EP3519101B1 - Magnetische trennvorrichtung mit unkörperlicher kopplung zwischen magnetanordnung und deren bewegungsantrieb - Google Patents

Magnetische trennvorrichtung mit unkörperlicher kopplung zwischen magnetanordnung und deren bewegungsantrieb Download PDF

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Publication number
EP3519101B1
EP3519101B1 EP17772062.0A EP17772062A EP3519101B1 EP 3519101 B1 EP3519101 B1 EP 3519101B1 EP 17772062 A EP17772062 A EP 17772062A EP 3519101 B1 EP3519101 B1 EP 3519101B1
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EP
European Patent Office
Prior art keywords
magnet arrangement
guidance
arrangement
magnetic
magnetic isolating
Prior art date
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Active
Application number
EP17772062.0A
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German (de)
English (en)
French (fr)
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EP3519101A1 (de
Inventor
Ingo Schwaiger
Hanspeter Romer
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Hamilton Bonaduz AG
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Hamilton Bonaduz AG
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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
    • B03C1/28—Magnetic plugs and dipsticks
    • B03C1/284—Magnetic plugs and dipsticks with associated cleaning means, e.g. retractable non-magnetic sleeve
    • 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
    • B03C1/005—Pretreatment specially adapted for magnetic separation
    • B03C1/01—Pretreatment specially adapted for magnetic separation by addition of magnetic adjuvants
    • 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
    • B03C1/28—Magnetic plugs and dipsticks
    • B03C1/286—Magnetic plugs and dipsticks disposed at the inner circumference of a recipient, e.g. magnetic drain bolt
    • 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
    • B03C1/30—Combinations with other devices, not otherwise provided for
    • 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
    • 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
    • B03C2201/26—Details of magnetic or electrostatic separation for use in medical or biological applications

Definitions

  • the present invention relates to a magnetic separator for separating magnetic particles from a suspension
  • a generic magnetic separator is from US6649419B1 known. More magnetic separators are from U.S. 2011/0205835 A1 and from the US 2006/0118494 A1 known.
  • a magnetic separation device which comprises a pipetting device which can aspirate a suspension of magnetic particles into a pipetting tip.
  • the magnetic particles can be attached to a permanent magnet that is located inside the pipette tip and can be displaced along the pipette tip and can thus be separated from the suspension liquid.
  • the shift between the inactive and active position is carried out by means of a manually operated drive device.
  • Such separating devices are used, for example, in chemical, biochemical and/or pharmaceutical laboratories in order to remove magnetic particles contained in a suspension from the suspension.
  • Such suspensions with magnetic particles can be used, for example, to purify DNA.
  • the magnetic particles serve only as a means of transport and are usually coated in such a way that only a certain component of the suspension can and will accumulate on the outer surface of the coating facing away from the particle, which then together with the particle can be removed from the suspension.
  • the magnetic particles are therefore usually only magnetic for the purpose of the planned removal of chemical or biological material from the suspension liquid.
  • magnetic is meant a material that is either magnetizable or is magnetized. In most applications of the magnetic separation device discussed herein, the magnetic particles will comprise or consist of ferromagnetic material.
  • Another magnetic separator is from the US7799281B2 known.
  • This document discloses a magnetic separating device with a soft-magnetic tip, which is rigidly coupled to a guide tube of the guide device at its longitudinal end remote from the immersion section.
  • a permanent magnet can be approached as a magnet arrangement along the tube axis up to the point of physical contact with the soft-magnetic tip and can be removed from it.
  • the movable permanent magnet is polarized along the guide track, so that one of its magnetic poles can be brought into physical contact with the soft-magnetic tip.
  • the soft-magnetic tip is magnetized for the duration of the physical contact, while it is essentially unmagnetized when the permanent magnet is arranged at a distance from the soft-magnetic tip.
  • this known magnetic separating device thus manages without electrically energized components, in particular without an electromagnet, which often represents an undesirable heat source in magnetic separating devices.
  • the guideway coinciding with the axis of the guide tube is collinear with the tip axis to provide a magnetic separator which is as slim as possible radially with respect to the tip axis.
  • a magnetic separation device in which an annular permanent magnet arrangement surrounds a pipette tip radially on the outside and is manually displaceable in the longitudinal direction of the pipette tip by a mechanical linkage in order to apply its magnetic field to different zones of the pipette tip.
  • the magnet arrangements of all the prior art documents mentioned above have a permanent magnet.
  • the magnet assemblies are with their respective drive device on a recorded in the guide tube and coaxially extending with the guide tube rod or in the case of US7799281B2 alternatively coupled via a cable which is accommodated in the guide tube and runs coaxially with the guide tube and can thus be driven to move within the guide tube.
  • the separating devices therefore require installation space, at least along the guide track.
  • Their magnet arrangements together with the coupling to the respective movement drive - if present at all - also have a relatively large moving mass, which makes the magnet arrangements sluggishly movable.
  • the present application is therefore based on the object of further developing the generic magnetic separation device in such a way that, without requiring excessive installation space, it allows both rapid displacement of the magnet arrangement between the active position and the inactive position and simple but precise handling of the magnetic separation device in a laboratory allows.
  • the magnetic separating device according to the invention can be implemented in a compact manner without a great deal of space being required or at least with less space being required than in the prior art.
