JPH0996643A - Enzyme immunoreaction measuring device - Google Patents

Abstract

(57) [Abstract] [PROBLEMS] To reduce the size of a device by reducing the number of auxiliary liquid suction tubes even when the same sample needs to be dispensed multiple times. SOLUTION: A sample / dispensing mechanism 8 is attached to a reagent / sample tray 1.
The auxiliary pipe case 16 accommodating a plurality of liquid suction auxiliary pipes (disposable chips) attached to the tip of the dispensing nozzle unit 7 is arranged, and the dispensing control unit 60 causes the liquid to reach the tip of the dispensing nozzle 7. An auxiliary pipe attachment / detachment control function 61 for controlling attachment / detachment of an auxiliary suction pipe (dispo tip),
A positioning control function 62 that controls the positioning of the dispensing nozzle 7 by the sample dispensing mechanism 8 and a reuse control function that controls the use of the same liquid suction auxiliary tube when dispensing the same sample to the microplate Equipped with 63.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an enzyme immunoassay measuring apparatus, and more particularly to an enzyme immunoassay measuring apparatus which dispenses the same sample a plurality of times in order to perform a double test, a two-item test or a high dilution.

[0002]

2. Description of the Related Art Regarding enzyme immunoreactions in clinical tests, reagent makers have been developing various techniques and various reagents used therefor as techniques for accurately grasping the immunological reactions. .

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. Washing (The reaction part of the reagent to the sample is
Remains on the wall surface even after washing) etc. is performed repeatedly by changing various reagents.

[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 sample and reagent are dispensed by a dispenser,
The vibration, temperature control, and cleaning were separately performed by the vibrator, temperature controller, and cleaning device.

Since human power is involved in the movement of the sample or reagent, the waiting time of each sample is increased in the process of reaction measurement, and sometimes the sample is placed in a wrong position. Therefore, the measurement of the enzyme immunoreaction is time-consuming, and at the same time, it is always accompanied by the inconvenience of requiring a lot of mental work for the worker.

Further, in the conventional dispensing device, the liquid suction auxiliary pipe (dispochip) for dispensing the sample, which has been used once in the dispensing process, is discarded at a specific place after the dispensing.

Therefore, even in a multi-item test in which the same sample is tested with several kinds of test agents, the disposable chips for the number of times of dispensing have been used even when the same sample is dispensed. Therefore, when the number of plates used in the apparatus is plural, as many disposable chips as the reaction recesses (wells) of those plates are required.

The present invention is intended to automate the steps of the enzyme immunoreaction at one time, and has a peculiar problem of making the entire apparatus as small as possible. If a large number of disposable chips are needed, a disposable chip storage area (auxiliary tube case)
There is a peculiar inconvenience that the installation area of the device increases and the size of the device increases.

[0009]

The object of the present invention is to improve the disadvantages of the prior art, to automate the steps of enzyme immunoreaction, and
It is an object of the present invention to provide an enzyme-linked immunosorbent assay device that can reduce the size of the device by reducing the number of auxiliary liquid suction tubes even when the same sample needs to be dispensed multiple times.

[0010]

Therefore, in the present invention, as a first means, a reagent / sample tray in which the arrangement positions of one or more reagents and samples are specified in advance, and this reagent / sample tray
It is provided with a dispensing means for dispensing a specimen and a reagent from a specimen tray to a microplate having a plurality of reaction recesses, and a microplate transfer means for transporting the microplate to an immunoreaction measurement site. Of these, the dispensing means
A dispensing nozzle unit that sucks a sample or the like based on a predetermined suction / discharge signal and discharges a predetermined amount of the sucked sample and the like, and vertically moves the dispensing nozzle unit based on a predetermined drive control signal. A sample dispensing mechanism that moves the dispensing nozzle section from the reagent / sample tray to the microplate, and outputs suction / discharge signals to the dispensing nozzle section based on preset settings according to the type of measurement. A dispensing control unit that outputs a drive control signal to the sample dispensing mechanism is also provided. Further, the reagent / sample tray is provided with an auxiliary tube case in which a plurality of liquid suction auxiliary tubes (dispo chips) attached to the tip of the dispensing nozzle portion by the sample dispensing mechanism are housed. Moreover, the dispensing control unit has an auxiliary tube attachment / detachment control function that controls attachment and detachment of the liquid suction auxiliary tube to the tip of the dispensing nozzle, and a positioning control function that controls the positioning of the dispensing nozzle by the sample dispensing mechanism. In addition, when the same sample was dispensed to the microplate, it was equipped with a reuse control function that controls to use the same liquid suction auxiliary tube.

In the first means, first, various settings are made in the dispensing control section according to the type of measurement such as double measurement and two-item inspection. The dispensing control unit controls the dispensing of the sample and the reagent based on the setting from the outside.

When reagents and samples required for immunoreaction measurement are placed in predetermined positions on a reagent / sample tray and a microplate to which a reagent according to the purpose is applied in advance is set on the microplate transfer means, dispensing is performed. The means initiates the dispensing of reagents and specimens.

