JPH02185387A - Transfer device for bead - Google Patents

Abstract

PURPOSE:To surely perform transfer and input even in case of the preservation state of a bead being in dry and wet states, by forming a double structure in which a pressure reducing pipe and pressurizing pipe of different diameters are provided co-axially respectively and providing a transfer nozzle fixing the bead by suction and releasing by arranged the pressure reducing pipe and pressurizing pipe to the bead attaching port of the tip. CONSTITUTION:A transfer nozzle 2 is made of a double structure with the pressurizing pipe 17 and pressure reducing pipe 10 consisting of two different diameters being co-axial. So at the bead suction time, pressurizing can be executed by a pressurizing pump 11 by a pressure reducing and pressurizing control means, with performing suction by a pressure reducing suction pump 6. Thus, the release of the bead 1 can surely be performed. Also, the reservation liquid accumulated at the tip part of the transfer nozzle 2 inside at the bead 1 suction time is fed onto a pressure reducing pipe 16 upper face or into a trap bottle by pressurizing. By the pressurizing by this pressurizing pump 11, the fall of the reversation liquid left at the tip of the transfer nozzle 2 can be prevented as well as the release of the bead 1.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a bead transfer device, particularly an analyzer that analyzes a sample by inserting beads with a reagent attached thereto. This invention relates to an improvement of a bead transfer device for transferring beads.

[Prior Art] In the medical field, EIA (enzyme immunoassay) and RIA (radioimmunoassay) for sample testing are widely used as testing methods for cancer, infectious diseases, hormones, and the like.

This type of analyzer includes the EIA method and RIA method that use bead solid phase, and this method is the most common method among the immunological ultratrace (constant jl) + 111 standard methods, and has a high measurement accuracy. It is widely used because it is safe, inexpensive, and has a high level of safety.

In this type of analysis method, antibodies are coated around beads, and the beads are transferred into a predetermined reaction container to perform a desired antigen-antibody reaction with a reagent.

The beads that perform this antigen-antibody reaction can be stored both in a dry state and in a storage buffer solution! ! ! (wet), and these beads are transported as follows.

(B) Transfer from the bead storage container to the reaction container (test tube, tray, etc.) (bead loading) (B) After washing the beads, transfer from the reaction container to another container (second reaction or &1 regular time) Bead transfer) (c) Transfer from the reaction container to another reaction waste container or washing container after the reaction is completed. Such a conventional bead transfer device is shown in FIG. 5.

There are those shown in FIGS. 6 and 7.

FIG. 5 shows an apparatus in which beads are transferred to a predetermined reaction container only by reduced pressure and suction.

In the figure, 1 is a bead coated with an antibody, 2 is a transfer nozzle for sucking and fixing the beads at the tip of the nozzle and transferring them to a reaction container at a predetermined position, and 3 is a bead 1.
This is a vacuum suction device that reduces the pressure in the tube in order to suck it with the transfer nozzle 2. An on-off valve 4 provided between the transfer nozzle 2 and the reduced pressure suction device 3 is a switching valve for selecting either to reduce the pressure inside the pipe or to release it to atmospheric pressure.

Further, the reduced pressure suction device 3 includes a trap bottle 5 and is composed of a reduced pressure suction pump 6, which uses the transfer nozzle 2 to reduce the pressure inside the tube for sucking the beads.

The trap pin 5 stores the storage solution remaining in the transfer nozzle, thereby preventing the storage solution remaining in the tube from flowing into the suction pump 6 during bead suction.

The conventional bead transfer device shown in FIG. 5 has the above structure, and its operation will be explained below.

That is, when a conventional bead transfer device suctions and fixes beads from a bead storage container or a reaction container using the transfer nozzle 2, the transfer nozzle 2 is moved to a fixed position by a drive mechanism (not shown), and one bead in the container is suctioned. do.

At this time, since the suction pump 6 is activated and the switching valve 4 is in a closed state, the beads are sucked into the tip of the transfer nozzle by the suction force of the vacuum suction pump 6. And after this,
The transfer nozzle 2 is pulled up together with the beads 1 by a drive mechanism and transferred to a predetermined reaction container.

Next, after transferring to a predetermined reaction container, to remove the beads, the vacuum suction pump 6 is stopped and the on-off valve 4 is opened to introduce atmospheric pressure into the tube. Then, the suction force by the vacuum suction pump 6 disappears, and the beads are removed from the transfer nozzle 2.