  • the mechanical driving force known from the prior art cited above Means such as rods or ropes can be omitted, so no installation space has to be provided for them. The moving mass is thus lower with an unchanged magnetic field of the magnet arrangement.
  • the magnet arrangement itself comprises at least one magnet, so that a magnetic field emanates from it, a magnetic field is advantageous as the force field that transmits the driving force.
  • the fluid transmitting the driving force can be a gas or a liquid. Liquid has the advantage of being incompressible, so that drive force can be transmitted from the drive device to the magnet arrangement with a liquid without play via any fluid channels, in particular fluid channels of any shape.
  • Pipetting devices such as are designed for standard laboratory equipment, not only have a pressure changing device for changing the pressure of a working fluid actually intended for aspiration and dispensing of dosing liquids, but also have movement drives for moving the pipetting channel along the pipetting channel axis, along which the pipetting channel extends, and along two movement axes that are orthogonal both to one another and to the pipetting channel axis.
  • the pipetting device can thus serve not only as a fluidically coupled drive device for the magnetic separation device, but also generally as a carrier and movement device for the magnetic separation device.
  • the pipetting device can thus be used to move the separating device in the movement space of the pipetting device and thus to dip into the above-mentioned suspension, move out of it and move parallel to a laboratory bench surface, for example to magnetically remove from the suspension and adhere to the immersion section Release particles elsewhere.
  • the pipetting channel axis is preferably oriented orthogonally to the surface of the laboratory bench.
  • the laboratory bench and its surface can be an integral part of the pipetting device.
  • the support and movement function of the pipetting device can also be used if the drive device is only coupled to the magnet arrangement by the force field and there is therefore no fluidic drive force coupling. Such an embodiment is not covered by the claimed invention. Due to the non-physical coupling of the drive device to the magnet arrangement, the drive device can also be spatially freer, d. H. taking into account fewer boundary conditions than in the case of the mechanical couplings of the drive device with the magnet arrangement known from the prior art.
  • drive device refers to that device of the separating device which provides the energy required to move the magnet arrangement between the active position and the inactive position in the form used for the move.
  • this can be an electromagnet that generates a magnetic field as the force field or a displaceable permanent magnet that generates the force field.
  • this can be any pressure-changing device, such as a pump, or a pressure accumulator that can be switched on and off via a valve to act on the magnet arrangement, the pump in turn being a continuously operating pump or a piston-cylinder arrangement can.
  • a continuously operating pump its pumping action can again be switched on and off with the interposition of a switchable valve, or the action of the pump can be switched on or off simply by switching the pump on and off.
  • a pipetting device can be a drive device for the magnetic separation device in the case of a fluidic coupling, this is correct at a rough level of abstraction.
  • its pressure-changing device is the drive device of the magnetic separation device, since this provides the change in fluid pressure necessary for the displacement of the magnet arrangement.
  • the magnetic separating device is a magnet arrangement at least in the active position, orthogonal to the guideway, radially outward and along the guideway, on the side facing away from the inactive position. It is thus possible to prevent the magnet arrangement from being wetted by the suspension in which the immersion section of the separating device is immersed. However, this is not intended to mean that such wetting must be prevented. It can also be considered, for example, that wetting of the magnet arrangement by the suspension is permissible and any suspension adhering to the magnet arrangement or particles magnetically detached from the suspension are wiped off when the magnet arrangement is moved from the active position to the inactive position.
  • the guide device can have a wiper lip, which is provided in such a way that the magnet arrangement wipes along it when shifting from the active position to the inactive position.
  • the use of the cover as a protective cover and thus at the same time as a protective shield against wetting for the magnet arrangement when the separating device is used as intended is preferred over the wiper solution described above because of the higher degree of hygiene.
  • a longitudinal end of the sleeve that is closer to the active position of the magnet arrangement can form the immersion section of the separating device as the immersion longitudinal end of the sleeve.
  • the immersion section of the separating device is formed by a soft-magnetic tip, to which the magnet arrangement is closer in the active position than in the inactive position, preferably up to the touching contact.
  • the sheath may be permanently attached to the separator.
  • the casing can be taken to a cleaning station, for example immersed in a cleaning solution, and cleaned there of any suspension residues present, which also include solid particles taken up in the suspension.
  • the sleeve is provided on the separating device in a detachable manner as intended.
  • the shell is disposable or Disposable sleeve for an immersion process was added to the separating device and is released from the separating device after the completion of the work process that includes the immersion process and is replaced by a new, clean and previously unused cover for a subsequent work process.
  • the separator has a coupling arrangement according to the invention, which is coupled to the guide device at a first coupling point as a guide coupling point and which at a second coupling point different from the first coupling point as a device coupling point for detachable coupling is formed with a pipetting channel of a pipetting device.
  • the pipetting device can at least be used to move the magnetic separating device three-dimensionally in the movement space of the pipetting device when it is coupled to the pipetting channel. There is no need for a separate manipulation device for the separating device if the laboratory using the separating device already has a pipetting device.
  • the targeted movement of the separating device in the movement space of the pipetting device is advantageous both for the force field coupling and for the fluid coupling between the drive device and the magnet device.
  • the pipette device or its pipette channel can also be used as a drive device of the separating device with a corresponding design of the coupling arrangement in the case of a fluidic coupling between the drive device and magnet arrangement. This is detailed below.