Since it is not desirable to use the same suction pipe for dispensing different samples, here, a disposable liquid suction auxiliary pipe (dispochip) is attached to the tip of the dispensing nozzle to perform dispensing. I have to. Therefore, it is necessary to prepare as many disposable chips as the number of samples to be dispensed. In the reagent / sample tray, an auxiliary tube case that stores a plurality of disposable chips is stored at a predetermined position.

First, the dispensing control unit controls the mounting of the disposable tip on the tip of the dispensing nozzle unit by the auxiliary tube detaching function. First, the sample dispensing mechanism is driven to position the dispensing nozzle portion on the disposable tip housed in the auxiliary tube case. Further, when the dispensing nozzle portion is moved downward, the disposable tip is attached to the tip of the dispensing nozzle portion.

Next, the dispensing control unit moves the dispensing nozzle unit with the disposable tip mounted upward, and then moves the dispensing nozzle unit to the sample position to be dispensed by the positioning control function. Since the position of the sample is predetermined on the reagent / tray, the dispensing control unit outputs the movement amount of the dispensing nozzle unit to the sample dispensing mechanism as a drive control signal. When the dispensing nozzle unit is positioned on the target sample, the dispensing control unit lowers the dispensing nozzle unit to the position where the tip of the disposable tip reaches the sample, and then the dispensing nozzle unit is started to start suction. Output the suction signal.

Further, the sample sucked by the disposable chip is conveyed to the microplate and discharged by a predetermined amount. This predetermined amount of control may be performed during inhalation. Then
The dispensing control unit normally removes the disposable chip from the dispensing nozzle unit using a removal mechanism or the like and discards it. However, here, in the case of the double inspection or the two-item inspection, the disposable chip that has been used once is reused according to the setting previously determined from the outside.

In the dispensing control unit, the reuse control unit reuses the disposable chip that has been used once. This is the control of reusing the disposable chip when dispensing the same sample, and there are two types of methods when roughly classified. The first method is control for continuously dispensing the same sample to another location immediately after the dispensing of one sample is finished, and the second method is the dispensing of one sample is finished. After that, return the used disposable chip to the auxiliary tube case, dispense another sample, and then dispense the same sample as the sample used for the disposable chip returned to the auxiliary tube case. , The control using the disposable chip.

These two methods are properly used depending on the type of enzyme immunoassay, the number of samples to be dispensed, and the like. If the same disposable tip is used for dispensing the same sample,
Since the total amount of disposable chips used decreases, the number of disposable chips that must be prepared in advance decreases. Therefore, the installation area of the auxiliary pipe case is reduced.

When the dispensing of the sample and the reagent to the microplate is completed, the microplate is transported to the immune reaction measurement site through various steps for promoting the immune reaction, and the immune reaction is measured for each reaction recess. To be done.

In the second means, in addition to the matters specifying the first means, the reuse control function has the same liquid suction assist when the same sample is dispensed into the reaction recesses of a plurality of microplates. A continuous dispensing control mode was provided for controlling to dispense into the plurality of reaction recesses with a tube.

In the second means, the same sample is continuously dispensed to a plurality of locations using the same disposable chip.

In the third means, in addition to the matter for specifying the first means, the sample dispensing mechanism is provided with a removing mechanism for removing the liquid suction auxiliary pipe attached to the dispensing nozzle. In addition, the dispensing control unit stores the position on the auxiliary pipe case of the liquid suction auxiliary pipe removed by the removal mechanism and held in the auxiliary pipe case, and the number of the sample in which the liquid suction auxiliary pipe is used. Auxiliary pipe use history storage section is also installed,
Further, the reuse control function has a reattachment control mode for controlling the attaching operation of the liquid suction auxiliary pipe to the dispensing nozzle based on the auxiliary pipe use history information stored in the auxiliary pipe use history storage means.

In the third means, the disposable tip which has been used once is returned to the auxiliary tube case, the use history of the disposable tip is stored, and this is reused when the same sample is dispensed. is there.

In the fourth means, in addition to the matters for specifying the third means, a liquid suction auxiliary pipe is attached to the tip of the dispensing nozzle portion, a specimen formed integrally with the joint portion, and the like. And an inhaler that inhales and holds the. Moreover, the removal mechanism has a locking portion that locks the upper end of the joint portion of the liquid suction auxiliary pipe when it is positioned at the predetermined locking position, and the removal lever from the locking position to the original position. And a take-out lever turning means for turning. Further, the auxiliary pipe attachment / detachment control function of the dispensing control unit controls the dispensing lever to rotate to the locking position near the upper end of the joining portion of the dispensing nozzle when the dispensing nozzle is positioned below the removal lever. It was equipped with an auxiliary pipe removal mode.

The fourth means is an example of a concrete means for returning the disposable tip used once to the auxiliary tube case. Here, the upper end of the disposable chip is locked by the locking portion of the removal lever, and the dispensing nozzle is moved to the upper part to remove the disposable chip and return it directly to the auxiliary tube case directly below.

[0026]

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

1 and 2 show the overall structure of the enzyme immunoassay measuring apparatus according to this embodiment. The enzyme immunoassay measuring device includes dispensing means 7 and 60 for dispensing a reagent, a diluent, and a sample arranged at a predetermined position of the reagent / sample tray 1 into a reaction recess of the microplate 2, and the dispensing means. 7,6
Reaction promoting means 5 and 9 for promoting the reaction between the sample and the reagent on the microplate 2 into which the sample and the like are dispensed by 0.
And a cleaning mechanism 6 for cleaning the respective reaction recesses of the microplate 2, and a measuring means for measuring the reacted sample.

