JPH09145719A - Reactor for automatic analyzer - Google Patents

Abstract

(57) Abstract: A single-line reaction device using a rotating disk that is attached to an analysis device, and a small reaction device capable of arbitrarily changing reaction time and detection time is provided. A reaction device for an automatic analyzer, comprising a rotating disk in which a plurality of reaction vessels are arranged on two or more concentric circles,
It comprises a container transfer mechanism for moving the arranged reaction containers between different concentric circles, a detector on the outer peripheral portion of the disk, and a control unit for controlling the transfer of the containers.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a reactor which is used together with an analyzer. More specifically, for example, a biochemical analyzer for analyzing components contained in a biological sample contained in a blood collection tube or a sample reaction container, for example, a liquid such as serum or urine or a liquid extracted from a tissue,
The present invention relates to a reaction device used for an immunochemical analysis device and the like.

[0002]

2. Description of the Related Art In the case of component analysis of biological samples such as serum and urine, sample components may be subjected to certain reaction treatment before being subjected to analysis. For example, in an analysis device such as a biochemical analysis device or an immunochemical analysis device, the biological sample and the reaction reagent mixed in the reaction container are controlled to a constant temperature, and if necessary, in a reaction device having a stirring device. Then, after reacting for a predetermined time, the progress of the reaction is detected by the absorbance or the fluorescence intensity to obtain the concentration of the substance to be measured, etc., and then to perform the analysis.

In recent biochemical analyzers and immunochemical analyzers, it is necessary to simultaneously measure many items with a single device, and therefore it is necessary to simultaneously react samples having different reaction times or measurement sensitivities. It was Therefore, there has been a need for a reaction apparatus that satisfies the conditions such as changing the reaction time depending on the type of measurement and performing detection by a detector multiple times.

On the other hand, the analyzer is required to be small and capable of many processes. In addition, since high accuracy is required for the analysis result, it is necessary that the reactions in the individual reaction vessels proceed under the same environment.

In many automatic analyzers, a sample and a reaction reagent are placed in a reaction container, and after the reaction is performed in the reaction device, the progress of the reaction is detected by the absorbance or fluorescence intensity to obtain the concentration of the substance to be measured. However, in the reaction apparatus used at this time, it is indispensable to control the temperature of the reaction liquid in the reaction container and to leave the sample for a certain period of time or agitate.

When a multi-step reaction is required, after the reaction for a certain period of time, the second reagent is dispensed and the reaction is further carried out. In the case of heterogeneous enzyme immunoassay, the reaction is performed by washing the reaction container (B / F separation) and then dispensing a second reagent (enzyme substrate). After that, the reaction container is sent under the detector to measure the absorbance or fluorescence intensity of the sample, or the reaction solution collected from the reaction container is sent to the detector. After that, the degree of progress of the reaction is obtained from the measured values of the absorbance and the fluorescence intensity, and the concentration of the substance to be measured is obtained using a calibration curve.

A carousel in which reaction vessels are lined up on the circumference, a snake chain in which the reaction vessels are connected in a chain, and the like are used as a reaction apparatus attached to such an analyzer.
With a multi-item analyzer that measures multiple items with a single device,
There are a single-line reaction apparatus in which a plurality of samples for measuring different items are flown in a line of a book, and a multi-line reaction apparatus in which a plurality of lines are provided and a sample is flown in a dedicated line for each item. Usually, the multi-line reaction apparatus is used in a limited large-scale apparatus because the reagent dispenser and the detector are required for the number of lines. Further, in a random access analyzer capable of selecting measurement items for each sample, a single line reactor is preferably used because the efficiency of a multi-line reactor having a dedicated line is not high.