  • the sleeve in particular a longitudinal end of the sleeve located closer to the inactive position, can be fixed to the guide device and/or to the coupling arrangement for connection to the separating device, preferably releasably for the reasons mentioned above.
  • the cover is preferably fixed to the coupling arrangement, so that the cover can surround not only the magnet arrangement in its active position, but also the entire guide device and thus protect it from contact with suspension. Therefore, when the sleeve is provided on the separating device, the guide device is preferably located along the guide track completely in the area of the sleeve and is surrounded by the sleeve at least radially outwards and axially in the immersion direction relative to the guide track.
  • the guiding device can have a guiding hose or a guiding tube or a guiding rod, which guides the magnet arrangement for displacement between the active and the inactive position.
  • the advantage of a guide tube lies in the almost arbitrary three-dimensional shape that it can assume, which, however, means restrictions in the structural design of the magnet arrangement, since it must also be able to be moved safely through curved tube runs.
  • a guide tube is preferred as a straight guide tube, since it has a minimum of weight or mass with the greatest possible guidance reliability and a comparatively large magnet arrangement, approximately long in the direction of the guide track, can be guided in it.
  • a guide rod or a guide tube can pass through the magnet arrangement centrally, so that the magnet arrangement can then be designed with a through-opening.
  • this configuration of the magnet arrangement, through which the guide device passes is less preferred since, due to the through opening of the magnet arrangement, its magnetic field is considerably weakened in comparison to a solid magnet arrangement with the same external dimensions.
  • the magnet arrangement preferably has a permanent magnet, so that the magnetic field of the magnet arrangement is permanently available without an external energy supply.
  • the magnetic field emanating from the magnet arrangement is preferably caused exclusively by at least one permanent magnet, so that it is impossible for the magnet arrangement to act as a heat source, as could be the case when using an electromagnet.
  • the guide tube surrounds the magnet arrangement radially on the outside in relation to a tube axis that coincides with the guideway. Moreover, the guide tube can then also contribute to the protection of the magnet arrangement, in addition to the cover mentioned above.
  • the magnet arrangement has a sealing arrangement which seals against the inner wall of the guide tube and which divides the volume enclosed by the guide tube into an actuation volume closer to the inactive position and a displacement volume closer to the active position.
  • a pressure difference between the fluid provided in the actuation volume and the fluid provided in the displacement volume can then be permanently maintained and have a permanent force-transmitting effect on the magnet arrangement.
  • the actuation volume which is the volume that communicates directly with the fluidically coupled drive device
  • the displacement volume which is the volume that is separated from the actuation volume by the magnet arrangement, in particular by the sealing arrangement, are variable, with the sum of the two volumes being constant is.
  • the annular gap between the magnet arrangement which in this embodiment preferably acts as a piston itself, and the guide tube can be dimensioned so small that a change in the fluid pressure in the actuating volume compared to the fluid pressure in the displacement volume is basically compensated for by an overflow through the annular gap past the magnet arrangement can be, but this overflow lasts so long due to the small dimensions of the annular gap and the resulting high flow resistance that the magnet assembly their target position: inactive position or active position, is reached before the pressure difference generated by the drive device between the fluid in the actuation volume and the fluid in the displacement volume is reduced too much or is even balanced.
  • the magnet arrangement guided in the guide tube divides the guide tube into two sections or two sides.
  • the actuating side is the side to which the drive device is connected, so that a change in the fluid pressure caused by it has a direct effect on the fluid in the actuating volume.
  • the force of the fluid pressure on the magnet arrangement causes it to be displaced in the guide tube, and this displacement indirectly changes the pressure of the fluid contained in the displacement volume, whereby, according to an advantageous development of the invention, when the displacement volume is reduced, fluid is pushed out of it and thus displaced, and with Increasing the displacement volume, fluid preferably flows into the displacement volume in order to prevent the pressure in the displacement volume from changing so much as a result of the movement of the magnet arrangement and thus the pressure difference between the fluid in the displacement volume and the fluid in the actuation volume being reduced so much that the movement the magnet arrangement undesirably comes to a premature standstill. Due to the possibility of fluid being expelled from the displacement volume or of fluid subsequently flowing into the displacement volume, large displacement distances can also be reliably effected by the non-physical coupling between the drive device and the magnet arrangement.
  • a gas duct is formed, which opens into the displacement volume of the guide tube.
  • the gas duct can be formed, for example, by one or more grooves in the radially outer side of the guide tube pointing to the sleeve and/or by one or more grooves on the radially inner side of the sleeve pointing to the guide tube.
  • the largest possible cross-sectional area of the gas duct can be formed by ribs protruding in the radial direction on the radially outer side of the guide tube pointing to the sleeve and/or on the radially inner side of the sleeve pointing to the guide tube.
  • the ribs then preferably determine the distance for the radial distance between the guide tube and the casing. In this case, these ribs do not have to extend axially along the guide track over the entire length along which the casing and guide tube extend together. It is sufficient if axially, i. H. along the guideway, spaced apart ribs are formed on one and/or the other component, so that the casing and guide tube cannot tilt relative to one another about a tilting axis orthogonal to the guideway.
  • a groove is present when a recess forming the groove has smaller dimensions in the circumferential direction than the component sections delimiting the recess in the circumferential direction, and that a rib is present when a component section forming the rib has smaller dimensions in the circumferential direction has than the component portion delimiting recesses in the circumferential direction.