FIG. 1 is a plan view of the apparatus, and reference numeral 1 is
The reagent / sample tray 1 has one or more reagents, diluents and samples, and the arrangement positions of the auxiliary tube case 16 specified in advance. In the reagent / sample tray 1, a microplate guide mechanism 3 for guiding a microplate 2 having a plurality of reaction recesses 2A to an immune reaction measurement site 100, and a microplate 2 provided adjacent to the microplate guide mechanism 3 A belt conveyor mechanism 4 as a microplate transfer mechanism for energizing a predetermined traveling force is provided side by side. In this belt conveyor mechanism 4, a stepped belt is used.

Further, as a reaction promoting means, a vibrating mechanism 5 for vibrating the microplate 2 into which the reagent and the sample are injected, and the microplate 2 into which the reagent and the sample are injected are maintained at a predetermined reaction temperature for a certain period of time. A constant temperature bath device 9 is provided.

Further, along the microplate guide mechanism 3, the microplate washing mechanism 6 for individually washing each reaction recess 2A of the microplate 2 after completion of the immune reaction.
And an immune reaction measuring unit 100 for measuring the immune reaction of the sample. The microplate transfer mechanism 4 conveys the microplate to each part. Reference numeral 10 indicates a main body case.

Further, a reagent / sample dispensing mechanism 8 having a dispensing nozzle portion 7 for sucking a predetermined amount of the sample or reagent is located above the microplate guiding mechanism 3 and the microplate guiding mechanism 3 and the reagent / sample tray 1 are provided. It is arranged in a state of straddling. This reagent / sample dispensing mechanism (sample dispensing mechanism)
Reference numeral 8 conveys and injects the sample or reagent sucked by the dispensing nozzle unit 7 to the predetermined concave portion 2A of the one microplate 2 described above.

Each configuration will be described in detail below.

[Dispensing Means] FIGS. 3 to 4 show the structure of the dispensing means. The dispensing means includes a dispensing nozzle unit 7 that sucks a sample and the like based on a predetermined suction / discharge signal and discharges a predetermined amount of the sucked sample and the like, and a dispensing nozzle unit based on a predetermined drive control signal. 7 is moved up and down and the dispensing nozzle part 7 is moved from the reagent / sample tray 1 to the microplate
And a sample / dispensing mechanism (sample dispensing mechanism) 8 that moves between the two, and outputs a suction / discharge signal to the dispensing nozzle unit 7 based on a preset setting according to the type of measurement and the reagent. A dispensing control unit 60 that outputs a drive control signal to the sample dispensing mechanism is provided.

The reagent / sample dispensing mechanism 8 applies a traveling force to the nozzle portion transfer support 41 provided so as to straddle the microplate guide mechanism 3 and the reagent / sample tray 1 and the dispensing nozzle portion 7. The nozzle part X-axis transfer means 43 is provided. The dispensing nozzle unit 7 includes a nozzle unit transfer support body 41.
And is mounted so as to be able to be transferred along the nozzle portion transfer frame body 41.

The dispensing nozzle unit 7 guides two dispensing nozzles 7A and 7B that are vertically movable, and guides the vertical movement of the dispensing nozzles 7A and 7B, and the dispensing nozzle 7A, 7B and the ball screw mechanisms 44A and 44B for individually urging the vertical movement thereof, and the ball screw mechanisms 44.
Dispensing nozzle portion lowering drive motors 45A and 45B for individually driving A and 44B are provided.

Reference numerals 45a and 45b denote joints made of elastic members for transmitting the rotational force of the dispensing nozzle section lowering drive motors 45A and 45B to the above-described ball screw mechanisms 44A and 44B. Further, reference numeral 46 indicates a nozzle portion frame. In the dispensing nozzles 7A and 7B shown in FIGS. 3 and 4, one dispensing nozzle 7A is a relatively thick disposable tip 7 for dispensing a reagent.
E, and the other dispensing nozzle 7B is equipped with a relatively thin disposable tip 7F for dispensing a sample.

By using different types of disposable chips, it is possible to cope with various different conditions in accordance with the difference in the size of the reagent bottle or the amount of the reagent used.

Further, the nozzle part X-axis transfer means 43 is a ball screw mechanism 43A for transferring the nozzle part frame 46 equipped with the dispensing nozzle part 7 along the nozzle part transfer frame 41, and this ball screw mechanism 43A. Nozzle unit X that urges the movement of
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. A belt mechanism may be used instead of the ball screw mechanism 43A.

Therefore, the reagent / sample dispensing mechanism 8 cooperates with the above-described reagent / sample tray transfer mechanism 16 so that each of the plurality of reagents and the sample on the reagent / sample tray 1 is 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.

The dispensing nozzle section 7 has a detaching mechanism 70 for removing the disposable tip mounted on the dispensing nozzle section.
Is attached. The removal mechanism 70 includes a removal lever 71 having a locking portion 71b that locks the upper end of the joint 7Fa of the disposable chip 7F when positioned at a predetermined locking position, and the removal lever 71 from the locking position to the origin. And a take-out lever rotating means (solenoid) 73 for rotating the take-out lever to a position.

