JPH04142462A - Distributing device for inspecting reaction container - Google Patents

Abstract

PURPOSE:To quickly detect the defective distribution of a reaction container by detecting the defective distribution of the reaction container with one sensor provided on a support member. CONSTITUTION:Four distributing micro-plates A, A... are arranged on a distributing station S1, and two distributing micro-plates B, B are arranged on a distributing station S2. A drive section 2 is constituted of an X-direction drive section 21 and a Y-direction drive section 22 moving a support member 1 and a Z- direction drive section 23 moving it vertically. A holding tool 3 holding a reaction container, a removing tool 4 removing the reaction container from the holding tool 3, and a sensor S are fitted to the support member 1. The defective distribution of the reaction container is detected by a sensor S provided on the support member 1, and the structure of a device is simplified. It is required to only detect the on/off-switching of the sensor S, the read-out result can be processed in a short time, and the reduction of the distribution processing speed of the reaction container by the device is prevented.

Description

Detailed Description of the Invention <Industrial Application Field> The present invention relates to a test reaction container dispensing device that automatically distributes a plurality of test reaction containers in which antigen-antibody reactions, etc. are carried out to microplates. It is.

<Five problems to be solved by conventional technology and invention> Conventionally, EIA using antigen-antibody reaction is one of the antigen measurement methods.
(encyme immunoassay) is known. This E
An example of IA will be explained with reference to Figure 1 which shows a process diagram. First, a solid-phase antibody (or antigen) is injected into a reaction container, and an antigen (or antibody) to be measured is added thereto. After the antigen-antibody reaction is carried out, the inside of the reaction vessel is washed with a washing solution in order to remove antigens (or antibodies) that have not bound to the immobilized antibody. Next, an enzyme-labeled antibody is added to cause the antigen-antibody reaction to occur again, and then washing is performed with a washing solution to remove enzyme-labeled antibodies that have not bound to the antigen.

Furthermore, after adding the substrate and injecting a reaction stop solution to stop the reaction, the amount of antigen can be determined by measuring the absorbance of each reaction container.

Among the EIAs mentioned above, in the microplate method that uses microplates, it is necessary to regularly arrange reaction vessels on which multiple types of antigens (or antibodies) for each test item are immobilized on the microplate. .

However, since there are a large number of reaction vessels arranged on the microplate, there is a problem in that manually distributing them one by one is time-consuming.

Therefore, an apparatus has been proposed that automatically dispenses each reaction container onto a microplate.

In the above device, a plurality of two types of microplates, preparative microplates and distribution microplates, are installed, and each preparative microplate has a reaction container containing the same type of antigen (or antibody). arranged on one side. On the other hand, each distribution microplate is for arranging reaction vessels in which different types of antigens (or antibodies) are immobilized in a fixed order. Then, the reaction vessels arranged on the preparative microplate are usually transferred one by one to each distribution microplate by a holder that holds the reaction vessels, in a predetermined arrangement.
Arranging on the distribution microplate is performed.

However, as mentioned above, in a device that automatically dispenses reaction vessels, there may be gaps in the reaction vessels arranged on the preparative microplate (empty sampling), or there may be gaps between the reaction vessels that were previously transported or the holder. Trying to dispense the next reaction vessel without it being removed from the container (double dispensing), or doubly dispensing the reaction vessel to a location where a reaction vessel has already been dispensed (double dispensing). This may cause maldistribution of the reaction vessel.

In order to eliminate poor distribution of reaction vessels, it is necessary to detect the presence or absence of reaction vessels at the accommodation positions of each reaction vessel on both microplates using multiple sensors installed at each accommodation position. It is conceivable to read the arrayed reaction containers row by row using an image sensor to check the presence or absence of reaction containers at each storage position.

However, as mentioned above, a large number of reaction vessels are accommodated on both microplates, so if sensors are to be provided corresponding to each accommodation position, an extremely large number of sensors will be required, making the structure complicated. , leading to increased sensor malfunctions and failures, increased costs, etc.