  • annular gap which may be interrupted by a plurality of ribs in the circumferential direction can form the gas duct radially between the guide tube and the casing.
  • the gas duct is connected to the displacement volume at one end area and to a fluid reservoir of essentially constant pressure, preferably to the ambient atmosphere, at its opposite end area, in order to be able to provide a constant pressure level in the displacement volume.
  • actuation volume and displacement volume is through the use of a seal assembly.
  • this sealing arrangement can be provided directly on the magnet arrangement, for example by gluing or by arranging it on a positive-locking formation formed on the magnet arrangement, such as in an annular receiving gap.
  • the sealing arrangement can therefore preferably be carried by a piston which is formed separately from the magnet arrangement and which is connected to the magnet arrangement for joint movement.
  • the piston can be made arbitrarily short along the guideway, such as shorter than the magnet assembly itself, so that its sole function is to support the seal assembly and provide a permanent connection to the magnet assembly.
  • the piston can be formed from a material that is easier than the material of the sealing arrangement to be connected to the magnet arrangement adhesively or by positive locking.
  • the magnet arrangement is preferably connected to the piston on a side facing the displacement volume or on a region of the piston located in the displacement volume. In this case it is ensured that even when the piston reaches an end position, there is a distance between the sealing arrangement and the longitudinal end of the guide arrangement, which distance depends on the dimensions of the magnet arrangement. Because of this distance, there is always a minimum residual displacement volume that communicates with the constant pressure fluid reservoir.
  • the permanent magnet of the magnet arrangement can be surrounded by a casing.
  • This covering can be a plastic covering, such as PTFE or polyethylene, to name just two possibilities.
  • the permanent magnet can also form the magnet arrangement without being coated and uncovered.
  • a piston rod can be arranged between the piston and the magnet arrangement, which connects the piston and the magnet arrangement for joint movement.
  • the magnet arrangement can be provided in the active position considerably more than just the displacement path away from the coupling arrangement.
  • the guiding device then does not have to be in direct guiding engagement with the magnet arrangement. Rather, it can indirectly cause the magnet arrangement to move along the guide track.
  • the guide device can directly guide the piston and possibly also the piston rod for movement along the guide track.
  • the guiding device can be made considerably shorter than if it were in guiding engagement with the piston and the magnet arrangement.
  • the magnet arrangement can then be located axially outside of the guide tube in each operating position: inactive position, active position and any intermediate position in between, relative to the tube axis of the guide tube. A distance between the magnet arrangement in the active position and the suspension can be shortened as a result.
  • the magnet assembly can be protected from external influences.
  • the guide tube of the guide device can have a guide component closing or narrowing the guide tube and penetrated by the piston rod, which guides the piston rod while the piston is guided in the guide tube itself.
  • the guide tube has openings that penetrate radially in its end region that is closer to the active position, in particular at its longitudinal end that is closer to the active position.
  • the longitudinal end of the guide tube that is closer to the active position of the magnet arrangement cannot reach a bottom or a shoulder formation of the sleeve surrounding the guide tube, so that there can be a completely circumferential annular gap between the guide tube and the sleeve in this area.
  • the gas duct can be formed in the guide tube so that the displacement volume communicates with a fluid reservoir of constant pressure, in particular with the ambient atmosphere, through the guide tube.
  • the magnet arrangement is either surrounded radially on the outside by a further tube in order to provide defined actuation and displacement volumes, or the volumes are defined by the casing surrounding the magnet arrangement radially on the outside.
  • a sealing arrangement should preferably be provided, which then seals against the shell.
  • the coupling arrangement that can be coupled to a pipetting channel can also transmit a pressure change in the working fluid of the pipetting channel caused by the pipetting channel into the actuation volume closer to the device coupling point
  • the coupling arrangement can have a connecting channel which connects the device coupling point to the volume enclosed by the guide tube.
  • the connected volume is preferably the actuation volume for the reasons mentioned above.
  • the connection allows the transmission of Fluid and fluid pressure between the pipetting channel filled with working fluid and the volume enclosed by the guide tube, in particular the actuation volume, and the fluid contained therein.
  • the design of the magnet arrangement for the fluid-based transmission of driving force is preferably achieved in that either the magnet arrangement itself is designed as a piston, as described above, or is coupled to a separately designed piston for joint movement. specified in this application advantageous developments of the immersion section, the guide device, the magnet arrangement and/or the coupling arrangement also apply to the presently described magnetic separating device without a drive device.
  • a holding device can be provided in the area of the inactive position, which holds the magnet device in the inactive position, so that a permanent exertion and transmission of holding or driving force by the drive device can be omitted in order to hold the magnet arrangement in the inactive position.
  • the holding device can comprise a holding magnet, preferably a holding permanent magnet to avoid unnecessary energy supply. It can also be sufficient to provide or form at least one end region of the coupling arrangement facing the inactive position of the magnet arrangement with a soft magnetic material, for example with a ferromagnetic or ferrimagnetic material that is not permanently magnetized but magnetizable.
  • the above-mentioned guide component that guides the piston rod can be a permanent magnetic component or a soft magnetic component that can be a holding component of the holding device.
  • the magnet arrangement can be held in the active position simply by a bottom of the guide device and/or the casing. For this, too, no force is then required to be exerted by the drive device.
