Target substance extraction device that allows replacement of magnetic bar blocks

Abstract

The present invention relates to an extraction device capable of extracting target substances from multiple biological samples at the same time, and more specifically to a target substance extraction device capable of replacing a magnetic bar block according to the type of a porous plate inserted into a sleeve. When in use, the target substance extraction device of the present invention operates by loading a porous plate suitable for the purpose of use into a sleeve in the device among various porous plates with different numbers of holes, and selecting and loading a magnetic bar block equipped with a magnetic bar suitable for this porous plate. Therefore, the device has the advantage of selectively applying various porous plates to a facility according to the number of samples from which the target substance is to be extracted or according to the amount of the target substance to be extracted.

Description

Technical Field

[0001] The present invention relates to an extraction device capable of extracting target substances from a plurality of biological samples at the same time, and more particularly to a target substance extraction device capable of replacing a magnetic bar block according to the type of a multi-well plate inserted into a sleeve. Background Art

[0002] A variety of methods have been developed to separate nucleic acids, proteins, etc. from biological samples, and commonly used methods include precipitation, liquid phase extraction, electrophoresis, chromatography, etc. However, solid phase extraction has been developed to make the operation simpler.

[0003] Solid phase extraction is a method using a selective solid or solid particles made by attaching a ligand with high selectivity to a solid. Solid phase extraction is performed based on the following principles: first dissolving a biological sample in a solution to which a target substance selectively attaches, attaching the target substance to a solid, separating the solid from the solution, washing away residual substances on the solid to remove other impurities, and separating the desired target substance from the solid.

[0004] In the case of using solid phase extraction to fill a column with solid particles or a filter membrane, the solution flows slowly between the micropores, so it takes a lot of time to separate the target substance. To solve this problem, a centrifugal separation method can be used. However, this method is difficult to automate. In the case of using pressurization or vacuum, the problem is that when applied to multiple samples, the results obtained from the samples are uneven due to the difference in solution flow rate between the samples.

[0005] To solve this problem, a technique is used in which a target substance in a suspended solution is attached to fine magnetic particles having a large surface area, agglomerated the magnetic particles attached with the target substance by applying a magnetic field, and the solution is removed to separate the target substance (US Pat. Nos. 3,970,518 and 3,985,649).

[0006] The method of separating a target substance using magnetic particles is mainly divided into a target substance attachment step, a solution removal and washing step, and a target substance detachment step. The target substance attachment step is a method of agglomerating magnetic particles by uniformly suspending the magnetic particles, wherein the magnetic field is mainly used to agglomerate the magnetic particles. The magnetic field is generated by a permanent magnet or an electromagnet. Generally speaking, unlike an electromagnet, a permanent magnet is able to generate a strong magnetic field without heat radiation. However, the magnetic flux of a permanent magnet cannot be switched on and off, which is also different from an electromagnet. In this regard, the magnetic particle solution must be physically moved between the magnets to control the conversion, so permanent magnets are not convenient for automation.

[0007] The position where the magnetic particles condense changes due to the position where the magnetic field is applied. The position where the magnetic particles condense is crucial for effectively removing the solution, and therefore a position-dependent technology has been developed. A separation device using magnetic particles has been developed so as to be widely used in diagnostic test equipment and nucleic acid extraction equipment that mainly use antigen-antibody reactions. Pasteur SanofiDiagnostics (US 5,558,839) has developed a method for condensing magnetic particles at the bottom of a 96-well plate and then suspending the magnetic particles. However, the problem with this method is that when the solution is completely removed, the magnetic particles at the bottom are lost. In order to solve this problem, a method (WO 96 / 26011) has been developed in which a magnet is installed on the side surface of a container, a rotating magnet or a container is used to suspend the magnetic particles, and then the magnet or container is stopped to condense the magnetic particles to the wall surface, and Hitachi has developed a system (US 5,770,461) that can condense and suspend using a uniform magnetic field and an alternating magnetic field. This method is a method in which a uniform magnetic field is used to attach magnetic particles to the surface of a tube wall to condense and clean the magnetic particles, and an alternating magnetic field is used to suspend the magnetic particles. Amersham International plc has developed a system that switches the magnetic field by moving a donut-shaped magnet in a direction perpendicular to the container (US 5,897,783). This is a method for agglomerating magnetic particles in a ring shape on the inner wall of a tube. All of these methods are methods of agglomerating magnetic particles in a reaction container, removing the solution, pouring a new solution, and resuspending the magnetic particles.