Furthermore, when an image sensor is used, a mechanism for moving the image sensor row by row, a processing device for analyzing the read image, and the like are required, resulting in a complicated structure.

Furthermore, even in the above-mentioned case, since it takes a long time to process the reading results by the sensor, there is a problem in that the speed of the dispensing process of the reaction vessels by the apparatus is reduced.

The present invention has been made in view of the above circumstances, and
It is an object of the present invention to provide a dispensing device for test reaction vessels that has a simpler structure and has a detection function that can detect maldistribution of reaction vessels more reliably and quickly.

Means for Solving the Problems> In order to solve the above problems, the test reaction container dispensing device of the present invention dispenses a predetermined reaction container from a plurality of test reaction containers or an arrayed preparative microplate. , comprising a transfer unit for transferring to a predetermined position on the dispensing microplate;
This transfer unit includes a holder that holds the reaction container by press-fitting its tip into the opening at the top of the reaction container from above, a detachment tool that detaches the reaction container from the tip of the holder, and the holder. A support member that supports the tool in a vertically movable manner and moves itself up and down by a predetermined amount to press the tip of the holder into the upper opening of the reaction vessel, and a support member that constantly presses the holder downward against the support member. A pressure spring and the support member,
a drive unit that moves between predetermined positions on both microplates; a sensor that detects whether the holder is pushed back upward against the pressing force of the pressing spring when the support member is lowered;
a determination means for determining maldistribution of the reaction vessels from the amount of descent of the support member and presence/absence of sensor detection when the support member is lowered at a predetermined position on any microplate; The apparatus is characterized by comprising a control means for stopping the operation of the apparatus when it is determined that

In addition, in the above distribution device, the amount of descent of the support member or g
1 and g2, which is shorter than this gl, and if the discrimination means detects the sensor before the support member descends by the amount of descent g1 on the preparative microplate, double preparative collection is performed. , and if the sensor does not detect it even after descending by the descending amount g1, it is determined that the reaction container is missing, and if it descends by the descending amount g2 on the support member or distribution microplate, the sensor detects it. It is preferable that if there is, it is determined that there is double distribution.

The above-mentioned descending amount g1 is, for example, the descending amount necessary for the holder to be able to hold the reaction container by press-fitting its tip from above into the opening at the top of the reaction container on the separation plate, p2 is the amount of descent by which the holder holding the reaction container can reliably drop the reaction container into a predetermined position on the distribution plate when the reaction container is separated from the tip of the holder on the distribution plate.

Furthermore, the distribution device includes a first hole that abuts the tip of the holder and pushes the holder back upward when the support member is lowered by a predetermined amount; ,
Only when the reaction vessel is held at the tip of the holder,
A simulated microplate having a second hole deeper than the first hole that contacts the tip of the reaction container and pushes the retainer upward, and the first hole of the simulated microplate allows the retainer to be pushed back upward. a sensor check means for detecting whether or not the holding tool is pushed back by the presence or absence of detection by the sensor, and checking whether or not there is an abnormality in the sensor itself; It is preferable to have reaction container checking means for detecting whether or not a reaction container with poor distribution is held in the holder.

In the test reaction container dispensing device of the present invention having the above configuration, the sensor detects whether or not the holder is pushed back upward against the pressing force of the pressing spring when the support member is lowered. The detecting and determining means determines whether there is a distribution failure in the reaction container based on the amount of descent of the support member and the presence or absence of detection by the sensor, and when it is determined that there is a distribution failure, the control means stops the operation of the apparatus.

The discriminating means determines that there is a poor distribution (double sorting) when the sensor detects a point in the middle of lowering the support member over the descending amount fI on the preparative microplate;
If the support member is lowered by the lowering amount R1 and there is no detection by the sensor, it is determined that there is a reaction container missing, and when the support member is lowered by the lowering amount P over the distribution microplate, the sensor detects no detection. If there is, there is poor distribution (double distribution)
It is possible to judge that.