In this way, the antibody-coated beads 1 are placed one by one into a reaction container at a predetermined position, and a desired antigen-antibody reaction is performed.

FIG. 6 shows a mechanical detachment mechanism as another device for detaching the beads sucked into the transfer nozzle 2. By using the above-mentioned atmospheric pressure method in combination, the beads are forcibly removed and the removal performance is improved.

That is, in the case of FIG. 6(a), on the top surface of the reaction vessel,
The sucked beads are pushed out from the side of the transfer nozzle 2 by the claw 12, and the beads 1 are dropped into a predetermined reaction container.

Further, in the case of FIG. 6(b), the transfer nozzle 2 to which the beads 1 are suctioned and fixed is moved laterally by a drive mechanism (not shown) to contact the upper inner wall of the reaction vessel 13, and the beads 1 are removed. It is something.

Next, FIG. 7 shows a conventional bead transfer device using a combination of reduced pressure suction and a pressurizing device.

In the bead transfer device shown in FIG. 5 described above, the beads were caused to fall under their own weight and detached due to atmospheric pressure, but in FIG. They are different in some respects.

That is, the apparatus shown in FIG. 7 is provided with a pressurizing pump 11 via an on-off valve 4 and a switching valve 10.

Therefore, when the beads are released as described above, the on-off valve 4
is switched and pressurized by the pressure pump 11, and the transfer nozzle 2
The pressure inside the tube is increased, and the beads 1 that have been suctioned are released by the pressurizing force.

In this way, the transfer nozzle 2 shown in FIGS. 5 and 7 alternately increases or decreases the pressure inside the nozzle tube in accordance with the suction fixation and detachment of beads through one tube, and transfers the beads 1. Is going.

Such specimen testing, that is, antigen-antibody reaction, requires bead transport and optimal analysis conditions, and operations and processing are based on manual methods that require complicated steps and time. Automation is happening.

[Problems to be Solved by the Invention] As described above, according to the conventional bead transfer device, when the beads sucked into the transfer nozzle are introduced into a predetermined reaction container, that is, when the beads are removed, the beads are In addition, there is a problem in that the storage solution remaining in the transfer nozzle during bead suction may fall off when the beads are detached.

For this reason, sample testing cannot be performed correctly due to bead transfer, and the reaction is affected, making it impossible to obtain accurate measurement accuracy.
It has been difficult to fully automate such a bead transfer device.

That is, in the conventional example shown in FIG. 5, when only atmospheric pressure is released when the beads are detached, the beads may not fall due to the adsorption effect of the reagent attached around the beads. The beads are made of polyethylene, etc., and have a light specific gravity of 1.05, so they are difficult to fall off.Especially, when the beads are stored in a wet state (when stored in a storage solution), they do not fall into the transfer nozzle. The storage solution accumulates and the beads are tightly fixed over a wide area at the tip of the transfer nozzle.
There was a problem with the beads not falling off due to surface tension.

Furthermore, according to the mechanical separation mechanism of beads shown in FIG.
Although the beads are reliably dropped by contact with the claw 12 or the inner wall surface of the container, there is a problem that the contact scratches the surface of the beads and causes the coating to peel off.

As a result, the antibodies around the beads were damaged, affecting the antibody reaction.

Furthermore, since the transfer nozzle comes into contact with the inner wall surface of the container, the transfer nozzle needs to be strong, and it is also necessary to securely fix the reaction container.

In the conventional example shown in FIG. 7, since the pressure is applied by the pressure pump 11, the beads can be removed reliably, but since the storage solution during suction remains in the transfer nozzle,
There was a problem in that the preservation solution would fall due to the increased pressure as the beads detached.

Therefore, there is a drawback that the reaction cannot be carried out at a constant concentration due to the influence of the dropped storage solution.

As described in detail, the present invention has been made in view of the above-mentioned conventional problems, and its purpose is to ensure the attachment and detachment of beads, fully automate bead transfer, and improve the process of removing beads. It is an object of the present invention to provide an improved bead transfer device that can reliably prevent the storage solution remaining in the transfer nozzle from falling, thereby allowing highly accurate inspection.

[Means for Solving the Problems] In order to achieve the above object, the present invention has a double structure in which a decompression tube and a pressurization tube having different diameters are coaxially provided, and a bead attachment/detachment port at the tip. a transfer nozzle that is provided with a pressure reduction tube and a pressure tube to suction fix and remove the beads; a vacuum suction pump that reduces the pressure in the pressure reduction tube; a pressure pump that increases the pressure in the pressure tube; The present invention is characterized by comprising a depressurization/pressurization control means that performs control by reducing the pressure inside the pressure reducing tube when suctioning and fixing the beads, and pressurizing the inside of the pressurizing tube when removing the beads.