  • the magnet arrangement can only be displaced from the active position to the inactive position by the drive device and the magnet arrangement can be displaced in the opposite direction by gravity from the inactive position to the active position can.
  • the drive device is preferably designed to drive the magnet arrangement in both opposite displacement directions.
  • the separating device can have a control magnet arrangement whose magnetic field can be changed as the force field in the area of the guide track.
  • the control magnet arrangement can be a spatially displaceable permanent magnet arrangement, but preferably comprises a switchable electromagnet which generates a magnetic field as a function of the current flow through its coils. The electromagnet can then advantageously be provided in a stationary manner on the separating device.
  • the separating device can have a base body which is coupled to the guide device and which thus carries the guide device.
  • the base body can be the above-mentioned coupling arrangement, so that the separating device can be coupled to the pipetting device.
  • the base body can also be designed for hand grip in order to manually move the separating device between different containers.
  • control magnet arrangement can be provided on the base body. This has the advantage that the separating device can be used with any containers and container carriers.
  • the separating device can have a container designed to receive the suspension and/or a container carrier designed to receive the container, with the control magnet arrangement being provided on the container and/or on the container carrier.
  • the base body which then does not necessarily have to carry a control magnet arrangement, can then be small, ie designed with low installation space requirements.
  • the separating device can then be designed so slim in relation to the guideway that a plurality of pipetting channels or even all pipetting channels can be coupled simultaneously to a magnetic separating device of the present application on a pipetting head with a plurality of pipetting channels. This also applies to a magnetic separating device that is only fluidly coupled to the pipetting device as the drive device.
  • control magnet arrangement is preferably provided on the container carrier, since this can be provided more easily than the container with the necessary energy supply for energizing the control magnet arrangement, which advantageously has an electromagnet, because the container carrier is usually moved less frequently in the laboratory than the container it accommodates.
  • the container carrier then preferably has a receiving recess, for example a recess, which is designed to receive a container section.
  • the receiving recess is preferably designed to be complementary to the container section to be received in it.
  • the control magnet arrangement can then be provided on the container carrier so as to surround the receiving recess and/or under a set-up surface on which the container accommodated on the container carrier is intended to stand on the container carrier.
  • the electromagnet preferably included in the control magnet arrangement can be designed to develop a sufficiently strong magnetic field from its location in the container carrier in order to move the magnet arrangement from the inactive position to the active position and back.
  • control magnet arrangement on the container carrier or on the container can comprise only one permanent magnet, which is however strong enough to counteract the effect of the preferably provided holding device when the guide arrangement and the magnet arrangement guided therein sufficiently approach the control magnet arrangement, the holding force of the holding device and to move the magnet arrangement to the active position closer to the immersion section and thus to the active position closer to the control magnet arrangement when the container carrier is approached as intended.
  • the magnet arrangement is then shifted into the active position when approaching the suspension to be processed or during immersion in it, without that a separate switching process or even an energy supply would be necessary for this.
  • the magnet arrangement After the separating device has been withdrawn from the suspension, the magnet arrangement remains in the active position, driven by gravity, and is taken with the magnetic particles which have been removed from the suspension and are adhering to its immersion section to a dispensing vessel which has another control magnet arrangement, but with the opposite polarity to that of the container or container carrier.
  • the magnet arrangement When approaching this further control magnet arrangement, the magnet arrangement is moved into the inactive position by the magnetic field of the further control magnet arrangement, again without a separate switching process or energy supply, and the particles located on the outside of the immersion section can fall off or flow away from the immersion section.
  • the holding device then holds the magnet arrangement in the inactive position until it approaches the control magnet arrangement of the container accommodating the suspension or the container carrier carrying it again.
  • an electromagnet allows a magnetic field to be produced and maintained for the displacement of the magnet arrangement only for as long as is actually necessary for the displacement of the magnet arrangement between the active position and the inactive position.
  • the magnetic field of the control magnet arrangement can be switched off, since the magnet arrangement is preferably held in one or the other of the inactive position and the active position either by the holding device or by gravity.
  • the magnetic separating device 10 comprises a coupling arrangement 12 on which a guide coupling point 14 and on the other end a device coupling point 15 is formed.
  • a guide tube 16 is fixed, in which a magnet arrangement 18 between the in figure 1 shown inactive position and in figure 2 shown active position along an in figure 2 shown guideway F is guided displaceably.
  • the guide tube 16 extends along a tube axis R which is collinear with the guide track F.
  • the device coupling point 15 has a coupling formation which is designed for detachable coupling to a pipetting channel 20 of a pipetting device 22 .
  • the coupling formation of the device coupling point 15 corresponds to the coupling formation of a pipette tip that can be detachably coupled to the pipette channel 20 .
  • a pipetting piston 24 is movably accommodated in a manner known per se in order to be able to change the pressure of a working fluid in the pipetting channel 20 by moving the pipetting piston 24 and thereby, for example, when coupling a pipetting tip to the pipetting channel 20 to be able to carry out an aspiration and/or a dispensing process.
  • the pipetting device 22 forms a drive device of the magnetic separation device 10.
  • the magnet arrangement 18 is therefore at least also fluidically coupled to the pipetting device 22 as the drive device.