In addition, when the dispensing device includes a simulated microplate, a sensor check means, and a reaction container check means, the sensor itself can be checked for abnormality, and
Since it is possible to automatically check whether or not there are any poorly distributed reaction vessels remaining in the holder, it is effective to perform this check before or after distributing the reaction vessels.

<Example> Below, regarding the dispensing device for the test reaction container of the present invention,
An explanation will be given with reference to drawings showing examples.

As shown in FIG. 1, the dispensing apparatus of this embodiment includes a table T, a sorting station S1 disposed on the table T, a dispensing station S2, a simulated microplate D, and a transfer unit U. We are prepared.

As shown in Fig. 2, on the sorting station Sl,
Four preparative microplates A, A, . . . are arranged, and two distribution microplates B, B are arranged on the distribution station S2. Each preparative microplate A and distribution microplate B contains
8 rows and 12 columns of holes AI, AI... for accommodating reaction vessels.
, Bl, Bl... are formed, and at the stage before distribution, only the holes AI, AI... of the preparative microplate A are filled with reaction vessels or arrays in which antigens (or antibodies) are immobilized. has been done.

In addition, on the table T, a plurality of preparative stations S1 are stacked and stocked, and the previous preparative station S
When the separation of the reaction vessels from 1 is completed, the separation station supply section T1 automatically supplies a new separation station S1 onto the table T, and the distribution stations S2 are stacked and stocked. distribution station S2
A dispensing station supply T2 is provided which automatically supplies a new dispensing station S2 onto the table T once the dispensing of the reaction vessels to is completed.

As shown in FIG. 4(a), the simulated microplate D has two types of holes Di and D2 with different depths for executing two types of check functions to be described later.

The transfer unit U includes a support member 1, and the support member 1.
It is equipped with a drive unit 2 that moves between predetermined positions on both microplates.

The drive unit 2 includes an X-direction drive unit 21 that moves the support member 1 in the longitudinal direction of the table T, a Y-direction drive unit 22 that moves the support member 1 in the width direction of the table T, and a Z-direction drive unit 23 that moves it up and down. . The amount of movement of the support member 1 by each of the drive units 21 to 23 is determined, for example, by the amount of pulses of a pulse motor serving as a drive source.

As shown in FIG. 3, the support member 1 is attached with a holder 3 for holding the reaction container, a detachment tool 4 for separating the reaction container from the holder 3, and a sensor S. .

The holder 3 is used to hold the reaction vessel R by press-fitting the tip 31 from above into the opening R1 (see FIG. 10) at the top of the reaction vessel R, and the guide portion of the support member 1 1, it is supported by the support member 1 so as to be vertically movable. Further, the holder 3 is always pushed downwardly with respect to the support member 1 by a coil spring 5 as a pressing spring, which is interposed between a flange portion 32 protruding from the outer periphery and the guide portion l. Being pressed.

The detachment tool 4 is slidably inserted into the holder 3 near the tip of the holder 3, and is lowered to the position indicated by the dashed line in the figure by activating the solenoid 6. Then, the reaction container held by the tip 31 of the holder 3 is removed from the tip 31. Note that the reference numeral 7 in the figure indicates a coil spring that holds the detachment tool 4 in the position shown by the solid line when the solenoid 6 is not operated.

As the sensor S for detecting whether or not the holder 3 has been pushed back upward against the pressing force of the coil spring 5, a so-called optical switch including a light emitting element and a light receiving element is used. When the holder 3 is pushed back upwards, this optical switch moves upward from the switch dog 33 at the upper end of the holder 3 to the position shown by the solid line in the figure and connects the light emitting element and the light receiving element. On-off switching is performed by interrupting the gap between the two, thereby detecting the rise of the holder 3.

The operation of the dispensing device for the test reaction container of this embodiment, which is composed of the above-mentioned parts, will be explained with reference to FIGS. , explained below.

When the device starts operating, the CPU (not shown) starts a sensor check to check whether there is any abnormality in the sensor S.