[0008] Different from these methods, Labsystems has developed a method for moving magnetic particles in a reaction vessel containing a solution in which the magnetic particles are suspended and for moving the magnetic particles again. This system includes a rod and a rod box that can move up and down like a fishing rod. A permanent magnet is installed at the lower end of the rod, and the rod box is made of plastic, which transmits magnetic force and seals the rod so that it does not contact the solution (US 6,040,192). Its operation is as follows: the rod box is introduced into the reaction solution under the state that the magnetic bar is pulled out from the rod box, the rod box moves up and down to suspend the magnetic particles so that the magnetic particles react, the magnetic bar is fully inserted into the rod box, and the magnetic particles are condensed on the surface of the magnetic bar box by the magnetic field of the magnetic bar, thereby making the desired target substance attached to the magnetic particles. The magnetic particles attached with the target substance can then be transferred to the next solution together with the magnetic bar and the rod box. After moving, the magnetic bar is pulled out from the rod box, the magnetic field is removed, and the rod box is moved up and down to suspend the condensed magnetic particles in the new solution. BIONEX has developed an automatic nucleic acid extractor with the same operating scheme as above (Korean registered patent No. 10-0483684). This is a method of attaching magnetic particles to a rod box with various magnetic rods inserted, moving the magnetic particles to another solution so that the magnetic particles are suspended in the solution to extract nucleic acids in the same manner as described in the above-mentioned US'192 patent. However, both the technology of Labsystems and the technology of BIONEX process samples in a row, so there are limitations on processing multiple samples. For this reason, Core Bio System has developed a technology that uses magnetic rods arranged in a two-dimensional array in an automatic extraction device to process multiple samples, such as samples contained in a 96-well plate (Korean patent No. 10-0720044).

[0009] However, the magnetic rod is manufactured in a plate format including 96 magnetic rods arranged in a two-dimensional array to fit into a 96-well plate kit, and thus there is a problem in that a 96-well plate must always be used regardless of the number of biological samples and the amount of target substances to be extracted.

[0010] In the present invention, in order to solve the above-mentioned problems, a device is developed which is configured to selectively use various multi-well plates, i.e., cannulas for distributing samples, according to the number of biological samples and the amount of target substances to be extracted in the case of extracting target substances from a plurality of samples at the same time. For this purpose, a method of replacing a magnetic bar block to adjust the number of magnetic bars to match the number of cannula holes is developed, thereby making it possible to efficiently extract target substances using a single device according to the number of biological samples and the amount of target substances to be extracted. Summary of the invention

[0011]

Technical issues

[0012] An object of the present invention is to provide a target substance extraction device, which is configured to select a porous plate suitable for the purpose of use for replacement, and is equipped with multiple porous plates with different numbers of holes to extract the target substance.

[0013]

Technical solution

[0014] To achieve the above-mentioned object, the present invention provides a target substance extraction device, which comprises a magnetic bar block replacement unit (100), which comprises:

[0015] A magnetic bar block (110) having a magnetic bar (111) configured to be introduced into each well of a multi-well plate to operate;

[0016] a magnetic bar block support (120) configured to allow the magnetic bar block (110) to be placed thereon; and

[0017] A fixing component (130) is configured to fix the magnetic bar block (110) to the magnetic bar block support (120). BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 is a perspective view of a target substance extraction device according to an embodiment of the present invention.

[0019] Figure 2 FIG. 1 is a diagram for explaining a method of installing a magnetic bar block replacement unit 100 according to an embodiment of the present invention.

[0020] Figure 3 is a perspective view of a magnetic bar block 110 according to an embodiment of the present invention.

[0021] Figure 4 is a perspective view of a magnetic bar cover block 140 according to an embodiment of the present invention.

[0022] Figure 5 1 is a diagram for explaining the installation method of a magnetic bar block replacement unit 100 suitable for a 96-well plate (A) or a 24-well plate (B) according to another embodiment of the present invention.

[0023] Figure 6 is a perspective view of a sleeve 210 according to one embodiment of the present invention. DETAILED DESCRIPTION

[0024] [Best Practice]

[0025] The present invention proposes a method for extracting a target substance using a target substance extraction device that does not need to consider the type of porous plate for distributing biological samples or the type of sleeve for installing the porous plate. As a means, the present invention proposes a target substance extraction device, which is configured to facilitate the selection of a porous plate suitable for the purpose of use for replacement, and is installed with a variety of porous plates with different numbers of holes to extract the target substance, and a magnetic bar block with a magnetic bar introduced into each hole of the porous plate for operation is selected accordingly for replacement and installation. The target substance extraction device of the present invention is characterized in that a variety of porous plates and a variety of magnetic bar blocks with magnetic bars suitable for the various porous plates are provided together, thereby making it possible to appropriately select and apply a porous plate to a device according to the number of samples to be extracted or the amount of target substance to be extracted.

[0026] Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings.

[0027] Figure 1 is a perspective view of a target substance extraction device according to an embodiment of the present invention.

[0028] According to one embodiment of the present invention, the target substance extraction device includes a magnetic bar block replacement unit 100 and a casing installation unit 200 .