The operation of the removing mechanism 70, the vertical movement and suction / discharge operation of the dispensing nozzle unit 7, and the positioning of the dispensing nozzle unit are drive-controlled by the dispensing control unit 60.

[Dispensing Control Unit] FIGS. 5 and 6 are functional block diagrams showing the configuration of the dispensing control unit. Dispensing control unit 60
5, the auxiliary tube attachment / detachment control function 61 for controlling attachment / detachment of the disposable tip 7F to the tip of the dispensing nozzle 7 and the sample dispensing mechanism (reagent / sample dispensing mechanism 8 and reagent / Positioning control function 62 that controls the positioning of the dispensing nozzle by the sample tray transfer mechanism) and reuse control function 63 that controls the use of the same disposable chip when dispensing the same sample to the microplate ing.

Further, as shown in FIG. 6, when the reuse control function 63 dispenses the same sample into the reaction wells of a plurality of microplates, the same disposable tip is used to fill the plurality of reaction wells. A continuous dispensing control mode 64 is provided for controlling the continuous dispensing.

In addition, the dispensing control unit 60 is provided with a detachment mechanism 7
The auxiliary pipe use history storage unit 66 for storing the position on the auxiliary pipe case of the disposable chip removed by 0 and held in the auxiliary pipe case and the number of the sample in which the liquid suction auxiliary pipe is used is provided side by side. Moreover, the reuse control function 63
A reattachment control mode 65 for controlling the attaching operation of the liquid suction auxiliary pipe to the dispensing nozzle based on the auxiliary pipe use history information stored in the auxiliary pipe use history storage means 66 is provided.

In the enzyme immunoassay measurement, 2 can be used for various purposes.
Multiple measurements are taken. In this method, one type of sample is measured every two holes, and the measurement is performed while confirming the difference between the two holes. For example, when 48 samples are dispensed in 96 wells by double measurement,
If one disposable tip is used for each dispensing, 96
You need a disposable chip. However, in the present embodiment, since the same sample is used in the same disposable chip, it is possible to dispense with 48 disposable chips. The details of the dispensing operation by the control using the same disposable chip for the same sample will be described later.

[Microplate] FIGS. 7 to 8 show a microplate 2 made of plastic and provided with a plurality of reaction recesses 2A. The microplate 2 is placed on the microplate guide mechanism 3 and the reagent and the sample are individually injected. If necessary, another microplate 2 is previously placed on the reagent / sample tray 1 for diluting the liquid. The microplate 2 placed on the microplate guide mechanism 3 is conveyed by the microplate transfer mechanism 4.

[Reagent / Sample Tray] As shown in FIG.
The reagent / sample tray 1 includes a reagent stocker area 13 that detachably houses one or more reagent stockers 11 and 12 equipped with a plurality of different reagents depending on the inspection method, and a plurality of samples that individually contain a plurality of samples. The sample stocker area 15 for storing the sample stocker 14 having the storage section 14A is provided. In the sample stocker region 15, if necessary, a dilution plate 17 and an auxiliary tube case 16 accommodating a plurality of disposable chips 7F used for sample dispensing are arranged.

[Auxiliary Pipe Case] FIG. 10 is a perspective view showing the structure of the auxiliary pipe case 16. This auxiliary pipe case (disposable chip case) is provided with a plurality of storage holes 16A in which the disposable chips 7F are stored. The auxiliary tube case lid portion 16B is provided with 8 × 12 storage holes at regular intervals, and the size thereof is set to be smaller than the outer circumference of the bonding portion 7Fa of the disposable chip. The auxiliary tube case body 16C is made of transparent plastic. Further, since there are various types of disposable tips, the shape of the auxiliary tube case is determined according to the type of disposable tips.

[Reagent Stocker] As shown in FIGS. 11 to 13, each reagent stocker 11, 12 requires a different reagent stocker 11, 12 depending on the inspection method. Identification means 11A and 12A for setting identification information are provided. This identification means 1
1A and 12A are a plurality of circular ultrasonic wave reflecting surfaces 11A ₁ , 11A ₂ , 11A ₃ , 11E _{4 having} different heights set in a line at the left end of each reagent stocker 11, 12;
It is composed of ₁ , 12A ₂ , 12A ₃ and 12A ₄ . In the illustrated example, there are four reflecting surfaces. This difference in height is sequentially detected by the ultrasonic sensor 10A attached to the above-mentioned dispensing nozzle unit 7, and the dispensing control unit 6
It is identified by 0 so that each component described later operates in accordance with the predetermined inspection method.

FIG. 8 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. Here, six reagent storage sections 11e and 12e having different sizes are provided in the central portion.
Is provided, and reagent bottles 11E and 12E as reagent storage containers are stored in the reagent storage portions 11e and 12e. Further, on the right side of the figure, five reagent storage portions 11f and 12f having the same size are provided.
Reagent bottles 11F and 12F are stored in 12f.