[Function] Therefore, according to the bead transfer device according to the present invention, since the transfer nozzle has a coaxial double structure with a pressure tube and a pressure reduction tube having two different diameters, when suctioning beads,
While suction is being performed by the vacuum suction pump, the pressure can be increased by the pressure pump by the pressure reduction/pressurization control means. This makes it possible to reliably remove the beads.

Further, the preservation solution accumulated at the tip of the transfer nozzle during bead suction can be sent to the top surface of the pressure reducing tube or to the trap bottle by applying pressure.

Therefore, the pressure applied by the pressure pump can prevent the beads from detaching and also prevent the preservation solution remaining at the tip of the transfer nozzle from falling.

[Embodiments] Hereinafter, preferred embodiments of the present invention will be described based on the drawings.

FIG. 1 shows an example of the configuration of a bead transfer device according to the present invention. In the figure, the same members as in FIG. 7 are given the same reference numerals, and their explanations will be omitted below.

The transfer nozzle 2 in the figure is composed of a pressure tube 17 and a pressure reduction tube 16, and the cross section shows a state in which beads 1 are being sucked.

The transfer nozzle 2, which is a feature of the present invention, has a decompression tube 16 and a pressurization tube 17 having different diameters, which are coaxially arranged in a double structure. However, a pressurizing pipe 17 is provided on its outer periphery. A bead detection mechanism 15 is provided on the upper surface of the transfer nozzle 2.
is a device that detects the presence or absence of beads in a storage or preservation container.It detects the presence or absence of beads in the container by detecting the vertical movement of the transfer nozzle 2 when the tip of the transfer nozzle 2 comes into contact with the beads 1. (Details will be described later). The bead detection mechanism 15 is also movable in the vertical direction in order to transfer the transfer nozzle 2 to a predetermined position by a drive mechanism (not shown) and to suck or remove the beads 1.

Further, the pressurizing pipe 17 of the transfer nozzle 2 is connected to the pressurizing pump 11 via the switching valve 10.

This pressurizing pump 11 is a pressurizing pump for removing beads, and supplies pressurizing force into the pressurizing tube.

The switching valve 10 is for supplying the pressurizing force supplied from the pressurizing pump 11 to the pressurizing pipe 17 of the transfer nozzle 2, and is switched when the beads are detached to introduce the pressurizing force.

Moreover, when beads are sucked, this switching valve 10 is closed,
Although it is released to the outside, such control is automatically performed by a control device (not shown).

Next, the pressure reducing pipe 16 in the transfer nozzle described above is connected to the on-off valve 4.
The on-off valve 4 is further connected to a vacuum suction pump 6 via a trap bottle 5.

Further, a pressure sensor 14 is provided in the pressure reducing tube 16 of the transfer nozzle 2 for suctioning and fixing the beads and monitoring the transfer state. Then, the pressure sensor 14 detects when the beads are sucked, that is, when the transfer nozzle 2 is in a reduced state, and confirms that the beads are suctioned and fixed.

Therefore, by checking the detection state of the pressure sensor 14, the user can know that the beads have been reliably transferred to the transfer destination when the pressure is reduced and if the pressure is reduced and maintained.

In this embodiment, the pressure sensor 14 is provided in the pressure reducing tube, but it can also be provided in the pressurizing tube to monitor pressurized conditions such as bead detachment.

The on-off valve 4 is a switching valve for reducing the pressure in the pressure reducing pipe by the pressure reducing suction pump 6 as described above. and,
This on-off valve 4 is automatically controlled by a control device (not shown) when the beads are suctioned and fixed together with the switching valve 10 which pressurizes when the beads are removed.

The bead transfer device according to this embodiment has the above-mentioned configuration, and the bead transfer state will be described below as an example of a case where beads are taken out from a reaction container and beads are put into another reaction container.

In the figure, the transfer nozzle 2 is moved by a drive mechanism (not shown) to a reaction container in which beads 1 are immersed in a reagent or the like at a predetermined position. Then, the tip of the transfer nozzle is immersed into the container, and here the bead detection mechanism 15 confirms the presence or absence of beads in the container. This is detected by moving the transfer nozzle up and down when the tip of the transfer nozzle 2 comes into contact with the beads 1, and when the presence or absence of beads is confirmed, the on-off valve 4 is opened and the vacuum suction pump 6 reduces the pressure in the pressure reduction tube.

