JP2019136686A - Purification apparatus and purification container - Google Patents

Abstract

To automate extraction and purification of a target substance from a biological sample by using a magnetic material without a purification apparatus becoming larger.SOLUTION: A purification apparatus includes a drive unit, a magnetic field generation unit, and a magnet control unit. A purification container comprises container body which has body recessed portions for receiving liquid including magnetic material particles, and a lid part which has lid recessed portions having a shape corresponding to the body recessed portions, the body recessed portions and the lid recessed portions being opposed to each other at a distance. The drive unit applies, to the purification container, a pressure such that the lid recessed portions are inserted into the body recessed portions to provide paths between the lid recessed portions and the body recessed portions. The magnetic field generation unit, while the pressure is being applied, generates a magnetic field on a rear side of a face of the container body opposite the lid part or on a rear side of a face of the lid part opposite the container body. The position at which the magnetic field generation unit generates a magnetic field is moved along a shape of the rear side of the container body or of the lid part.SELECTED DRAWING: Figure 6

Description

  Embodiments described herein relate generally to a purification apparatus and a purification container.

  In recent years, the field of molecular biology has been remarkably developed, and its application to medical technology has also expanded. Among them, a method of purifying DNA (Deoxyribonucleic Acid), RNA (Ribonucleic acid), and protein from a biological sample is one of the most important steps. There are various methods for extracting and purifying these target substances. Among them, a technique using a magnetic substance that can bind a target substance is widely used because it does not use a dangerous substance and can be easily handled because the magnetic substance can be induced by controlling magnetic force.

  In a method for purifying a target substance using a magnetic substance, particularly magnetic substance particles, extraction of the target substance from a biological sample, binding of the target substance to the magnetic substance particles, washing of the magnetic substance particles, and target substance from the magnetic substance particles Elution work is required. If these operations are to be fully automated with a refining apparatus, a mechanism for transferring the solution between the operations is required, and there is a problem that the apparatus becomes large.

JP-T-2006-509475

  The problem to be solved by the present invention is to automate the extraction and purification of a target substance from a biological sample using a magnetic substance while avoiding an increase in the size of a purification apparatus.

  According to the embodiment, the purification apparatus includes a drive unit, a magnetic field generation unit, and a magnet control unit. The drive unit includes: a container body having a body recess for containing a liquid containing magnetic particles; a lid having a lid recess having a shape corresponding to the body recess; and the body recess and the lid recess. A pressure for providing a path between the lid recess and the main body recess is applied to the purification container provided oppositely and spaced apart by inserting the lid recess into the main body recess. The magnetic field generator generates a magnetic field on the back side of the surface of the container body facing the lid portion or the back side of the surface of the lid portion facing the container body in the state where the pressure is applied. The position where the magnetic field generator generates a magnetic field is moved along the shape of the back surface of the container body or the shape of the back surface of the lid.

FIG. 1 is a block diagram schematically showing a purification apparatus and a purification container according to the first embodiment. FIG. 2 is a diagram illustrating a top view, a side view, and a bottom view of the purification container shown in FIG. 1. 3 is a cross-sectional view taken along line AA in FIG. FIG. 4 is a diagram illustrating another example of the top view, the side view, and the bottom view of the purification container shown in FIG. FIG. 5 is a diagram showing the configuration of the purification mechanism shown in FIG. 6 is a diagram illustrating a cross-sectional view of the purification container and the purification mechanism 11 when the purification container is placed on the placement unit shown in FIG. FIG. 7 is a diagram illustrating the state of the purification container when the lowering of the first magnetic field generation unit illustrated in FIG. 6 is stopped. FIG. 8 is a diagram illustrating a state in the purification container when the processing circuit sets all the electromagnets in the first convex region to the off state. FIG. 9 is a diagram illustrating a state in the purification container when the processing circuit turns on the electromagnet after the predetermined electromagnet in the first convex region. FIG. 10 is a diagram illustrating a state in the purification vessel when one of the electromagnets in which the processing circuit is in the on state is in the off state. FIG. 11 is a diagram illustrating a state in the refining vessel when one electromagnet whose processing circuit is turned on is turned off. FIG. 12 is a diagram illustrating a state in the refining vessel when one electromagnet whose processing circuit is turned on is turned off. FIG. 13 is a diagram illustrating a state in the refining vessel when one electromagnet whose processing circuit is turned on is turned off. FIG. 14 is a diagram illustrating a state in the purification container when the processing circuit turns off the predetermined electromagnet on the first convex region side of the second convex region. FIG. 15 is a diagram illustrating an operation in which the processing circuit controls the moving mechanism of the permanent magnet. FIG. 16 is a block diagram schematically showing a purification apparatus and a purification container according to the second embodiment. FIG. 17 is a diagram showing a configuration of a purification mechanism provided in the purification apparatus shown in FIG. 18 is a diagram illustrating a cross-sectional view of the purification container and the purification mechanism when the purification container is placed on the first magnetic field generation unit illustrated in FIG. FIG. 19 is a diagram illustrating an operation in which the processing circuit controls the first magnetic field generation unit. FIG. 20 is a diagram illustrating an operation in which the processing circuit controls the moving mechanism of the permanent magnet.

  Hereinafter, embodiments will be described with reference to the drawings.

(First embodiment)
FIG. 1 is a block diagram schematically showing a purification apparatus 1 and a purification container 2 according to the first embodiment. The purification apparatus 1 is an apparatus that takes in a purification container 2 from which a biological sample has been discharged into a purification mechanism 11 and automatically extracts and purifies a target substance in the purification container 2. In the present embodiment, the biological sample includes, for example, cells, bacteria, viruses, and other biological materials. In addition, the target substance includes, for example, DNA, RNA, protein, and the like.

  Below, the refinement | purification container 2 is demonstrated first, and the refiner | purifier 1 is demonstrated after that.

(Purification container 2)
FIG. 2 is a schematic diagram illustrating an example of a top view, a side view, and a bottom view of the purification container 2 shown in FIG. 3 is a cross-sectional view taken along line AA in FIG.

  As shown in FIGS. 2 and 3, the purification container 2 includes a container body 21 and a lid portion 22.

  The container body 21 is made of, for example, a soft and permeable thermoplastic resin such as low density polyethylene. The container main body 21 has, for example, a bottom 211, a peripheral wall 212 that extends continuously around the bottom 211, and an opening 213 surrounded by the upper end of the peripheral wall 212.

  The bottom part 211 has a substantially rectangular shape. Formed on the bottom portion 211 are a first main body recess 2111 to a third main body recess 2113 and a fourth main body recess 2115 for containing the processing liquid. In addition, a small diameter portion 21141 that can be engaged with the storage container 2114 is formed on the bottom portion 211. The small diameter portion 21141 is an example of an engaging portion. The first main body concave portion 2111 to the third main body concave portion 2113, the small diameter portion 21141, and the fourth main body concave portion 2115 are formed in alignment with the longitudinal direction of the bottom portion 211.

  The first main body recess 2111 is pre-loaded with a predetermined volume of dissolved adsorption liquid and a predetermined amount of magnetic particles. The dissolved adsorbent can denature the target substance by the chaotropic effect so that the target substance can bind to the magnetic particles, and can further dissolve cells, bacteria, viruses, and other biological substances in the biological sample. It is a processing liquid. The dissolved adsorption solution is a treatment solution that denatures nucleic acid so that the nucleic acid can specifically bind to magnetic particles. For example, a solution containing guanidine hydrochloride that is a chaotropic agent or Triton X-100 that is a surfactant is used as the dissolved adsorption solution. The volume of the dissolved adsorption solution to be loaded is set according to the volume of the biological sample to be injected, for example. Further, the amount of the magnetic particles to be loaded is set according to the amount of the target substance to be purified, for example. For example, the magnetic particles preferably have a particle size of about several hundred μm and the same particle size.

  When the target substance is extracted from the biological sample and purified, the lid portion 22 of the purification container 2 is pushed toward the container body 21 by the purification apparatus 1. At this time, the first lid concave portion 221 to the third lid concave portion 223 and the fifth lid concave portion 225 provided in the lid portion 22 are the first main body concave portion 2111 to the third main body concave portion 2113 and the fourth main body concave portion. The fourth lid recesses 224 that are respectively inserted into 2115 and provided in the lid portion 22 are inserted into the storage container 2114.

  The first main body recess 2111 is formed in a shape into which the first cover recess 221 of the lid 22 can be inserted. The first body recess 2111 is formed on the surface of the first lid recess 221 on the container body 21 side when the first lid recess 221 is inserted in a state where the biological sample, the dissolved adsorption liquid, and the magnetic particles are accommodated. The liquid is in contact with the liquid and is formed so as to be able to secure a capacity that does not allow the liquid to overflow from the first main body recess 2111.