First, the X-direction drive section 21 and the Y-direction drive section 22 of the drive section 2
is activated, horizontally moves the support member 1, and places the tip 31 of the holder 3 into the first hole Dl of the simulated microplate D.
Align the top (Figure 4(a)).

Next, the X-direction drive section 23 of the drive section 2 is operated to lower the support member 1 and insert the tip 31 of the holder 3 into the first hole D1. The first hole D1 is set to a depth that pushes back the holder 3 upward when the support member 1 is lowered by a predetermined distance (N, which will be described later). For this reason, Fig. 4
As shown in +, when the support member 1 descends over a distance g, the holder 3 is pushed back upwards against the pressing force of the coil spring 5, and the switch dog 33 moves to the position where the sensor S is switched on and off. rises to. In this state, sensor S
If the sensor is turned on and off, there is no abnormality with the sensor, and the operation of the device proceeds to the next stage.

On the other hand, if the switch dog 33 rises to the position where the sensor S is turned on and off, but the sensor S cannot be turned on and off, there is something wrong with the sensor.
The CPU stops the operation of the device and issues an alarm to notify the user of the abnormality.

If there is no abnormality with the sensor, the CPU starts a reaction container check to check whether or not there remains a reaction container with poor distribution at the tip end 31 of the holder 3.

First, the X-direction drive section 23 of the drive section 2 operates to raise the support member 1 to its original height, and then the X-direction drive section 21 and the Y-direction drive section 22 of the drive section 2 operate to support it. Part 1
, and align the tip 31 of the holder 3 with the second hole D2 of the simulated microplate D (see Fig. 5).
a)).

Next, the two-way drive unit 23 of the drive unit 2 operates to lower the support member 1 and insert the tip 31 of the holder 3 into the second hole D2. The second hole D2 is set to a depth that pushes the holder 3 upward only when the reaction vessel is held at the tip 31 of the holder 3 when the support member 1 is lowered by a distance fl. ing.

Therefore, as shown in FIG. 5), if the reaction vessel R is not held at the tip 31 of the holder 3, even if the support member 1 is lowered by the distance g1, the holder 3 will not move upward. The switch dog 33 does not turn the sensor S on and off. Therefore, the CPU determines that there is no poorly distributed reaction container remaining in the distal end portion 31 of the holder 3, and the operation of the apparatus proceeds to the next stage.

On the other hand, as shown in FIG. 6(a), the tip 3 of the holder 3
In 1, when the reaction container R that was forgotten to be dispensed is retained,
As shown in FIG. 6), when the support member 1 is lowered by a distance l1, the holder 3 is pushed back upward against the pressing force of the coil spring 5, the switch dog 33 is raised, and the sensor S
can be switched on and off. When the on-off switching is performed, the CPU detects that a poorly distributed reaction container remains in the holder 3, stops the operation of the device, and issues an alarm to notify of the abnormality.

When it is determined that there are no poorly distributed reaction vessels remaining at the tip 31 of the holder 3, the CPU starts distributing the reaction vessels R from the preparative microplate A to the distribution microplate B according to a predetermined distribution program. do.

First, the X-direction drive section 21 and the Y-direction drive section 22 of the drive section 2
is activated, horizontally moves the support member 1, and moves the tip 31 of the holder 3 to a predetermined position on the preparative microplate A.
(Fig. 7(a)
).

Next, the two-way drive unit 23 of the drive unit 2 is activated to lower the support member 1 by a distance fl, press the tip 31 of the holder 3 into the upper opening R1 of the reaction vessel, and press the tip 31 of the holder 3 into the upper opening R1 of the reaction vessel R. is held by the tip 31 of the holder 3 (FIG. 7(b)). At this time, the distance that the holder 3 can descend is set to be smaller than the moving distance p1 of the support member 1, and when the press fitting is performed, the holder 3 resists the pressing force of the coil spring 5. The switch dog 33 is pushed back upwards, and the sensor S is turned on and off. When the on-off switching is performed, the CPU determines that the holder 3 has completed holding the reaction vessel, and the operation of the apparatus proceeds to the next stage.