Therefore, the beads are suctioned and fixed in the vacuum tube of the transfer nozzle 2 at the time of contact. Furthermore, at this point, the storage liquid in the container is flowing into the tip of the transfer nozzle 2, but is also flowing into the pressure reducing pipe 16 located on the same axis. Here, since the switching valve 10 is closed, the storage liquid does not flow into the pressurizing pipe 17.

The beads suctioned and fixed to the transfer nozzle 2 in this manner are transferred to the next reaction container by the drive mechanism in this state.

When removing the beads, the pressure tube side of the switching valve 10 is opened to pressurize the inside of the pressure tube, thereby causing the beads 1 to fall.

Although the case where the beads are stored in a wet state has been described above, the beads can be transferred and removed without any problem even when the beads are stored in a dry state.

In the above case, a case has been described in which the pressure reduction control and the pressure increase control are performed separately, but in this case, a small amount of storage liquid may accumulate at the tip of the transfer nozzle 2. Therefore,
In this embodiment, control can be performed to simultaneously perform depressurization and pressurization.

Here, the transfer nozzle 2, which is a feature of the present invention, is fixed to bead suction, that is, if the switching valve IO is switched at the same time as the pressure is reduced, and the pressurizing pipe side is opened, the inside of the pressurizing pipe can be pressurized by the pressurizing pump 11. . Of course, this applied force is smaller than the vacuum pressure, and the beads remain attracted by the vacuum suction force.

Therefore, since the inside of the pressure tube is pressurized, most of the storage liquid in the transfer nozzle flows into the pressure reduction tube.

Then, when the beads 1 are transferred to another predetermined reaction container, when the on-off valve 4 is switched to drop the beads into the reaction container, the pressure reducing pipe is closed and the transfer nozzle 2 is only pressurized, so that the beads can be dropped into the reaction container. can be dropped.

In this case, most of the residual storage solution in the pressure tube flows into the pressure reduction tube, so it is possible to prevent the residual storage solution from falling.

In this way, since the pressure tube 17 and the pressure reduction tube 16 are each coaxially formed into a double structure by the transfer nozzle 2 of the present invention, it is possible to apply not only suction but also pressure when beads are suctioned and fixed. As a result, the storage solution does not remain in the tip of the transfer nozzle 2, that is, in the pressurizing tube, so that it is possible to reliably prevent the residual storage solution from falling when the beads are separated by pressure. Therefore,
It is optimal if the beads are stored wet.

Next, FIG. 2 shows another embodiment of the transfer nozzle 2 according to the present invention, and the two-wheeled structure is shown in cross section in the figure. That is, in the figure, a pressure reduction pipe 16 and a pressure application pipe 17 are provided separately and in parallel, and the pressure reduction pipe 16 and pressure application pipe 17 are arranged at the tip of the transfer nozzle, forming a bead opening. It is characterized by what it does. As described above, in this transfer nozzle 8 having a biaxial structure, storage solution accumulates at the tip of the transfer nozzle during bead suction, but as with the transfer nozzle 2 having a coaxial structure shown in Fig. Pressure can be applied to move the storage solution to the upper part of the vacuum tube or allow it to flow into the trap bottle 5.

As a result, there is an effect of preventing the storage solution from falling when the beads are detached by pressure.

Next, an embodiment of the bead detection mechanism 15 described above will be described using FIG. g83 and FIG. 4.

FIG. 3 is an example of a drive mechanism for a transfer nozzle that detects the presence or absence of beads, and is a side view.

In the figure, the transfer nozzle 2 is connected to the tip of a movable arm 21, which has a drive shaft 22, a drive part 25
It is set in.

Note that the drive shaft 22 moves the transfer nozzle 2 to zero.
It can be moved freely.

The drive section 25 and the movable arm 21 are held by a fulcrum 21b and a spring 24, and a detection switch 23 is provided on the end surface of the drive section 25. And this detection switch 23
The contact portion 23a is adapted to contact the upper end surface portion of the movable arm 21 when it is movable. That is, when the beads 1 come into contact with the tip of the transfer nozzle 2, the transfer nozzle 2 and the movable arm 21 are integrated, so the movable arm 21
moves with 21b as a fulcrum, pushes up the contact portion 23a, and switches the detection switch 23 from the off state to the on state. In this way, by detecting the vertical movement of the transfer nozzle 2, the presence or absence of the beads 1 in the container is detected, and then the on-off valve 4 and the switching valve 10 are controlled, and the beads 1 are sucked.

