample tray 1, and the tip of the dispensing nozzle 7 to be replaced for each sample and each reagent. The liquid suction auxiliary pipe 7D as a part is supplied by this disposable chip stocker 16.

When the dispensing operation is completed, the belt conveyor mechanism 4 transfers the microplate 2 to the vibrating mechanism 5. Then, the vibrating mechanism 5 is operated to vibrate the microplate 2 for a predetermined time to promote the reaction, and thereafter the microplate 2 is carried into the constant temperature bath mechanism 9 to adjust the temperature to further promote the reaction. Let When the reaction accelerating process in the constant temperature bath mechanism 9 is completed, the belt conveyor mechanism 4 is operated again to convey the microplate 2 to the position of the microplate cleaning mechanism 6, where the inside of each reaction recess 2A is cleaned. Be seen.

When the washing by the microplate washing mechanism 6 is completed, the enzyme-labeled antibody reagent is selected and dispensed from the above-mentioned reagent stocker 11 (or 12) into each reaction recess 2A of the microplate 2. . After dispensing the enzyme-labeled antibody reagent, the microplate 2 is again carried into the thermostat bath mechanism 9 where the temperature is adjusted to promote the reaction. After completion of the reaction in the constant temperature bath mechanism 9, each reaction recess 2A of the microplate 2 is again washed by the microplate washing mechanism 6.

When the steps of dispensing, reacting, and washing the enzyme-labeled antibody reagent are completed, next, the chromogenic reagent is selected from within the reagent stocker 11 (or 12), and the reaction recesses of the microplate 2 are selected. Dispensed in 2A. After this dispensing,
The microplate 2 is again carried into the thermostat mechanism 9 and the temperature is adjusted to promote the reaction.

When the steps of dispensing and reacting the color-developing reagent are completed, the stop solution reagent is added to the reagent stocker 11 next.
(Or 12) and is dispensed into each reaction recess 2A of the microplate 2. After the stop solution reagent is dispensed, the microplate 2 is placed at the immunoreaction measurement site 10
It is conveyed to 0, the above-mentioned immune reaction measurement is carried out, a predetermined analysis is performed based on the measurement result at this immune reaction measurement point 100, and the result is determined.

When it is necessary to dilute the reagent or sample in the pre-operation and measurement of the enzyme immunoassay, there are a plurality of dilution plates 17 arranged in the disposable chip stocker area 18 described above. In the recess,
Using the required number, the reagent / sample dispensing mechanism 8 and the reagent / sample tray transfer mechanism 21 cooperate to make the reagent stocker 11
(Or 12) or a reagent or sample to be diluted in the sample stocker 14 is dispensed. Further, the diluting liquid is dispensed by the reagent / specimen dispensing mechanism 8 into the concave portion of the dilution plate 17 into which the reagent or the specimen has been dispensed.

In this enzyme immunoassay measuring apparatus, the minimum guaranteed sampling amount of the dispensing nozzle unit 7 is 10 [μl], and the concave portion of the dilution plate 17 is about 300 [μl]. It is possible to When the dilution is performed at a higher magnification, the diluted reagent or sample is further diluted by using the unused concave portion of the dilution plate 17, or on the microplate guide mechanism 3. It is also possible to carry out the dilution in each of the reaction recesses 2A of the microplate 2 in FIG.

The diluting liquid used for the above operation is preferably prepared in advance in one of the reagent bottles of the reagent stocker 11. Further, the reagent / sample dispensing mechanism 8 is provided with a supply means to which the liquid for dilution is supplied from the outside, so that the reagent / sample dispensing mechanism 8 dispenses to the dilution plate 17 according to a certain control. You can

Furthermore, if the total number of reagents or specimens used for measurement is large and it is expected that a large amount of the liquid suction auxiliary pipe 7D will be used, the dilution plate 17 will be used. The disposable tip stocker 16 is removed from the disposable tip stocker area 18, and instead, the disposable tip stocker 16 accommodating a plurality of liquid suction auxiliary tubes 7D is placed. As a result, the total number of the liquid suction auxiliary tubes is doubled, and it is possible to cope with a large number of reagents or specimens.

