JP2012152213A - Device for aggregating/dispersing magnetic particle in liquid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a device for performing the separation and dispersion of magnetic particles and liquid in a high efficiency by aggregating the magnetic particles mixed and suspended in the liquid in a container at an optional position by moving a magnetic means.SOLUTION: In the device for aggregating/dispersing the magnetic particles in the liquid, the magnetic particles 11 are mixed and dispersed in the liquid 10 housed in the container 1, the magnetic particles 11 are moved to a predetermined position in the container 1 by using the magnetic means 4 from the outside of the container 1, thereby the suction of the liquid 10 can be carried out by using a sucking means 2, the magnetic means 4 is moved relatively to the container 1 via a moving means, the magnetic particles are aggregated 11 at the optional position in the container 1.

Description

  The present invention relates to an apparatus for assembling / dispersing magnetic particles in a liquid, and in particular, magnetic particles mixed and suspended in a liquid in a container are aggregated at an arbitrary position by moving magnetic means, thereby magnetic particles The present invention relates to a novel improvement for efficiently separating and dispersing liquids and liquids.

For example, the configuration disclosed in Patent Documents 1 and 2 can be shown in FIG. 18 as an apparatus for dispersing and dispersing magnetic particles of a DNA protein screening apparatus of this type that has been conventionally used.
That is, in the protein screening apparatus disclosed in Patent Document 1 described above, in order to extract protein from the liquid to be screened contained in the container 1, the binding step A, the washing step B and the extraction shown in FIG. A screening process consisting of process C is employed.

  First, in the binding step A, a protein or chemical substance, which is a sample of a reagent, and magnetic fine particles are injected into a container 1 through a piston pump 3 with a tip 2 which is a suction means and stirred, and then the bottom of the container 1 By providing the magnet 4 as a magnetic means, the magnetic fine particles are gathered at the bottom of the container 1 to perform solid-liquid separation by magnetism.

Next, after the supernatant in the solid-liquid separated container 1 is sucked with the chip 2 and taken out to the outside, the cleaning liquid is put into the container 1 using the piston pump 3 in the cleaning step B, and the chip 2 is placed in the container 1. Stirring is performed by inserting into the tube and repelling (pipetting) suction and discharge.
Thereafter, similarly to the coupling step A, the magnet 4 is provided at the bottom of the container 1 to perform solid-liquid separation by magnetism, and the cleaning is completed by sucking and discarding the supernatant.

Next, in the extraction step C, an extraction liquid, which is a dissociation reagent, is injected into the container 1 and separated by stirring by pipetting by suction and discharge of the chip 2. By providing the magnet 4 at the bottom, magnetic solid-liquid separation is performed.
In this state, since the supernatant contains a protein or chemical sample, the extracted sample can be recovered by aspirating and removing the supernatant with the chip 2.

JP 2006-194671 A JP 2001-70827 A

Since the conventional apparatus for collecting / dispersing magnetic particles in a liquid is configured as described above, the following problems exist.
That is, in the case of solid-liquid separation in which the liquid is sucked in each of the processes A, B, and C using the magnetic means described above, if there is a magnetic particle near the suction port of the chip that sucks the liquid, it may be mistakenly sucked. Since the property is high, the position for collecting the magnetic particles is preferably near the liquid surface as far as possible from the suction port of the chip.
On the other hand, when the magnetic particles are dispersed using the water flow generated by the suction and discharge of the liquid by the piston pump provided on the tip in the separation by stirring, the position of the magnetic particles collected near the liquid surface far from the tip suction port is remarkably increased. There is a concern that the water flow is attenuated and the dispersion time is prolonged. Therefore, it is desirable that the magnetic particles are collected near the tip suction port where the liquid flow is fast. As described above, the ideal magnetic particle recovery position differs between “solid-liquid separation” and “dispersion”. Therefore, the magnetic position can be moved arbitrarily to change the recovery position, and the recovered magnetic particles can be guided to an arbitrary position. If a possible structure and process can be added, the efficiency of the process can be improved and the magnetic position can be moved to an appropriate position even with respect to changes in the liquid volume, but the magnetic means is attached to the bottom of the container. However, it is difficult to reduce the solid-liquid separation and dispersion time because the gathering position of the magnetic particles in the container by magnetic attraction cannot be changed according to various purposes.