Note that if the reaction vessel R is not accommodated in the predetermined hole A1 on the preparative microplate A, even if the support member 1 is lowered by a distance [l], as shown in FIG. The holder 3 is not pushed back upwards, and the switch dog 33 does not turn on and off the sensor S. Therefore, the CPU determines that the required reaction vessel R is not on the preparative microplate A. The system stops the operation of the device and issues an alarm to notify the user of any abnormality.

In addition, when a reaction container R that has been forgotten to be dispensed is held at the tip 31 of the holder 3, as shown in FIG. 8+b+,
The support member 1 is lowered by a distance g shorter than a predetermined descending distance ff.
At the stage of straddling and descending, the two reaction vessels R and R overlap and are pushed back upward against the pressing force of the holder 3 or the coil spring 5, causing the switch dog 33 to rise and the sensor S
can be switched on and off. For this reason, the CPU
It is detected that a reaction container with poor distribution remains in the holder 3, it is determined that double fractionation has occurred, the operation of the apparatus is stopped, and an alarm is issued to notify of the abnormality.

When the reaction container R is successfully held by the holder 3, the X direction drive section 21 and the Y direction drive section 22 of the drive section 2
is actuated to horizontally move the support member l and place the tip 31 of the holder 3 into a predetermined hole B on the distribution microplate B.
Set to 1.

Next, the Z-direction drive unit 23 of the drive unit 2 is activated to lower the support member 1 by a distance g2 (FIG. 9(al). As shown in the figure, the reaction vessel R is inserted into the hole B without any support.
1, the holder 3 is not pushed back upwards,
The sensor S is not switched on and off by the switch dog 33.

Therefore, the CPU determines that the predetermined hole B1 is open, and operates the solenoid 6 as shown in FIG. It is removed from the tip 31. The removed reaction container R is accommodated in a predetermined hole B1, as shown in the figure, and the distribution of one reaction container R is completed.

Note that if the reaction container R is already accommodated in the predetermined hole B1 on the distribution microplate B, the process shown in FIG. 9(C)
As shown in , when the support member 1 has descended by a distance g2, the two reaction vessels R and R overlap, and the holder 3
is pushed back upward against the pressing force of the coil spring 5, the switch dog 33 rises, and the sensor S is switched on and off.

Therefore, the CPU determines that double distribution has occurred, and
Stops the operation of the device and issues an alarm to notify you of any abnormality.

When the distribution of one reaction vessel R is completed without any problems, CP
U again places the support member 1 on the simulated microplate D.
Then, a reaction container check is started to check whether there are any poorly distributed reaction containers remaining at the tip 31 of the holder 3.

Then, after confirming that there are no reaction containers remaining with poor distribution, distribution of the next reaction container is started.

As described above, in the testing reaction container dispensing device of this embodiment, the single sensor S provided on the support member detects the poor distribution of the reaction containers R, so the structure of the device is not complicated. . Furthermore, since it is sufficient to detect the on-off switching of the sensor S, the time required to process the reading results is short, and there is no fear that the dispensing processing speed of the reaction vessels by the apparatus will be reduced. Therefore, the device of this embodiment has a simpler structure and can detect maldistribution in reaction vessels more reliably and quickly.

Note that the dispensing device for testing reaction containers of the present invention is not limited to the embodiment shown in the above figures.

For example, in the illustrated embodiment, a preparative stain supply T1 for supplying a preparative station S1 and a dispensing station supply T2 for supplying a dispensing station S2 are provided; It's not necessarily necessary.

Furthermore, in the illustrated embodiment, an optical switch equipped with a light emitting element and a light receiving element is used as a sensor S that detects whether the holder is pushed back upward against the pressing force of the pressing spring. Alternatively, other conventionally known sensors such as limit switches may also be used.

In addition, various design changes can be made without changing the gist of the present invention.