As described above, according to the enzyme immunoassay measuring apparatus of the first embodiment, it is more difficult to measure the enzyme immunoassay than in the past because the steps of dispensing, reaction and washing are often repeated. The automation that was previously possible is now possible,
Therefore, there is an advantage that the enzyme immunoassay can be measured quickly and with high accuracy, and that various devices can be inspected by one device by different manufacturers.

Further, as described above, in the first embodiment, the dilution tray 17 is stored in one of the plurality of disposable chip stocker areas provided on the flat plate surface of the reagent / sample tray 1, so that the dilution tray 17 can be separated from the conventional one. The dilution work, which has been a factor that complicates the injection work, is automated, and when performing the dilution, the reagent / sample dispensing mechanism 8 dilutes within a narrow range of the flat plate surface 1A of the reagent / sample tray 1. Therefore, since the moving amount of the dispensing nozzle portion 7 by the reagent / sample dispensing mechanism 8 is short, the dilution operation can be performed quickly.

In the first embodiment, the dilution operation is
By performing the dilution on the plate 17 for dilution and further repeating the dilution on the microplate 2, it becomes possible to perform high-magnification dilution. For example, in the case of the first embodiment, if the reaction recess 2A of the microplate 2 has substantially the same volume as the recess of the dilution plate 17, it is possible to dilute 900 times with 30 ^2. .

Further, in this first embodiment, the disposable chip stocker 16 is placed instead of the dilution plate 17 to double the number of the liquid suction auxiliary tubes 7D of the enzyme immunoassay measuring device. Therefore, even if there are a large number of reagents or specimens, it becomes possible to carry out the enzyme immunoassay measurement without shortage of the liquid suction auxiliary tube.

The second embodiment of the present invention will be described with reference to FIG.

In this second embodiment, the reagent / sample tray 1
Two disposable chip stocker areas 18 provided above
The disposable chip stocker 16 is housed in one side, and the interposition member 19 on which the microplate 2 is removably placed is provided in the other side, and other configurations are the same as those in the first embodiment. .

The bottom surface of the frame 19 is detachably formed in the concave recess of the disposable chip stocker area 18 provided on the flat plate surface 1A of the reagent / sample tray 1, and the top surface of the frame 19 is also removable. Has a concave mounting portion on which the microplate 2 is detachably mounted. The microplate 2 used here has the same size and shape as the microplate 2 used by being mounted on the microplate guide mechanism 3 in the first embodiment. As a result, it becomes possible to mount the microplate 2 that does not fit in the disposable chip stocker area 18 on the reagent / sample tray in a fitted state.

The operation of the second embodiment during dilution will be described.

By the cooperation of the reagent / sample dispensing mechanism 8 and the reagent / sample tray transfer mechanism 21, the reagent for diluting the reagent stocker 11 (or 12) is stored in the plurality of reaction recesses 2 A of the microplate 2. ， Distribute using the required number. Further, the reagent / sample dispensing mechanism 8 dispenses a diluting liquid into the reaction recess 2A of the microplate 2 into which the reagent has been dispensed.

In the enzyme immunoassay measuring apparatus of the present invention, the minimum guaranteed collection amount of the dispensing nozzle section 7 is 10 [μl], while the reaction recess 2A of the microplate 2 is the dilution plate 17
Since it is approximately equal to the concave portion of about 300 [μl], it is possible to perform dilution up to about 30 times. Further, when the dilution is performed at a higher magnification, the diluted reagent is further diluted by using the unused reaction concave portion 2A of the microplate 2 or is on the microplate guide mechanism 3. It is also possible to perform dilution in each reaction recess 2A of the microplate 2.