In a single-line reactor, when a relatively large amount of treatment with a long reaction time is performed, the reaction vessel is
It must be held in the reactor, which inevitably increases the line length. With a single-line reactor that uses a snake chain, it is possible to reduce the size of the storage unit by folding the snake chain, but it is difficult to move the snake chain back and forth as quickly as possible. It was difficult to detect many times by transferring it under the detector of many times. On the other hand, in the carousel, such a large number of times of transfer and detection are easy, but in order to increase the processing capacity, the carousel needs to be upsized, and as a result, upsizing of the entire device is inevitable. There was a problem. In addition, as the carousel becomes larger, it becomes difficult to rotate the carousel at high speed.

As a reactor for solving these problems,
A scroll type carousel has been proposed. This reactor has a fixed bottom plate with scroll (spiral) grooves formed inside and circular grooves formed on the outermost periphery, and radial slit holes inside and a large number of holes on the outermost periphery. And a detector such as a fluorescence detector and, if necessary, a BF separator used for heterogeneous immune reaction.

In this example, the reaction starts when the reaction container is set at the position where the scroll and the slit intersect, and the slit rotates, so that the reaction container moves from the inner circumference to the outer circumference or from the outer circumference to the inner circumference. . When a preset time elapses, the reaction container is moved from the scroll to the outermost circle by using a suitable pickup device, and the reaction time is determined by the time for removing the reaction container. Further, by rotating the rotary plate, the reaction container at an arbitrary position on the outermost periphery can be brought under the detector.

In such a scroll type carousel,
The reaction container installed on the scroll can be more than one circumference, but in the scroll, the container is held at the intersection of the radial slit plate and the groove on the scroll, so the mechanism for setting the container Requires high accuracy,
If the position where the reaction container is installed is slightly displaced, the reaction container may fall, and the reaction container may fall due to the centrifugal force that rotates the slit plate at high speed. Not the right one.

[0012]

SUMMARY OF THE INVENTION An object of the present invention is to provide a reactor which is installed in an analyzer and which is a single line reactor using a rotating disk and which can be downsized as a whole. is there. Another object of the present invention is to provide a reaction device capable of arbitrarily changing the reaction time and the detection time, and to provide an analyzer having high measurement accuracy and high reliability by using the reaction device.

[0013]

The present invention has been made in view of the above problems. That is, the present invention is a rotating disk in which a plurality of reaction vessels are arranged on a double or more concentric circles,
The present invention relates to a reactor for an automatic analyzer, which comprises a container transfer mechanism for moving the arranged reaction containers between different concentric circles, a detector, and a controller for controlling the transfer of the containers.

The present invention will be further described below with reference to the drawings. FIG. 1 is a plan view showing the whole reaction apparatus of one embodiment of the present invention. The reaction apparatus of the present invention is configured such that a thick disk having a bottomed hole for setting a reaction container is rotated, or a thin disk having an opening is stacked on a fixed disk and only the upper disk is rotated to fix the reaction container to a fixed disk. It may be one that slides on top (1 indicates a disc in the figure). Hole on the disk (2 in the figure)
Has openings on two or more concentric circles on the disk, and may have an area sufficient to hold the sample container. In the outermost hole of the disk, a sample for detecting BF separation after reaction or fluorescence is usually installed. The biochemical analyzer and the homogeneous immunoassay device do not require a BF separator.

The number of reaction vessels installed in one round of a concentric circle may be even or odd. By rotating the disk by one pitch every unit time, the unit returns to the original position after a unit time equal to the number of reaction vessels arranged in one round has elapsed.
When the number of reaction vessels is odd, it can be rotated by 2 pitches per unit time. In that case, when the unit time equal to half of the number of reaction vessels installed in one lap elapses, the original position is restored. And a unit time equal to the number of reaction vessels installed in one round has passed, it rotates two rounds and returns to the original position. The number of reaction vessels installed in one round is the time and operation required for the reaction vessels on the reaction device, the position of the detector (5 in the figure) and / or the cleaning device (3 in the figure), and the transfer of the reaction vessel. It is appropriately determined according to the performance of the changing mechanism. further,
The number of holes provided on each concentric circle is usually determined to be equal or a simple integer ratio.