  An apparatus for collecting / dispersing magnetic particles in a liquid according to the present invention mixes and disperses magnetic particles in a liquid contained in a container, and disperses the magnetic particles in the container using magnetic means from the outside of the container. By moving to a predetermined position, at least the liquid can be sucked using a suction means, and the magnetic means is moved with respect to the container via the moving means, so that any position in the container can be obtained. In the apparatus for collecting / dispersing magnetic particles in a liquid in which the magnetic particles are assembled to each other, the magnetic means is a permanent magnet or an electromagnet, and the moving means moves the magnetic means on the side of the container. The container is made of any one of a tube, a chip, a microplate, and a PCR plate, and the moving means is a side portion of a housing having a number of containers held in each holding hole. A motor controlled by a controller, a pinion provided on the motor, a rack that is vertically movable on the side of the housing and meshes with the pinion, and guides the rack to be vertically movable A rack guide body provided in the casing, the rack guide body including a rack coupling body having a C-shaped sliding body having the rack and a C-shape; And a guide body that is provided and engages with the C-shaped sliding body.

Since the apparatus for collecting / dispersing magnetic particles in a liquid according to the present invention is configured as described above, the following effects can be obtained.
That is, since the corresponding position of the magnetic means in the container can be arbitrarily changed, the magnetic means can be moved via the moving means having the rack / pinion to the optimum position for the solid-liquid separation and dispersion process. And the steps of solid-liquid separation and dispersion can be shortened. At the same time, since it is possible to follow the change in the liquid amount, the time of the process, which was a problem when using magnetic particles having a small particle size, can be shortened.

1 is a configuration diagram showing an apparatus for collecting / dispersing magnetic particles in a liquid according to the present invention. 1 is a configuration diagram showing an apparatus for collecting / dispersing magnetic particles in a liquid according to the present invention. 1 is a specific configuration diagram illustrating an aggregation / distribution device according to the present invention. FIG. 4 is a cross-sectional view of FIG. 3. FIG. 3 is an excerpt of the magnetic moving means in FIG. It is a top view of the principal part of FIG. FIG. 7 is a right side view of FIG. 6. It is a block diagram which shows the other form of FIG. It is a block diagram which shows the magnetic means with respect to a container. It is a block diagram which shows the other form of FIG. It is a block diagram which shows the other form of FIG. It is a block diagram which shows the other form of FIG. It is a block diagram which shows the other form of FIG. It is a block diagram which shows the other form of FIG. It is a block diagram which shows the other form of FIG. It is a block diagram which shows the aggregate | assembly of a magnetic particle. It is a block diagram which shows re-dispersion from solid-liquid separation. It is process drawing which shows the conventional coupling | bonding, washing | cleaning, and extraction process.

  The present invention is a liquid in which magnetic particles mixed and suspended in a liquid in a container are gathered at an arbitrary position by moving a magnetic means, and separation and dispersion of magnetic particles and liquid are performed with high efficiency. It is an object to provide an apparatus for collecting / dispersing magnetic particles therein.

Hereinafter, preferred embodiments of an apparatus for collecting / dispersing magnetic particles in a liquid according to the present invention will be described with reference to the drawings.
In addition, the same code | symbol is attached | subjected and demonstrated to a part the same as that of a prior art example, or an equivalent part.
FIG. 1 shows an ideal position of magnetic particles in the solid-liquid separation process according to the present invention (that is, gathering to a specific position in the container 1). (Made of a permanent magnet or electromagnet) 4 is moved, the suction port 2a at the tip of the suction means 2 made of a chip is positioned at the bottom of the container 1, and only the liquid 10 is efficiently collected in a short time without sucking the magnetic particles 11. It can be sucked well and only the magnetic particles 11 can remain in the container 1.