Here, the reagent bottles 11E, 11F, 12E and 12F housed in the reagent stockers 11 and 12, respectively.
Are arranged in a horizontal plane whose positions are substantially the same in the opening. 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 the reagent is actually detected by the ultrasonic sensor 10A provided side by side with the above-mentioned dispensing nozzle section 7, and when the reagent is insufficient, the case (even when the amount of the sample is insufficient is detected. ), That effect is externally displayed by a display means (not shown). In addition, since the remaining amount of this reagent is captured as liquid level data,
Based on such information, the above-mentioned dispensing control unit 60 can adjust the descending amount of the dispensing nozzle unit 7.

Furthermore, FIG. 5 on each reagent stocker 11, 12 is shown.
In the lower area of the
Plural kinds of disposable tips 7E, 7F having different thicknesses for the dispensing nozzle portion 7 described above are arranged corresponding to the size of the opening of each reagent bottle accommodated in 12.
Here, six relatively thick disposable chips 7E are prepared corresponding to the above-mentioned reagent bottles 11E and 12E, respectively, and relatively thin disposable chips 7F are used for the above-mentioned reagent bottles 11F and 12F and for sample inhalation. 10 pieces are prepared for each reagent stocker 11 and 12.

[Reagent / Sample Tray Transfer Mechanism] As shown in FIGS. 14 to 16, the reagent / sample tray 1 is supported by the reagent / sample tray 1 described above.
The reagent / sample tray transfer mechanism 21 for transferring the sample tray 1 in a direction substantially orthogonal to the moving direction of the dispensing nozzle portion 7 of the reagent / sample dispensing mechanism 8 is provided.

Here, the reagent / sample tray 1 in FIG. 14 has a counterclockwise direction of 9 as compared with that of FIG.
It is rotated by 0 °. Figure 14 (A) shows the reagents
FIG. 14B shows a state in which the sample tray 1 is projected from the main body case 10. The reagent / sample tray 1 is shown in FIG.
An example of a state in which it is almost housed in 0 is shown.

Further, FIG. 15 shows a case where the reagent / sample tray 1 is arranged at a deep portion in the main body case 10, and FIG. 16 shows a right side view of FIG. 19 (B) described above.

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.

The reagent / sample tray transfer mechanism 21 has a Y-axis direction transfer function for transferring the reagent / sample tray 1 in the vertical direction of FIG. 1 in FIG. Has a function of transferring the dispensing nozzle portion 7 in the left-right direction of FIG. 1, that is, a function of transferring in the X-axis direction. As a result, each reagent or sample on the reagent / sample tray 1 can be freely and quickly distributed from any position to the above-mentioned one microplate 2 (and, if necessary, the other dilution plate 2). It's ready to be poured.

This reagent / sample tray transfer mechanism 21 supports the above-mentioned reagent / sample tray 1 and guide frame body 21A for guiding the reagent / sample tray 1 to move in the vertical direction of 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, the reagent / sample tray 1 may be transferred by a belt mechanism instead of the ball screw mechanism section 21B.

Further, reference numeral 21a indicates a linear guide which is mounted on the reagent / sample tray 1 corresponding to the guide frame 21A, and reference numeral 21Ba indicates a driven member which is transferred and driven by the screw shaft of the ball screw mechanism portion 21B. A member is shown. The driven member 21Ba is attached to the back surface of the reagent / sample tray 1, and thereby the reagent / sample tray 1 is driven to travel in the Y-axis direction described above, and as described above, the amount of each reagent or sample to the microplate 2 is divided. The injection operation becomes possible, and at the same time, the above-mentioned reagent stockers 11 and 12 and the sample stocker 14 can be projected from the main body case 10 as shown in FIG. 9 (A). Therefore, each reagent stocker 1
The loading and unloading operations of 1 and 12 and the sample stocker 14 can be performed smoothly and quickly.

Next, the operation of the enzyme immunoassay device will be described.

[Dispensing Operation] In this embodiment, as described above, the same disposable sample is controlled for the same sample. First, continuous dispensing control mode 64
An example of the operation by will be described with reference to FIG.

When the sample and the microplate on which the reagent is applied in advance are set in the reagent / sample tray 1 or the microplate guide mechanism 3, the dispensing control unit 60 starts the control of the sample dispensing.

First, the dispensing controller 60 drives and controls the reagent / sample tray transfer mechanism 21 to match the Y-coordinates of the disposable chip 7B with the disposable chip corresponding to the sample to be dispensed. At the same time, the reagent / dispensing mechanism 8 is drive-controlled to match the X coordinates of the disposable chip and the dispensing nozzle 7B (step S1).

Next, the nozzle part X-axis transfer means 43 of the reagent / dispensing mechanism 8 is drive-controlled to move the dispensing nozzle 7B downward so that the tip of the dispensing nozzle 7B and the disposable tip are fitted together ( Step S2). Furthermore, dispensing nozzle 7B
To rise.

Next, the dispensing nozzle part to which the disposable chip is attached is moved to the target sample position of the sample stocker 14 (step S3). This is performed by outputting a drive control signal to the reagent / sample dispensing mechanism 8 and the reagent / sample tray transfer mechanism. Since each mechanism is driven by a motor, the positioning control function 62 is actually realized by outputting a pulse according to the movement amount to the motor of each mechanism.