Further, by removing the microplate 2 and the insertion member 19 from the disposable chip stocker region 18 and mounting the disposable chip stocker 16 instead, the number of liquid suction auxiliary tubes of the enzyme immunoassay measuring apparatus is retained. Is doubled, and it becomes possible to handle a large number of reagents or specimens.

In the second embodiment, the reagent / sample tray 1
With the interposition member 19 provided above, not only for the reaction and measurement of the microplate 2 but also for the reagent / sample tray 1
It can be used for dilution above. In this case, even if the size of the microplate 2 is not set to a fixed size, the disposable chip stocker area 18 of the reagent / sample tray 1 is changed by changing the setting of the size of the placement portion of the insertion member 19. It is possible to place it on top.

Here, in the state where the microplate 2 is accommodated in the frame body 19, the height of the upper surface of the microplate 2 is almost the same as the upper end portions of the reagent bottles accommodated in the reagent stockers 11 and 12. This frame 1 so that it becomes the height
A height of 9 may be set. This makes it possible to prevent the reagent / sample dispensing mechanism 8 from colliding with the reagent bottle and the microplate 2 housed in the frame 19. Further, by setting the height at the same level as the reagent bottle, the vertical movement of the dispensing nozzle portion 7 of the reagent / sample dispensing mechanism 8 can be minimized, so that the dilution operation can be performed quickly. Becomes

Furthermore, since the microplate 2 as a dilution container and the microplate 2 as a reaction / measurement container are of the same shape, each reaction recess 2A of one microplate 2 and the other It is possible to clarify the correspondence with each reaction recess 2A that it has, and to simplify the movement operation of the dispensing nozzle unit 7 of the reagent / sample dispensing mechanism 8 when diluting each reaction recess 2A. Becomes

[0082]

According to the present invention as set forth in claim 1, when measuring an enzyme immunoreaction, it is possible to perform automation, which has been regarded as difficult than before because many steps of dispensing, reaction and washing are repeated. Therefore, there is an advantage that the enzyme immunoreaction can be measured quickly and with high accuracy, and various items different for each reagent manufacturer can be tested by one device.

Further, by storing the dilution tray in one of the plurality of disposable chip stocker areas provided on the flat plate surface of the reagent / sample tray, the dilution which has been a factor of complicating the dispensing work as compared with the conventional case. The work is automated, and when diluting, the reagent / sample dispensing mechanism can dilute within a narrow range of the reagent / sample tray.
The movement amount of the dispensing nozzle part by the sample dispensing mechanism is short, and the dilution operation can be performed quickly.

Furthermore, by performing the dilution operation on the plate for dilution and further repeating the dilution on the microplate, it becomes possible to perform high-magnification dilution.

Furthermore, by mounting a disposable chip stocker instead of the dilution plate, it is possible to double the number of disposable chips in the enzyme immunoassay measuring apparatus, and there are a large number of reagents or samples. Even in such a case, it becomes possible to carry out the enzyme immunoassay measurement without causing a shortage of the liquid suction auxiliary tube.

According to the present invention described in claim 2, the same effect as that of the present invention described in claim 1 can be obtained, and the microplate can be reacted by the interposing member provided on the reagent / sample tray. It can be used not only for measurement but also for dilution on the reagent / sample tray. In this case, even if the size of the microplate is not set to a fixed size, by changing the setting of the size of the placement part of the insertion member, it is possible to place it on the disposable chip stocker area of the reagent / sample tray. It becomes possible to do.

Furthermore, since the microplate as the diluting container and the microplate as the reaction / measuring container are of the same shape, one of the microplates for each reaction has a recess for each reaction and the other has a microplate for each reaction. Correspondence with the concave portion is clarified, and it is possible to simplify the movement operation of the dispensing nozzle portion of the reagent / sample dispensing mechanism when diluting each reaction concave portion.