FIG. 2 shows the ideal magnetic particle collection position (that is, collection at a specific position in the container 1) in the dispersion process by moving the magnetic means 4 to the bottom side of the container 1.
Therefore, at the position of FIG. 2, the magnetic particles 11 are gathered to the bottom side of the container 1 and the suction port 2 a at the tip of the suction means 2 is located in the vicinity of the magnetic particles 11. By reversing the suction and discharge of 10 (pipetting), dispersion by stirring of the liquid 10 and the magnetic particles 11 can be achieved quickly in a short time.

As shown in FIGS. 1 and 2, the magnetic means 4 is moved along the side of the container 1, for example, along its longitudinal direction, as shown in FIGS. A moving means 20 is used.
The moving means 20 includes a motor 23 provided on a side portion of a housing 22 having a large number of containers 1 held in the holding holes 21 and controlled by a controller C, and a pinion 24 provided on the motor 23. A rack 25 provided on the side of the housing 22 so as to be movable up and down and meshing with the pinion 24; a rack guide body 26 provided on the housing 22 for guiding the rack 25 so as to move up and down; The rack guide body 26 includes a rack connecting body 27 having a C-shaped sliding body 28 having the rack 25 and a C-shape, and the C-shaped sliding body 28 provided in the housing 22. And a guide body 29 to be engaged.

  The holding body 30 connected to the rack 25 via the connection member 25a is arranged in parallel in the same direction as the longitudinal direction of the rack 25, and penetrates the through hole 31 of the housing 22 to form the housing. The magnetic means 4 which protrudes in 22 and consists of a permanent magnet at the front-end | tip of the said holding body 30 is provided.

As the motor 23 rotates, the holding body 30 moves up and down via the pinion 24 and the rack 25, so that the magnetic means 4 is moved in the direction of arrow A, and is moved to the side of the container 1 provided in the housing 22. On the other hand, the magnetic means 4 can be arbitrarily moved to the position shown in FIG. The moving position of the rack coupling body 27 is configured to be detected by a position sensor 40 that performs well-known optical or magnetic detection.
The moving means 20 is not limited to the rack and pinion configuration described above, and may be replaced with, for example, a screw feed mechanism such as a ball screw or a trapezoidal screw, a timing belt, or a linear motor, which is a known rotational linear motion conversion mechanism. it can.

5, FIG. 6 and FIG. 7 show other forms of the above-described FIG. 3 and FIG. 4. The same parts as those in FIG. 3 and FIG. Only explained.
A rack 25 is engaged with the pinion 24 of the motor 23 provided in the housing 22, and a plurality of mounting holes 30 a are provided in the holding body 30 provided in the rack guide body 26, and each mounting hole 30 a is permanent. Magnetic means 4 composed of magnets are arranged in parallel, and each magnetic means 4 corresponds to each of a plurality of juxtaposed containers 1 (not shown), and the magnetic means 4 can be moved simultaneously with respect to each container 1. It is configured as follows. That is, the magnetic means 4 can be moved simultaneously with respect to each of the containers 1 arranged in parallel.

  8 does not directly move the magnetic means 4 mechanically as described above, but uses an electromagnet 4A composed of an iron core 35 and a coil 36 as the magnetic means 4, and the electromagnet 4A includes a plurality of stages. The iron cores 35 are arranged at predetermined intervals and in a non-contact state along the length (height) direction of the container 1 of the casing 22. .

Since each of the electromagnets 4A is used, if five channels A to E are used, by selectively applying the drive signal 40a from the current generator 41 connected to the controller C to each coil 36, Any of the iron cores 35 can be excited arbitrarily, and the same effect as that obtained by moving the magnetic means 4 mechanically can be obtained.
Therefore, the selective excitation means 50 for each electromagnet 4A can be configured by the controller C and the current generator 41, and this selective excitation means 50 constitutes the moving means 20 of FIG. Note that the number of channels described above is not limited to five and can be any number of channels.