  • the coupling arrangement 12 has a connecting channel 26 passing through it centrally, which completely passes through the coupling arrangement from the device coupling point 15 to the guide coupling point 14, so that the pressure of the working fluid in the pipetting channel 20 can act directly on the magnet arrangement 18.
  • the connecting channel 26 is preferably of cylindrical design. Its cylinder axis is collinear with the pipetting channel axis P and also collinear with the guideway F (see Fig figure 2 ).
  • the separating device 10 also has a roughly schematic cup-like sleeve 28 which is arranged on the coupling arrangement 12 and on the guide tube 16 in a detachable manner, namely so that it can be stripped off along the guideway F. In order to achieve a high standard of hygiene, the sleeve 28 is replaced after each operation of the separating device 10 that includes an immersion process.
  • the cover 28 is thus a disposable cover 28.
  • the sleeve 28 surrounds the guide tube 16 radially on the outside along its entire axial extension relative to its tube axis and forms an immersion section 30 at its longitudinal end remote from the coupling arrangement 12 .
  • This immersion section 30 is designed to be immersed in a suspension in order to remove magnetic particles therefrom due to the effect of the magnetic field emanating from the magnet arrangement 18 .
  • the immersion section 30 of the shell 18 and thus of the separating device 10 is designed with a smaller diameter than the remaining section of the shell 28 .
  • the diameter of the immersion portion 30 of the shell 28 is just large enough to accommodate the cylindrical magnet assembly 18 therein.
  • the magnet arrangement 18 is designed as a solid cylindrical permanent magnet, the cylinder axis of which is connected to the guide track F (see figure 2 ) is collinear and which is preferably polarized along the cylinder axis, i.e. has a north or south pole at one end and the other pole at its other end: south or north pole.
  • the magnet arrangement 18 is connected at its longitudinal end facing the coupling arrangement 12 to a piston 32 for joint movement, for example by gluing.
  • the piston 32 which is designed much shorter than the magnet arrangement 18 in the direction of the guide track F, for example less than a third of the length of the magnet arrangement 18, carries a sealing arrangement 34, which is movable together with the piston 32 along the guide track F, and which seals against the inside of the guide tube 16.
  • the sealing arrangement 34 divides the volume enclosed by the guide tube 16 along the guide track F into a displacement volume 36 located on the side of the sealing arrangement 34 facing away from the coupling arrangement 12 and into an actuation volume 38 located on the side of the sealing arrangement 34 facing the coupling arrangement 12.
  • the actuation volume 38 and the displacement volume 36 can be changed depending on the relative position of the magnet arrangement 18 and the sealing arrangement 34 connected to it for joint movement, the sum of the actuation volume 38 and the displacement volume 36 being essentially constant due to the unchangeable shape of the guide tube 16.
  • the guide tube 16 and the sleeve 28 are made of non-magnetic and non-magnetizable material.
  • the coupling arrangement 12 is provided with ferromagnetic material at least at its longitudinal guide end 14, so that the magnet arrangement 18 in figure 1 shown inactive position is held due to its magnetic field in the inactive position by force with the coupling arrangement 12.
  • the coupling arrangement 12 could be decoupled from the pipetting channel 20 without the magnet arrangement 18 reaching the active position.
  • a container 40 is also shown, in which a suspension, not shown in detail, of a liquid and magnetic particles contained therein is accommodated.
  • the container 40 which is essentially cylindrical radially on the outside, is accommodated in a container carrier 42 , which can likewise be part of the separating device 10 .
  • the container carrier 42 has a shoulder 44 which is cylindrical in the illustrated exemplary embodiment and in whose recess 46 it includes a bottom section of the container 40 is accommodated.
  • the shoulder 44 with the receiving recess 46 is surrounded radially on the outside by a coil 48 of an electromagnet 50 .
  • the electromagnet 50 forms a control magnet arrangement within the meaning of the present invention.
  • a coil of an electromagnetic control magnet arrangement could also be accommodated in the coupling arrangement 12, for example surrounding the connecting channel 26.
  • the electromagnet 50 is only shown in figure 1 connected to the control device 52 shown, which controls the operation of the electromagnet 50.
  • the control device 52 can be a control device of the pipetting device 22, which also controls its operation.
  • the control device 52 is therefore connected to the electromagnet 50 by a signal and/or energy-transmitting line 54 and can also be connected to the pipetting device 52 for signal and/or energy transmission by a line 56 that is only shown in dashed lines because of the optionality.
  • figure 2 is the device of figure 1 shown with the magnet arrangement 18 adjusted into the active position.
  • the pipetting piston 24 was moved to the in figure 2 lower position shown, as a result of which the pressure of the working fluid in the pipetting channel 20 was increased to such an extent that the magnet arrangement 18 was released from its coupling arrangement 12, which is also designed as a holding device by using ferromagnetic material at least at the guide coupling point 14, and was released together under the influence of the increased working fluid pressure with the force of gravity acting along the guideway F in the in figure 2 active position shown has been adjusted.
  • figure 3 is the device of figure 2 shown with the immersion section 30 immersed in the suspension, which is not shown.
  • the permanent magnetic field emanating from the magnet arrangement 18 thus acts on the suspension.
  • the magnetic field acting in the area of the immersion section 30 of the separating device 10 is variable over time.