Next, the dispensing nozzle is lowered to a position determined based on the output of the ultrasonic sensor 10A, and the sample is sucked (step S4). Further, the nozzle is raised, the sample held on the disposable chip 7F is conveyed to the microplate 2, and then a predetermined amount of the sample is discharged to the reaction recess at a predetermined position (step S5).

Here, the dispensing control unit 60 causes the sample remaining in the disposable chip 7F to be discharged to another reaction recess without discarding the disposable chip (step S5). Further, if the amount of the sample to be used for the test is determined at the time of suction instead of at the time of discharging, the suction operation of the same sample is performed again.

When a plurality of times of dispensing of the same sample is completed, the used disposable chip is removed and a new disposable chip is attached (step S6). The process is returned to step S4 until the required number of dispensings are completed.

In the example shown in FIG. 17, in the case where the same sample is double-measured or when a plurality of items of the same sample are tested, the same sample is dispensed to a plurality of locations. In this case, since the same disposable chip is used, the consumption amount of the disposable chip is reduced, and therefore, the installation area of the disposable chip is narrowed, so that the entire apparatus can be made compact.

Next, the dispensing operation in the reattachment control mode in which the disposable chip once removed is reused will be described.

18 to 21 are views showing details of the removing mechanism 70 shown in FIG. As shown in FIG.
The removal mechanism 70 is attached to the lower portion of the nozzle portion frame 46. The removal lever 71 that locks the disposable tip 7F is held by the nozzle portion frame 46 so as to be rotatable around the rotation shaft 71b. Further, the solenoid 73 as the lever rotating means is held by the solenoid holding member 74. A tension spring 72 is provided on the removal lever side of the solenoid holding member 74, and the tension spring 72 urges the removal lever 71 toward the solenoid 73 side in a normal state. Also, the solenoid 73
Is turned on under the control of the dispensing control unit 60, the movable iron core 73a is arranged so as to push out the removal lever to the dispensing nozzle side.

FIG. 19 is a diagram showing the relationship between the removing mechanism 70 and the dispensing nozzle 7B when the solenoid is turned on. When the solenoid is turned on after the dispensing nozzle 7B has been sufficiently moved downward, the movable iron core rotates the removal lever to the position shown in FIG. The position of the removal lever 71 shown in FIG. 19 is called a locking position here.

The engaging portion 71a of the removal lever 71a is provided with a semicircular notch 71c having a diameter substantially equal to the diameter of the dispensing nozzle 7B. When the locking portion 71a is rotated to the locking position, the semicircular cutout 71c is in a state in which it can substantially contact the dispensing nozzle 7b. Further, as shown in the drawing, the disposable chip 7F is locked by the locking portion 71a for upward movement.

Further, the auxiliary pipe attachment / detachment control function 61 of the dispensing control unit 60 controls the removal lever 7B to be located near the upper end of the joining portion of the dispensing nozzle 7B when the dispensing nozzle 7B is positioned below the removal lever 71. It is equipped with an auxiliary pipe removal mode for controlling the rotation to the locking position. The process of removing the disposable chip in the auxiliary pipe removing mode will be described with reference to FIGS.

First, the dispensing nozzle portion 7 is attached to the auxiliary pipe case 16
To a predetermined position. Then, the dispensing nozzle 7B is lowered. Further, the dispensing control unit 60 turns on the solenoid 73 to rotate the removal lever 71 to the locking position. FIG. 20 shows the state where the removal lever is positioned at the locking position.

The dispensing control unit 60 then continues to the dispensing nozzle 7
Increase b. Then, the removal lever 71 locks the rise of the disposable chip 7F. Therefore, the disposable tip 7F is removed from the dispensing nozzle portion 7B. Since the dispensing nozzle portion 7 is positioned at a predetermined position of the auxiliary pipe case 16, the removed disposable tip is stored in the auxiliary pipe case 16 in a reusable state. Reference numeral 7Ba is a packing for sealing.

Next, referring to FIG. 22, the dispensing operation in the reattachment control mode 65 will be described by taking the case of performing high dilution as an example.
Here, the dispensing control unit 60 has a function of controlling the repeated operation of suction and discharge of the dispensing nozzle unit 7 for the diluent and the sample injected into the diluting recess 17A.

First, the dispensing controller 60 controls the transport operation of the reagent / sample dispensing mechanism 8 to dilute the sample in the plate 17 for dilution.
Dispense into The disposable chip used by this dispensing operation is re-stored in the auxiliary tube case 16 by the removing mechanism 70 (step K10). At this time, the auxiliary tube use history storage unit 66 stores the sample number (code for identifying the sample) of each disposable chip.

Further, the diluted solution is dispensed to the dilution microplate (step K12). The order of dispensing the diluent and the sample may be reversed. Then, the diluting concave portion in which the sample and the diluting liquid are dispensed is stirred (step K14). In this embodiment, this stirring is performed by repeatedly sucking and discharging the mixed liquid of the sample and the diluting liquid by the dispensing nozzle unit 7. The disposable chip used for this stirring is
The disposable chips used at the time of dispensing the sample are used.

Specifically, when changing the disposable tip for the stirring operation, the dispensing control unit selects the disposable tip for each stirring operation according to the history information stored in the auxiliary tube usage history storage unit 66. ing. Further, when the stirring operation is completed for each of the specimens, the disposable tip is removed again by using the removal mechanism 70.
Re-store.