When the reaction container is rotated once on the disk, the reaction container is moved to another circumference by the reaction container transfer mechanism. Also, when the reaction for a predetermined time is completed,
The reaction container is moved to the outer circumference, for example, on the circumference where the cleaning device or the detector is installed. In the two-step immunoassay method, it is necessary to separate BF and dispense the second reagent during the reaction. B
The F separation device may be provided at a position where the intermediate BF separation is required, but the reaction container requiring the intermediate BF separation is moved to the outermost periphery, and the intermediate BF separation is performed at the outermost periphery to separate the second reagent. After pouring, it can be returned to an appropriate position on the inner circumference again. After that, when the reaction in the second stage is completed, the reaction container is moved to, for example, the outermost circumference. BF separation is performed at the outermost circumference, and the enzyme substrate is dispensed. 4 is an enzyme substrate dispenser.

Although the structure of the reaction container transfer mechanism is not particularly limited, for example, as shown in FIG. 1, the reaction container chuck mechanism (6 in the figure) held by the reaction container transfer mechanism is a lane 8. To move horizontally. The reaction vessels are gripped one by one by the reaction vessel chuck mechanism, moved, and opened. Further, the reaction container transfer mechanism can be used to transfer the container from the outside of the reaction container to the reaction device or to discharge the used reaction container from the reaction device. Dispensing lane 7 is another reaction container transfer mechanism, and the reaction container is placed on the holder and moved in the front-rear direction. 9
Is a used reaction container holding part.

The controller for controlling the transfer of the container is used to control at least the rotation of the disk and the drive of the reaction container transfer mechanism, but it is not limited to an independent controller.
A computer for controlling other mechanisms, dispensing reagents, and processing signals obtained from detectors can be shared. On the other hand, the controller that controls the transfer of the container may be composed of a plurality of computers.

[0019]

In the reaction apparatus of the present invention, the reaction vessels can be arranged on multiple circles, so that a large number of reaction vessels can be accommodated in a small area. By moving containers from the inner circumference to the outer circumference or from the outer circumference to the inner circumference in a concentric circle, each reaction container can follow the same route, and for the measurement items using the same reaction environment. , It is possible to match the reaction environment of all reaction vessels. Also, since all reaction vessels can be passed under a single detector, there is no need to install multiple detectors. Further, by rotating the disk forward and backward a plurality of times during one unit time, it is possible to detect the reaction at a plurality of time points.

Further, even if the position of the reaction container grasped by the reaction container chuck mechanism is slightly shifted, if the reaction container enters the entrance of the hole formed in the disc, the reaction container can be installed without tipping. Furthermore, since the reaction container is deeply inserted in the hole formed in the disc, the reaction container does not fall down while the disc is rotating.

According to the present invention, the reaction time can be appropriately selected from a plurality of times. Moreover, since many reaction vessels can be accommodated for the size of the disk, the entire analyzer can be made small. Further, if the reaction protocol is the same, all reaction vessels go through the same route, so that the reaction environment is less likely to vary.

[0022]

BEST MODE FOR CARRYING OUT THE INVENTION An embodiment in which the present invention is applied to an enzyme immunoassay device will be described below with reference to the drawings. An example is not shown here, but the same applies to a biochemical measuring device.

The reactor shown in FIG. 1 was used. The disk (1 in the figure) used in the reaction apparatus was provided with openings (2 in the figure) each having 40 holes for mounting the reaction vessels on three concentric circles. At the outermost periphery, a B / F separator for heterogeneous immunoassay (3 in the figure), an enzyme substrate dispenser (4 in the figure), a fluorescence detector (5 in the figure), and a second reagent dispenser (not shown) ) Was installed.
A reaction container transfer mechanism was attached above the carousel. Although not shown in the figure, a heater on the sheet and a temperature detecting element were attached under the disk to control the power supply to the heater so as to maintain a constant temperature. In addition, a donut-shaped plate in which a plurality of small magnets as shown in FIG. 2 are embedded is arranged in or under the disk, and the magnetic particles contained in the reaction vessel by vibrating the plate in rotation are arranged. And the reaction solution was stirred.