  In the example shown in FIG. 2, for example, the first main body recess 2111 is formed so that the opening 2111 a has a substantially circular shape. The first main body recess 2111 is formed such that the bottom 2111b has a substantially circular shape with a smaller diameter than the opening 2111a. Further, the first main body recess 2111 is formed such that an inclined portion 2111c between the opening 2111a and the bottom portion 2111b has a predetermined downward gradient. The downward slope of the inclined portion 2111c may be uniform or non-uniform. The opening 2111a is sealed with a sealing material 216 so as to avoid cross contamination of the liquid accommodated therein. For example, an aluminum film is used as the sealing material 216.

  The second main body recess 2112 is preloaded with a predetermined volume of the first cleaning liquid. The first cleaning liquid is a treatment liquid for removing a biological substance that is not a target substance and a dissolved adsorbed liquid that are attached to the magnetic particles. As the first cleaning liquid, for example, a solution containing sodium dodecyl sulfate as a surfactant is used. The volume of the first cleaning liquid to be loaded is set in accordance with, for example, the amount of magnetic particles to be moved by magnetic force, that is, the amount of magnetic particles loaded in the first main body recess 2111.

  The second main body recess 2112 is formed in a shape into which the second lid recess 222 of the lid 22 can be inserted. In addition, the second body recess 2112 is in contact with the surface of the second lid recess 222 on the container body 21 side when the second lid recess 222 is inserted in a state where the first cleaning liquid and magnetic particles are accommodated. In addition, the liquid is formed so as to be able to secure a capacity that does not allow the liquid to overflow from the second main body recess 2112.

  In the example shown in FIG. 2, for example, the second main body concave portion 2112 has the same shape as the first main body concave portion 2111. The shape of the second main body recess 2112 is not necessarily the same shape as the first main body recess 2111. The opening 2112a of the second main body recess 2112 is sealed with a sealing material 216 so as to avoid cross contamination of the liquid contained therein.

  The third main body recess 2113 is pre-loaded with a predetermined capacity of the second cleaning liquid. The second cleaning liquid is a processing liquid for diluting and cleaning the first cleaning liquid attached to the magnetic particles and the biological material that is not the target substance. As the second cleaning liquid, for example, a solution containing 2-propanol is used. The volume of the second cleaning liquid to be loaded is set according to, for example, the amount of magnetic particles to be moved by magnetic force, that is, the amount of magnetic particles loaded in the first main body recess 2111. Note that the second cleaning liquid does not necessarily have to be loaded in the third main body recess 2113, and the first cleaning liquid may be loaded in some cases.

  The third main body concave portion 2113 is formed in a shape into which the third lid concave portion 223 of the lid portion 22 can be inserted. In addition, the third main body concave portion 2113 is in contact with the surface of the third lid concave portion 223 on the container main body 21 side when the third lid concave portion 223 is inserted in a state where the second cleaning liquid and the magnetic particles are accommodated. In addition, the liquid is formed so as to be able to secure a capacity that does not allow the liquid to overflow from the third main body recess 2113.

  In the example shown in FIG. 2, for example, the third main body recess 2113 has the same shape as the first main body recess 2111. Note that the shape of the third main body recess 2113 is not necessarily the same shape as the first main body recess 2111. The opening 2113a of the third main body recess 2113 is sealed with a sealing material 216 so as to avoid cross contamination of the liquid accommodated therein.

  The small diameter portion 21141 is formed so that the opening portion 21141a has a substantially circular shape smaller than the opening portions of the first main body concave portion 2111 to the third main body concave portion 2113. The opening 21141a has a female thread portion 21142 formed on the inner peripheral surface thereof.

  The storage container 2114 is a container for storing the purified liquid, and is formed in a cylindrical shape having an opening 2114a at one end and a bottom 2114b at the other end. The opening 2114a has a male screw 21143 that is screwed into the female screw 21142 of the small-diameter portion 21141 on the outer peripheral surface thereof. The container 2114 is formed so that the bottom 2114b has a substantially conical shape.

  The storage container 2114 is preloaded with a predetermined volume of processing liquid. The treatment liquid is a treatment liquid for eluting the target substance bound to the magnetic particles. As the treatment liquid, for example, ultrapure water not containing DNase and RNase is used. The volume of the processing liquid to be loaded is set according to, for example, the amount of magnetic particles to be moved by magnetic force, that is, the amount of magnetic particles loaded into the first main body recess 2111.

  When the fourth lid recess 224 is inserted in a state where the processing liquid and magnetic particles are stored, the storage container 2114 comes into contact with the surface of the fourth lid recess 224 on the container body 21 side, and this It is formed so as to be able to secure a capacity that does not allow liquid to overflow from the storage container 2114. The opening 21141a of the small diameter portion 21141 is sealed with a sealing material 216 so as to avoid cross contamination of the liquid stored in the storage container 2114. When the purification of the target substance is completed, the storage container 2114 is removed from the container body 21 and collected as necessary.

  The fourth main body recess 2115 is formed in a shape into which the fifth lid recess 225 of the lid 22 can be inserted. The fourth main body recess 2115 is formed so as to ensure a capacity capable of storing the purified liquid derived from the storage container 2114. In the example shown in FIG. 2, for example, the fourth main body recess 2115 is formed so that the opening 2115 a has a substantially circular shape with a smaller diameter than the openings of the first main body recess 2111 to the third main body recess 2113. . The fourth main body recess 2115 is formed so that the bottom 2115b has a substantially circular shape with a smaller diameter than the opening 2115a. Further, the fourth main body recess 2115 is formed such that an inclined portion 2115c between the opening 2115a and the bottom 2115b has a predetermined downward slope. The descending slope of the inclined portion 2115c may be uniform or not uniform.

  In the example shown in FIG. 2, the first main body concave portion 2111 to the third main body concave portion 2113, the fourth main body concave portion 2115, and the accommodation container 2114 have the same depth, but the present invention is not limited to this. The depths of the first main body concave portion 2111 to the third main body concave portion 2113, the fourth main body concave portion 2115, and the storage container 2114 are the same as the depths of the first main body concave portion 2111 to the third main body concave portion 2113, the fourth main body concave portion 2115, and the storage container 2114. As long as the first lid recess 221 to the fifth lid recess 225 of the lid part 22 can be inserted, and the respective capacities satisfy a predetermined capacity, they are not necessarily the same.

  An elastic part 2121 is formed on at least a part of the peripheral wall part 212 of the container body 21 so as to surround the peripheral wall part 212. The stretchable part 2121 has a structure that can be stretched in the extending direction of the peripheral wall part 212. The expansion / contraction part 2121 is implement | achieved by the bellows structure, the nesting structure, etc., for example.

  The lid portion 22 is made of, for example, a soft and permeable thermoplastic resin such as low density polyethylene. The lid 22 may be formed of, for example, a thermoplastic resin such as high-density polyethylene that is harder than the container body 21. The lid portion 22 has a substantially rectangular shape. The lid portion 22 seals the container body 21 by covering the opening 213 of the container body 21. The lid portion 22 is fixed to the container body 21 by, for example, heat welding.

  The lid portion 22 is formed with a first lid recess 221 to a fifth lid recess 225. The first lid concave portion 221 to the fifth lid concave portion 225 are formed so as to substantially match the shape of the first magnetic field generation unit 111 provided in the purification device 1. Specifically, in the example shown in FIG. 2, the first lid recess 221 is formed so that the opening 221a has a substantially circular shape. In addition, the first lid recess 221 is formed with an inclined portion 221b with a predetermined downward gradient from the opening 221a. The downward slope of the inclined portion 221b may be uniform or non-uniform.

  The second lid recess 222 and the third lid recess 223 are formed in the same shape as the first lid recess 221. The fourth lid recess 224 is formed such that the opening 224a has a substantially circular shape with a smaller diameter than the opening 221a of the first lid recess 221. The fourth lid recess 224 is formed with an inclined portion 224b with a predetermined downward gradient from the opening 224a. The downward slope of the inclined portion 224b may be uniform or non-uniform. The fifth lid recess 225 is formed in the same shape as the fourth lid recess 224.

  The peripheral wall portion 212 of the container body 21 is formed so that the height satisfies the following requirements. That is, when the lid 22 is fixed to the opening 213 of the container body 21, that is, in a state where no pressure is applied to the container body 21 to the lid 22, the first lid recess 221 to the fourth lid recess 224. Must be separated from the first main body recess 2111 to the third main body recess 2113 of the container main body 21 and the sealing material 216 that seals the opening of the small diameter portion 21141.