Steps K10 to K14 are repeated until the required number of specimens have been diluted (step K1).
6). This completes the dilution process. This diluting treatment may be performed prior to normal dispensing.

Further, when the reaction promoting process of shaking or heating is started for the diluted sample, the diluted sample of the dilution plate 17 is dispensed to the microplate 2 on the microplate guide mechanism 3. At the time of this dispensing, the disposable tip used at the time of stirring is reused.

In the diluting process shown in FIG. 14, in order to dispense the sample and the diluent placed on the reagent / sample tray 1 onto the dilution plate 17 also placed on the reagent / sample tray 1. The operation of the reagent / specimen dispensing mechanism 8 is performed in a short distance, so that the dilution process can be performed at high speed.

Further, since the diluting liquid and the sample are agitated by repeating suction and discharge by the dispensing nozzle portion 7, the diluting liquid and the sample are mixed very well and at high speed.

Further, by re-diluting with the thus-diluted microplate, it is possible to dramatically perform high-magnification dilution.

In such a dilution process, the reaction times of the reagent and the sample need to be the same in the respective reaction recesses of the microplate. Therefore, depending on the dispensing speed, dispensing and stirring must be performed in separate steps. May occur. In such a case, if the disposable chip is changed every time, a huge amount of disposable chips will be consumed. Therefore, like the present embodiment, it is possible to reuse the disposable chip based on the usage history information of the disposable chip. desirable.

Further, even if the disposable chip after the dispensing operation of the sample is returned to the original position of the disposable chip case, when the disposable chip of the same sample is dispensed again, it is confused with another disposable chip. It becomes possible to use the disposable chip multiple times.

Further, when a sample is dispensed, it is also possible to set which disposable chip is to be used for which sample by, for example, setting the same sample to be dispensed using the same disposable chip. By performing the above, it becomes possible to dispense the sample by preparing disposable chips for the number of samples.

[Operation During Immune Reaction Measurement] Next, an example of a standard operation when performing the immune reaction measurement according to the above-described embodiment will be described.

First, the microplate 2 having a predetermined reagent applied in advance to each reaction recess 2A is 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.

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 9 to adjust the temperature to further promote the reaction. .

When the reaction accelerating step in the constant temperature bath 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, and the reaction concave portions are carried out by the above-mentioned operation. The inside of 2A is cleaned.

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

When the steps of dispensing the enzyme-labeled antibody reagent, reaction, and washing are completed, the chromogenic reagent is then 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 constant temperature bath 9 and its temperature is adjusted to promote the reaction.

When the steps of dispensing and reaction of the chromogenic reagent are completed, next, the stop solution reagent is added to the reagent stocker 11
(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.

As described above, according to the above-described embodiment, in the measurement of the enzyme immunoreaction, the steps of dispensing, reaction, and washing are often repeated, so that automation, which has been considered difficult, can be performed. Therefore, there is an advantage that the enzyme immunoassay can be measured quickly and with high accuracy, and various items different for each reagent manufacturer can be tested by one device.

In the above embodiment, the belt conveyor mechanism 4 is used as the microplate transfer mechanism, but any mechanism other than the belt conveyor mechanism may be used as long as it functions as the microplate transfer mechanism. May be.

Also, the case where the reagent / sample tray transfer mechanism 16 is provided in the reagent / sample tray 1 has been exemplified.
By using the sample tray 1 in a row along the reagent / sample dispensing mechanism 8 described above, the reagent / sample tray transfer mechanism 16 does not need to be particularly equipped. Further, the reagent / sample dispensing mechanism 8 may be configured to be movable in the Y-axis direction.

[0102]

EFFECTS OF THE INVENTION Since the present invention is constructed and functions as described above, according to this, a liquid suction auxiliary tube (dispo tip) attached to the tip of the dispensing nozzle portion by the sample dispensing mechanism in the reagent / sample tray. Multiple auxiliary storage cases are placed, and the dispensing control unit controls the use of the same auxiliary liquid suction tube when dispensing the same sample to the microplate. Even when the same sample is dispensed multiple times, such as when performing multiple-item tests, high-dilution tests, etc., it is possible to reduce the amount of disposable chips used. The installation area of the unused disposable tip required for fully automatic dispensing into the recess for use is reduced, and the installation location of the auxiliary tube case is newly added even when performing multi-item inspection. Necessary to ensure there is no. In this way, the size of the device can be made compact by automating the steps of the enzyme immunoreaction and further reducing the number of liquid suction auxiliary tubes used even when the same sample needs to be dispensed multiple times. It is possible to provide an unprecedented excellent enzyme immunoassay measuring device.

[Brief description of drawings]

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

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

FIG. 3 is a partially omitted front view showing an example of a reagent / sample dispensing mechanism disclosed in FIG. 1.

4 is a right side view of the reagent / specimen dispensing mechanism shown in FIG. 3 with a part thereof omitted.

5 is a functional block diagram showing a configuration of a dispensing control unit shown in FIG.

FIG. 6 is a functional block diagram showing a configuration of a reuse control unit shown in FIG.

