WO2022080970A1 - Solution mixing device and solution mixing method - Google Patents

Solution mixing device and solution mixing method Download PDF

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Publication number
WO2022080970A1
WO2022080970A1 PCT/KR2021/014407 KR2021014407W WO2022080970A1 WO 2022080970 A1 WO2022080970 A1 WO 2022080970A1 KR 2021014407 W KR2021014407 W KR 2021014407W WO 2022080970 A1 WO2022080970 A1 WO 2022080970A1
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WO
WIPO (PCT)
Prior art keywords
electromagnets
solution
accommodating portion
mixing device
solution mixing
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2021/014407
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French (fr)
Inventor
Jae Young Kim
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Seegene Inc
Original Assignee
Seegene Inc
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Filing date
Publication date
Application filed by Seegene Inc filed Critical Seegene Inc
Priority to KR1020237012369A priority Critical patent/KR20230066096A/en
Publication of WO2022080970A1 publication Critical patent/WO2022080970A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00Other mixers; Mixing plants; Combinations of mixers
    • B01F33/45Magnetic mixers; Mixers with magnetically driven stirrers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00Other mixers; Mixing plants; Combinations of mixers
    • B01F33/45Magnetic mixers; Mixers with magnetically driven stirrers
    • B01F33/452Magnetic mixers; Mixers with magnetically driven stirrers using independent floating stirring elements
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/40Mixing liquids with liquids; Emulsifying
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/20Measuring; Control or regulation
    • B01F35/22Control or regulation
    • HELECTRICITY
    • H01ELECTRIC ELEMENTS
    • H01FMAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
    • H01F7/00Magnets
    • H01F7/06Electromagnets; Actuators including electromagnets
    • HELECTRICITY
    • H01ELECTRIC ELEMENTS
    • H01FMAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
    • H01F7/00Magnets
    • H01F7/06Electromagnets; Actuators including electromagnets
    • H01F7/064Circuit arrangements for actuating electromagnets

Definitions

  • the disclosure relates to a solution mixing device and a solution mixing method.
  • nucleic acid-based in vitro molecular diagnosis such as accurate analysis of pathogens and gene analysis of patients becomes more significant and its demand is on the rise.
  • Nucleic acid-based molecular diagnosis is performed by extracting nucleic acids from a sample and then checking the presence or absence of a target nucleic acid among the extracted nucleic acids.
  • the sample processing process of extracting nucleic acid from a sample includes sequentially mixing the sample and various reagents and removing residues other than the nucleic acid. Such a sample processing process requires an elaborate processing of a small amount of solution and, thus, is mostly performed manually by an experimenter or using a piece of liquid handling equipment that may be precisely controlled. Conventional liquid handling equipment is costly and needs professional manpower.
  • the POC system for nucleic acid detection processes extraction and nucleic acid detection from a sample in one step in one cartridge.
  • the POC system is designed to be able to proceed with sample processing as soon as the sample is collected, so it has strengths in the local medical site.
  • the POC-based extraction process and nucleic acid detection process are performed while sequentially moving a sample to a plurality of sample processing chambers and nucleic acid reaction chambers.
  • a method is to form an inter-chamber flow path and control it using valves, and another method is to move the solution by a lyotropic means.
  • Another type of POS system configures a cartridge with sample processing chambers and moves the liquid from chamber to chamber using a pipette module and processes the liquid using a moving module for moving the pipette module up, down, left, and right.
  • Various reagents for nucleic acid extraction are provided in the chambers of the cartridge, and liquid movement for a sample processing reaction is performed by the pipette module and the moving module.
  • the sample is mixed with the various reagents.
  • the conventional POC system repeats, multiple times, the pipetting process of putting and pulling the pipette tip into and out of the solution containing various reagents and the sample received in the chamber while mixing the sample and various reagents.
  • leakage of the solution may cause fatal errors in the results of detection, as well as contamination.
  • the present inventors have attempted to develop a device and method for mixing a solution, which may uniformly mix the solution. Further, the present inventors have tried to develop a device and method for mixing a solution which may prevent leakage of the solution during the mixing process. As a result, the present inventors have developed a solution mixing device including an electromagnet module including a accommodating portion in which a solution containing magnetic beads is positioned and a plurality of electromagnets arranged to the accommodating portion and a controller individually controlling magnetic forces of the plurality of electromagnets to move the magnetic beads.
  • the disclosure aims to provide a solution mixing device including an electromagnet module including an accommodating portion in which a solution containing magnetic beads is positioned and a plurality of electromagnets arranged with regard to the accommodating portion and a controller individually controlling magnetic forces of the plurality of electromagnets to move the magnetic beads.
  • the disclosure also aims to arrange a solution mixing method using a solution mixing device including an electromagnet module including an accommodating portion in which a solution containing magnetic beads is positioned and a plurality of electromagnets arranged with regard to the accommodating portion and a controller individually controlling magnetic forces of the plurality of electromagnets to move the magnetic beads, the solution mixing method comprising a preparation step of positioning the solution in the accommodating portion and a mixing step of individually adjusting magnetic forces of the plurality of electromagnets to mix the solution.
  • a solution mixing device including an electromagnet module including an accommodating portion in which a solution containing magnetic beads is positioned and a plurality of electromagnets arranged with regard to the accommodating portion and a controller individually controlling magnetic forces of the plurality of electromagnets to move the magnetic beads.
  • a solution mixing method using a solution mixing device including an electromagnet module including an accommodating portion in which a solution containing magnetic beads is positioned and a plurality of electromagnets arranged with regard to the accommodating portion and a controller individually controlling magnetic forces of the plurality of electromagnets to move the magnetic beads, the solution mixing method comprising a preparation step of positioning the solution in the accommodating portion and a mixing step of individually adjusting magnetic forces of the plurality of electromagnets to mix the solution.
  • the disclosure may more uniformly mix the solution in the container using the electromagnets.
  • the disclosure may separate the material bound to the magnetic beads from the waste liquid by capturing the magnetic beads in the solution in a specific area in the container through the magnetically controllable electromagnets.
  • the disclosure controls the movement of the magnetic beads in the container only by turning on/off the current even without pipetting the solution, thus eliminating the concern about contamination due to separate physical manipulation while saving costs for replacing pipettes. Further, as magnetic force is adjusted using current, more accurate control in forming a flow path is possible than pipetting.
  • the solution mixing device and solution mixing method according to the disclosure may uniformly mix the solution.
  • the solution mixing device and solution mixing method may uniformly mix the sample and various reagents in a sample processing reaction.
  • solution mixing device and solution mixing method according to the disclosure may uniformly mix the sample and the lysis buffer during a sample processing reaction, preventing errors in detection results and enhancing the reliability of detection results.
  • solution mixing device and solution mixing method according to the disclosure may enhance the accuracy of detection results by increasing the yield of binding between nucleic acids and magnetic beads during a sample processing reaction.
  • the solution mixing device and solution mixing method according to the disclosure may prevent leakage of the solution while mixing the solution.
  • the solution mixing device and solution mixing method may prevent leakage of the sample in a sample processing reaction, preventing contamination of the sample processing device.
  • FIG. 1 is a perspective view illustrating a solution mixing device according to an embodiment of the disclosure
  • FIG. 2 is a side view illustrating a solution mixing device according to an embodiment of the disclosure
  • FIG. 3A is a view illustrating a positional relationship between a container and a plurality of electromagnets disposed on a side and lower surface of a accommodating portion, with the accommodating portion excluded, according to the disclosure;
  • FIG. 3B is a view illustrating a positional relationship between a container and a plurality of electromagnets disposed along the circumference of a accommodating portion, with the accommodating portion excluded, according to the disclosure;
  • FIG. 3C is a view illustrating a positional relationship between a container and a plurality of electromagnets disposed at different heights of a accommodating portion, with the accommodating portion excluded, according to the disclosure.
  • FIG. 4 is a perspective view illustrating a solution mixing device according to an embodiment of the disclosure.
  • Such denotations as “first,” “second,” “A,” “B,” “(a),” and “(b),” may be used in describing the components of the present invention. These denotations are provided merely to distinguish a component from another, and the essence of the components is not limited by the denotations in light of order or sequence.
  • a component is described as “connected,” “coupled,” or “linked” to another component, the component may be directly connected or linked to the other component, but it should also be appreciated that other components may be “connected,” “coupled,” or “linked” between the components.
  • a solution mixing device 100 including an electromagnet module 110 including an accommodating portion 111 in which a solution containing magnetic beads is positioned and a plurality of electromagnets 112 arranged with regard to the accommodating portion to electromagnetically effect the magnetic beads 111 and a controller 120 controlling magnetic forces of the plurality of electromagnets 112 to move the magnetic beads.
  • sample may encompass biological samples (e.g., cells, tissues, or fluids from biological sources) and non-biological samples (e.g., foods, water, and soil).
  • the biological samples include virus, germs, tissues, cells, blood (e.g., whole blood, plasma, and serum), lymph, bone marrow fluid, saliva, sputum, swab, aspiration, milk, urine, stool, ocular humor, semen, brain extracts, spinal fluid, joint fluid, thymus fluid, bronchoalveolar lavage fluid, ascites, and amniotic fluid.
  • Sample processing refers to a series of processes to primarily separate an analyte from the sample to thereby obtain a material in the state capable of detection reaction.
  • the term 'sample processing' may be used as further meaning the process of detecting a target analyte from the substance in the detection reaction-capable state.
  • the analyte may be, for example, a nucleic acid.
  • the sample processing may include the process of extracting a nucleic acid.
  • a solution mixing device 100 includes an electromagnet module 110 and a controller 120.
  • the electromagnet module 110 includes an accommodating portion 111 and a plurality of electromagnets 112.
  • the shape of the accommodating portion 111 is not particularly limited, but may be a rectangular prism shape that is opened upward as illustrated in the drawings.
  • the solution containing magnetic beads may contain a sample.
  • various liquids, such as samples, reagents, and solutions may be transferred to or from the accommodating portion 111 by a pipette.
  • a sample may be transferred to the accommodating portion 111 in which a solution containing magnetic beads but not containing a sample has previously been prepared, or a solution containing magnetic beads but not containing a sample may be transferred to the accommodating portion 111 in which a sample has previously been prepared.
  • a solution containing magnetic beads but not containing a sample and a sample may be individually transferred to the accommodating portion 111 (regardless of order), or a solution containing both magnetic beads and a sample may be transferred to the accommodating portion 111.
  • the solution containing magnetic beads may include the sample.
  • the solution containing both the magnetic beads and the sample may be formed while a solution containing the magnetic beads but not containing the sample and the sample are separately positioned in different spaces (e.g., cartridge chambers).
  • the plurality of electromagnets 112 are arranged with regard to the accommodating portion 111 to arrange magnetic force to the magnetic beads in the solution.
  • the magnetic force of each electromagnet is controlled by the controller 120.
  • the controller 120 controls the magnetic force of the plurality of electromagnets 112 to move the magnetic beads. As the magnetic force of the plurality of electromagnets 112 is adjusted by the controller 120, the magnetic beads are moved in the solution, creating a flow of the solution and thereby mixing the solution.
  • the controller 120 adjusts the strength of the current applied to each electromagnet and controls the magnetic force of each electromagnet. For example, as the controller 120 repeats the process of individually strengthening, maintaining, or weakening the magnetic force of the electromagnets, the magnetic beads move toward the electromagnet having a relatively high magnetic force, creating a flow of the solution.
  • the electromagnets may be arranged with regard to positions where they are capable of providing a magnetic force to the solution positioned in the accommodating portion 111, and the positions are not limited.
  • the electromagnets may be arranged to outside or inside or the outside and the inside of the accommodating portion 111.
  • the electromagnets may be magnetized to have a magnetic force by the magnetic field generated through a current supplied under the control of the controller 120.
  • the degree of magnetic force may be adjusted according to the strength of the supplied current, so that the moving speed of the magnetic beads may be adjusted, creating a flow of the solution. If the current supply is cut off, the electromagnets lose the magnetism. In such a case, the movement of the magnetic beads is stopped and so is the flow of the solution.
  • the electromagnet includes a coil winding or a compressed wire configured to allow current to flow well, and a current may be supplied through an exposed positive electrode.
  • the number of the electromagnets is not particularly limited, but may be, e.g., 2, 3, 4 or 5 or more, or may be, e.g., 10, 9, 8, 7 or less.
  • the solution mixing device is described below with reference to FIGS. 2, 3A, 3B, and 3C.
  • the plurality of electromagnets 112 may be arranged with regard to the accommodating portion 111 to electromagnetically effect the magnetic beads.
  • the electromagnets may be arranged to an outside the accommodating unit.
  • the electromagnets may be arranged to an inside the accommodating unit.
  • the electromagnets may be arranged both the outside and the inside the accommodating unit.
  • the electromagnets are arranged to the side of the accommodating portion 111 laterally face the empty space of the accommodating portion 111, and the electromagnet arranged to the bottom of the accommodating portion 111 vertically faces the empty space of the receiving unit 111.
  • FIG. 2 is a side view illustrating a solution mixing device according to an embodiment of the disclosure.
  • FIG. 2 illustrates an example in which a plurality of electromagnets 112 are arranged to side and/or the bottom of the accommodating portion 111.
  • the electromagnets on the side of the accommodating portion 111 may be partially exposed to the outside of the accommodating portion 111 while being partially inserted into the inside of the accommodating portion 111 to be positioned adjacent to a container 200.
  • the entire electromagnet may be arranged to the outside the accommodating portion (111).
  • a part of the entire electromagnet may be attached to the outside of the accommodating portion(111).
  • the electromagnet may be arranged at a predetermined distance from the accommodating portion(111) outside.
  • the entire electromagnet may be arranged to the inside the accommodating portion(111).
  • a part of the entire electromagnet may be attached to the inside of the accommodating portion(111).
  • the electromagnet may be arranged at a predetermined distance from the inside of the accommodating portion(111).
  • the bottom of the accommodating portion 111 may be arranged to a flat shape to stably support the accommodating portion, e.g., seat it on a means for supporting the accommodating portion 111, i.e., the moving member 511 described below.
  • the electromagnet arranged to the bottom may be fully inserted in the bottom of the accommodating portion 111 not to be exposed to the outside, unlike the electromagnets on the side.
  • the electromagnet fully inserted in the bottom of the accommodating portion 111 is merely a preferable embodiment of the disclosure.
  • the electromagnet arranged to the side and/or the bottom of the accommodating portion 111 may be partially exposed and partially inserted or may be fully inserted or fully exposed, and other various changes may also be possible.
  • At least one of the plurality of electromagnets 112 may be arranged to the bottom of the accommodating portion 111.
  • the accommodating portion 111 may have a shape in which the empty space formed therein is narrowed and tapered downwards.
  • the electromagnet arranged to the bottom of the accommodating portion 111 may be disposed to face the empty space of the accommodating portion 111 in an inclined direction or be disposed vertically in the straight line direction of the empty space.
  • the disclosure intends to mix the solution by moving the magnetic beads included in the solution through the magnetic force of the plurality of electromagnets 112. Accordingly, various embodiments according to the positions of the container 200 containing the solution and the plurality of electromagnets 112 in the accommodating portion 111 are described with reference to FIGS. 3A, 3B, and 3C.
  • FIGS. 3A, 3B, and 3C illustrate the positional relationships between the container 200 and the plurality of electromagnets 112 arranged to the side and bottom of the accommodating portion 111, with the accommodating portion 111 excluded.
  • the plurality of electromagnets 112 arranged to the accommodating portion 111 according to the disclosure are intended for mixing the solution in the container, As illustrated in FIGS. 3A, 3B, and 3C, the electromagnets 112 are arranged to various positions of the accommodating portion to mix the solution.
  • FIG. 3A illustrates the positions of the electromagnets 112 on the container 200 when the plurality of electromagnets 112 are arranged to the side and bottom of the accommodating portion 111 according to an embodiment of the disclosure.
  • FIG. 3B illustrates the positions of the electromagnets 112 on the container 200 when the plurality of electromagnets 112 are arranged to the circumference of the accommodating portion 111 according to another embodiment of the disclosure.
  • at least two or more of the plurality of electromagnets 112 may be arranged to the circumference of the accommodating portion111.
  • an electromagnet may be arranged to each side of the accommodating portion 111.
  • At least two of the electromagnets arranged to the circumference of the accommodating portion 111 may be arranged to side each other with the solution interposed therebetween.
  • the electromagnets are arranged to opposite sides of the accommodating portion 111 in the rectangular column shape and may be arranged to side each other.
  • the electromagnets arranged to the upper sides may face each other, and the electromagnets arranged to the bottom sides may side each other.
  • At least two of the electromagnets 112 arranged to the circumference of the accommodating portion 111 may be arranged at different heights.
  • a plurality of electromagnets 112 are arranged to the side and bottom of the accommodating portion111, and the electromagnets 112 arranged to the sides may be arranged at different heights.
  • the positions of the electromagnets 112 on the container 200 are as shown in FIG. 3C. If four electromagnets are arranged, two may be arranged to on the upper sides and the other two may be arranged to the bottom sides.
  • the flow of the solution is generated in various forms when the controller 120 controls the magnetic force of the electromagnets to move the magnetic beads.
  • the number of the plurality of electromagnets 112 and the shape in which the plurality of electromagnets 112 are arranged to the accommodating portion 111 are not limited to those illustrated in the drawings, and various changes may be made thereto according to the shape of the accommodating portion 111 or the characteristics of the solution to be mixed.
  • the controller 120 may controls magnetic forces of the plurality of electromagnets 112 individually or in group.
  • the controller 120 may control the magnetic forces of the individual electromagnets, or the controller 120 may group two or more of the plurality of electromagnets 112 and control the magnetic force of the grouped electromagnets.
  • the plurality of electromagnets 112 may include two or more groups.
  • the controller 120 may control to allow the electromagnets belonging to the same group to have the same magnetic force.
  • the grouped electromagnets may be positioned adjacent to each other or spaced apart from each other, and the grouped electromagnets may include those adjacent to each other and spaced apart from each other.
  • electromagnets positioned at the same height on the accommodating portion 111 may belong to the same group, and the electromagnets disposed to face each other with the solution containing the magnetic beads interposed therebetween may belong to different groups.
  • the plurality of electromagnets 112 may be divided into individual electromagnets, into individual electromagnets and grouped electromagnets, or into grouped electromagnets.
  • the controller 120 may individually control the magnetic force of all the electromagnets, or the controller 120 may group at least some of the electromagnets, like 1, 1, and 2, or 1 and 3, or 2 and 2.
  • the controller 120 groups and controls the plurality of electromagnets 112
  • the grouped form of the electromagnets may be changed during the control process. For example, if four electromagnets are arranged as illustrated in the drawings, the controller 120 may group them into 1, 1, and 2 and control them and may then change the group into 1 and 3 or 2 and 2 and control them.
  • the controller 120 may control to allow all of the plurality of electromagnets 112 to have the same magnetic force, but it is preferable to differently control at least some of the magnetic forces for the purpose of creating a flow of the solution while moving the magnetic beads.
  • the controller 120 may control to allow at least two of the plurality of electromagnets 112 to have different magnetic forces, thereby moving the magnetic beads.
  • the controller 120 may individually strengthen, maintain, or weaken the magnetic force of the electromagnets, allowing at least two electromagnets to have different magnetic forces.
  • the magnetic beads are moved toward the electromagnet having a relatively stronger magnetic force. As the magnetic beads move, a flow of the solution is created, mixing the solution.
  • the controller 120 may control to allow at least two individual electromagnets to have different magnetic forces, control to allow at least one individual electromagnet and at least one group of electromagnets to have different magnetic forces, or control at least two or more groups of electromagnets to have different magnetic forces.
  • the controller 120 may move the magnetic beads while changing at least two electromagnets having different magnetic forces.
  • the controller 120 may perform control so that any one of at least two individual electromagnets has a stronger magnetic force than the other one and then the one electromagnet has a weaker magnetic force than the other one, so that an individual electromagnet or a group of electromagnets, other than the at least two individual electromagnets, has a different magnetic force than at least one of the at least two individual electromagnets, or so that at least two individual electromagnets, other than the at least two individual electromagnets, or at least one individual electromagnet and at least one grouped electromagnet, or at least two or more grouped electromagnets have different magnetic forces.
  • the controller 120 changes at least two electromagnets with different magnetic forces, the electromagnet having a relatively stronger magnetic force, toward which the magnetic forces are moved, is changed, so that a flow of the solution by the magnetic forces is continuously created to thereby mix the solution.
  • the controller 120 may sequentially or randomly change at least two electromagnets having different magnetic forces according to the order in which the plurality of electromagnets 112 are arranged.
  • the order in which the plurality of electromagnets 112 are arranged may be, e.g., the vertical direction, the circumferential direction, the front-back direction (lateral direction) of the accommodating portion 111.
  • the controller 120 may generate a flow of the solution in the vertical direction by controlling the magnetic forces of the electromagnets differently on the upper side and lower side.
  • the controller 120 may create a flow of the solution, which rotates clockwise or counterclockwise, by sequentially and differently controlling the magnetic forces of the electromagnets along the circumferential direction.
  • the controller 120 may generate a flow of the solution in the front-back direction by controlling the magnetic forces of the electromagnets on the front and back.
  • a combination of the vertical direction, the circumferential direction, and the front-back direction (lateral direction) is also possible. For example, control may be performed so that the rotating flow of the solution is moved up and down.
  • the controller 120 may change at least two electromagnets having different magnetic forces in a random order regardless of the order in which the plurality of electromagnets 112 are arranged.
  • the sample and the lysis buffer are mixed using the solution mixing device according to the disclosure in the sample processing device, it is possible to uniformly mix the sample and the lysis buffer by the magnetic beads and to prevent non-exposure of the nucleic acid due to failure to destroy the cell walls of some cells. Thus, it is possible to prevent errors in detection results and to enhance reliability.
  • the controller 120 since a flow of magnetic beads is created in the solution by the controller 120, the yield of combination between the exposed nucleic acids and the magnetic beads is increased, so that some nucleic acids may be prevented from being removed during the washing process for removing the cell debris without combining with the magnetic beads. It is thus possible to enhance the accuracy of the detection result.
  • the solution is mixed by the flow of magnetic beads created inside the solution rather than mixing the solution in a pipetting manner, leakage of the solution does not occur during the mixing process, and contamination due to leakage of the sample in the sample processing device may be prevented.
  • the solution containing magnetic beads is received in the container 200, the container 200 is positioned in the receiving unit 111, and the solution containing the magnetic beads may be positioned in the accommodating portion 111.
  • the container 200 and the accommodating portion 111 may be formed in shapes corresponding to each other.
  • the container 200 may be inserted into the opening of the accommodating portion 111, and the container 200 may be positioned in the accommodating portion 111.
  • the container 200 may be any one of a plurality of chambers included in a cartridge actuated by the sample processing device.
  • the plurality of chambers of the cartridge are spaces in which a material necessary for the process of extracting a detection target material (e.g., nucleic acid) from a sample is stored, and a physical and chemical process for extraction is performed.
  • At least one of the plurality of chambers is a sample chamber and a space in which the sample collected is received.
  • the sample received in the sample chamber may be transferred to the container 200 by, e.g., a pipette.
  • the cartridge may be produced in a state in which the solution containing the magnetic beads is positioned in the container 200.
  • the electromagnet module 110 may be arranged to be movable in a direction in which the container 200 is inserted into the accommodating portion 111 and in a direction in which the container 200 is removed from the accommodating portion 111. As illustrated in the drawings, if the accommodating portion 111 is opened upward, the electromagnet module 110 may be arranged to be movable in the vertical direction from the lower side of the container 200.
  • a heating element (not shown) and an insulation element (not shown) may be disposed between the container 200 and the accommodating portion 111.
  • the heating element may be configured to increase the temperature of the reaction solution in the container 200. If the temperature of the reaction solution is increased through the heating element, the reaction may proceed more efficiently. For example, in a case where the container 200 is a dissolution chamber, if the temperature of the lysis buffer is increased through the heating element, the dissolution reaction is more activated, so that the sample may be dissolved more effectively.
  • the heating element is thermally connected to the container 200. The temperature of the reaction solution in the container 200 may be increased using the heat provided from the heating element.
  • "thermal connection" means that the heating element is in direct or indirect contact to the container 200 to transfer or conduct heat to the container 200.
  • the heating element may be provided in a position where it may provide heat to the container 200, and its position is not limited.
  • the heating element may be provided on the outer surface of the container 200.
  • the heating element may have various shapes depending on implementation examples of the container 200 or schemes for supplying heat.
  • the heating element may be shaped to have an area sufficient to cover a specific area or the entire area of the container 200 or may have a hot wire shape obtained by compressing an electrically conductive terminal in a linear form.
  • the heating element may be electrically connected with a power module and may generate heat using the power received from the power module.
  • the heating element may be formed of a material, such as metal, ceramic, or semiconductor.
  • the heating element may have a shape of one or more strands, a plate, a foil, or a film.
  • the insulation element is positioned between the heating element and the accommodating portion 111 and performs thermal insulation so that the heat of the heating element is not transferred to the accommodating portion 111.
  • the position of the insulation element is not limited as long as it may block the heat of the heating element to the accommodating portion 111.
  • the insulation element may be arranged to the outer surface of the heating element.
  • the container 200 in which the solution containing the magnetic beads is positioned is fixed, and the electromagnet module 110 is moved upward from the lower side of the container 200, so that the container 200 may be inserted into the accommodating portion 111.
  • the controller 120 may individually control the magnetic forces of the plurality of electromagnets 112 to mix the solution. As the electromagnet module 110 is moved downward, the container 200 may be removed from the accommodating portion 111.
  • the solution mixing device 100 may further include a driver 510 for moving the electromagnet module 110.
  • the driver 510 may include a moving member 511 coupled with the electromagnet module 110, a guide member 512 for providing the moving member 511 with a movement path in a direction in which the electromagnet module 110 may move, and a motor 513 for moving the moving member 511 along the movement path.
  • the driver 510 may further include a base member 515 supporting the guide member 512 and the motor 513.
  • the moving member 511 may be formed in a plate shape and coupled with the accommodating portion111.
  • the moving member 511 may include a recess in which the accommodating portion 111 is seated. As illustrated in the drawings, the recess may be formed in the upper surface of the moving member 511, and the accommodating portion 111 may be seated on the upper surface of the moving member 511.
  • the accommodating portion 111 and the moving member 511 may be coupled by bolting.
  • the guide member 512 may be a shaft penetrating the moving member 511. Two opposite ends of the guide member 512 are fixed to the base member 515. The guide member 512 provides the movement path to the moving member 511. Two or more guide members 512 may be provided.
  • the motor 513 may move the moving member 511 along the movement path provided by the guide member 512, e.g., in the vertical direction.
  • a nut may be coupled to the moving member 511, and a bolt 514 engaged with the nut may be rotatably provided to the base member 515.
  • the motor 513 may rotate the bolt 514 to move the nut.
  • the motor 513 and the bolt 514 may be connected by a gear set.
  • a PCB substrate 516 may be provided on the base member 515.
  • the controller 120 for controlling the plurality of electromagnets 112 may be mounted on the PCB substrate 516.
  • the motor 513 may be controlled by the PCB substrate 516.
  • the mixing device 100 may further include a vibration generator (not shown).
  • Moisture condensed on the outer surface of the accommodating portion 111 (or the container 200) may be removed by the vibration generated by the vibration generator.
  • Depressed coupling recesses are formed in the outer surface of the accommodating portion 111, in the positions where the plurality of electromagnets 112 are arranged.
  • the plurality of electromagnets 112 may be individually seated in the coupling recesses, and so is the vibration generator.
  • Each electromagnet may be coupled to the accommodating portion 111 by, e.g., press-fitting or bonding in the coupling recess.
  • a solution mixing method includes a preparation step and a mixing step.
  • the solution mixing method is a solution mixing method using the solution mixing device 100 according to the above-described embodiment of the disclosure.
  • the solution mixing method includes the preparation step of positioning a solution containing magnetic beads in the accommodating portion 111 and the mixing step of mixing the solution while individually adjusting the magnetic forces of the plurality of electromagnets 112.
  • the solution containing magnetic beads may be transferred to the accommodating portion 111 using, e.g., a pipette.
  • the solution containing the magnetic beads is positioned in the container 200, and the electromagnet module 110 may be moved in the direction in which the container 200 is inserted into the accommodating portion 111.
  • the controller 120 mixes the solution containing the magnetic beads while individually adjusting the magnetic forces of the plurality of electromagnets 112.
  • the mixing step may include a setting step for controlling to allow at least two of the plurality of electromagnets 112 to have different magnetic forces while individually controlling the magnetic force of individual electromagnets or grouped electromagnets among the plurality of electromagnets 112 and may change at least two electromagnets having different magnetic forces.
  • the setting step it is possible to sequentially or randomly change at least two electromagnets having different magnetic forces according to the order in which the plurality of electromagnets 112 are arranged.

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Abstract

The disclosure provides a solution mixing device including an electromagnet module including an accommodating portion in which a solution containing magnetic beads is positioned and a plurality of electromagnets arranged with the regard to the accommodating portion and a controller controlling magnetic forces of the plurality of electromagnets to move the magnetic beads and a solution mixing method. According to the disclosure, it is possible to uniformly mix the solution and to prevent leakage of the solution during the mixing process.

Description

SOLUTION MIXING DEVICE AND SOLUTION MIXING METHOD
The disclosure relates to a solution mixing device and a solution mixing method.
As modern people's interest in health increases and life expectancy is prolonged, nucleic acid-based in vitro molecular diagnosis, such as accurate analysis of pathogens and gene analysis of patients becomes more significant and its demand is on the rise.
Nucleic acid-based molecular diagnosis is performed by extracting nucleic acids from a sample and then checking the presence or absence of a target nucleic acid among the extracted nucleic acids. The sample processing process of extracting nucleic acid from a sample includes sequentially mixing the sample and various reagents and removing residues other than the nucleic acid. Such a sample processing process requires an elaborate processing of a small amount of solution and, thus, is mostly performed manually by an experimenter or using a piece of liquid handling equipment that may be precisely controlled. Conventional liquid handling equipment is costly and needs professional manpower. Further, since it is a system that simultaneously processes a large number of samples, it takes a long time from sample collection to confirming the test result when the number of samples generated per hour is small, so it is not suitable for use in local hospitals and clinics where a small number of samples are to be processed.
The POC system for nucleic acid detection processes extraction and nucleic acid detection from a sample in one step in one cartridge. The POC system is designed to be able to proceed with sample processing as soon as the sample is collected, so it has strengths in the local medical site. The POC-based extraction process and nucleic acid detection process are performed while sequentially moving a sample to a plurality of sample processing chambers and nucleic acid reaction chambers. To move a sample or its processed material between chambers, a method is to form an inter-chamber flow path and control it using valves, and another method is to move the solution by a lyotropic means.
These methods should allow or prevent the solution to pass or from passing through a specific flow path channel and thus requires cooperation with a compressor, such as a plunger or syringe, resulting in inaccuracy in the volume of the processed solution or poor versatility for various sample processing methods as compared with typical pipetting.
Another type of POS system configures a cartridge with sample processing chambers and moves the liquid from chamber to chamber using a pipette module and processes the liquid using a moving module for moving the pipette module up, down, left, and right. Various reagents for nucleic acid extraction are provided in the chambers of the cartridge, and liquid movement for a sample processing reaction is performed by the pipette module and the moving module.
During the sample processing reaction, the sample is mixed with the various reagents. The conventional POC system repeats, multiple times, the pipetting process of putting and pulling the pipette tip into and out of the solution containing various reagents and the sample received in the chamber while mixing the sample and various reagents. However, according to this scheme, it is difficult to uniformly mix the sample with various reagents. For example, when the sample and a lysis buffer are mixed, the cell walls of some cells are not destroyed, so the nucleic acid may not be extracted. Further, as the pipette tip may have the solution on it, part of the solution may leak out. By the nature of the POC system that processes a small amount of solution, leakage of the solution may cause fatal errors in the results of detection, as well as contamination.
Therefore, it is necessary to develop a device and method for mixing a solution, which is capable of uniformly mixing the solution while preventing the solution from leaking.
In the above-described background, the present inventors have attempted to develop a device and method for mixing a solution, which may uniformly mix the solution. Further, the present inventors have tried to develop a device and method for mixing a solution which may prevent leakage of the solution during the mixing process. As a result, the present inventors have developed a solution mixing device including an electromagnet module including a accommodating portion in which a solution containing magnetic beads is positioned and a plurality of electromagnets arranged to the accommodating portion and a controller individually controlling magnetic forces of the plurality of electromagnets to move the magnetic beads.
Thus, the disclosure aims to provide a solution mixing device including an electromagnet module including an accommodating portion in which a solution containing magnetic beads is positioned and a plurality of electromagnets arranged with regard to the accommodating portion and a controller individually controlling magnetic forces of the plurality of electromagnets to move the magnetic beads.
The disclosure also aims to arrange a solution mixing method using a solution mixing device including an electromagnet module including an accommodating portion in which a solution containing magnetic beads is positioned and a plurality of electromagnets arranged with regard to the accommodating portion and a controller individually controlling magnetic forces of the plurality of electromagnets to move the magnetic beads, the solution mixing method comprising a preparation step of positioning the solution in the accommodating portion and a mixing step of individually adjusting magnetic forces of the plurality of electromagnets to mix the solution.
To achieve the foregoing objectives, according to the disclosure, there is provided a solution mixing device including an electromagnet module including an accommodating portion in which a solution containing magnetic beads is positioned and a plurality of electromagnets arranged with regard to the accommodating portion and a controller individually controlling magnetic forces of the plurality of electromagnets to move the magnetic beads.
According to the disclosure, there is provided a solution mixing method using a solution mixing device including an electromagnet module including an accommodating portion in which a solution containing magnetic beads is positioned and a plurality of electromagnets arranged with regard to the accommodating portion and a controller individually controlling magnetic forces of the plurality of electromagnets to move the magnetic beads, the solution mixing method comprising a preparation step of positioning the solution in the accommodating portion and a mixing step of individually adjusting magnetic forces of the plurality of electromagnets to mix the solution.
The disclosure may more uniformly mix the solution in the container using the electromagnets. In particular, it is possible to efficiently perform cell lysis by rotating the magnetic beads in the solution by controlling the magnetic force of the electromagnets while processing the sample.
Further, the disclosure may separate the material bound to the magnetic beads from the waste liquid by capturing the magnetic beads in the solution in a specific area in the container through the magnetically controllable electromagnets.
The disclosure controls the movement of the magnetic beads in the container only by turning on/off the current even without pipetting the solution, thus eliminating the concern about contamination due to separate physical manipulation while saving costs for replacing pipettes. Further, as magnetic force is adjusted using current, more accurate control in forming a flow path is possible than pipetting.
The solution mixing device and solution mixing method according to the disclosure may uniformly mix the solution. In particular, the solution mixing device and solution mixing method may uniformly mix the sample and various reagents in a sample processing reaction.
Further, the solution mixing device and solution mixing method according to the disclosure may uniformly mix the sample and the lysis buffer during a sample processing reaction, preventing errors in detection results and enhancing the reliability of detection results.
Further, the solution mixing device and solution mixing method according to the disclosure may enhance the accuracy of detection results by increasing the yield of binding between nucleic acids and magnetic beads during a sample processing reaction.
Further, the solution mixing device and solution mixing method according to the disclosure may prevent leakage of the solution while mixing the solution. In particular, the solution mixing device and solution mixing method may prevent leakage of the sample in a sample processing reaction, preventing contamination of the sample processing device.
FIG. 1 is a perspective view illustrating a solution mixing device according to an embodiment of the disclosure;
FIG. 2 is a side view illustrating a solution mixing device according to an embodiment of the disclosure;
FIG. 3A is a view illustrating a positional relationship between a container and a plurality of electromagnets disposed on a side and lower surface of a accommodating portion, with the accommodating portion excluded, according to the disclosure;
FIG. 3B is a view illustrating a positional relationship between a container and a plurality of electromagnets disposed along the circumference of a accommodating portion, with the accommodating portion excluded, according to the disclosure;
FIG. 3C is a view illustrating a positional relationship between a container and a plurality of electromagnets disposed at different heights of a accommodating portion, with the accommodating portion excluded, according to the disclosure; and
FIG. 4 is a perspective view illustrating a solution mixing device according to an embodiment of the disclosure.
The disclosure is now described in further detail in connection with embodiments thereof. The embodiments are provided merely to specifically describe the present invention, and it is obvious to one of ordinary skill in the art that the scope of the present invention is not limited to the embodiments.
The same or substantially the same reference denotations are used to refer to the same or substantially the same elements throughout the specification and the drawings. When determined to make the subject matter of the present invention unclear, the detailed description of the known configurations or functions may be skipped.
Such denotations as "first," "second," "A," "B," "(a)," and "(b)," may be used in describing the components of the present invention. These denotations are provided merely to distinguish a component from another, and the essence of the components is not limited by the denotations in light of order or sequence. When a component is described as "connected," "coupled," or "linked" to another component, the component may be directly connected or linked to the other component, but it should also be appreciated that other components may be "connected," "coupled," or "linked" between the components.
According to an embodiment of the disclosure, there is provided a solution mixing device 100 including an electromagnet module 110 including an accommodating portion 111 in which a solution containing magnetic beads is positioned and a plurality of electromagnets 112 arranged with regard to the accommodating portion to electromagnetically effect the magnetic beads 111 and a controller 120 controlling magnetic forces of the plurality of electromagnets 112 to move the magnetic beads.
As used herein, the term "sample" may encompass biological samples (e.g., cells, tissues, or fluids from biological sources) and non-biological samples (e.g., foods, water, and soil). The biological samples include virus, germs, tissues, cells, blood (e.g., whole blood, plasma, and serum), lymph, bone marrow fluid, saliva, sputum, swab, aspiration, milk, urine, stool, ocular humor, semen, brain extracts, spinal fluid, joint fluid, thymus fluid, bronchoalveolar lavage fluid, ascites, and amniotic fluid.
Sample processing refers to a series of processes to primarily separate an analyte from the sample to thereby obtain a material in the state capable of detection reaction. The term 'sample processing' may be used as further meaning the process of detecting a target analyte from the substance in the detection reaction-capable state. The analyte may be, for example, a nucleic acid. According to an embodiment of the disclosure, the sample processing may include the process of extracting a nucleic acid.
Referring to FIG. 1, according to the disclosure, a solution mixing device 100 includes an electromagnet module 110 and a controller 120.
The electromagnet module 110 includes an accommodating portion 111 and a plurality of electromagnets 112.
An empty space is formed inside the accommodating portion 111, and a solution containing magnetic beads is positioned in the empty space. The shape of the accommodating portion 111 is not particularly limited, but may be a rectangular prism shape that is opened upward as illustrated in the drawings.
The solution containing magnetic beads may contain a sample. For example, various liquids, such as samples, reagents, and solutions may be transferred to or from the accommodating portion 111 by a pipette. A sample may be transferred to the accommodating portion 111 in which a solution containing magnetic beads but not containing a sample has previously been prepared, or a solution containing magnetic beads but not containing a sample may be transferred to the accommodating portion 111 in which a sample has previously been prepared. A solution containing magnetic beads but not containing a sample and a sample may be individually transferred to the accommodating portion 111 (regardless of order), or a solution containing both magnetic beads and a sample may be transferred to the accommodating portion 111. In such a manner, the solution containing magnetic beads may include the sample. The solution containing both the magnetic beads and the sample may be formed while a solution containing the magnetic beads but not containing the sample and the sample are separately positioned in different spaces (e.g., cartridge chambers).
The plurality of electromagnets 112 are arranged with regard to the accommodating portion 111 to arrange magnetic force to the magnetic beads in the solution. The magnetic force of each electromagnet is controlled by the controller 120.
The controller 120 controls the magnetic force of the plurality of electromagnets 112 to move the magnetic beads. As the magnetic force of the plurality of electromagnets 112 is adjusted by the controller 120, the magnetic beads are moved in the solution, creating a flow of the solution and thereby mixing the solution.
In other words, the controller 120 adjusts the strength of the current applied to each electromagnet and controls the magnetic force of each electromagnet. For example, as the controller 120 repeats the process of individually strengthening, maintaining, or weakening the magnetic force of the electromagnets, the magnetic beads move toward the electromagnet having a relatively high magnetic force, creating a flow of the solution.
The electromagnets may be arranged with regard to positions where they are capable of providing a magnetic force to the solution positioned in the accommodating portion 111, and the positions are not limited. Preferably, as illustrated in the drawings, the electromagnets may be arranged to outside or inside or the outside and the inside of the accommodating portion 111.
The electromagnets may be magnetized to have a magnetic force by the magnetic field generated through a current supplied under the control of the controller 120. The degree of magnetic force may be adjusted according to the strength of the supplied current, so that the moving speed of the magnetic beads may be adjusted, creating a flow of the solution. If the current supply is cut off, the electromagnets lose the magnetism. In such a case, the movement of the magnetic beads is stopped and so is the flow of the solution.
The electromagnet includes a coil winding or a compressed wire configured to allow current to flow well, and a current may be supplied through an exposed positive electrode.
The number of the electromagnets is not particularly limited, but may be, e.g., 2, 3, 4 or 5 or more, or may be, e.g., 10, 9, 8, 7 or less.
The solution mixing device is described below with reference to FIGS. 2, 3A, 3B, and 3C.
According to an embodiment of the disclosure, the plurality of electromagnets 112 may be arranged with regard to the accommodating portion 111 to electromagnetically effect the magnetic beads.
According to an embodiment of the disclosure, the electromagnets may be arranged to an outside the accommodating unit.
According to an embodiment of the disclosure, the electromagnets may be arranged to an inside the accommodating unit.
According to an embodiment of the disclosure, the electromagnets may be arranged both the outside and the inside the accommodating unit.
The electromagnets are arranged to the side of the accommodating portion 111 laterally face the empty space of the accommodating portion 111, and the electromagnet arranged to the bottom of the accommodating portion 111 vertically faces the empty space of the receiving unit 111.
FIG. 2 is a side view illustrating a solution mixing device according to an embodiment of the disclosure. FIG. 2 illustrates an example in which a plurality of electromagnets 112 are arranged to side and/or the bottom of the accommodating portion 111. The electromagnets on the side of the accommodating portion 111 may be partially exposed to the outside of the accommodating portion 111 while being partially inserted into the inside of the accommodating portion 111 to be positioned adjacent to a container 200.
Alternatively, the entire electromagnet may be arranged to the outside the accommodating portion (111). A part of the entire electromagnet may be attached to the outside of the accommodating portion(111). The electromagnet may be arranged at a predetermined distance from the accommodating portion(111) outside.
Alternatively, the entire electromagnet may be arranged to the inside the accommodating portion(111). A part of the entire electromagnet may be attached to the inside of the accommodating portion(111). The electromagnet may be arranged at a predetermined distance from the inside of the accommodating portion(111).
In FIG. 2, the bottom of the accommodating portion 111 may be arranged to a flat shape to stably support the accommodating portion, e.g., seat it on a means for supporting the accommodating portion 111, i.e., the moving member 511 described below. In such a case, the electromagnet arranged to the bottom may be fully inserted in the bottom of the accommodating portion 111 not to be exposed to the outside, unlike the electromagnets on the side.
However, the electromagnet fully inserted in the bottom of the accommodating portion 111 is merely a preferable embodiment of the disclosure. Depending on the shape of the accommodating portion 111 or the means to stably support the accommodating portion 111 or the moving member 511, the electromagnet arranged to the side and/or the bottom of the accommodating portion 111 may be partially exposed and partially inserted or may be fully inserted or fully exposed, and other various changes may also be possible.
At least one of the plurality of electromagnets 112 may be arranged to the bottom of the accommodating portion 111. The accommodating portion 111 may have a shape in which the empty space formed therein is narrowed and tapered downwards. The electromagnet arranged to the bottom of the accommodating portion 111 may be disposed to face the empty space of the accommodating portion 111 in an inclined direction or be disposed vertically in the straight line direction of the empty space.
The disclosure intends to mix the solution by moving the magnetic beads included in the solution through the magnetic force of the plurality of electromagnets 112. Accordingly, various embodiments according to the positions of the container 200 containing the solution and the plurality of electromagnets 112 in the accommodating portion 111 are described with reference to FIGS. 3A, 3B, and 3C.
FIGS. 3A, 3B, and 3C illustrate the positional relationships between the container 200 and the plurality of electromagnets 112 arranged to the side and bottom of the accommodating portion 111, with the accommodating portion 111 excluded.
The plurality of electromagnets 112 arranged to the accommodating portion 111 according to the disclosure are intended for mixing the solution in the container, As illustrated in FIGS. 3A, 3B, and 3C, the electromagnets 112 are arranged to various positions of the accommodating portion to mix the solution.
FIG. 3A illustrates the positions of the electromagnets 112 on the container 200 when the plurality of electromagnets 112 are arranged to the side and bottom of the accommodating portion 111 according to an embodiment of the disclosure.
FIG. 3B illustrates the positions of the electromagnets 112 on the container 200 when the plurality of electromagnets 112 are arranged to the circumference of the accommodating portion 111 according to another embodiment of the disclosure. According to an embodiment, at least two or more of the plurality of electromagnets 112 may be arranged to the circumference of the accommodating portion111. For example, if the accommodating portion 111 has a rectangular prism shape, an electromagnet may be arranged to each side of the accommodating portion 111.
At least two of the electromagnets arranged to the circumference of the accommodating portion 111 may be arranged to side each other with the solution interposed therebetween. As illustrated in the drawings, the electromagnets are arranged to opposite sides of the accommodating portion 111 in the rectangular column shape and may be arranged to side each other. The electromagnets arranged to the upper sides may face each other, and the electromagnets arranged to the bottom sides may side each other.
According to an embodiment, at least two of the electromagnets 112 arranged to the circumference of the accommodating portion 111 may be arranged at different heights.
According to another embodiment of the disclosure, a plurality of electromagnets 112 are arranged to the side and bottom of the accommodating portion111, and the electromagnets 112 arranged to the sides may be arranged at different heights. In this case, the positions of the electromagnets 112 on the container 200 are as shown in FIG. 3C. If four electromagnets are arranged, two may be arranged to on the upper sides and the other two may be arranged to the bottom sides.
As described above, since the plurality of electromagnets 112 are disposed in various positions of the accommodating portion 111, the flow of the solution is generated in various forms when the controller 120 controls the magnetic force of the electromagnets to move the magnetic beads. The number of the plurality of electromagnets 112 and the shape in which the plurality of electromagnets 112 are arranged to the accommodating portion 111 are not limited to those illustrated in the drawings, and various changes may be made thereto according to the shape of the accommodating portion 111 or the characteristics of the solution to be mixed.
According to an embodiment of the disclosure, the controller 120 may controls magnetic forces of the plurality of electromagnets 112 individually or in group.
In other words, the controller 120 may control the magnetic forces of the individual electromagnets, or the controller 120 may group two or more of the plurality of electromagnets 112 and control the magnetic force of the grouped electromagnets. The plurality of electromagnets 112 may include two or more groups. The controller 120 may control to allow the electromagnets belonging to the same group to have the same magnetic force. The grouped electromagnets may be positioned adjacent to each other or spaced apart from each other, and the grouped electromagnets may include those adjacent to each other and spaced apart from each other. For example, electromagnets positioned at the same height on the accommodating portion 111 may belong to the same group, and the electromagnets disposed to face each other with the solution containing the magnetic beads interposed therebetween may belong to different groups. The plurality of electromagnets 112 may be divided into individual electromagnets, into individual electromagnets and grouped electromagnets, or into grouped electromagnets. For example, if four electromagnets are arranged as illustrated in the drawings, the controller 120 may individually control the magnetic force of all the electromagnets, or the controller 120 may group at least some of the electromagnets, like 1, 1, and 2, or 1 and 3, or 2 and 2. When the controller 120 groups and controls the plurality of electromagnets 112, the grouped form of the electromagnets may be changed during the control process. For example, if four electromagnets are arranged as illustrated in the drawings, the controller 120 may group them into 1, 1, and 2 and control them and may then change the group into 1 and 3 or 2 and 2 and control them.
The controller 120 may control to allow all of the plurality of electromagnets 112 to have the same magnetic force, but it is preferable to differently control at least some of the magnetic forces for the purpose of creating a flow of the solution while moving the magnetic beads. In other words, the controller 120 may control to allow at least two of the plurality of electromagnets 112 to have different magnetic forces, thereby moving the magnetic beads. The controller 120 may individually strengthen, maintain, or weaken the magnetic force of the electromagnets, allowing at least two electromagnets to have different magnetic forces. As at least two electromagnets among the plurality of electromagnets 112 have different magnetic forces, the magnetic beads are moved toward the electromagnet having a relatively stronger magnetic force. As the magnetic beads move, a flow of the solution is created, mixing the solution.
According to an embodiment of the disclosure, the controller 120 may control to allow at least two individual electromagnets to have different magnetic forces, control to allow at least one individual electromagnet and at least one group of electromagnets to have different magnetic forces, or control at least two or more groups of electromagnets to have different magnetic forces.
According to an embodiment of the disclosure, the controller 120 may move the magnetic beads while changing at least two electromagnets having different magnetic forces. For example, the controller 120 may perform control so that any one of at least two individual electromagnets has a stronger magnetic force than the other one and then the one electromagnet has a weaker magnetic force than the other one, so that an individual electromagnet or a group of electromagnets, other than the at least two individual electromagnets, has a different magnetic force than at least one of the at least two individual electromagnets, or so that at least two individual electromagnets, other than the at least two individual electromagnets, or at least one individual electromagnet and at least one grouped electromagnet, or at least two or more grouped electromagnets have different magnetic forces.
As the controller 120 changes at least two electromagnets with different magnetic forces, the electromagnet having a relatively stronger magnetic force, toward which the magnetic forces are moved, is changed, so that a flow of the solution by the magnetic forces is continuously created to thereby mix the solution.
According to an embodiment of the disclosure, the controller 120 may sequentially or randomly change at least two electromagnets having different magnetic forces according to the order in which the plurality of electromagnets 112 are arranged.
The order in which the plurality of electromagnets 112 are arranged may be, e.g., the vertical direction, the circumferential direction, the front-back direction (lateral direction) of the accommodating portion 111. In other words, in a case where some of the plurality of electromagnets 112 are arranged to a bottom side of the accommodating portion 111, and the others are arranged to an upper side, the controller 120 may generate a flow of the solution in the vertical direction by controlling the magnetic forces of the electromagnets differently on the upper side and lower side. In a case where the plurality of electromagnets 112 are arranged in the circumferential direction of the accommodating portion 111, the controller 120 may create a flow of the solution, which rotates clockwise or counterclockwise, by sequentially and differently controlling the magnetic forces of the electromagnets along the circumferential direction. In a case where some of the plurality of electromagnets 112 are arranged to the front of the accommodating portion 111, and the others are arranged to the back, the controller 120 may generate a flow of the solution in the front-back direction by controlling the magnetic forces of the electromagnets on the front and back. Alternatively, a combination of the vertical direction, the circumferential direction, and the front-back direction (lateral direction) is also possible. For example, control may be performed so that the rotating flow of the solution is moved up and down.
Alternatively, according to an embodiment of the disclosure, the controller 120 may change at least two electromagnets having different magnetic forces in a random order regardless of the order in which the plurality of electromagnets 112 are arranged.
It is possible to generate various flows of the solution and uniformly mix the solution by changing at least two electromagnets having different magnetic forces sequentially according to the order in which the plurality of electromagnets 112 are arranged or randomly.
In particular, when the sample and the lysis buffer are mixed using the solution mixing device according to the disclosure in the sample processing device, it is possible to uniformly mix the sample and the lysis buffer by the magnetic beads and to prevent non-exposure of the nucleic acid due to failure to destroy the cell walls of some cells. Thus, it is possible to prevent errors in detection results and to enhance reliability.
Further, since a flow of magnetic beads is created in the solution by the controller 120, the yield of combination between the exposed nucleic acids and the magnetic beads is increased, so that some nucleic acids may be prevented from being removed during the washing process for removing the cell debris without combining with the magnetic beads. It is thus possible to enhance the accuracy of the detection result.
Further, since the solution is mixed by the flow of magnetic beads created inside the solution rather than mixing the solution in a pipetting manner, leakage of the solution does not occur during the mixing process, and contamination due to leakage of the sample in the sample processing device may be prevented.
As described above with reference to FIGS. 2 and 3, according to one embodiment of the disclosure, the solution containing magnetic beads is received in the container 200, the container 200 is positioned in the receiving unit 111, and the solution containing the magnetic beads may be positioned in the accommodating portion 111.
The container 200 and the accommodating portion 111 may be formed in shapes corresponding to each other. The container 200 may be inserted into the opening of the accommodating portion 111, and the container 200 may be positioned in the accommodating portion 111.
The container 200 may be any one of a plurality of chambers included in a cartridge actuated by the sample processing device. The plurality of chambers of the cartridge are spaces in which a material necessary for the process of extracting a detection target material (e.g., nucleic acid) from a sample is stored, and a physical and chemical process for extraction is performed. At least one of the plurality of chambers is a sample chamber and a space in which the sample collected is received. The sample received in the sample chamber may be transferred to the container 200 by, e.g., a pipette. The cartridge may be produced in a state in which the solution containing the magnetic beads is positioned in the container 200.
According to an embodiment of the disclosure, the electromagnet module 110 may be arranged to be movable in a direction in which the container 200 is inserted into the accommodating portion 111 and in a direction in which the container 200 is removed from the accommodating portion 111. As illustrated in the drawings, if the accommodating portion 111 is opened upward, the electromagnet module 110 may be arranged to be movable in the vertical direction from the lower side of the container 200.
In the mixing device 100 according to the disclosure, a heating element (not shown) and an insulation element (not shown) may be disposed between the container 200 and the accommodating portion 111. The heating element may be configured to increase the temperature of the reaction solution in the container 200. If the temperature of the reaction solution is increased through the heating element, the reaction may proceed more efficiently. For example, in a case where the container 200 is a dissolution chamber, if the temperature of the lysis buffer is increased through the heating element, the dissolution reaction is more activated, so that the sample may be dissolved more effectively. As such, the heating element is thermally connected to the container 200. The temperature of the reaction solution in the container 200 may be increased using the heat provided from the heating element. In this case, "thermal connection" means that the heating element is in direct or indirect contact to the container 200 to transfer or conduct heat to the container 200.
The heating element may be provided in a position where it may provide heat to the container 200, and its position is not limited. Preferably, the heating element may be provided on the outer surface of the container 200. The heating element may have various shapes depending on implementation examples of the container 200 or schemes for supplying heat. For example, the heating element may be shaped to have an area sufficient to cover a specific area or the entire area of the container 200 or may have a hot wire shape obtained by compressing an electrically conductive terminal in a linear form. The heating element may be electrically connected with a power module and may generate heat using the power received from the power module.
The heating element may be formed of a material, such as metal, ceramic, or semiconductor. The heating element may have a shape of one or more strands, a plate, a foil, or a film.
The insulation element is positioned between the heating element and the accommodating portion 111 and performs thermal insulation so that the heat of the heating element is not transferred to the accommodating portion 111. The position of the insulation element is not limited as long as it may block the heat of the heating element to the accommodating portion 111. Preferably, the insulation element may be arranged to the outer surface of the heating element.
An operation sequence of the solution mixing device 100 according to an embodiment of the disclosure is described. The container 200 in which the solution containing the magnetic beads is positioned is fixed, and the electromagnet module 110 is moved upward from the lower side of the container 200, so that the container 200 may be inserted into the accommodating portion 111. The controller 120 may individually control the magnetic forces of the plurality of electromagnets 112 to mix the solution. As the electromagnet module 110 is moved downward, the container 200 may be removed from the accommodating portion 111.
This is described below with reference to FIG. 4. According to an embodiment of the disclosure, the solution mixing device 100 may further include a driver 510 for moving the electromagnet module 110.
The driver 510 may include a moving member 511 coupled with the electromagnet module 110, a guide member 512 for providing the moving member 511 with a movement path in a direction in which the electromagnet module 110 may move, and a motor 513 for moving the moving member 511 along the movement path. The driver 510 may further include a base member 515 supporting the guide member 512 and the motor 513.
The moving member 511 may be formed in a plate shape and coupled with the accommodating portion111. The moving member 511 may include a recess in which the accommodating portion 111 is seated. As illustrated in the drawings, the recess may be formed in the upper surface of the moving member 511, and the accommodating portion 111 may be seated on the upper surface of the moving member 511. The accommodating portion 111 and the moving member 511 may be coupled by bolting.
The guide member 512 may be a shaft penetrating the moving member 511. Two opposite ends of the guide member 512 are fixed to the base member 515. The guide member 512 provides the movement path to the moving member 511. Two or more guide members 512 may be provided.
The motor 513 may move the moving member 511 along the movement path provided by the guide member 512, e.g., in the vertical direction. A nut may be coupled to the moving member 511, and a bolt 514 engaged with the nut may be rotatably provided to the base member 515. The motor 513 may rotate the bolt 514 to move the nut. The motor 513 and the bolt 514 may be connected by a gear set.
A PCB substrate 516 may be provided on the base member 515. The controller 120 for controlling the plurality of electromagnets 112 may be mounted on the PCB substrate 516. The motor 513 may be controlled by the PCB substrate 516.
Additionally, the mixing device 100 according to the disclosure may further include a vibration generator (not shown). Moisture condensed on the outer surface of the accommodating portion 111 (or the container 200) may be removed by the vibration generated by the vibration generator. Depressed coupling recesses are formed in the outer surface of the accommodating portion 111, in the positions where the plurality of electromagnets 112 are arranged. The plurality of electromagnets 112 may be individually seated in the coupling recesses, and so is the vibration generator. Each electromagnet may be coupled to the accommodating portion 111 by, e.g., press-fitting or bonding in the coupling recess.
A solution mixing method according to an embodiment of the disclosure includes a preparation step and a mixing step.
The solution mixing method according to an embodiment of the disclosure is a solution mixing method using the solution mixing device 100 according to the above-described embodiment of the disclosure. The solution mixing method includes the preparation step of positioning a solution containing magnetic beads in the accommodating portion 111 and the mixing step of mixing the solution while individually adjusting the magnetic forces of the plurality of electromagnets 112.
In the preparation step, the solution containing magnetic beads may be transferred to the accommodating portion 111 using, e.g., a pipette. Alternatively, the solution containing the magnetic beads is positioned in the container 200, and the electromagnet module 110 may be moved in the direction in which the container 200 is inserted into the accommodating portion 111.
In the mixing step, the controller 120 mixes the solution containing the magnetic beads while individually adjusting the magnetic forces of the plurality of electromagnets 112.
The mixing step may include a setting step for controlling to allow at least two of the plurality of electromagnets 112 to have different magnetic forces while individually controlling the magnetic force of individual electromagnets or grouped electromagnets among the plurality of electromagnets 112 and may change at least two electromagnets having different magnetic forces.
Further, in the setting step, it is possible to sequentially or randomly change at least two electromagnets having different magnetic forces according to the order in which the plurality of electromagnets 112 are arranged.
While embodiments of the disclosure have been described above, it will be easily appreciated by one of ordinary skill in the art that the scope of the disclosure is not limited thereto. Thus, the scope of the disclosure is defined by the appended claims and equivalents thereof.
[CROSS-REFERENCE TO RELATED APPLICATIONS]
This application claims priority from Korean patent Application No. 10-2020-0133689, filed on October 15, 2020, in the Korean Intellectual Property Office, the disclosure of which is incorporated herein by reference in its entirety.