  The lid portion 22 includes an insertion port 226 for inserting a pipette or the like in the vicinity of the first lid recess 221. A cap 2261 is attached to the insertion port 226. The cap 2261 can be loosened when necessary, such as when pressure is applied to the purification container 2. The lid portion 22 includes an insertion hole 2262 into which a pipette inserted into the insertion port 226 can be inserted.

  The structure of the purification container 2 is not limited to the above. For example, the number of fourth body recesses 2115 through which the purified liquid stored in the storage container 2114 is guided is not limited to one. A plurality of fourth main body recesses 2115 may be formed in the bottom portion 211 of the container body 21, and the purified liquid may be guided from the storage container 2114.

  In addition, the shape of the opening and bottom of the first main body recess 2111 to the third main body recess 2113 and the fourth main body recess 2115 of the container main body 21, and the first lid recess 221 to the third lid recess 223 of the lid 22, And the shape of the opening part of the 5th cover recessed part 225 is not limited to substantially circular shape. As shown in FIG. 4, the first main body recess 2111 to the third main body recess 2113 and the fourth main body recess 2115 may have an opening and a bottom formed in a substantially rectangular shape. Moreover, the opening part of the 1st cover recessed part 221-the 3rd cover recessed part 223 and the 5th cover recessed part 225 may be formed in the substantially rectangular shape.

(Purification device 1)
Next, the purification apparatus 1 will be described. The refining device 1 is, for example, a device that is large enough to be placed on a desk, and includes a refining mechanism 11, an input interface 12, a memory 13, and a processing circuit 14, as shown in FIG. The refining mechanism 11, the input interface 12, the memory 13, and the processing circuit 14 are connected to be communicable with each other via, for example, a bus.

  The purification mechanism 11 is a mechanism that accommodates the purification container 2 and extracts and purifies the target substance from the biological sample injected into the purification container 2. For example, as illustrated in FIG. 1, the purification mechanism 11 includes a first magnetic field generation unit 111, a drive unit 112, a placement unit 113, and a second magnetic field generation unit 114.

  FIG. 5 is a schematic diagram showing a configuration example of the purification mechanism 11 shown in FIG. FIG. 5 illustrates a case where an electromagnet having a magnetic body and a coil is used as the first magnetic field generator 111 and the second magnetic field generator 114.

  The first magnetic field generator 111 is formed by arranging a plurality of electromagnets. Although FIG. 5 shows an example in which the electromagnets are arranged in a line having a predetermined depth, the present invention is not limited to this. The electromagnets each have a bar shape and may be arranged in a lattice shape.

  The first magnetic field generator 111 also serves as a pressurizing member for applying pressure to the purification vessel 2. In the example shown in FIG. 5, by arranging a plurality of electromagnets, the first magnetic field generator 111 is formed with the first convex region 1111 to the fifth convex region 1115 having apexes in the direction of the mounting portion 113. Yes. The heights of the tops of the first convex region 1111 to the fifth convex region 1115 are substantially the same. The widths of the first convex region 1111 to the third convex region 1113 are larger than the widths of the fourth convex region 1114 and the fifth convex region 1115. The plurality of electromagnets forming the first magnetic field generation unit 111 generates a magnetic field according to the control of the processing circuit 14.

  The placement unit 113 is, for example, a table for placing the purification container 2 horizontally. The placement unit 113 is provided below the first magnetic field generation unit 111 so as to face the first magnetic field generation unit 111. The placement unit 113 supports the purification container 2 from, for example, the first main body concave portion 2111 to the third main body concave portion 2113 and the fourth main body concave portion 2115 of the container main body 21 and the bottom of the storage container 2114. Further, the placing unit 113 may support the purification container 2 from the collar part 2116 of the container main body 21.

  The drive unit 112 moves the first magnetic field generation unit 111 in a direction approaching the placement unit 113 or a direction away from the placement unit 113 according to the control of the processing circuit 14. The drive unit 112 is realized by, for example, a gear, a stepping motor, a belt conveyor, and a lead screw.

  The second magnetic field generation unit 114 is provided on the back side of the placement unit 113 at a position facing the fifth convex region 1115. The electromagnet used as the second magnetic field generation unit 114 generates a magnetic field according to the control of the processing circuit 14.

  The input interface 12 receives various instructions and information input from the operator, and outputs the received instructions and information to the processing circuit 14. The input interface 12 is connected to an input device such as a mouse, a keyboard, a trackball, a switch, a button, a joystick, a touch pad, and a touch panel on which an instruction is input by touching an operation surface. The input device connected to the input interface 12 may be an input device provided in another computer connected via a network or the like.

  The memory 13 is a storage device such as a ROM (Read Only Memory), a RAM (Random Access Memory), an HDD (Hard Disk Drive), an SSD (Solid State Drive), and an integrated circuit storage device for storing various information. The memory 13 may be a drive device that reads / writes various information from / to a portable storage medium such as a CD-ROM drive, a DVD drive, and a flash memory. Note that the memory 13 is not necessarily realized by a single storage device. For example, the memory 13 may be realized by a plurality of storage devices. The memory 13 may be in another computer connected via a network.

  The memory 13 stores programs corresponding to various functions executed by the processing circuit 14. Note that programs corresponding to these various functions may be stored in advance in the memory 13, for example. Further, for example, it may be stored and distributed in a non-transitory storage medium, read from the non-transitory storage medium, and installed in the memory 13.

  In addition, the refiner | purifier 1 may have a display. The display displays various information according to instructions from the processing circuit 14. The display may display a GUI (Graphical User Interface) for receiving various operations from the user. As the display, for example, an arbitrary display such as a CRT (Cathode Ray Tube) display, a liquid crystal display, an organic EL display, an LED display, and a plasma display can be used as appropriate.

  Moreover, the refiner | purifier 1 may have a communication interface. The communication interface performs data communication with a system connected via a network. For example, the communication interface performs data communication in accordance with a known standard set in advance.

  The processing circuit 14 shown in FIG. 1 is a processor that functions as the center of the purification apparatus 1. The processing circuit 14 implements a function corresponding to the program by executing the program stored in the memory 13 or the like. For example, the processing circuit 14 has a pressurizing function 141 and a magnet control function 142 by executing a program. In the present embodiment, a case where the pressurizing function 141 and the magnet control function 142 are realized by a single processor will be described, but the present invention is not limited to this. For example, a processing circuit may be configured by combining a plurality of independent processors, and the pressurizing function 141 and the magnet control function 142 may be realized by each processor executing a program.

  The pressurizing function 141 is a function of controlling the driving unit 112 to apply pressure to the purification container 2 and is an example of a pressurizing unit. Specifically, for example, in the pressurizing function 141, the processing circuit 14 controls the drive unit 112 so that the first magnetic field generation unit 111 is lowered by a preset distance. Thereby, the 1st magnetic field generation part 111 pushes the cover part 22 of the refinement | purification container 2 mounted in the mounting part 113 toward the container main body 21 direction. By pushing the lid portion 22 toward the container main body 21, the first lid concave portion 221 to the fourth lid concave portion 224 of the lid portion 22 open the openings of the first main body concave portion 2111 to the third main body concave portion 2113 and the small diameter portion 21141. The sealing material 216 is pressed against the sealing material 216 being sealed, and the sealing material 216 is torn.

  When the first magnetic field generation unit 111 is lowered by a preset distance, the processing circuit 14 controls the drive unit 112 so that the first magnetic field generation unit 111 is increased by a minute distance, for example, about several mm. Thereby, a gap is generated between the cleaved sealing material 216 and the surface of the lid portion 22 on the container body 21 side.

  The processing circuit 14 may stop the lowering of the first magnetic field generation unit 111 when detecting a pressure equal to or higher than a preset pressure. At this time, the drive unit 112 is provided with a sensor for detecting the pressure, and transmits the pressure detected while the first magnetic field generation unit 111 is lowered to the processing circuit 14.

  The magnet control function 142 is a function for controlling a plurality of electromagnets forming the first magnetic field generation unit 111 and an electromagnet used as the second magnetic field generation unit 114, and is an example of a magnet control unit. Specifically, for example, in the magnet control function 142, the processing circuit 14 generates a magnetic field from among a plurality of electromagnets forming the first magnetic field generator 111 according to a preset procedure. To supply current. Thereby, a magnetic field is applied to the purification container 2. In addition, for example, the processing circuit 14 supplies current so that the electromagnet used as the second magnetic field generation unit 114 generates a magnetic field according to a preset procedure. As a result, a magnetic field is applied to the fourth main body recess 2115 of the container main body 21.

(Purification treatment by the purification apparatus 1 using the purification container 2)
Next, the operation in which the purification apparatus 1 extracts and purifies the target substance using the purification container 2 will be specifically described. First, an operator such as a doctor sucks a biological sample using a pipette or the like from a sample container or the like in which the biological sample is stored. The operator removes the cap 2261 from the insertion port 226 and inserts the pipette that has sucked the biological sample into the insertion port 226 of the purification container 2. The operator causes the pipette to enter the purification container 2 through the insertion hole 2262 of the lid portion 22. When the tip of the pipette comes into contact with the sealing material 216 of the first main body recess 2111 formed in the container main body 21, the operator penetrates the sealing material 216 with the tip of the pipette. The operator discharges the biological sample into the first main body recess 2111, pulls out the pipette from the insertion port 226, and attaches the cap 2261 to the insertion port 226.

  When the operator attaches the cap 2261 to the insertion port 226, the operator places the purification container 2 into which the biological sample is discharged on the placement unit 113 of the purification apparatus 1. FIG. 6 is a diagram illustrating an example of a cross-sectional view of the purification container 2 and the purification mechanism 11 when the purification container 2 is placed on the placement unit 113. In FIG. 6, the refining container 2 has the first lid recess 221 to the fifth lid recess 225 of the lid portion 22 so as to substantially face the first convex region 1111 to the fifth convex region 1115 of the first magnetic field generation unit 111, respectively. Is mounted on the mounting portion 113. When the purification container 2 is placed, the operator inputs an instruction to start the pressurizing process via the input interface 12, for example.

  The processing circuit 14 executes the pressurizing function 141 when an instruction to start the pressurizing process is input. When the pressurizing function 141 is executed, the processing circuit 14 loosens the cap 2261 attached to the insertion port 226. Then, the processing circuit 14 controls the drive unit 112 so that the first magnetic field generation unit 111 is lowered by a preset distance. Here, the preset distance is, for example, that the surface on the container body 21 side of the flat surface portion 227 of the lid portion 22 pushed by the first magnetic field generation unit 111 from the top dead center is on the bottom 211 of the container body 21. It is the distance that touches. The cap 2261 of the insertion port 226 may be loosened by the operator at the start of the pressurizing process.

  When the first magnetic field generation unit 111 is lowered in the direction of the purification container 2 by the driving unit 112, the first convex region 1111 to the fifth convex region 1115 of the first magnetic field generation unit 111 become the first lid concave portion of the lid unit 22. 221 to the fifth lid recess 225 are respectively inserted, and the first magnetic field generation unit 111 and the facing surface of the lid unit 22 are substantially integrated. The first magnetic field generator 111 continues to descend while the surface is substantially integrated with the surface of the lid 22, compresses the purification container 2, and contracts the expansion / contraction part 2121 formed on the peripheral wall 212 of the container body 21. Let While the first magnetic field generation unit 111 is lowered and the expansion and contraction unit 2121 is contracted, the air existing in the purification container 2 is released from the insertion port 226.

  When the first magnetic field generation unit 111 is lowered while contracting the expansion / contraction part 2121, the first lid recess part 221 to the fourth lid recess part 224 of the lid part 22 are changed to the first body recess part 2111 to the third body recess part 2113, and It is pressed against the sealing material 216 sealing the opening of the small diameter portion 21141. By the pressing of the first lid concave portion 221 to the fourth lid concave portion 224 of the lid portion 22, the sealing material 216 is cleaved. The first magnetic field generator 111 continues to descend even after the sealing material 216 has been cleaved, and the container main body 21 side surfaces of the first lid recess 221 to the fourth lid recess 224 are in the first body recess 2111 to third. The main body recess 2113 and the liquid loaded in the container 2114 come into contact. Then, when the surface of the flat surface portion 227 of the lid portion 22 on the container body 21 side comes into contact with the bottom portion 211 of the container body 21, the processing circuit 14 causes the driving unit 112 to stop the first magnetic field generation unit 111 from descending.

  FIG. 7 is a schematic diagram illustrating an example of the state of the purification container 2 when the lowering of the first magnetic field generation unit 111 is stopped. At this time, the first main body concave portion 2111 to the third main body concave portion 2113 of the container main body 21 and the sealing material 216 that seals the opening of the small diameter portion 21141 are the first lid concave portion 221 to the fourth lid concave portion of the lid portion 22. By 224, everything is broken. Even in the state shown in FIG. 7, the liquid loaded in the first main body recess 2111 to the third main body recess 2113 and the storage container 2114 does not overflow to the outside of the recess.

  When the processing circuit 14 stops the lowering of the first magnetic field generation unit 111, the processing circuit 14 controls the drive unit 112 to raise the first magnetic field generation unit 111 by a minute distance, for example, about several mm. When the first magnetic field generation unit 111 rises several mm, the expansion / contraction part 2121 of the peripheral wall part 212 extends, and the lid part 22 moves to the stop position of the first magnetic field generation part 111. Thereby, a gap is generated between the surface of the flat surface portion 227 of the lid portion 22 on the container main body 21 side and the bottom portion 211 of the container main body 21. Further, a gap is generated between the cleaved sealing material 216 and the surface of the lid portion 22 on the container body 21 side. At this time, a path capable of transporting the magnetic particles and the substance attracted to the magnetic particles is formed between the surface of the lid 22 on the container main body 21 side and the surface of the container main body 21 on the lid 22 side. Is done.

  After the first magnetic field generation unit 111 is raised by a minute distance, the processing circuit 14 retightens the loosened cap 2261 when a sufficient time has passed for the lid 22 to move. Thereby, the pressurization process with respect to the refinement | purification container 2 is completed. Furthermore, a sealed state is ensured.

  The operation of loosening the cap 2261 of the insertion port 226 at the start of the pressurizing process and the operation of retightening the cap 2261 at the end of the pressurizing process are not limited to being performed by the purification mechanism 11. For example, the operation of loosening the cap 2261 of the insertion port 226 at the start of the pressurizing process and the operation of retightening the cap 2261 at the end of the pressurizing process may be performed by the operator.

  The processing circuit 14 executes the magnet control function 142 when the pressurizing process on the purification container 2 is completed. At this time, the processing circuit 14 may automatically execute the magnet control function 142 after the pressurization processing of the purification container 2 is completed, or wait for an instruction to start the purification processing from the operator. Also good.

  When the magnet control function 142 is executed, the processing circuit 14 moves the magnetic particles accommodated in the first main body recess 2111 by switching between the on state and the off state of the electromagnet forming the first convex region 1111, and the first The dissolution adsorption by the dissolution adsorption liquid accommodated in the main body recess 2111 is promoted. Specifically, for example, the processing circuit 14 moves the magnetic particles by repeating the operation of turning all the electromagnets of the first convex region 1111 on and then turning it off a predetermined number of times. The processing circuit 14 may move the magnetic particles by moving the electromagnet ON state from one end to the other end of the first convex region 1111 and further moving from the other end to the one end. In addition, when the electromagnets are arranged in a grid, the processing circuit 14 controls the electromagnet ON state to move three-dimensionally, thereby moving the magnetic particles to efficiently move the first main body. The liquid in the recess 2111 may be stirred.

  When the liquid in the first main body concave portion 2111 is stirred, the processing circuit 14 turns off all the electromagnets in the first convex region 1111. FIG. 8 is a schematic diagram showing a state in the purification container 2 when the processing circuit 14 turns off all the electromagnets in the first convex region 1111.

  After all the electromagnets in the first convex region 1111 are turned off, the processing circuit 14 turns on the electromagnet after the predetermined electromagnet on the insertion port 226 side in the first convex region 1111. In other words, the processing circuit 14 turns on the electromagnet of the first magnetic field generation unit 111 after the electromagnet on the insertion port 226 side that is not in contact with the liquid in the first convex region 1111.

  FIG. 9 is a schematic diagram showing a state in the purification container 2 when the processing circuit 14 turns on the electromagnet after the predetermined electromagnet in the first convex region 1111. According to FIG. 9, the processing circuit 14 turns on the electromagnets after the electromagnet M13 in the first convex region 1111. Thereby, the magnetic particles contained in the liquid in the first main body recess 2111 are attracted to the electromagnets M13 to M15. At this time, the target substance dissolved from the biological substance is bound to at least one of the attracted magnetic particles.

  At this time, the electromagnets other than the first convex region 1111 may be in an off state.

  When a sufficient time has passed for the magnetic particles to be attracted after the electromagnet is turned on, the processing circuit 14 turns the electromagnets turned on at least one by one from the insertion port 226 side. FIG. 10 is a schematic diagram showing a state in the purification container 2 when one of the electromagnets in which the processing circuit 14 is turned on is turned off. According to FIG. 10, the processing circuit 14 switches the electromagnet M13 from the on state to the off state. As a result, the magnetic particles attracted to the electromagnet M13 are attracted to the electromagnets M14 and M15.

  FIG. 11 is a schematic diagram showing a state in the purification container 2 when one electromagnet that is turned on by the processing circuit 14 is turned off. According to FIG. 11, the processing circuit 14 switches the electromagnet M14 from the on state to the off state. As a result, the magnetic particles attracted to the electromagnet M14 are collected in the electromagnet M15.

  FIG. 12 is a schematic diagram showing the state in the purification container 2 when one electromagnet that is turned on by the processing circuit 14 is turned off. According to FIG. 12, the processing circuit 14 switches the electromagnet M15 from the on state to the off state. Thereby, the magnetic particles collected in the electromagnet M15 are separated from the water and moved to the electromagnet M16.

  When the aggregated magnetic particles are separated from the water, the processing circuit 14 supplies the electromagnets to the electromagnets so as to sequentially move the electromagnets in the on state toward the second convex region 1112 while maintaining at least one electromagnet in the on state. Control the supply of current. FIG. 13 shows the state in the refining container 2 when the processing circuit 14 turns on the electromagnet M16 to the electromagnet of the second convex region 1112 and turns off the electromagnets one by one from the electromagnet M16 at a predetermined cycle. It is a schematic diagram to represent. Thereby, the magnetic particles are transported along a path formed between the surface of the lid 22 on the container main body 21 side and the surface of the container main body 21 on the lid 22 side.

  When the predetermined electromagnet on the first convex region 1111 side in the second convex region 1112 is turned off, the processing circuit 14 turns off all the electromagnets. This can be said in other words that all the electromagnets are turned off when the conveyed magnetic particles land on the liquid contained in the second main body recess 2112.

  FIG. 14 is a schematic diagram showing a state in the purification container 2 when the processing circuit 14 turns off the predetermined electromagnet on the first convex region 1111 side of the second convex region 1112. According to FIG. 14, when the processing circuit 14 turns off the electromagnet M22 in the second convex region 1112, it turns off all the electromagnets. As a result, the conveyed magnetic particles are dispersed in the liquid in the second main body recess 2112.

  When all the electromagnets are turned off, the processing circuit 14 moves the magnetic particles dispersed in the second main body concave portion 2112 by switching between the on state and the off state of the electromagnet forming the second convex region 1112. Accordingly, the cleaning of the biological material other than the target material bound to the magnetic particles and the molten adsorbed liquid with the first cleaning liquid accommodated in the second main body recess 2112 is promoted.

  When the liquid in the second main body recess 2112 is agitated, the processing circuit 14 performs the processing shown in FIGS. 8 to 11 again. Thereby, the magnetic particles dispersed in the second main body concave portion 2112 are collected in the electromagnet M25 near the liquid surface on the third convex region 1113 side of the second convex region 1112.

  When the magnetic particles are concentrated on the electromagnet M25 in the second convex region 1112, the processing circuit 14 performs the processing shown in FIGS. 12 to 14 again. Thereby, the magnetic particles collected in the electromagnet M25 are separated from the water, and the separated magnetic particles are transported to the third convex region 1113.

  When the predetermined electromagnet M32 on the second convex region 1112 side in the third convex region 1113 is turned off, the processing circuit 14 turns off all the electromagnets. This can be said in other words that all the electromagnets are turned off when the conveyed magnetic particles land on the liquid contained in the third main body recess 2113. As a result, the magnetic particles transported to the third convex region 1113 are dispersed in the liquid in the third main body concave portion 2113.

  When all the electromagnets are turned off, the processing circuit 14 moves the magnetic particles dispersed in the third main body recess 2113 by switching between the on state and the off state of the electromagnet forming the third convex region 1113. Thereby, the dilution cleaning of the 1st washing | cleaning liquid adhering to a magnetic body particle | grain by the 2nd washing | cleaning liquid accommodated in the 3rd main body recessed part 2113 is promoted.

  When the liquid in the third main body recess 2113 is stirred, the processing circuit 14 performs the processing shown in FIGS. 8 to 11 again. As a result, the magnetic particles dispersed in the third main body concave portion 2113 are concentrated on the electromagnet M35 near the liquid surface on the fourth convex region 1114 side of the third convex region 1113.

  When the magnetic particles are concentrated on the electromagnet M35 in the third convex region 1113, the processing circuit 14 performs the processing shown in FIGS. 12 to 14 again. As a result, the magnetic particles collected in the electromagnet M35 are separated from the water, and the separated magnetic particles are conveyed to the fourth convex region 1114.

  When the predetermined electromagnet M41 on the third convex region 1113 side in the fourth convex region 1114 is turned off, the processing circuit 14 turns off all the electromagnets. This can be said in other words that all the electromagnets are turned off when the conveyed magnetic particles land on the liquid stored in the storage container 2114. It is assumed that the fourth convex region 1114 is formed by fewer electromagnets M41 to M45 than the electromagnets that form the first convex region 1111 to the third convex region 1113. As a result, the magnetic particles transported to the fourth convex region 1114 are dispersed in the liquid in the container 2114.

  When all the electromagnets are turned off, the processing circuit 14 moves the magnetic particles dispersed in the storage container 2114 by switching between the on state and the off state of the electromagnet forming the fourth convex region 1114. Thereby, the elution of the target substance bound to the magnetic particles by the treatment liquid stored in the storage container 2114 is promoted, and a purified liquid of the target substance is created.

  When stirring of the storage container 2114 is completed and a preset time has elapsed, it is determined that the production of the purified liquid is completed. When the purified liquid is used in another inspection device, the container 2114 for storing the prepared purified liquid is removed from the container body 21 and collected as necessary. In the case where there is a subsequent process in the fourth main body recess 2115, the storage container 2114 is removed from the container main body 21 and collected after moving the necessary amount of magnetic particles to the fourth main body recess 2115.

  When there is a subsequent process in the fourth main body recess 2115, when the liquid in the container 2114 is stirred, the processing circuit 14 performs the process shown in FIGS. 8 to 11 again. Thereby, the magnetic particles dispersed in the storage container 2114 are collected in the electromagnet M44 near the liquid surface on the fifth convex region 1115 side of the fourth convex region 1114.

  When the magnetic particles are concentrated on the electromagnet M44 in the fourth convex region 1114, the processing circuit 14 sequentially moves the electromagnet in the on state toward the fifth convex region 1115 while maintaining at least one electromagnet in the on state. To control the supply of current to the electromagnet. As a result, the magnetic particles having the purified liquid adsorbed by the surface tension pass through the path formed between the container body 21 side surface of the lid part 22 and the lid part 22 side surface of the container body 21 to the fifth convex region. Transported in the direction.

  At this time, the processing circuit 14 controls the magnetic force by the electromagnet by adjusting the amount of current supplied to the electromagnet. This makes it possible to control the number of magnetic particles transported in the direction of the fifth convex region 1115. That is, an arbitrary amount of purified liquid can be guided to the fourth main body recess 2115. Using an arbitrary amount of the purified solution thus induced, for example, a measurement method such as a PCR method in which a small amount of sample is sufficient is assumed.

  When the predetermined electromagnet M53 on the fourth convex region 1114 side in the fifth convex region 1115 is turned off, the processing circuit 14 turns off all the electromagnets. In other words, when the conveyed magnetic particles reach the top electromagnet in the fifth convex region 1115, all the electromagnets are turned off. As a result, the magnetic particles and the purified liquid adsorbed on the magnetic particles are accommodated in the fourth main body recess 2115.

  When all the electromagnets are turned off, the processing circuit 14 generates a second magnetic field provided on the back side of the mounting portion 113 at a position facing the fifth convex region 1115, that is, immediately below the fourth main body concave portion 2115. A magnetic field is generated in the unit 114. As a result, magnetic particles unnecessary for measurement in the purified liquid contained in the fourth main body recess 2115 are deposited on the bottom of the fourth main body recess 2115.

  In the first embodiment, the lid 22 side surface of the first magnetic field generator 111 of the purification apparatus 1 corresponds to the shape of the lid 22, and the first magnetic field generator 111 is pressed against the purification container 2. The case where it can be explained as an example. However, it is not limited to this. The first magnetic field generator 111 may have a permanent magnet 1116 and a moving mechanism 1117 for moving the permanent magnet 1116. At this time, the drive unit 112 includes a pressurizing member (not shown) for pushing the lid 22 into the container body 21. The pressurizing member is realized by, for example, a metal having a shape that allows the lid portion 22 to be pushed in, plastic, or the like.