FIG. 7 is a plan view showing an example of the microplate shown in FIG.

8 is a cross-sectional view of the microplate shown in FIG.

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

10 is a perspective view showing an example of the auxiliary pipe case shown in FIGS. 1 and 9. FIG.

FIG. 11 is a front view of the reagent / sample tray portion shown in FIG. 9 with some parts omitted.

FIG. 12 is a left side view of the reagent / sample tray portion shown in FIG. 9 with a part thereof omitted.

FIG. 13 is a perspective view showing an example of the reagent stocker disclosed in FIG.

14 is a diagram showing the relationship between the reagent / sample tray disclosed in FIG. 1 and its drive mechanism (Y-axis direction), and FIG.
180 in the counterclockwise direction for the reagent / sample tray in Fig. 1.
FIG. 14 (B) is an explanatory view showing the operation of FIG. 14 (A), showing a plan view showing a state of being rotated by a degree.

15 is an explanatory diagram showing the operation of the reagent / sample tray portion shown in FIG. 14 (A).

16 is a right side view of the reagent / sample tray portion shown in FIG.

17 is a flowchart showing an example of a dispensing process with the configuration shown in FIG.

FIG. 18 is a front view showing details of a removing mechanism for removing the disposable chip shown in FIG. 3;

19 is a plan view of the removing mechanism shown in FIG. 18. FIG.

FIG. 20 is a first explanatory diagram showing the operation of the removal mechanism shown in FIG. 18.

FIG. 21 is a second explanatory diagram showing the operation of the removal mechanism shown in FIG. 18.

22 is a flowchart showing an example of a sample dilution process with the configurations shown in FIGS. 1 and 18. FIG.

[Explanation of symbols]

1 Reagent / Sample Tray 2 Microplate 7 Dispensing Nozzle 8 Reagent / Sample Dispensing Mechanism
(Including reagent / sample tray transfer mechanism) 16 Auxiliary tube case 60 Dispensing control section 61 Auxiliary tube attachment / detachment control function 62 Positioning control function 63 Reuse control function 66 Auxiliary tube use history storage

Claims (4)

[Claims] 1. A reagent / sample tray in which arrangement positions of one or more reagents and samples are specified in advance, and the sample / reagent is dispensed from the reagent / sample tray into a microplate having a plurality of reaction recesses. And a microplate transfer means for transporting the microplate to an immune reaction measurement site, and the dispensing means sucks the sample and the like based on a predetermined suction / discharge signal and sucks the sample. A dispensing nozzle portion that discharges a predetermined amount of a sample or the like, and the dispensing nozzle portion is moved up and down based on a predetermined drive control signal, and the dispensing nozzle portion is placed between the reagent / sample tray and the microplate. And a sample dispensing mechanism that moves the sample dispensing mechanism and outputs a suction / discharge signal to the dispensing nozzle unit based on a preset setting according to the type of measurement. An auxiliary tube in which a plurality of liquid suction auxiliary tubes attached to the tip of the dispensing nozzle section by the sample dispensing mechanism are housed in the reagent / sample tray. An auxiliary tube attachment / detachment control function for arranging a case, the dispensing control section controlling attachment and detachment of the liquid suction auxiliary tube to the tip of the dispensing nozzle section, and a dispensing nozzle section by the sample dispensing mechanism And a reuse control function for controlling the use of the same liquid suction auxiliary tube when the same sample is dispensed to the microplate. Enzyme immunoassay measuring device. 2. The reuse control function, when the same sample is dispensed to the reaction recesses of a plurality of microplates, is continuously dispensed to the reaction recesses by the same liquid suction auxiliary pipe. The enzyme immunoassay measuring device according to claim 1, further comprising a continuous dispensing control mode for controlling the injection. 3. The sample dispensing mechanism is provided with a detaching mechanism for detaching the liquid suction auxiliary pipe attached to the dispensing nozzle section, and the dispensing control section is detached by the detaching mechanism to support the auxiliary. The auxiliary pipe use history storage unit for storing the position of the liquid suction auxiliary pipe held in the pipe case on the auxiliary pipe case and the number of the sample in which the liquid suction auxiliary pipe is used is provided, and the reuse control function is provided. Is equipped with a reattachment control mode for controlling an attaching operation of the liquid suction auxiliary pipe to the dispensing nozzle portion based on auxiliary pipe use history information stored in the auxiliary pipe use history storage means. The enzyme immunoassay measuring device according to claim 1. 4. The liquid suction auxiliary pipe comprises a joint portion mounted on the tip of the dispensing nozzle portion, and a suction portion formed integrally with the joint portion for sucking and holding the sample and the like, A removal lever having a locking portion that locks the upper end of the joint portion of the liquid suction auxiliary pipe when the removal mechanism is positioned at a predetermined locking position, and the removal lever from the locking position to the origin position. A take-out lever turning means for turning the take-out lever, and the auxiliary tube attachment / detachment control function of the dispensing control unit causes the dispensing lever to dispense the dispensing lever when the dispensing nozzle is positioned below the dispensing lever. The enzyme immunoassay measuring device according to claim 3, further comprising an auxiliary tube removal mode for controlling to rotate the nozzle portion to a locking position near the upper end of the joint portion.