Dispensing lane (7 in the figure) beside the carousel
Was provided. The reaction vessel is a holder (1 in the figure) on the dispensing lane.
0) to move, the seal is opened by a seal breaker (not shown), and the sample is dispensed by a dispensing device (not shown). The reaction container into which the sample has been dispensed is held by the reaction container chuck mechanism (6 in the drawing) and transferred onto the reaction device by the lane (8 in the drawing).

An example of the flow of the reaction container is shown below.

10 minutes reaction system: Dispensing lane-> Lane 1-
> Lane 3-> Discard 40 minutes Reaction system: Dispensing lane-> Lane 1-> Lane 2-
> Lane 3-> Discard 40-minute two-step reaction system: Dispensing lane-> Lane 1-> Lane 3-> Lane 2-> Lane 3-> Discard Here, the 40-minute reaction system will be described. The reaction container is inserted into the innermost circumference of the concentric circles (lane 1), and when it returns to the original position after 20 minutes, it is transferred to the middle circumference (lane 2). After moving to the middle lap (lane 2) and returning to the original position 20 minutes later, it is moved to the outermost rim (lane 3). Outermost (lane 3)
After removing the unreacted substances in the reaction vessel by the B / F separator, the enzyme reaction substrate is dispensed and detected by the detector.

In this Example, alkaline phosphatase is bound to the label of the labeled antibody used as a reagent, and when 4-methylumbelliferyl phosphate is used as the enzyme substrate, 4-methylumbelliferone is converted to 4-methylumbelliferone by the action of the enzyme. It will change and become fluorescent. As is known, the concentration of the substance to be analyzed can be calculated by calculating the rate (rate of increase in fluorescence intensity) from the fluorescence measurement value and using a calibration curve prepared using a standard substance having a known concentration.

Table 1 shows an example of the control sequence of the controller that controls the transfer of the container.

[0029]

[Table 1]

The control sequence was determined such that the destination of the reaction vessel was first emptied and then the reaction vessel was moved to the vacant position. In this sequence, the unit time is 30 seconds,
The carousel is stopped at 6 positions in 30 seconds, and during the stop, transfer of the reaction vessel is performed up to 5 times, fluorescence photometry is performed up to 4 times, and B / F separation washing is performed up to 2 times. . This sequence could correspond to a 10-minute reaction system, a 40-minute reaction system, and a 40-minute two-step reaction system.

One reaction vessel is stopped under the detector after 18 seconds, 55 seconds, 135 seconds, and 281 seconds after dispensing the enzyme and the substrate, and the fluorescent substance in the reaction vessel is stopped. The quantity is measured. When the increase in fluorescence intensity was slow, the rate of increase in fluorescence intensity was determined using four fluorescence measurements. When the increase in the fluorescence intensity is fast, the subsequent measurement value saturates the detector, so that the increase rate of the fluorescence intensity can be obtained by using only the measurement values of the previous two or three times.

[Brief description of the drawings]

FIG. 1 is a diagram showing an embodiment of the present invention.

FIG. 2 is a diagram showing a doughnut-shaped plate in which a large number of magnets used in an example of the present invention are embedded.

[Explanation of symbols]

 1: Disc 2: Opening for holding sample container 3: Washer (B / F separator) 4: Dispenser 5: Detector 6: Chuck 7: Dispensing lane 8: Lane 9: Sample discarding unit 10: Holder 11: Magnet

Claims (2)

[Claims] 1. A rotating disk in which a plurality of reaction vessels are arranged on two or more concentric circles, a vessel transfer mechanism for moving the arranged reaction vessels between different concentric circles, a detector, and a vessel transfer control. Reactor for automatic analyzer consisting of control unit 2. A reactor for an automatic analyzer according to claim 1, further comprising a container cleaning device and / or a reagent dispensing device.