  The processing circuit 14 executes the pressurizing function 141 when the start instruction of the pressurizing process is input, and controls the driving unit 112 to push the lid portion 22 into the container main body 21 by the pressurizing member.

  When the pressurizing process on the purification container 2 is completed, the processing circuit 14 executes the magnet control function 142 and controls the moving mechanism 1117 so that the moving mechanism 1117 moves the permanent magnet 1116. FIG. 15 is a schematic diagram illustrating an operation in which the processing circuit 14 controls the moving mechanism 1117 of the permanent magnet 1116. The container main body 21 side surfaces of the first lid concave portion 221 to the fourth lid concave portion 224 of the lid portion 22 are liquids loaded in the first main body concave portion 2111 to the third main body concave portion 2113 of the container main body 21 and the storage container 2114. In the contact state, the processing circuit 14 controls the moving mechanism 1117 so that the permanent magnet 1116 moves along the pressure side surface of the lid portion 22.

  The processing circuit 14 may control the moving mechanism 1117 so that the permanent magnet 1116 moves at a constant speed, or may change the speed depending on whether or not the magnetic particles are in contact with the liquid. Also good. The processing circuit 14 may control the moving mechanism 1117 so that the permanent magnet 1116 moves back and forth on the surface of the lid recess when the magnetic particles are in contact with the liquid.

  Moreover, in 1st Embodiment, the case where the refinement | purification container 2 had the 4th main body recessed part 2115 was demonstrated to the example. However, it is not limited to this. The fourth main body recess 2115 may not be provided. At this time, the process of the purification apparatus 1 is completed by the creation of the purified liquid in the storage container 2114.

  Moreover, in 1st Embodiment, the small diameter part 21141 was provided in the container main body 21, and the case where the cylindrical storage container 2114 which can be removed was detachably attached was demonstrated to the example. However, it is not limited to this. The processing liquid for eluting the target substance bound to the magnetic particles may be loaded in advance in the concave portion provided in the container main body 21 instead of the storage container 2114 attached to the small diameter portion 21141.

  Moreover, in 1st Embodiment, the drive part 112 demonstrated the case where the 1st magnetic field generation part 111 pressed the cover part 22 of the refinement | purification container 2 toward the container main body 21 as an example. However, it is not limited to this. The drive unit 112 may be configured to press the container main body 21 toward the lid unit 22 by moving the mounting unit 113 toward the first magnetic field generation unit 111.

  As described above, in the first embodiment, the purification container 2 is made of a non-magnetic material and has a container main body 21 having a main body recess for containing a liquid, and a lid recess having a shape corresponding to the main body recess. The corresponding main body concave portion and the lid concave portion are opposed to each other and are separated from each other. The purifying apparatus 1 controls the drive unit 112 with the pressurizing function 141 to push the lid 22 into the container body 21, and into the liquid containing the biological sample and the magnetic particles loaded in the recess of the container body 21. Then, the container body 21 side surface of the lid recess of the lid portion 22 is brought into contact. The refining device 1 causes the first magnetic field generator 111 to generate a magnetic field on the back side of the surface of the lid portion 22 that faces the container body 21. And the refiner | purifier 1 is made to move the generated magnetic field along the shape of the back side surface of the cover part 22 by the magnet control function 142. FIG. As a result, the magnetic particles bonded to the biological sample are aggregated, and the aggregated magnetic particles move in the solution contained in the main body recess of the container body 21, and the magnetic particles in the main body recess. Can be executed.

  Moreover, in 1st Embodiment, the container main body 21 and the cover part 22 are expansion-contraction which can shrink | contract in the direction which the cover part 22 side surface of the container main body 21 and the container main body 21 side surface of the cover part 22 contact. The parts 2121 are connected. The expansion / contraction part 2121 contracts when the lid part 22 is pushed into the container body 21. And the refiner | purifier 1 is made to move the position which generate | occur | produces a magnetic field along the shape of the cover part 22 by the magnet control function 142 in the refinement | purification container 2 in the state by which the expansion-contraction part 2121 was contracted. That is, the magnetic particles move in the sealed purification container 2.

  In a conventional purification apparatus, when a target substance is extracted and purified fully automatically, a biological sample may be open to the outside air. However, in this type of open system apparatus, for example, when nucleic acid is extracted from an infectious virus, there is a risk of secondary infection via air. According to the purification apparatus 1 and the purification container 2 according to the first embodiment, since the purification apparatus 1 moves the magnetic particles in the sealed purification container 2, the sealing property of the purification container 2 is improved. It is possible to carry out the treatment on the magnetic particles while maintaining the state. Thereby, according to the refiner | purifier 1 which concerns on 1st Embodiment, even if it is a case where a nucleic acid is extracted from an infectious virus, it becomes possible to reduce the risk of the secondary infection via air.

  Moreover, in 1st Embodiment, the refiner | purifier 1 is made to stop generation | occurrence | production of a magnetic field, when the position of the generated magnetic field arrives at the position corresponding to the liquid accommodated in a main body recessed part. That is, the refiner 1 stops the generation of the magnetic field when the aggregated magnetic particles come into contact with the liquid stored in the main body recess of the container main body 21. Thereby, the aggregated magnetic particles are dispersed by the liquid contained in the main body recess.

  Moreover, in 1st Embodiment, the refiner | purifier 1 changes a magnetic body in the liquid which contacts the container main body 21 side surface of this cover recessed part by fluctuating the position which generate | occur | produces a magnetic field along a single cover recessed part. I try to move the particles.

  In a conventional purification apparatus, when a target substance is extracted and purified fully automatically, a biological sample may be held in an unstable state such as a droplet. In such a case, it is difficult to carry out vigorous stirring work, and there is a concern that efficiency may be lowered in each processing step when the target substance is purified. According to the purification apparatus 1 and the purification container 2 according to the first embodiment, the purification apparatus 1 moves the magnetic particles in the liquid within the main body recess of the sealed purification container 2, so that the liquid is There is no leakage to the outside. For this reason, it is possible to effectively stir the liquid containing the biological sample and the magnetic particles, and it is possible to suppress a decrease in efficiency in each processing step when the target substance is purified.

  In the first embodiment, the container main body 21 is formed with a plurality of main body recesses, and at least one first main body recess is loaded with a dissolved adsorption liquid and magnetic particles. The second main body concave portion adjacent to the first main body concave portion is loaded with a cleaning liquid for the dissolved adsorption liquid. Thereby, in the refinement | purification container 2, the process process at the time of refine | purifying a target substance for every main body recessed part will be implemented.

  For this reason, for example, the magnetic particles that can specifically bind nucleic acid move between the main body recesses of the container main body 21, whereby nucleic acid extraction, adsorption to the magnetic particles, washing, and elution steps are performed. It becomes possible to obtain a purified solution. In addition, the magnetic particles capable of specifically binding proteins move between the main body recesses of the container main body 21, thereby performing protein extraction, adsorption to the magnetic particles, washing, and elution steps. Can be obtained.

  In the first embodiment, the purification container 2 is configured to perform the process of eluting the target substance from the magnetic particles in a container that can be detached from the container body 21. Thereby, it becomes possible to collect the purified liquid prepared using the purification container 2 as it is.

  Moreover, in 1st Embodiment, the refinement | purification container 2 is further equipped with the main body recessed part adjacent to the area | region which implements the process which elutes a target substance from a magnetic particle. And the refiner | purifier 1 is made to move a magnetic body particle to this main body recessed part, controlling the magnetic force to generate | occur | produce. As a result, it is possible to induce an arbitrary amount of purified liquid using the surface tension of the magnetic particles.

(Second Embodiment)
In 1st Embodiment, the case where the 1st magnetic field generation part 111 generated a magnetic field on the back side of the cover part 22 of the refinement | purification container 2 was demonstrated to the example. In the second embodiment, an example in which a magnetic field is generated by the first magnetic field generator 111a on the back side of the container body 21 will be described.

  FIG. 16 is a block diagram schematically showing the purification device 1a and the purification container 2 according to the second embodiment. A purification apparatus 1a shown in FIG. 16 includes a purification mechanism 11a, an input interface 12, a memory 13, and a processing circuit 14a. The refining mechanism 11a, the input interface 12, the memory 13, and the processing circuit 14a are connected to be communicable with each other via a bus, for example.

  The purification mechanism 11 a is a mechanism that accommodates the purification container 2 and extracts and purifies the target substance from the biological sample injected into the purification container 2. For example, as illustrated in FIG. 16, the purification mechanism 11a includes a first magnetic field generation unit 111a, a drive unit 112a, and a pressurizing member 1121.