  FIGS. 9 to 15 show other forms of the magnetic means 4. FIGS. 9A and 9B show a case where a cylindrical or prismatic permanent magnet is used for the container 1 made of a tube. And the case where a ring-shaped permanent magnet is used is shown.

FIG. 10 shows a case where a ring-shaped permanent magnet is used for a container 1 made of a known microplate, and FIG. 11 shows a case where a cylindrical or prismatic permanent magnet is used for the tube-like container 1. ing.
FIG. 12 shows a case where the magnetic means 4 made of a cylindrical or prismatic permanent magnet is moved up and down with respect to the container 1 of the well-known PCR plate 1A.

FIG. 13 shows a configuration in which a magnetic means 4 made of a ring-shaped permanent magnet is provided so as to be movable up and down with respect to a container 1 made of a PCR plate 1A similar to FIG.
FIG. 14 shows a configuration in which the magnetic means 4 using a permanent magnet made of a cylinder or a prism is moved up and down on the side of the container 1 made of a known chip.
FIG. 15 shows a configuration in which the magnetic means 4 made of a ring-shaped permanent magnet is moved up and down on the side of the container 1 made of a known chip.

  FIG. 16 shows a state in which the magnetic means 4 located on the side of the container 1 is located near the lower part of the container 1 and the magnetic particles 11 are gathered to the lower part. This shows a state in which the magnetic particles 11 gather at the position B near the liquid surface.

FIG. 17 shows a state of changing from the solid-liquid separation step to the redispersion step.
That is, in the solid-liquid separation step, since the magnetic means 4 moves to the upper B position, the magnetic particles 11 are moved upward, so that the liquid can be sucked by the chip 2 from the lower part. By lowering to the C position, the magnetic particles 11 are gathered and guided to the lower part of the container 1, and by further retracting the magnetic means 11 to a position further away from the lower part of the container 1, the magnetic particles 11 in the liquid 10 are recovered. Changes from a collective state to a distributed state.

1 container 2 suction means (chip)
2a Suction port 3 Piston pump 4 Magnetic means 10 Liquid 11 Magnetic particles 20 Moving means 21 Holding hole 22 Housing 23 Motor 24 Pinion 25 Rack 25a Connection member 26 Rack guide body 27 Rack coupling body 28 C-shaped slide body 29 Guide body 30 Holding body 30a Mounting hole 31 Through hole C Control controller 35 Iron core 4A Electromagnet 36 Coil 37 Unit 40 Position sensor 40a Drive signal 41 Current generator 50 Selective excitation means

Claims (1)

The magnetic particles (11) are mixed and dispersed in the liquid (10) contained in the container (1), and the magnetic particles (11) are separated from the outside of the container (1) using magnetic means (4). By moving the container (1) to a predetermined position, the liquid (10) can be sucked at least using the suction means (2),
A liquid in which the magnetic means (4) is moved relative to the container (1) via a moving means (20), and the magnetic particles (11) are gathered at an arbitrary position in the container (1). Aggregation of magnetic particles /
In the dispersion device,
The magnetic means (4) is made of a permanent magnet or an electromagnet, and the moving means (20) moves the magnetic means (4) along the side of the container (1).
The container (1) consists of any of a tube, a chip, a microplate and a PCR plate,
The moving means (20) is a motor (23) provided on the side of a housing (22) having a number of containers (1) held in the holding holes (21) and controlled by a controller (C). A pinion (24) provided in the motor (23), a rack (25) provided on the side of the housing (22) so as to be movable up and down and meshing with the pinion (24), and the rack ( 25) and a rack guide body (26) provided in the housing (22) for guiding the rack 25 to move up and down. The rack guide body (26) includes the rack (25) and has a C-shape. A rack coupling body (27) having a C-shaped sliding body (28) forming a mold, and a guide body (29) provided on the casing (22) and engaged with the C-shaped sliding body (28); An apparatus for collecting / dispersing magnetic particles in a liquid, characterized by comprising:

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