  • annular gap 58 between the coupling arrangement 12 and the guide tube 16 on the one hand and the section of the sleeve 28 surrounding the coupling arrangement 12 and the guide tube 16 radially on the outside on the other hand, which gap extends towards the device coupling point 15 via the insertion bevel 60 of the sleeve 28 the external environment U and is therefore connected to the atmosphere.
  • the external environment U has an essentially constant pressure level apart from the usual and here negligible meteorological pressure fluctuations.
  • the guide tube 16 has through openings 62 penetrating the guide tube 16 in the radial direction, through which the annular gap 58 communicates with the displacement volume 36 always present below the sealing arrangement 34 .
  • the longitudinal end of the guide tube 16 that is closer to the active position and that is further away from the coupling arrangement 12 can thus be designed like a crown, for example, so that its pinnacles form an end stop for the shoulder 64 of the shell 28 extending in the radial direction and the spaces between the pinnacles as through-openings 62 ensure communication of the displacement volume 36 with the outside environment U.
  • the sleeve 38 is brought close to the magnet arrangement 18 in order to avoid an unnecessary air gap and to achieve the most effective possible effect of the magnetic field emanating from the magnet arrangement 18 on the suspension then surrounding this section 30.
  • the immersion portion 30 is connected to the portion of the sheath 28 surrounding the guide tube 16 and the docking assembly 12 by the shoulder 64 previously mentioned.
  • Ribs can be formed on the coupling arrangement 12, on the sleeve 28 and/or on the guide tube 16, in particular in the region of the longitudinal end of the guide tube 16 closer to the active position, which radially connect the coupling arrangement 12 and the guide tube 16 on the one hand and the sleeve 28 on the other position that the annular gap 58 is secure. If they are formed on the coupling arrangement 12 and the guide tube 16, the ribs protrude radially outwards therefrom and if they are formed on the sleeve 28, they protrude radially inwards therefrom.
  • piston 32 ' is shown, which differs from the piston 32 of Figures 1 to 3 and 5 until 7 differs.
  • This is double-T-shaped with a circumferential groove in which the sealing arrangement 34' is arranged with the sealing lip protruding therefrom.
  • the piston 32' surrounds a longitudinal end of the cylindrical magnet arrangement 18 facing it, which simplifies the fastening of the magnet arrangement 18 to the piston 32'.
  • This comprehensive formation of the piston can also be implemented on the piston 32 .
  • the advantage of the fluidic actuation of the magnet arrangement 18 for shifting the same between the inactive and active position is that the magnet arrangement 18 can be shifted independently of an approach to the control magnet arrangement 50 . It is thus possible to bring the magnet arrangement 18 into the active position before the immersion section 30 even gets close to the suspension in which it is to be immersed.
  • the coupling arrangement could then be produced by injection molding using thermoplastic material, in which case the coils of the control magnet arrangement surrounding the connecting channel 26 can be cast into the material of the coupling arrangement 12 . If the magnet arrangement 18 is to be moved exclusively magnetically, the connecting channel 26 can also be omitted.
  • a ferromagnetic cylinder can be cast into the injection-molded coupling arrangement 12 in the area of its guide coupling point 14, which as a soft-magnetic component forms a holding device for holding the magnet arrangement 18 in the inactive position.
  • figure 5 is the device of figure 3 shown in an unchanged configuration, only a globe 66 of soft magnetic particles from the suspension has accumulated around the immersion section 30 due to the effect of the magnetic field of the magnet arrangement 18 .
  • figure 6 shows the separator 10 in the configuration of FIG figure 2 , but with the particle globe 66 arranged on the immersion section 30.
  • figure 7 shows the separating device 10 immersed in a dispensing vessel 68 with the magnet arrangement 18 adjusted into the inactive position.
  • the combined effect of negative fluid pressure by means of the pipetting piston 24 in the pipetting channel 20 on the one hand and the repelling magnetic field effect of the control magnet arrangement 50 can be used to move the magnet arrangement 18 from the active position to the inactive position at very high speed, causing the soft magnetic particles initially adhering to the immersion section 30 to enter the dispensing vessel 68 are given.
  • the dispensing vessel 68 is structurally identical to the suspension vessel 40.
  • FIG. 8 and 9 a second embodiment of the magnetic separation device of the present invention is shown, but without a pipetting device as a driving device.
  • the piston 132 ′ is connected to the magnet arrangement 118 by means of a piston rod 170 .
  • the piston rod 170 is circular-cylindrical at least over a large part of its longitudinal extent, with its cylinder axis being oriented collinear with the tube axis R of the guide tube 116 .
  • a guide component 172 is arranged nearer the longitudinal end of the guide tube 116 in the active position of the magnet arrangement 118 shown, through which the piston rod 170 passes with a small radial gap, so that the guide component 172 guides the piston rod 170 . Due to the direct guidance of the piston 132 ′ and the piston rod 170 through the guide tube 116 or the guide component 172 , the magnet arrangement 118 is indirectly guided for movement along the guide track F .
  • the magnet assembly 118 is located entirely outside of the guide tube 116.
  • the cover 128 is in the active position (see FIG figure 8 ) further longitudinal end fixed to the coupling arrangement 112.
  • grooves 174 formed on the coupling arrangement 112 are shown, which are distributed equidistantly around the guide track F in the circumferential direction and which extend along the guide track F in their main direction of extension.
  • the gas duct 158 between the shell 128 and the guide tube 116 is connected to the outside environment U by these grooves 174 .