  FIG. 17 is a schematic diagram illustrating a configuration example of the purification mechanism 11a provided in the purification device 1a illustrated in FIG. FIG. 17 shows a case where an electromagnet having a magnetic body and a coil is used as the first magnetic field generator 111a.

  The first magnetic field generator 111a is formed by arranging a plurality of electromagnets. FIG. 17 shows an example in which the electromagnets are arranged in a line having a predetermined depth, but the present invention is not limited to this. The electromagnets each have a bar shape and may be arranged in a lattice shape.

  The first magnetic field generation unit 111a also serves as a mounting unit for mounting the purification container 2. In the example shown in FIG. 17, a plurality of electromagnets are aligned to form a first concave region 1111 a to a fifth concave region 1115 a in the first magnetic field generator 111 a. The depths of the bottoms of the first recessed area 1111a to the fifth recessed area 1115a are substantially the same. The widths of the first concave region 1111a to the third concave region 1113a are larger than the widths of the fourth concave region 1114a and the fifth concave region 1115a. The plurality of electromagnets forming the first magnetic field generator 111a generates a magnetic field according to the control of the processing circuit 14a.

  The pressurizing member 1121 is, for example, a member for pushing the lid portion 22 of the purification container 2 into the container main body 21 and is realized by, for example, metal, plastic, or the like. The pressurizing member 1121 is provided above the first magnetic field generator 111a so as to face the first magnetic field generator 111a.

  The drive unit 112a moves the pressurizing member 1121 in a direction approaching the first magnetic field generation unit 111a as the placement unit or a direction away from the first magnetic field generation unit 111a according to the control of the processing circuit 14a. The drive unit 112a is realized by, for example, a gear, a stepping motor, a belt conveyor, and a lead screw.

  FIG. 18 is a diagram illustrating an example of a cross-sectional view of the purification container 2 and the purification mechanism 11a when the purification container 2 is placed on the first magnetic field generation unit 111a. In FIG. 18, the first main body concave portion 2111 to the third main body concave portion 2113, the receiving container 2114, and the fourth main body concave portion 2115 of the container main body 21 are the first concave region 1111 a to the fifth concave region 1115 a of the first magnetic field generator 111 a. The purification container 2 is placed on the first magnetic field generator 111a so as to be inserted into the first magnetic field generator 111a.

  The processing circuit 14a is a processor that functions as the center of the purification apparatus 1a. The processing circuit 14a implements a function corresponding to the program by executing the program stored in the memory 13 or the like. For example, the processing circuit 14a has a pressurizing function 141a and a magnet control function 142a by executing a program.

  The pressurizing function 141a is a function of controlling the driving unit 112a and applying pressure to the purification container 2. Specifically, for example, in the pressurizing function 141a, the processing circuit 14a controls the drive unit 112a so that the pressurizing member 1121 is lowered by a preset distance. Accordingly, the pressurizing member 1121 pushes the lid portion 22 of the purification container 2 placed on the first magnetic field generation unit 111a toward the container body 21.

  When the pressurizing member 1121 is lowered by a preset distance, the processing circuit 14a controls the drive unit 112a so that the pressurizing member 1121 rises by a minute distance, for example, about several mm. Thereby, a gap is generated between the cleaved sealing material 216 and the surface of the lid portion 22 on the container body 21 side.

  The magnet control function 142a is a function for controlling a plurality of electromagnets forming the first magnetic field generator 111a. Specifically, for example, in the magnet control function 142a, the processing circuit 14a generates a magnetic field from among a plurality of electromagnets forming the first magnetic field generator 111 according to a preset procedure. To supply current.

  Subsequently, an operation in which the purification apparatus 1a according to the present embodiment extracts and purifies the target substance using the purification container 2 will be described.

  The processing circuit 14a executes the pressurizing function 141a when the operator places the purification container 2 on the first magnetic field generation unit 111a and inputs an instruction to start the pressurizing process. When the pressurizing function 141a is executed, the processing circuit 14a controls the driving unit 112a so that the pressurizing member 1121 pushes the lid portion 22 into the container main body 21. By the pressure treatment, a path capable of transporting the magnetic particles and the substance attracted to the magnetic particles is formed between the surface of the lid 22 on the container body 21 side and the surface of the container main body 21 on the lid 22 side. Is done.

  When the pressurizing process for the purification container 2 is completed, the processing circuit 14a executes the magnet control function 142a. When the magnet control function 142a is executed, the processing circuit 14a switches the on state and the off state of the electromagnet that forms the first concave region 1111a, so that the magnetic particles contained in the first main body concave portion 2111 of the container main body 21 are changed. It moves and promotes the dissolution adsorption by the dissolution adsorbing liquid accommodated in the first main body recess 2111.

  When the liquid in the first main body concave portion 2111 is stirred, the processing circuit 14a turns off all the electromagnets in the first concave region 1111a. After all the electromagnets in the first concave region 1111a are turned off, the processing circuit 14a controls the electromagnets in the first concave region 1111a, for example, according to the procedure shown in FIG. Thereby, the magnetic particles dispersed in the liquid in the first main body recess 2111 are collected and transported to the adjacent second main body recess 2112.

  When the magnetic particles reach the second main body concave portion 2112 of the container main body 21, the processing circuit 14a is accommodated in the second main body concave portion 2112 by switching the on state and the off state of the electromagnet forming the second concave region 1112a. The magnetic material particles are moved, and the cleaning of the biological material other than the target material bound to the magnetic material particles and the melted adsorbed liquid by the first cleaning liquid accommodated in the second main body recess 2112 is promoted.

  When the liquid in the second main body concave portion 2112 is stirred, the processing circuit 14a turns off all the electromagnets in the second concave region 1112a. After all the electromagnets in the second concave region 1112a are turned off, the processing circuit 14a controls the electromagnets in the second concave region 1112a, for example, according to the procedure shown in FIG. Thereby, the magnetic particles dispersed in the liquid in the first main body recess 2111 are collected and transported to the adjacent third main body recess 2113.

  The processing circuit 14 a repeats the same processing as the processing shown in FIG. 19 and transports the magnetic particles to the storage container 2114 of the container main body 21. In the storage container 2114, the magnetic particles are dispersed in the treated water for eluting the target substance, and a purified liquid is created.

  When there is a subsequent process in the fourth main body recess 2115, the processing circuit 14a repeats the same process as that shown in FIG. 19, and conveys the magnetic particles adsorbing the purified liquid by the surface tension to the fourth main body recess 2115. To do. At this time, the processing circuit 14a controls the magnetic force by the electromagnet by adjusting the amount of current supplied to the electromagnets of the fourth concave region 1114a and the fifth concave region 1115a. This makes it possible to control the number of magnetic particles transported in the direction of the fifth concave region 1115a. That is, an arbitrary amount of purified liquid can be guided to the fourth main body recess 2115.

  In the second embodiment, the purification container 2 is placed on the first magnetic field generator 111a having a surface shape corresponding to the shape of the container body 21 of the purification container 2, and is given by the pressurizing member 1121. The case where pressure is applied has been described as an example. However, it is not limited to this. The first magnetic field generator 111a may have a permanent magnet 1116a and a moving mechanism 1117a for moving the permanent magnet 1116a. At this time, the purification mechanism 11a includes a mounting portion (not shown) for mounting the purification container 2.

  When the start instruction of the pressurizing process is input, the processing circuit 14a executes the pressurizing function 141a and controls the driving unit 112a so that the pressurizing member 1121 pushes the lid portion 22 into the container main body 21.

  When the pressurizing process on the purification container 2 is completed, the processing circuit 14a executes the magnet control function 142a and controls the moving mechanism 1117a so that the moving mechanism 1117a moves the permanent magnet 1116a. FIG. 20 is a schematic diagram illustrating an operation in which the processing circuit 14a controls the moving mechanism 1117a of the permanent magnet 1116a. The container main body 21 side surfaces of the first lid concave portion 221 to the fourth lid concave portion 224 of the lid portion 22 are liquids loaded in the first main body concave portion 2111 to the third main body concave portion 2113 of the container main body 21 and the storage container 2114. In the contact state, the processing circuit 14a controls the moving mechanism 1117a so that the permanent magnet 1116a moves along the placement side surface of the container body 21.

  The processing circuit 14a may control the moving mechanism 1117a so that the permanent magnet 1116a moves at a constant speed, or may change the speed depending on whether or not the magnetic particles are in contact with the liquid. Also good. Further, the processing circuit 14a may control the moving mechanism 1117a so that the permanent magnet 1116a moves back and forth on the placement side surface of the main body concave portion of the container main body 21 when the magnetic particles are in contact with the liquid.