[0029] In the present invention, the magnetic bar block replacement unit 100 includes: a magnetic bar block (110) having a magnetic bar (111), wherein the magnetic bar (111) is configured to be introduced into each hole of a multi-well plate to operate; a magnetic bar block holder (120) configured to allow the magnetic bar block (110) to be placed thereon; and a fixing member (130) configured to fix the magnetic bar block (110) to the magnetic bar block holder (120).

[0030] In the present invention, if Figure 2 As shown in FIG. 1 , the magnetic bar block replacement unit 100 may be prepared by fixing the magnetic bar block 110 to the magnetic bar block holder 120 using the fixing member 130. However, as another embodiment, the magnetic bar block 110 may be fixed to the magnetic bar block holder 120 by a male and female coupling type.

[0031] In the present invention, if Figure 3 As shown in , the magnetic bar block 110 is configured in a shape in which a plurality of magnetic bars are connected to the lower surface of the plate. The present invention is characterized in that the number of magnetic bars is equal to the number of wells formed in the multi-well plate containing the sample to be extracted using the magnetic bar block 110.

[0032] The magnetic bar block 110 may be in various forms with different numbers of magnetic bars so that it can be replaced according to the type of the multi-well plate inserted in the sleeve installed in the single target substance extraction device installed together. For example, three magnetic bar blocks each connected with 32 magnetic bars can be connected to each other to be suitable for 96-well plates, two magnetic bar blocks each connected with 32 magnetic bars can be provided for 64-well plates, a magnetic bar block with the above structure can be provided for 32-well plates, three magnetic bar blocks each connected with 8 magnetic bars can be provided for 24-well plates, two magnetic bar blocks each connected with 8 magnetic bars can be provided for 16-well plates, or a magnetic bar block with 8 magnetic bars that can be used to connect to 8-well plates can be prepared so that the magnetic bar block can be replaced and used according to the type of plate used. However, the present invention is not limited to a magnetic bar block connection method.

[0033] At the same time, if Figure 4 As shown in , the magnetic bar block replacement unit 100 may further include a magnetic bar covering block 140 fastened to the outside of the magnetic bars 111 of the magnetic bar block 110 to prevent the magnetic bars 111 from being contaminated.

[0034] In the present invention, the magnetic bar cover block 140 is fastened to the outside of the magnetic bars 111 of the magnetic bar block 110, which means that the magnetic bar cover block 140 is fixed around the entire or a part of the surface of each magnetic bar 111 of the magnetic bar block 110 to prevent the magnetic bars 111 of the magnetic bar block 110 from being contaminated by contacting the sample. In the present invention, the magnetic bar cover block 140 is preferably prepared to be disposable, and can be made of various materials suitable for disposal, such as plastic.

[0035] In one aspect of the present invention, the present invention is characterized in that the magnetic bar covering block 140 is fixed to the magnetic bar covering block bracket 150, wherein the magnetic bar covering block 140 and the magnetic bar covering block bracket 150 are fixed to each other by a male-female coupling therebetween, or the magnetic bar covering block 140 is fixed to the magnetic bar covering block bracket 150 using a fixing member 130'. In another aspect of the present invention, the present invention is characterized in that the magnetic bar covering block 140 is fixed to the magnetic bar block bracket 120, thereby fixing the magnetic bar block 110, wherein the magnetic bar covering block 140 is fixed to the magnetic bar block bracket 120 by using a fixing member 130' instead of a fixing member 130, thereby fixing the magnetic bar block 110 to the magnetic bar block bracket 120 ( Figure 5 ).

[0036] In addition, the present invention is characterized in that the magnetic bar block 110 and the magnetic bar covering block 140 are detachable, wherein the magnetic bar block and the magnetic bar covering block are replaced with magnetic bar blocks 110 connected with different numbers of magnetic bars and magnetic bar covering blocks 140 connected with different numbers of magnetic bar coverings according to the purpose, and the magnetic bar block and the magnetic bar covering block are installed to the magnetic bar block bracket 120 or the magnetic bar covering block bracket 150.

[0037] Meanwhile, the present invention is characterized in that the sleeve installation unit 200 is configured such that a plurality of sleeves (210) are stacked up and down, each of the sleeves can be inserted into a multi-well plate, wherein each sleeve (210) is installed to a sleeve transfer tray (220).

[0038] The multi-well plate can be a 96-well plate, a 64-well plate, a 32-well plate, a 24-well plate, a 16-well plate or an 8-well plate, and can be appropriately selected and used according to the number of samples to be extracted or the amount of target substances to be extracted. In another aspect of the present invention, each sleeve 210 can be made in the form of a multi-well plate so that the sleeves can be stacked up and down in a manner mounted on the sleeve transfer tray 220 without inserting a separate multi-well plate.

[0039] The present invention is characterized in that the magnetic bar block 110 and the magnetic bar covering block 140 each have the same number of magnetic bars as the number of wells of the installed multi-well plate.