According to the present invention, which is constructed and functions as described above, the diluting work which causes a complicated dispensing work,
Alternatively, it is possible to effectively deal with an increase in the number of reagents and the number of samples, and to provide an unprecedented excellent enzyme immunological reaction measuring device that is versatile.

[Brief description of drawings]

FIG. 1 is a partially omitted plan view showing an enzyme immunoassay measuring apparatus to which a first embodiment of the present invention is applied.

FIG. 2 is a schematic perspective view showing a positional relationship between the respective constituent members disclosed in FIG.

3 is a detailed explanatory view showing the reagent / sample tray portion disclosed in FIG. 1. FIG.

FIG. 4 is a left side view of FIG.

5 is a perspective view showing an example of the reagent stocker disclosed in FIG. 1. FIG.

6 is a diagram showing the relationship between the reagent / sample tray disclosed in FIG. 1 and its drive mechanism (Y-axis direction). FIG. 6 (A) shows the reagent / sample tray portion in FIG. 1 in a counterclockwise direction. FIG. 6 (B) is a plan view showing a state rotated by 90 ° in FIG.
It is explanatory drawing which shows the operation | movement.

FIG. 7 is an explanatory diagram showing the operation of FIG. 6 (A).

FIG. 8 is a right side view of FIG.

FIG. 9 is a partially omitted front view showing the reagent / sample dispensing mechanism disclosed in FIG. 1;

FIG. 10 is a right side view of FIG.

FIG. 11 is a diagram showing a microplate used in the enzyme immunoassay measuring apparatus, FIG. 11 (A) is a plan view of the microplate, and FIG. 11 (B) is a cross-sectional view seen from the front direction of the microplate. is there.

FIG. 12 is a partially omitted explanatory view showing the arrangement of each part of the reagent / sample tray according to the second embodiment of the present invention.

[Explanation of symbols]

1 Reagent / Sample tray 2 micro plates 2A Reaction recess 7 dispensing nozzle 7D, 7E, 7F Liquid suction auxiliary pipe (dispo tip) 8 Reagent / Sample Dispensing Mechanism 16 Disposable Chip Stocker 17 Dilution plate 18 Disposable chip stocker area 19 Insertion member 100 immune reaction measurement points

─────────────────────────────────────────────────── ─── Continuation of the front page (56) Reference JP-A-1-239457 (JP, A) JP-A-60-111160 (JP, A) JP-A-5-99932 (JP, A) JP-A-1- 112162 (JP, A) Registered utility model 3002287 (JP, U) (58) Fields investigated (Int.Cl. ⁷ , DB name) G01N 35/10 G01N 33/543 545 G01N 33/543 571 G01N 35/02

Claims (2)

(57) [Claims] 1. A reagent / sample tray in which the positions where one or more reagents and samples are arranged are specified in advance, and a plurality of reaction recesses provided in the reagent / sample tray for reaction of the reagents and samples. And a microplate transfer means for urging a force for transferring the microplate provided with to the immunoreaction measurement site, and having a dispensing nozzle part for sucking a predetermined amount of the sample or reagent, and the dispensing nozzle part. A reagent / sample dispensing mechanism that conveys to the entire area of the reagent / sample tray and the respective reaction recesses of the microplate is provided, and the reagent / sample tray is in the area excluding the arrangement position of the reagent and the sample. The dispensing mechanism has at least two or more disposable chip stocker areas on which a disposable chip stocker on which a plurality of disposable chips, which are detachably mounted, are mounted is attached. An enzyme-linked immunosorbent assay characterized in that each of the disposable chip stocker areas is equipped with a dilution plate having a plurality of recesses formed in a size detachably attached to the disposable chip stocker area, and the disposable chip stocker. apparatus. 2. The dilution plate has the microplate and a mounting portion on which the microplate is removably mounted, and is formed to have a size removably mounted on a region where the disposable chip stocker is mounted. An enzyme immunoassay measuring device, comprising: