EP1919625B1 - Dispositif et procede de separation de particules magnetiques d'un liquide - Google Patents

Dispositif et procede de separation de particules magnetiques d'un liquide Download PDF

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Publication number
EP1919625B1
EP1919625B1 EP06792895.2A EP06792895A EP1919625B1 EP 1919625 B1 EP1919625 B1 EP 1919625B1 EP 06792895 A EP06792895 A EP 06792895A EP 1919625 B1 EP1919625 B1 EP 1919625B1
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EP
European Patent Office
Prior art keywords
vessel
guiding means
magnet
magnetic field
magnetic particles
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.)
Active
Application number
EP06792895.2A
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German (de)
English (en)
Other versions
EP1919625A1 (fr
Inventor
Thomas Rothmann
Thomas Deutschmann
Christian c/o QIAGEN GmbH LENZ
Cordula Leurs
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Qiagen GmbH
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Qiagen GmbH
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Publication date
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Publication of EP1919625A1 publication Critical patent/EP1919625A1/fr
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/025—High gradient magnetic separators
    • B03C1/031—Component parts; Auxiliary operations
    • B03C1/033—Component parts; Auxiliary operations characterised by the magnetic circuit
    • B03C1/0332—Component parts; Auxiliary operations characterised by the magnetic circuit using permanent magnets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/025—High gradient magnetic separators
    • B03C1/029—High gradient magnetic separators with circulating matrix or matrix elements
    • B03C1/03—High gradient magnetic separators with circulating matrix or matrix elements rotating, e.g. of the carousel type
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/28—Magnetic plugs and dipsticks
    • B03C1/288—Magnetic plugs and dipsticks disposed at the outer circumference of a recipient
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C2201/00—Details of magnetic or electrostatic separation
    • B03C2201/18—Magnetic separation whereby the particles are suspended in a liquid

Definitions

  • the present invention relates to a device for separating magnetic particles from a liquid and to a method for separating magnetic particles from a liquid.
  • the device and method are suitable for applications in biochemistry, molecular genetics, microbiology, medical diagnostics or forensic medicine, for example.
  • the basic principle of the magnetic separation of substances from complex mixtures is based on the fact that magnetic particles, for example by chemical treatment of their surface with specific binding properties are equipped for the target substances to be separated.
  • the size of such magnetic particles is generally in the range of about 0.05 to 500 microns so as to provide a large surface area for the binding reaction.
  • the magnetic particles may have a density similar to the density of the liquid in which they are suspended. In this case, sedimentation of the magnetic particles can take several hours.
  • the magnetic particles are immobilized by applying magnetic forces or a magnetic field, for example by means of a permanent magnet, at one point. This accumulation of magnetic particles is also referred to as pellet. Subsequently, the liquid supernatant is separated, for example, by suction or decantation and discarded. Since the magnetic particles are immobilized by the magnetic forces, it is largely prevented that magnetic particles are separated together with the supernatant.
  • the immobilized magnetic particles are then resuspended.
  • an elution liquid or an elution buffer is used, which is suitable for dissolving the bond between the target substance and the magnetic particles, so that the target substance molecules are released from the magnetic particles.
  • the target substance molecules can then be separated together with the elution liquid, while the magnetic particles are immobilized by the action of a magnetic field.
  • one or more washing steps can be carried out.
  • the magnetic particles remain in the same reaction vessel while the liquid is exchanged in this vessel.
  • the pellets can be immobilized at a desired height on the side wall of the reaction vessel for adaptation to a respective process step. This is done by providing magnets which are arranged on different arms of a rotatably mounted carrier at a different distance from the axis of rotation. By rotating the carrier, a particular arm can be brought into the vicinity of the side wall of the reaction vessel, and thus a specific magnet. At this point, the magnetic particles are then immobilized as a pellet.
  • the said conventional devices and methods all have the common feature that they are designed as so-called open systems, since according to their respective principle of action magnetic rods or pipettes must be inserted one or more times in the reaction vessel. As a result, these conventional devices and methods run the risk of cross-contamination of other reaction vessels by aerosol and / or droplet formation. As a result, examination results can be falsified or even rendered unusable.
  • the present invention provides an apparatus according to claim 1 and a method according to claim 27. Further details, advantages and aspects of the present invention will become apparent from the dependent claims, the description and the accompanying drawings.
  • the magnetic particles suspended in a liquid in the first vessel can be separated from this liquid without the need to insert a magnetic rod or a pipette tip into the first vessel. Rather, the magnetic particles can be formed into a pellet by the magnetic field, and this pellet can be transferred to the second vessel along the joint surface by the guide means located outside the vessel. In this way, the risk of cross-contamination, for example, by dripping the liquid from the magnetic rod or the pipette tip, significantly reduced or even excluded. Furthermore, the device can be provided as a closed system, further reducing the risk of cross-contamination.
  • the length of the connection surface can be chosen so that an influence of the particles, for example, the drying of the particles, is supported or reduced.
  • connection surface is formed by a first side wall of the first vessel, a second side wall of the second vessel, and a connection region connecting the first and second side walls.
  • first and the second vessel could thus be formed as depressions (wells) in a microtiter plate.
  • first and the second vessel as well as the bonding surface can be provided as separate elements.
  • the connection surface could be formed as a bridge or hose.
  • a permanent magnet is used.
  • the magnetic field can be provided inexpensively.
  • the guide means is then to be designed such that the magnet can be guided mechanically along the connection surface.
  • the at least one magnet may also be designed as an electromagnet.
  • the electromagnet can be guided mechanically along the connection surface.
  • a plurality of electromagnets for example, on an underside of the connecting surface, be arranged one behind the other. The guide means would then sequentially energize and turn the electromagnets on and off so that the magnetic field generated by the electromagnets travels along the interface from the first to the second vessel.
  • the guide means is designed so that the at least one magnet can be guided at a fixed predetermined distance from the connection surface.
  • the fixed predetermined distance may be zero so that the magnet is in contact with the bonding surface as it is passed past it.
  • At least one heating and / or cooling element for example a heating wire and / or Peltier element, is provided on the connecting surface.
  • the magnetic particles can be kept on their way to a predetermined temperature.
  • connection surface along the path of the at least one magnet is formed as a circular arc.
  • guide means is formed so that the at least one magnet is guidable on a circular path, the radius of the circular path being less than or equal to the radius of the arc formed by the connection surface.
  • the guide means can be mounted on a rotation axis, whereby the drive and the control of the guide means can be designed particularly simple. This also allows easy automation of the machining operations.
  • At least a third vessel is further provided, which is connected via a second connection surface with the first and the second vessel, and a second guide means on which at least one further magnet is arranged.
  • the first and the second vessel together with the third vessel, the second connection surface, the second guide means and the further magnet form a further device for separating magnetic particles as described above.
  • At least one of the vessels has a functional element, in particular an outlet opening and / or a filter.
  • a functional element for example, subsequent analysis steps, such as a PCR step (Polymerase Chain Reaction), can be prepared.
  • the outlet opening preferably has fastening possibilities with the aid of which, for example, reaction stubs can be fastened to the outlet opening.
  • the vessels are formed in a cartridge.
  • a so-called lab-on-a-chip can be realized in this way.
  • all devices necessary for carrying out an examination are integrated on a chip or a cartridge.
  • Such a method can for example be carried out in an automated manner in a device according to an embodiment of the present invention in a simple manner.
  • the risk of cross-contamination compared to the prior art is considerably reduced, since it is not necessary to introduce a magnetic rod or a pipette tip into the vessel. Therefore, here the risk of dripping liquid from the magnetic rod or the pipette tip is excluded.
  • Fig. 1A shows a schematic representation of a device according to an embodiment.
  • a first vessel 10 is a liquid 15 in which magnetic particles 60 are suspended.
  • a second vessel 20 is shown in which a second liquid 25, for example a washing solution or an elution solution, is located.
  • the first vessel 10 has a first side wall 11, which is connected to a second side wall 21 of the second vessel 20 via a connection region 30.
  • the first side wall 11, the second side wall 21 and the connection portion 30 form a connection surface extending from the interior of the first vessel 10 to the inside of the second vessel 20.
  • a connection surface could also be provided as a bridge formed in the form of a reverse Us separately from the first and the second vessel, which is inserted into the first and the second vessel.
  • the connection surface could also be formed by a tube, one end of which is arranged in the interior of the first vessel and the other end is arranged in the interior of the second vessel.
  • a magnet 40 is provided, which may be embodied for example as a neodymium permanent magnet or as an electromagnet.
  • the magnet 40 is arranged on a guide means 50.
  • the guide means 50 is arranged so that it can guide the magnet 40, and thus the magnetic field generated by it, along the connection surface from the interior of the first vessel 10 into the interior of the second vessel 20.
  • a guide means 50 for example, a cylindrical roller or a rotary arm can be used, as will be explained later in this application.
  • the magnet 40 on a flexible band which is guided along the side walls 11, 21 and the underside of the connecting portion 30.
  • the guide means 50 is designed to hold the magnet 40 at a fixed predetermined distance from the connecting surface, ie the side walls 11, 21 and the underside of the connecting region 30.
  • the fixed predetermined distance is selected so that the magnetic attraction, the magnet 40 exerts on the suspended magnetic particles 60 when it is guided to the side wall 11, sufficient that the suspended particles are immobilized in a pellet 61 on the side wall 11 (please refer Fig. 1B ).
  • the distance between the magnet 40 and the side walls 11, 21 and the underside of the connection region 30 may be zero.
  • the magnet 40 is in contact with the sidewalls 11, 21 as well as the underside of the connecting portion 30 when it is passed therethrough.
  • connection surface may be channel-shaped.
  • Fig. 7 shows a cross section of the connecting portion 30 which is formed on its upper side between the first vessel 10 and the second vessel 20 in the form of a groove-shaped depression.
  • FIG. 1A is the initial state in which the magnetic particles 60 are suspended in the liquid 15 in the first vessel 10.
  • the magnet 40 is arranged outside the region of the side wall 11 of the first vessel 10.
  • the magnet 40 is then brought by the guide means 50 to the side wall 11 of the first vessel 10.
  • the magnet 40 is guided by the guide means 50 along the side wall 11 via the connecting portion 30 to the side wall 21 of the second vessel 20, see FIGS.
  • a first and a second vessel 10, 20 are provided, which are connected to each other via a connecting surface 11, 21, 30.
  • the connection surface is in turn formed by a first side wall 11, a second side wall 21 and a connection region 30.
  • the connecting surface ie here the first side wall 11, the second side wall 21 and the connecting portion 30, is formed so that it forms a circular arc with radius R.
  • the side walls 11, 21 and the connecting portion 30 are integrally formed as a connecting surface.
  • the first and the second vessel as well as the connection surface can also be provided as separate elements.
  • the guide means 50 is formed as a four-armed turnstile, as enlarged in Fig. 5 is shown.
  • Fig. 5 is the guide means on four pivot arms 51, 52, 53, 54 which are rotatably mounted about an axis 55. At the ends remote from the axis of rotation 55 of the pivot arms 51, 52, 53, 54 are each magnets 40, 41, 42, 43 are arranged.
  • the total length r of the rotating arms 51, 52, 53, 54 including the magnets 40, 41, 42, 43 is less than or equal to the radius R of the circular arc, so that the magnets 40, 41, 42, 43 at a distance Rr on the side walls 11th , 21 and the connection area 30 can be passed.
  • the magnets 40, 41, 42, 43 are in contact with the side walls 11, 21 and the connecting portion 30 as they are passed therethrough.
  • the surfaces of the magnets 40, 41, 42, 43, which are in contact with the side walls 11, 21 and the connection region 30, are advantageous are curved, wherein the radius of curvature is smaller than the circular arc radius R.
  • the four pivot arms are integrally formed, but they could also be formed as a single pivot arms and individually secured to the axis of rotation 55.
  • the number of four rotating arms is merely exemplary, because depending on the application, fewer or more rotating arms can be provided. In particular, it is possible to provide only a single rotary arm.
  • the four rotating arms in Fig. 5 each offset by 90 °, ie evenly distributed over the swept by the turntable circumference 2 ⁇ r.
  • the two or more rotating arms can also be arranged offset to one another in arbitrarily adjustable angular distances.
  • a guide means 50 which in the in Fig. 2A can be used, is shown in Fig. 6 shown.
  • the guide means 50 is formed as a cylindrical roller or wheel with a radius r, which is less than or equal to the circular arc radius R.
  • the magnets 40, 41, 42 each offset by 120 ° in receptacles 56, 57, 58 are arranged.
  • the magnets are arranged on the surface of the cylindrical guide means, in which case the radius r together with the thickness of the magnets must be less than or equal to the circular arc radius R.
  • the number and mutual position of the magnets can be varied according to the requirements of a particular application accordingly.
  • the magnets 40, 41, 42 can be removed from the receptacles 56, 57, 58, so that the number of magnets between one and the number of receptacles can be varied.
  • FIGS. 2A to 2E The functioning of the in Fig. 2A shown embodiment is in the FIGS. 2A to 2E played.
  • the magnet 40 is moved to the side wall 11 of the first vessel 10, where then the magnetic particles form a pellet 61 ( Fig. 2B ).
  • the magnet 40 is then guided along the circular arc with the pellet 61 following it ( FIGS. 2C and 2D ).
  • the pellet 61 is then introduced into the second vessel 20 ( Fig. 2E )
  • the magnet 40 led away from the second side wall 21, so that the magnetic particles in the located in the second vessel Resuspend fluid (not shown). In this way, the pellet is guided from inside the first vessel along the bonding surface to the interior of the second vessel.
  • FIGS. 3A to 3C Another embodiment is in the FIGS. 3A to 3C shown.
  • a third vessel 70 is provided, which is connected to the second vessel 20 via a second connection region 80.
  • the interconnected side walls of the second and the third vessel and the second connection region form a second connection surface, which is formed as a circular arc with radius R '.
  • the circular arc radius R ' is equal to the circular arc radius R between the first and second vessels, but may be selected differently from R depending on the nature of the application.
  • a second guide means 100 is arranged between each opposite side walls of the second and the third vessel, which has at least one further magnet 90.
  • the magnetic particles transferred from the first vessel 10 into the second vessel 20 and resuspended there can be combined in a second pellet 62 on the side wall of the second vessel.
  • the pellet 62 can now be transferred from the second vessel to the third vessel 70 via the second connecting surface.
  • the magnetic particles may be resuspended in the liquid 75 contained in the third vessel 70.
  • a washing solution can be provided in the second vessel and an elution solution in the third vessel.
  • the eluted magnetic particles could be transported back by opposite rotation of the second guide means in the second vessel and disposed of there.
  • further vessels and interposed connecting surfaces and guide means may be provided with magnets, wherein in the respective vessels for a particular method required liquids are provided.
  • the in Fig. 3A the apparatus shown also for executing a washing process.
  • the first pellet 61 from the first vessel 10 into the washing solution filled second vessel 20 transferred.
  • the magnet 40 is then led away from the side wall of the second vessel along a first direction of rotation, so that the magnetic particles are resuspended in the washing solution.
  • the magnet 90 arranged on the second guide means 100 is guided along a first rotational direction to the opposite side wall of the second vessel, so that the magnetic particles form a second pellet 62 there.
  • the first direction of rotation of the first guide means 50 is opposite to the first direction of rotation of the second guide means 100.
  • the magnet 90 is then led away from the side wall of the second vessel again along a second direction of rotation.
  • the second pellet 62 dissolves and the magnetic particles are resuspended in the wash solution.
  • the magnet 40 arranged on the first guide means 50 is guided along a second rotational direction to the opposite side wall of the second vessel, so that the magnetic particles again form a first pellet 61 there.
  • the second direction of rotation of the first guide means 50 is opposite to the second direction of rotation of the second guide means 100.
  • the first and second rotational direction of the first guide means may be the same or opposite.
  • the first and second rotational direction of the second guide means may be the same or opposite. The process can be repeated until the washing process is completed successfully.
  • connection surface 200 is formed as a bridge in the form of an inverted Us, wherein a first end of the connection surface 200 is arranged in the first vessel 10 and a second end of the connection surface 200 in the second vessel 20 is arranged.
  • the connecting surface 200 is formed on its upper side groove-shaped.
  • a plurality of electromagnets 40 are arranged in the connection surface 200, arranged one behind the other from the first vessel 10 to the second vessel 20.
  • the connecting surface 200 could be formed as an injection molded part, in which the electromagnets are embedded.
  • the electromagnets are individually controllable by a guide means 50, that is individually switched on and off.
  • the separation of the magnetic particles is as follows: First, all of the electromagnets 40 under the connection surface 200 are turned off, and the connection surface is placed in the first and second vessels as shown. Then, the guide means 50 controls the lowermost solenoid (s) at the first end of the interface located in the first vessel. There then forms a pellet of magnetic particles due to the magnetic attraction. Now adjacent electromagnets, which are arranged closer to the end located in the second vessel along the connection surface 200, are switched on one after the other and the electromagnets are switched off again from the first end of the connection surface. In this way, the magnetic field travels from the first end of the bonding surface to the second end of the bonding surface, and the pellet retraces this motion due to the magnetic attraction.
  • the electromagnets are switched off and the magnetic particles forming the pellet resuspend in a liquid 25 in the second vessel 20. In this way separation of the magnetic particles can take place without the device moving parts must have. In this way, the device is particularly reliable and low maintenance.
  • a first and a second vessel 10, 20 are provided, which are connected to each other via a connecting surface 11, 21, 30.
  • the connection surface is in turn formed by a first side wall 11, a second side wall 21 and a connection region 30.
  • heating elements 110 are provided on the connecting surface 11, 21, 30. Through these heating elements, the temperature of the magnetic particles can be increased, so that, for example, the drying of the particles is supported.
  • cooling elements for example Peltier elements
  • connection surface 11, 21, 30 may also be provided on the connection surface 11, 21, 30 in order to effect cooling of the magnetic particles and of the substances adhering to the magnetic particles. In this way, for example, a drying of the particles could be reduced, if the analysis carried out so required.
  • the vessel 20 at the in Fig. 9 embodiment shown additional functional elements 120, 130, which serve to prepare subsequent analysis steps.
  • the vessel 20 has at the bottom of the vessel an outlet opening 120, on the inside of a filter 130 is attached.
  • the connecting surfaces may be designed channel-shaped.
  • the guide means can be designed so that the speed with which they guide the magnetic field (s) along the connecting surfaces is controllable. In particular, the speed can be set to zero so that the pellet can be immobilized at the current position.
  • the guide means may be designed so that the direction in which they guide the magnetic field or fields along the connecting surfaces is controllable. In particular, then a reversal of direction in the movement of the pellets is possible.
  • all embodiments mentioned above can be designed as closed systems.
  • Fig. 10 Yet another embodiment is shown schematically. This is a so-called lab-on-a-chip, in which a first and a second vessel 1010, 1020 are integrated in a cartridge 1000.
  • the first and second vessels 1010, 1020 are interconnected by a connection area 1030.
  • Both vessels 1010, 1020 are formed as chambers in the cartridge 1000 and filled with liquid.
  • the second vessel 1020 could contain an elution liquid.
  • Fig. 10 is only a schematic representation in which the first and the second vessel are the same size. Of course, the sizes of each Vessels but differ from each other. In particular, typically the volume of an elution vessel will be less than that of a wash vessel.
  • closure 1100 prevents mixing of the liquids.
  • closure 1100 may be removed using the cartridge.
  • closure 1100 is designed so that it can be brought into the closed position after removal and again serves as a closure.
  • the cartridge 1000 is provided with a lid in which two access openings 1012, 1022 are located.
  • the access openings 1012, 1022 serve to bring magnetic particles into and out of the vessels.
  • the access openings 1012, 1022 may be provided with lids.
  • the cartridge has a magnet 1040 which can be guided by a guide means 1050 along a wall of the first vessel 1010, the connection region 1030 to a wall of the second vessel 1020.
  • the magnet 1040 may not only be attached to a sidewall but also along the ceiling wall, i. the lid, or the bottom of the cartridge 1000 be feasible.
  • FIGS. 11A to 11F briefly the functioning of the in Fig. 10 described embodiment described.
  • magnetic particles 1060 are introduced into the first vessel 1010 through the access opening 1012. If these particles 1060 are now to be removed from the liquid present in the first vessel 1010, then the magnet 1040 is brought in by means of the guide means 1050. This forms a pellet 1061 immobilized on the sidewall of the first vessel 1010 (see Fig. 11B ). The pellet 1061 is then fed to closure 1100 (see Fig. 11C ). Now, the shutter 1100 is opened and the path for the pellet 1061 is released into the connection portion 1030 (see FIG Fig. 11D ).
  • the pellet 1061 is then inserted into the second vessel 1020 by means of the magnet 1040 (see Fig. 11E ), where it can subsequently be released (see Fig. 11F ). If the magnetic particles 1060 are to be removed from the second vessel 1020 through the second access opening 1022, it makes sense to again form the magnetic particles 1060 by means of the magnet 1040 into a compact pellet 1061, which can be easily removed through the opening 1022. Via the second access opening 1022 it is likewise possible to remove the liquid without the magnetic particles 1060. typically, For example, during the removal of the liquid, the magnet 1040 would keep the pellet 1061 at a distance from the access opening 1022, thus allowing us to remove the liquid without entrainment of the magnetic particles.
  • FIG. 12 Another embodiment is in Fig. 12 shown.
  • the structure corresponds to the in Fig. 10 however, a magnet arrangement similar to that shown in FIG Fig. 8 shown embodiment provided.
  • the cartridge 1000 could be formed as an injection-molded part, in which the electromagnets 1040 are embedded.
  • the electromagnets can be controlled individually by a guide means 1050, ie individually switched on and off. In this way, a magnetic field extending from the first vessel 1010 via the connection region 1030 to the second vessel 1020 can be generated. Pelleting and transport of the pellet from the first vessel 1010 to the second vessel 1020 is then similar to that in FIG Fig. 8 shown embodiment, which is why a more detailed explanation is omitted here.
  • Fig. 13 shows a perspective view, wherein the interior of the cartridge 1000 is substantially the in Fig. 10 corresponds shown construction.
  • the magnet 1040 is disposed outside of the cartridge 1000. It can be guided along the surface of the cartridge 1000 by means of a guide means 1050 such that a pellet moves under the influence of the magnetic force from the first vessel via the connection region to the second vessel.
  • the magnet 1040 may be directed away from or toward the surface by the guide means 1050. In this way, for example, a pellet may be formed by lowering the magnet 1040 above the first vessel onto the surface of the cartridge. Likewise, the magnetic particles bound in a pellet can be released again by the magnet 1040 being lifted off the surface of the cartridge again.
  • Fig. 14 the cartridge 1000 is arranged on a guide means 1050, which is designed as a movable carrier.
  • the carrier 1050 is movable in its plane, but preferably also perpendicular thereto, so that it supports the ones mounted on it Cartridge 1000 can move along a predetermined path.
  • a magnet 1040 is held substantially stationary by a retaining means 1045.
  • By raising or lowering the carrier 1050 the surface of the cartridge 1000 can be brought to the magnet 1040.
  • the carrier 1050 By moving the carrier 1050 in its plane, the cartridge 1000 is then moved on a predeterminable path under the magnet 1040.
  • Fig. 15 shows a training of in Fig. 10 shown embodiment.
  • 1020 in addition to the first and the second vessel 1010, 1020 still a third vessel 1070 on the cartridge 1000 is arranged.
  • This third vessel 1070 is separated from the third vessel 1070 by a second closure 1200.
  • the second vessel 1020 could contain a washing liquid and the third vessel 1070 an elution solution.
  • any number of other vessels can be integrated on a cartridge and the exact number of vessels and the liquids contained in them are tailored to the specific application.
  • the devices according to the above embodiments can be designed and operated as closed systems.
  • the devices and methods according to the embodiments are simple and to a considerable extent automation-friendly.

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Claims (30)

  1. Dispositif pour séparer des particules magnétiques d'un liquide, comprenant
    un premier récipient (10 ; 1010),
    un deuxième récipient (20 ; 1020),
    une surface de liaison (11, 21, 30 ; 200) qui s'étend de l'intérieur du premier récipient (10) vers l'intérieur du deuxième récipient (20), la surface de liaison (11, 21, 30 ; 200) étant formée par une première paroi latérale (11) du premier récipient (10), une deuxième paroi latérale (21) du deuxième récipient (20) qui fait face à la première paroi latérale (11) du premier récipient (10) et une zone de liaison (30) reliant les première et deuxième parois latérales (11 ; 21) et ayant une face supérieure et une face inférieure,
    au moins un aimant (40) pour fournir un champ magnétique,
    et un moyen de guidage (50) qui est disposé à l'extérieur du premier récipient (10) et du deuxième récipient (20) et au moyen duquel le champ magnétique peut être guidé le long d'un côté de la surface de liaison (11, 21, 30 ; 200) comprenant la face inférieure de la zone de liaison (30), de sorte qu'une boulette (61) de particules magnétiques (60) peut être guidée le long de la face intérieure de la première paroi latérale (11) vers la face intérieure de la deuxième paroi latérale (21) en passant par la face supérieure de la zone de liaison (30), l'aimant (40) étant disposé sur le moyen de guidage (50).
  2. Dispositif selon la revendication 1, dans lequel ledit au moins un aimant (40) est un aimant permanent.
  3. Dispositif selon la revendication 1, dans lequel ledit au moins un aimant (40) est un électro-aimant.
  4. Dispositif selon l'une des revendications précédentes, dans lequel le moyen de guidage (50) est réalisé de telle sorte que ledit au moins un aimant (40) peut être guidé à une distance prédéfinie de manière fixe du côté de la surface de liaison (11, 21, 30 ; 200).
  5. Dispositif selon la revendication 4, dans lequel la distance prédéfinie de manière fixe est nulle, de sorte que l'aimant est en contact avec le côté de la surface de liaison (11, 21, 30 ; 200) lorsqu'il est guidé devant celle-ci.
  6. Dispositif selon l'une des revendications précédentes, dans lequel le moyen de guidage (50) comprend au moins un autre aimant (41, 42, 43) qui est espacé du premier aimant (40).
  7. Dispositif selon l'une des revendications précédentes, dans lequel au moins un élément de chauffage et/ou de refroidissement (110) est prévu sur la surface de liaison (11, 21, 30 ; 200).
  8. Dispositif selon l'une des revendications précédentes, dans lequel la surface de liaison (11, 21, 30 ; 200) est formée en arc de cercle.
  9. Dispositif selon la revendication 8, dans lequel le moyen de guidage (50) est réalisé de telle sorte que ledit au moins un aimant (40) peut être guidé sur une trajectoire circulaire, le rayon (r) de la trajectoire circulaire étant inférieur ou égal au rayon (R) de l'arc de cercle formé par la surface de liaison (11, 21, 30 ; 200).
  10. Dispositif selon la revendication 9, dans lequel le moyen de guidage (50) présente au moins un premier bras rotatif (51), dont une extrémité est disposée sur un axe de rotation (55) et à l'autre extrémité duquel est disposé ledit au moins un aimant (40).
  11. Dispositif selon la revendication 10, dans lequel le moyen de guidage (50) présente un ou plusieurs autres bras rotatifs (52, 53, 54) dont chaque extrémité est disposée sur l'axe rotatif (55) et à l'autre extrémité respective desquels est disposé un autre aimant (41, 42, 43).
  12. Dispositif selon la revendication 11, dans lequel les bras rotatifs (51, 52, 53, 54) sont réalisés d'une seule pièce.
  13. Dispositif selon la revendication 9, dans lequel le moyen de guidage (50) est réalisé sous forme cylindrique et est monté rotatif autour d'un axe (55).
  14. Dispositif selon la revendication 13, dans lequel ledit au moins un aimant (40) et/ou les autres aimants (41, 42) sont disposés sur la surface du moyen de guidage cylindrique (50).
  15. Dispositif selon la revendication 13, dans lequel ledit au moins un aimant (40) et/ou les autres aimants (41, 42) sont disposés chacun dans un logement (56, 57, 58) formé dans le moyen de guidage cylindrique (50).
  16. Dispositif selon l'une des revendications 11, 12, 14 ou 15, dans lequel ledit au moins un aimant (40) et lesdits un ou plusieurs autres aimants (41, 42, 43) sont disposés de manière décalée d'un même angle les uns par rapport aux autres.
  17. Dispositif selon l'une des revendications précédentes, dans lequel le moyen de guidage (50) est réalisé de telle sorte que la vitesse à laquelle il guide le champ magnétique de l'un (40) et/ou des plusieurs autres aimants (41, 42, 43) le long de la surface de liaison (11, 21, 30 ; 200) peut être commandée.
  18. Dispositif selon l'une des revendications précédentes, dans lequel le moyen de guidage (50) est réalisé de telle sorte que le sens dans lequel il guide le champ magnétique de l'un (40) et/ou des plusieurs autres aimants (41, 42, 43) le long de la surface de liaison (11, 21, 30 ; 200) peut être commandé.
  19. Dispositif selon l'une des revendications précédentes, comprenant en outre au moins un troisième récipient (70) qui est relié au premier ou au deuxième récipient par une deuxième surface de liaison, et un deuxième moyen de guidage (100) pour guider au moins un autre champ magnétique, dans lequel le premier ou le deuxième récipient (10, 20) forme avec le troisième récipient (70), la deuxième surface de liaison, le deuxième moyen de guidage (100) et l'autre champ magnétique un dispositif selon l'une des revendications 1 à 17.
  20. Dispositif selon la revendication 19, dans lequel les premier et deuxième moyens de guidage (50, 100) sont disposés sur des côtés opposés du deuxième récipient (20).
  21. Dispositif selon la revendication 19 ou 20, dans lequel le deuxième récipient (20) contient une solution de lavage et le troisième récipient contient une solution d'élution.
  22. Dispositif selon l'une des revendications précédentes, dans lequel au moins l'un des récipients (10, 20, 70) présente un élément fonctionnel, en particulier une ouverture de sortie et/ou un filtre.
  23. Dispositif selon l'une des revendications précédentes, dans lequel la surface de liaison (30) est réalisée en forme de rigole.
  24. Dispositif selon l'une des revendications précédentes, dans lequel les premier et deuxième récipients (1010, 1020) et/ou le troisième récipient (1070) sont réalisés dans une cartouche (1000).
  25. Dispositif selon la revendication 24, dans lequel des récipients adjacents respectifs (1010, 1020 ; 1020, 1070) sont séparés les uns des autres par un moyen de fermeture amovible (1100, 1200).
  26. Dispositif selon la revendication 24 ou 25, dans lequel la cartouche (1000) présente un couvercle qui présente une première ouverture d'accès (1012) à un premier récipient (1010) et une deuxième ouverture d'accès (1022, 1072) à un deuxième récipient.
  27. Procédé pour séparer des particules magnétiques d'un liquide, comprenant les étapes consistant à :
    (a) fournir un dispositif selon l'une des revendications 1 à 26 ;
    (b) fournir une suspension de particules magnétiques (60) dans un premier liquide (70) dans le premier récipient (10) du dispositif ;
    (c) fournir ledit au moins un champ magnétique par le moyen de guidage (50) du dispositif à une zone (11) de la surface de liaison (11, 21, 30 ; 200) du dispositif disposée à l'intérieur du premier récipient (10), de sorte qu'une boulette (61) de particules magnétiques se forme dans cette zone (11) ;
    (d) guider ledit au moins un champ magnétique par le moyen de guidage (50) le long d'un côté de la surface de liaison (11, 21, 30 ; 200) comprenant la face inférieure de la zone de liaison (30), de sorte que la boulette (61) de particules magnétiques est guidée le long d'un côté opposé de la surface de liaison (11, 21, 30 ; 200) comprenant la face supérieure de la zone de liaison (30) vers une zone (21) de la surface de liaison disposée à l'intérieur du deuxième récipient (20) du dispositif ;
    (e) retirer ledit au moins un champ magnétique par le moyen de guidage (50) de la zone (21) de la surface de liaison disposée à l'intérieur du deuxième récipient (20) afin de libérer à nouveau les particules magnétiques (60) formant la boulette (60).
  28. Procédé selon la revendication 27, dans lequel un dispositif selon la revendication 19 est fourni à l'étape (a),
    dans lequel, après l'étape (e), les particules magnétiques (60) sont lavées dans le deuxième récipient (20) et
    les particules magnétiques (60) sont ensuite transférées, de manière analogue aux étapes (a) à (e), du deuxième récipient (20) dans le troisième récipient (70) par le deuxième moyen de guidage (100) et l'autre champ magnétique.
  29. Procédé selon la revendication 28, dans lequel l'étape consistant à laver les particules magnétiques dans le deuxième récipient comprend les sous-étapes suivantes consistant à :
    libérer les particules magnétiques (60) formant une boulette (61) en retirant ledit au moins un champ magnétique par le premier moyen de guidage (50),
    former une boulette (62) en fournissant ledit au moins un autre champ magnétique par le deuxième moyen de guidage (100),
    libérer les particules magnétiques (60) formant une boulette (62) en retirant ledit au moins un autre champ magnétique par le deuxième moyen de guidage (100),
    former une boulette (61) en fournissant ledit au moins un champ magnétique par le premier moyen de guidage (50).
  30. Procédé selon la revendication 29, dans lequel l'étape consistant à fournir ledit au moins un champ magnétique ou ledit au moins un autre champ magnétique est exécutée en faisant tourner le premier, respectivement le deuxième moyen de guidage (50, 100) dans un premier sens de rotation, le premier sens de rotation du premier moyen de guidage (50) étant opposé au premier sens de rotation du deuxième moyen de guidage (100), et dans lequel l'étape consistant à retirer ledit au moins un champ magnétique ou ledit au moins un autre champ magnétique est exécutée en faisant tourner le premier, respectivement le deuxième moyen de guidage (50, 100) dans un deuxième sens de rotation opposé au premier sens de rotation, le deuxième sens de rotation du premier moyen de guidage (50) étant opposé au deuxième sens de rotation du deuxième moyen de guidage (100).
EP06792895.2A 2005-08-18 2006-08-18 Dispositif et procede de separation de particules magnetiques d'un liquide Active EP1919625B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102005039175A DE102005039175A1 (de) 2005-08-18 2005-08-18 Vorrichtung und Verfahren zum Abtrennen von magnetischen Partikeln aus einer Flüssigkeit
PCT/EP2006/065451 WO2007020294A1 (fr) 2005-08-18 2006-08-18 Dispositif et procede de separation de particules magnetiques d'un liquide

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EP1919625B1 true EP1919625B1 (fr) 2019-12-11

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JP (1) JP5027128B2 (fr)
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WO (1) WO2007020294A1 (fr)

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EP1919625A1 (fr) 2008-05-14
US8323507B2 (en) 2012-12-04
US20090206039A1 (en) 2009-08-20
JP5027128B2 (ja) 2012-09-19
DE102005039175A1 (de) 2007-02-22
WO2007020294A1 (fr) 2007-02-22

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