On the other hand, FIG. 4 shows another example of the drive mechanism of the transfer nozzle for detecting the presence or absence of beads, and is a partially cross-sectional view seen from the side.

In the figure, the transfer nozzle 2 is supported by a support portion 27 via a spring 24, and the transfer nozzle 2 is configured to move vertically by expansion and contraction of the spring 24.

This support part 27 is a drive part 25 having a drive shaft 22.
A detection switch 23 is provided at the upper end of the support portion 27, and its contact portion 23a is pressed by a stopper 26 integrally provided at the upper end of the transfer nozzle 2. is in the on state.

Therefore, when the bead comes into contact with the tip of the transfer nozzle 2, the transfer nozzle 2 moves in the vertical direction, that is, toward the top surface, and the contact portion 23a of the detection switch 23 comes off the stopper 26, and the detection switch 23 changes from the on state to the off state. Switch. This makes it possible to detect the presence or absence of beads in the container.

[Effects of the Invention] As explained above, according to the present invention, a double-structured transfer nozzle is provided at the bead attachment/detachment port at the tip, and a pressure reducing tube and a pressurizing tube each having a different diameter are coaxially provided. Alternatively, by having a transfer nozzle in which a decompression tube and a pressurization tube are provided separately and in parallel, it is possible to reliably transfer and input the beads even when the beads are stored in a dry or wet state.

In addition, in the present invention, by simultaneously controlling depressurization and pressurization when attaching and detaching beads, unnecessary storage solution or cleaning solution remaining in the transfer nozzle is not dropped, and analysis accuracy and reliability can be ensured. Analyzers can be obtained.

Furthermore, in the present invention, by using a bead detection mechanism,
It is possible to detect the presence or absence of beads in the container, and
By using a monitoring function using a pressure sensor, the user can easily check whether the beads are suctioned, fixed, detached, or transferred.

Therefore, according to the bead transfer device of the present invention, it is possible to fully automatically carry out manual inspections that require complicated steps and time.

[Brief explanation of the drawing]

FIG. 1 is a block diagram of the bead transfer device of the present invention, FIG. 2 is a diagram showing a double-structured transfer nozzle of the present invention, and FIGS. 3 and 4 are transfer nozzles for detecting the presence or absence of beads. FIG. 5 is a configuration diagram of a conventional bead transfer device using vacuum suction. FIG. 6 is an explanatory diagram showing a conventional mechanical detachment mechanism. FIG. 7 is a diagram showing a conventional vacuum suction mechanism. FIG. 2 is a configuration diagram of a bead transfer device that uses a combination of suction and pressurization. 1...Beads 2.8...Transfer nozzle 4...Opening/closing valve 6...Reducing pressure suction pump 10...Switching valve 11...Pressure pump 14...Pressure sensor 15...Beads Detection mechanism 16... Pressure reducing tube 17... Pressurizing tube 23... Detection switch 23a... Contact portion. 4 ton light piece sensuality compensation 1st diagram 2nd axis 7 speed ) Outline of discipline, duty and death - Figure 6

Claims (3)

[Claims] (1) A double structure in which a decompression tube and a pressurization tube of different diameters are installed coaxially, and a decompression tube and a pressurization tube are placed in the bead attachment/detachment port at the tip to suction, fix, and remove the beads. a transfer nozzle that reduces the pressure in the pressure reduction tube, a pressure reduction suction pump that reduces the pressure in the pressure reduction tube, and a pressure pump that increases the pressure in the pressure reduction tube, and when the beads are suctioned and fixed, the pressure in the pressure reduction tube is reduced and the beads are separated. A bead transfer device characterized by comprising a depressurization/pressurization control means that sometimes pressurizes and controls the inside of a pressurizing tube. (2) The bead transfer device according to claim (1), wherein the transfer nozzle has the pressure reducing tube and the pressurizing tube arranged side by side separately and independently, and sucks and fixes the beads and removes them. (3) In the apparatus according to claim (1) or (2), a bead detection device determines the presence or absence of beads by detecting vertical movement of a transfer nozzle when suctioning and fixing beads, and the vacuum suction pump or A bead transfer device characterized by comprising: a pressure detection device that is provided between a pressure pump and the transfer nozzle, and detects the suction and detachment state of beads by reducing and pressurizing a predetermined pressure.