Claims (16)

  1. A solution mixing device, comprising:
    an electromagnet module comprising an accommodating portion in which a solution containing magnetic beads is positioned and a plurality of electromagnets arranged with regard to the accommodating portion to electromagnetically effect the magnetic beads
    ; and a controller controlling magnetic forces of the plurality of electromagnets to move the magnetic beads.
  2. The solution mixing device of claim 1, wherein the controller the controller controls magnetic forces of the plurality of electromagnets individually or in group.
  3. The solution mixing device of claim 1, wherein the controller controls to allow at least two of the plurality of electromagnets to have different magnetic forces to move the magnetic beads.
  4. The solution mixing device of claim 3, wherein the controller moves the magnetic beads while changing the at least two electromagnets having the different magnetic forces.
  5. The solution mixing device of claim 4, wherein the controller changes the at least two electromagnets having the different magnetic forces, sequentially according to an order in which the plurality of electromagnets are arranged, or randomly.
  6. The solution mixing device of claim 1, wherein the plurality of electromagnets are arranged to a side and/or bottom of the accommodating portion.
  7. The solution mixing device of claim 1, wherein at least two or more of the plurality of electromagnets are arranged to a circumference of the accommodating portion.
  8. The solution mixing device of claim 7, wherein at least two of the electromagnets arranged to the circumference of the accommodating portion are arranged at different heights.
  9. The solution mixing device of claim 7, wherein at least two of the electromagnets arranged to the circumference of the accommodating portion are disposed to face each other, with the solution positioned therebetween.
  10. The solution mixing device of claim 7, wherein at least one of the plurality of electromagnets is arranged to a bottom of the accommodating portion.
  11. The solution mixing device of claim 1, wherein the solution is accommodated in a container, and the container is positioned in the accommodating portion.
  12. The solution mixing device of claim 11, wherein the electromagnet module is provided to be movable in a direction in which the container is inserted into the accommodating portion and a direction in which the container is removed.
  13. The solution mixing device of claim 1, further comprising a driver moving the electromagnet module.
  14. A method of mixing a solution using a solution mixing device comprising an electromagnet module comprising an accommodating portion in which a solution containing magnetic beads is positioned and a plurality of electromagnets arranged with regard to the accommodating portion to electromagnetically effect the magnetic beads
    and a controller controlling magnetic forces of the plurality of electromagnets to move the magnetic beads, the solution mixing method comprising:
    a preparation step of positioning the solution in the accommodating portion ; and
    a mixing step of individually adjusting magnetic forces of the plurality of electromagnets to mix the solution.
  15. The solution mixing method of claim 14, wherein the mixing step includes individually controlling magnetic forces of individual electromagnets or grouped electromagnets among the plurality of electromagnets,
    wherein the mixing step includes a setting step of controlling to allow at least two of the plurality of electromagnets to have different magnetic forces, and
    wherein the mixing step changes the at least two electromagnets having the different magnetic forces.
  16. The solution mixing method of claim 15, wherein the setting step changes the at least two electromagnets having the different magnetic forces, sequentially according to an order in which the plurality of electromagnets are arranged or randomly.
PCT/KR2021/014407 2020-10-15 2021-10-15 Solution mixing device and solution mixing method Ceased WO2022080970A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KR1020237012369A KR20230066096A (en) 2020-10-15 2021-10-15 Solution mixing device and solution mixing method

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2020-0133689 2020-10-15
KR20200133689 2020-10-15

Publications (1)

Publication Number Publication Date
WO2022080970A1 true WO2022080970A1 (en) 2022-04-21

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KR (1) KR20230066096A (en)
WO (1) WO2022080970A1 (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009108501A2 (en) * 2008-02-27 2009-09-03 Hach Company Reaction vessel for heating and mixing a fluid
WO2014100416A1 (en) * 2012-12-19 2014-06-26 Dxna Llc Mixing apparatus and methods
KR101762295B1 (en) * 2012-02-10 2017-08-04 (주)바이오니아 Automatic analysis apparatus and method of biological samples
KR20170101823A (en) * 2016-02-29 2017-09-06 프리시젼바이오 주식회사 Apparatus for mixing sample solution and method of mixing sample solution using the same
KR20190011367A (en) * 2017-07-24 2019-02-07 한국과학기술원 Automatic gene integrated chip

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009108501A2 (en) * 2008-02-27 2009-09-03 Hach Company Reaction vessel for heating and mixing a fluid
KR101762295B1 (en) * 2012-02-10 2017-08-04 (주)바이오니아 Automatic analysis apparatus and method of biological samples
WO2014100416A1 (en) * 2012-12-19 2014-06-26 Dxna Llc Mixing apparatus and methods
KR20170101823A (en) * 2016-02-29 2017-09-06 프리시젼바이오 주식회사 Apparatus for mixing sample solution and method of mixing sample solution using the same
KR20190011367A (en) * 2017-07-24 2019-02-07 한국과학기술원 Automatic gene integrated chip

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