[0040] The present invention is characterized in that the fixing member 130 or 130' (a member for fixing the magnetic bar block 110 or the magnetic bar covering block 140 to the magnetic bar block holder 120 or the magnetic bar covering block holder 150, respectively) is a fastening member such as a permanent magnet, an electromagnet, a vacuum suction member, a clamp, a fixture, a bolt, a pin, a snap ring, a ball plunger or a combination thereof. In the case of using the above-mentioned member, the fixing member used in the present invention can be prepared so as to fix the magnetic bar block 110 or the magnetic bar covering block 140 to the magnetic bar block holder 120 or the magnetic bar covering block holder 150, or to remove the magnetic bar block 110 or the magnetic bar covering block 140 from the magnetic bar block holder 120 or the magnetic bar covering block holder 150 without using a separate tool or equipment. The present invention is characterized in that a fixing component 130 or 130' is used to couple the magnetic bar block 110 or the magnetic bar covering block 140 and the magnetic bar block bracket 120 or the magnetic bar covering block bracket 150 at the correct position so as to fix the magnetic bar block 110 or the magnetic bar covering block 140 to the correct position of the magnetic bar block bracket 120 or the magnetic bar covering block bracket 150 respectively, and the fixed position does not change under any conditions.

[0041] The present invention is characterized in that the target substance is nucleic acid. However, the present invention is not limited thereto. Any substance (including protein) that can be extracted using magnetic particles and magnetic rods is applicable without limitation.

[0042] Description of Reference Numerals

[0043] 100: Magnetic bar block replacement unit

[0044] 110: Magnetic bar block

[0045] 111: Magnetic bar

[0046] 120: Magnetic bar block bracket

[0047] 130, 130': Fixed parts

[0048] 140: Magnetic bar cover block

[0049] 150: Magnetic bar cover block bracket

[0050] 200: Casing installation unit

[0051] 210: Casing

[0052] 211: Multi-hole plate

[0053] 220: Casing transfer tray

[0054] Although the specific configuration of the present invention has been described in detail, it should be understood by those skilled in the art that the preferred embodiments given in the specification are for illustrative purposes and should not be construed as limiting the scope of the present invention. Therefore, the essential scope of the present invention is determined by the appended claims and their equivalents.

[0055] Industrial Availability

[0056] In the case of using the target substance extraction device of the present invention, a porous plate suitable for the purpose of use, especially various porous plates with different numbers of holes, is installed in the casing of the device, and a magnetic bar block with magnetic bars adapted thereto is selected and installed, thereby making it possible to selectively use various porous plates for a piece of equipment according to the number of samples of the target substance to be extracted or the amount of the target substance to be extracted.

Claims

1. A target substance extraction device, comprising: (A) A magnetic bar block replacement unit (100), the magnetic bar block replacement unit (100) comprising: (i) a magnetic bar block (110) having a magnetic bar (111) configured to be introduced into each well of a multi-well plate to operate; (ii) a magnetic bar block support (120) configured to allow the magnetic bar block (110) to be placed thereon; (iii) a fixing member (130) configured to fix the magnetic bar block (110) to the magnetic bar block support (120); and (iv) a magnetic bar covering block (140) fastened to the outside of the magnetic bar (111) of the magnetic bar block (110), the magnetic bar covering block being configured to prevent the magnetic bar (111) from being contaminated, wherein the magnetic bar covering block (140) is mounted on a magnetic bar covering block bracket (150), and the magnetic bar covering block (140) is fixed to the magnetic bar covering block bracket (150) via a fixing member (130'), and (B) A sleeve installation unit (200), wherein the sleeve installation unit (200) is configured such that a plurality of sleeves (210) are stacked up and down, wherein each sleeve (210) is mounted to a sleeve transfer tray (220), and each sleeve (210) is made in the form of a porous plate so as to be mounted on the sleeve transfer tray (220) and stacked up and down in a manner without inserting a separate porous plate.

2. The target substance extraction device according to claim 1, wherein the magnetic bar block (110) and the magnetic bar covering block (140) are detachable. 3 . The target substance extraction device according to claim 1 , wherein the multi-well plate is a 96-well plate, a 64-well plate, a 32-well plate, a 24-well plate, a 16-well plate or an 8-well plate.

4. The target substance extraction device according to claim 1, wherein the magnetic bar block (110) and the magnetic bar covering block (140) each have the same number of magnetic bars as the number of wells of the installed multi-well plate.

5. The target substance extraction device according to claim 1, wherein the fixing component (130 or 130') is the following fastening means: permanent magnet, electromagnet, vacuum suction component, clamp, fixture, bolt, pin, snap ring, ball plunger or a combination thereof. The target substance extraction device according to claim 1 , wherein the target substance is nucleic acid.

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