  In addition, in 2nd Embodiment, the drive part 112a demonstrated as an example the case where the cover part 22 of the refinement | purification container 2 was pressed toward the container main body 21 with the pressurization member 1121. However, it is not limited to this. The drive unit 112a may be configured to press the container body 21 toward the lid 22 by moving the first magnetic field generation unit 111a in the direction of the pressurizing member 1121.

  As described above, in the second embodiment, the purification container 2 is made of a non-magnetic material and has a container body 21 having a body recess for containing a liquid and a lid recess having a shape corresponding to the body recess. And a lid portion 22 having a distance between the main body recess and the lid recess so as to face each other. The purification apparatus 1a controls the driving unit 112a by the pressurizing function 141a, thereby pushing the lid 22 into the container main body 21 and the liquid containing the biological sample and magnetic particles loaded in the main body recess of the container main body 21. Then, the container main body 21 side surface of the lid recess of the lid portion 22 is brought into contact. The refiner 1a causes the first magnetic field generator 111a to generate a magnetic field on the back side of the surface of the container body 21 that faces the lid portion 22. And the refiner | purifier 1a is made to move the generated magnetic field along the shape of the back side surface of the container main body 21 by the magnet control function 142a. As a result, the magnetic particles bonded to the biological sample are aggregated, and the aggregated magnetic particles move in the solution contained in the main body recess of the container body 21, and the magnetic particles in the main body recess. Can be executed.

  In the second embodiment, the purifier 1a moves the magnetic particles in the liquid contained in the main body recess by moving the position where the magnetic field is generated along the single main body recess. ing. Thereby, it becomes possible to effectively stir the liquid containing the biological sample and the magnetic particles, and it is possible to suppress a decrease in efficiency in each processing step when the target substance is purified.

  By the way, the opening of the first main body recess 2111 to the third main body recess 2113, the small diameter portion 21141, and the fourth main body recess 2115 of the container main body 21 was cleaved by the first lid recess 221 to the fourth lid recess 224. A trace of the sealing material 216 remains. The trace of the sealing material 216 can hinder the movement of the magnetic particles along the surface of the container body 21 on the lid portion 22 side. Therefore, the purification apparatus 1 according to the first embodiment can purify the target substance with higher accuracy than the purification apparatus 1a according to the second embodiment.

  According to at least one embodiment described above, the purification apparatus and the purification container can automate the extraction and purification of a target substance from a biological sample using a magnetic material while avoiding an increase in the size of the purification apparatus. .

  The term “processor” used in the description of the embodiment refers to, for example, a central processing unit (CPU), a graphics processing unit (GPU), or an application specific integrated circuit (ASIC)), a programmable logic device. (For example, a simple programmable logic device (SPLD), a complex programmable logic device (CPLD), and a field programmable gate array (FPGA)). The processor implements a function by reading and executing a program stored in the storage circuit. Instead of storing the program in the storage circuit, the program may be directly incorporated in the processor circuit. In this case, the processor realizes the function by reading and executing the program incorporated in the circuit. Each processor in each of the above embodiments is not limited to being configured as a single circuit for each processor, but is configured as a single processor by combining a plurality of independent circuits so as to realize the function. Also good. Further, the functions may be realized by integrating a plurality of components in each of the above embodiments into one processor.

  Although several embodiments of the present invention have been described, these embodiments are presented by way of example and are not intended to limit the scope of the invention. These embodiments can be implemented in various other forms, and various omissions, replacements, changes, and combinations can be made without departing from the scope of the invention. These embodiments and their modifications are included in the scope and gist of the invention, and are also included in the invention described in the claims and the equivalents thereof.

DESCRIPTION OF SYMBOLS 1, 1a ... Purification apparatus 11, 11a ... Purification mechanism 111, 111a ... 1st magnetic field generation | occurrence | production part 1111 ... 1st convex area | region 1111a ... 1st concave area | region 1112 ... 2nd convex area | region 1112a ... 2nd concave area | region 1113 ... 3rd convexity Area 1113a ... 3rd concave area 1114 ... 4th convex area 1114a ... 4th concave area 1115 ... 5th convex area 1115a ... 5th concave area 1116, 1116a ... Permanent magnet 1117, 1117a ... Moving mechanism 112, 112a ... Drive part 1121 ... Pressure member 113 ... Placement part 114 ... Second magnetic field generation part 12 ... Input interface 13 ... Memory 14, 14a ... Processing circuits 141, 141a ... Pressurization function 142, 142a ... Magnet control function 2 ... Purification container 21 ... Container Main body 211 ... Bottom 2111 ... First main body recess 2112 ... Second main body recess 2113 ... Third main body recess 2114 ... Storage container 21141 Small diameter part 21142 ... Female thread part 21143 ... Male thread part 2115 ... 4th main body recessed part 2116 ... Collar part 212 ... Peripheral wall part 2121 ... Expansion and contraction part 213 ... Opening part 216 ... Sealing material 22 ... Lid part 221 ... 1st lid recessed part 222 ... 1st 2 lid recess 223 3rd lid recess 224 4th lid recess 225 5th lid recess 226 Insert 2261 Cap 2262 Insertion hole 227 Flat part

Claims (13)

A container body having a body recess for containing a liquid containing magnetic particles, and a lid having a lid recess having a shape corresponding to the body recess, the body recess and the lid recess facing each other, and A driving unit that applies pressure to the purification container provided separately from the lid recess and the main body recess by inserting the lid recess into the main body recess; and
In the state where the pressure is applied, a magnetic field generation unit that generates a magnetic field on the back side of the surface of the container body that faces the lid, or on the back side of the surface of the lid that faces the container body,
The refinement | purification apparatus which comprises the magnet control part which moves the position which the said magnetic field generation part produces | generates a magnetic field along the shape of the back side surface of the said container main body, or the shape of the back side surface of the said cover part.   The said magnet control part is a refinement | purification apparatus of Claim 1 which stops the generation | occurrence | production of the said magnetic field, when the position of the said magnetic field reaches the position corresponding to the liquid accommodated in the said main body recessed part.   The magnet control unit varies the position at which the magnetic field is generated on the back surface of the single main body recess before moving the position at which the magnetic field is generated along the shape of the back surface of the container body. The purification apparatus according to 1 or 2.   The magnet control unit varies the position of generating the magnetic field on the back surface of the single lid recess before moving the position of generating the magnetic field along the shape of the back surface of the lid. The purification apparatus according to 1 or 2. The refining container further includes an expansion / contraction part that couples the container body and the lid part so as to be contractible in a direction in which the container body and the lid part approach each other.
The drive unit causes the lid recess to be inserted into the body recess by contracting the extendable part,
The purification apparatus according to claim 1, wherein the magnet control unit moves a position where the magnetic field is generated with respect to the sealed purification container. The container body has a plurality of the body recesses,
Any one of the plurality of main body recesses contains a liquid containing the magnetic particles,
The lid has a plurality of lid recesses each having a shape corresponding to the plurality of body recesses,
The drive unit is configured to bring at least one of the plurality of lid recesses into contact with the liquid contained in the plurality of main body recesses with respect to the purification container, and between the plurality of lid recesses and the plurality of main body recesses. Pressure to provide a path,
The refining device according to claim 1, wherein the magnet controller transports the magnetic particles through the path by moving a position where the magnetic field is generated. At least one of the plurality of main body recesses contains a cleaning liquid for cleaning the magnetic particles,
The purification apparatus according to claim 6, wherein the magnet controller is configured to clean the magnetic particles with the cleaning liquid by moving a position where the magnetic field is generated.   The said magnet control part is a refinement | purification apparatus of Claim 6 or 7 which controls the number of the said magnetic body particles to convey by controlling the magnetic force of the said magnetic field.   The purification apparatus according to claim 1, further comprising the purification container. A container body having a plurality of body recesses in which at least one of the liquids containing magnetic particles is accommodated;
A plurality of lid recesses each having a shape corresponding to each of the plurality of main body recesses, the plurality of lid recesses facing the plurality of main body recesses and spaced apart from the plurality of main body recesses; ,
A refining container comprising: a container body; and an expansion / contraction section that couples the lid section so as to be contractible in a direction in which the container body and the lid section are brought close to each other.   The purification container according to claim 10, wherein at least one of the plurality of main body recesses contains a cleaning liquid for cleaning the magnetic particles.   The purification container according to claim 10, wherein a purified solution after purifying the target substance is guided into at least one of the plurality of main body recesses.   The purification container according to any one of claims 10 to 12, wherein the container main body includes an engaging portion that detachably engages with a storage container that stores a processing liquid for eluting a target substance from the magnetic particles.