<Effects of the Invention> The testing reaction container distributing device of the present invention is configured as described above, and maldistribution of the reaction containers is detected by one sensor provided on the support member, which makes it easier to use. With this structure, maldistribution in reaction vessels can be detected more reliably and quickly.

In addition, when a simulated microplate, a sensor check means, and a reaction vessel check means are provided, in addition to detecting poor distribution, the sensor itself can be checked for abnormalities, and the reaction vessel in the holder can be checked. There is an advantage that it is possible to automatically check whether or not there is any remaining data.

[Brief explanation of the drawing]

FIG. 1 is a perspective view showing an embodiment of the dispensing device for a test reaction container according to the present invention, 'I! Figure N2 is a plan view showing the arrangement of the preparative microplate, distribution microplate and simulated microplate in the above example, Figure 3 is a front view of the support member which is the main part of the above example, and Figure 4 <aJ+b+
5 (ω-mount) and FIG. 6 (ω+b+ are partially cut-away front views showing the reaction vessel check process in the above example, and FIG. 7 The figure (mountain aJ) is a partially cutaway front view showing the reaction vessel separation process in the reaction vessel distribution process in the above example, and Figure 8 (ω curve indicates a poor distribution state in the reaction vessel separation process). Partially cutaway front view, FIG. 9 (a) is a partially cutaway front view showing the reaction container distribution step of the reaction container distribution process in the above example, FIG. 9 (C1 is the reaction container distribution step) 10 is a perspective view of a reaction vessel used in the example, and FIG. 1 is a process diagram showing an example of conventional EIA. 1... Support member , 2... Drive part, 3... Holder, 31... Tip part, 4... Removal tool, 5... Pressing spring, A... Preparative microplate, B... Distribution Microplate, 9... Simulated microplate, Dl... First hole, D2... Second hole, S... Sensor, transfer unit for U. Patent 8 Kojin Otsuka Electronics Co., Ltd. Agent

Claims (1)

[Claims] 1. A transfer unit that transfers a predetermined reaction container from a preparative microplate in which a plurality of test reaction containers are arranged to a predetermined position on a distribution microplate; A holder that holds the reaction container by press-fitting its tip into the opening at the top of the reaction container from above; a detachment tool that detaches the reaction container from the tip of the holder; and a detachment tool that allows the holder to move up and down. a support member that presses the tip of the holder into the upper opening of the reaction vessel by moving itself up and down by a predetermined amount; a pressing spring that constantly presses the holder downward against the support member; a drive unit that moves the support member between predetermined positions on both microplates; a sensor that detects whether the holder is pushed back upward against the pressing force of the pressing spring when the support member is lowered; a determining means for determining maldistribution of the reaction container from the amount of descent of the support member and presence or absence of detection by a sensor when the support member is lowered at a predetermined position on any microplate; A dispensing device for a test reaction container, comprising: a control means for stopping the operation of the device when it is determined that 2. The descending amount of the support member is set to two stages, l_1 and l_2, which is shorter than this l_1, and the discriminating means detects the detection by the sensor before the support member descends by the descending amount l_1 on the preparative microplate. distribution of the reaction vessel, if there is no sensor detection after descending by a descending amount l_1, and if there is a sensor detection when the support member has descended by a descending amount l_2 on the dispensing microplate. The dispensing device for testing reaction containers according to claim 1, which determines whether or not the container is defective. 3. When the support member is lowered by a predetermined amount, the first hole contacts the tip of the holder and pushes the holder back upward; and when the support member is lowered by a predetermined amount, the tip of the holder A simulated microplate having a second hole deeper than the first hole that comes into contact with the tip of the reaction container and pushes the holder back upward only when the reaction container is held in the part; A sensor check means for detecting whether or not the holder is pushed back by the first hole of the simulated microplate based on the presence or absence of detection by the sensor, and checking whether there is any abnormality in the sensor itself; Detects whether or not it is pushed back based on the presence or absence of sensor detection,
2. The testing reaction container dispensing device according to claim 1, further comprising reaction container checking means for checking whether or not a reaction container with improper distribution is held in the holder.