  • through-openings 162 are again formed that radially pass through the guide tube, through which the in figure 8 minimum displacement volume 136 via the gas duct 158 and the grooves 174 communicating with the outside environment U is connected.
  • the through openings 162 are provided at a distance from the longitudinal end of the guide tube that is closer to the active position, in order to be able to use the longitudinal end itself for attaching the guide component 172 .
  • figure 9 is the arrangement of figure 8 shown with only the magnet assembly 118 being moved to the inactive position.
  • the guide component 172 can act as a holding component and for this purpose can be designed to be permanent magnetic or soft magnetic, so that magnetic holding forces can act between the guide component 172 and the magnet arrangement 118 in the inactive position.
  • the sleeve 128 is considerably longer in the axial direction than the guide tube 116.
  • the sleeve 128 surrounds both a large part of the guide tube 116, at least a large part of its extension starting from the longitudinal end closer to the active position, and surrounds the entire displacement path of the magnet arrangement 118
  • the guide component 172 can project beyond the guide tube 116 in a radially outward direction in order to radially support the sleeve 128 .

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  • Physical Or Chemical Processes And Apparatus (AREA)
  • Sampling And Sample Adjustment (AREA)
EP17772062.0A 2016-09-30 2017-09-25 Magnetische trennvorrichtung mit unkörperlicher kopplung zwischen magnetanordnung und deren bewegungsantrieb Active EP3519101B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102016219053.9A DE102016219053A1 (de) 2016-09-30 2016-09-30 Magnetische Trennvorrichtung mit unkörperlicher Kopplung zwischen Magnetanordnung und deren Bewegungsantrieb
PCT/EP2017/074228 WO2018060137A1 (de) 2016-09-30 2017-09-25 Magnetische trennvorrichtung mit unkörperlicher kopplung zwischen magnetanordnung und deren bewegungsantrieb

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EP3519101A1 EP3519101A1 (de) 2019-08-07
EP3519101B1 true EP3519101B1 (de) 2022-06-01

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US (1) US11413625B2 (zh)
EP (1) EP3519101B1 (zh)
JP (1) JP7217228B2 (zh)
CN (1) CN109789427B (zh)
DE (1) DE102016219053A1 (zh)
WO (1) WO2018060137A1 (zh)

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WO2021029991A1 (en) * 2019-08-15 2021-02-18 Siemens Healthcare Diagnostics Inc. Magnetic particle collection apparatus, systems, and methods

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Publication number Priority date Publication date Assignee Title
US3985649A (en) 1974-11-25 1976-10-12 Eddelman Roy T Ferromagnetic separation process and material
FI932866A0 (fi) 1993-06-21 1993-06-21 Labsystems Oy Separeringsfoerfarande
IL123210A0 (en) 1998-02-06 1998-09-24 Gombinsky Moshe A device and system for the collection of magnetic particles
FI102906B (fi) * 1998-02-23 1999-03-15 Bio Nobile Oy Menetelmä ja väline aineen siirtämiseksi
US6409952B1 (en) 1998-11-25 2002-06-25 Crane Plastics Company Limited Partnership Drying and processing cellulosic compounds
FI20000583A0 (fi) 2000-03-14 2000-03-14 Labsystems Oy Astia ja sauva
US6649419B1 (en) * 2000-11-28 2003-11-18 Large Scale Proteomics Corp. Method and apparatus for protein manipulation
FI120863B (fi) 2002-10-18 2010-04-15 Biocontrol Systems Inc Magneettinen siirtomenetelmä ja mikropartikkelien siirtolaite
US7597520B2 (en) * 2005-05-24 2009-10-06 Festo Corporation Apparatus and method for transferring samples from a source to a target
US7534081B2 (en) * 2005-05-24 2009-05-19 Festo Corporation Apparatus and method for transferring samples from a source to a target
CN200945454Y (zh) * 2006-06-16 2007-09-12 复旦大学 一种便携式磁性分离笔
US7799281B2 (en) 2007-01-16 2010-09-21 Festo Corporation Flux concentrator for biomagnetic particle transfer device
ATE471761T1 (de) * 2007-08-14 2010-07-15 Qiagen Gmbh Verfahren zum suspendieren oder resuspendieren von partikeln in einer lösung sowie daran angepasste vorrichtung
DE102010000690A1 (de) * 2010-01-05 2011-07-07 Hamilton Bonaduz Ag Dosiervorrichtung und Dosierverfahren
FI20115175A0 (fi) 2011-02-23 2011-02-23 Helsinki Thermo Fisher Scient Oy Partikkelien prosessointi
CN104646176B (zh) 2015-02-11 2017-03-01 英芮诚生化科技（上海）有限公司 手动磁性固相萃取器
DE102015218010A1 (de) * 2015-09-18 2017-03-23 Hamilton Bonaduz Ag Magnetische Trennvorrichtung mit magnetischer Aktivierung und Deaktivierung

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DE102016219053A1 (de) 2018-04-05
WO2018060137A1 (de) 2018-04-05
EP3519101A1 (de) 2019-08-07
CN109789427A (zh) 2019-05-21
CN109789427B (zh) 2021-07-20
JP2019530573A (ja) 2019-10-24
US20200139379A1 (en) 2020-05-07
JP7217228B2 (ja) 2023-02-02
US11413625B2 (en) 2022-08-16

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