EP1644120B1 - Device and method for removing magnetic or magnetisable particles from a liquid - Google Patents

Device and method for removing magnetic or magnetisable particles from a liquid Download PDF

Info

Publication number
EP1644120B1
EP1644120B1 EP04740646A EP04740646A EP1644120B1 EP 1644120 B1 EP1644120 B1 EP 1644120B1 EP 04740646 A EP04740646 A EP 04740646A EP 04740646 A EP04740646 A EP 04740646A EP 1644120 B1 EP1644120 B1 EP 1644120B1
Authority
EP
European Patent Office
Prior art keywords
magnetic field
magnetic
bar
liquid
permanent magnet
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
EP04740646A
Other languages
German (de)
French (fr)
Other versions
EP1644120A1 (en
Inventor
Lothar A Brassard
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
PerkinElmer Chemagen Technologie GmbH
Original Assignee
Chemagen Biopolymer Technologie AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Chemagen Biopolymer Technologie AG filed Critical Chemagen Biopolymer Technologie AG
Publication of EP1644120A1 publication Critical patent/EP1644120A1/en
Application granted granted Critical
Publication of EP1644120B1 publication Critical patent/EP1644120B1/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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
    • B03C1/28—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
    • 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
    • B03C1/04—Magnetic separation acting directly on the substance being separated with the material carriers in the form of trays or with tables
    • B03C1/06—Magnetic separation acting directly on the substance being separated with the material carriers in the form of trays or with tables with magnets moving during operation
    • 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 applications

Definitions

  • the invention relates to devices for separating magnetic or magnetizable particles from liquids by means of a magnetic field generated by one or more permanent magnets.
  • the invention further relates to methods for separating magnetic or magnetizable particles from liquids by means of a magnetic field generated by one or more permanent magnets.
  • the devices and methods are suitable for, for example, applications in biochemistry, molecular genetics, microbiology, medical diagnostics and forensic medicine.
  • the basic principle of the magnetic separation of substances from complex mixtures is based on the fact that magnetic particles (magnetizable or magnetically attractable particles) are specifically functionalized for the intended separation process, ie they are equipped by chemical treatment with specific binding properties 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.
  • Magnetic particles which have specific binding properties for certain substances and are suitable for separating these substances from complex mixtures are described, for example, in US Pat DE 195 28 029 A1 and are commercially available (eg, Chemagen Biopolymer-Technologie AG, DE-52499 Baesweiler).
  • the functionalized magnetic particles are added in a first step ("binding step") to a mixture to be purified, which contains the target substance (s) in a liquid which favors the binding of the target substance molecules to the magnetic particles (binding buffer).
  • binding step a first step
  • these magnetic particles are immobilized by application of magnetic forces or a magnetic field, for example by means of a permanent magnet, at a location of the reaction vessel inner wall ("pellet").
  • pellet the liquid supernatant is separated and discarded, for example by suction or decantation. Since the magnetic particles are immobilized in the aforementioned manner, it is largely prevented that these particles are separated with the supernatant.
  • the immobilized magnetic particles are resuspended again.
  • an elution liquid or an elution buffer is used, which is suitable to dissolve the bond between the target substance (s) and the magnetic particles, so that the target substance molecules of the magnetic particles are released and can be separated 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.
  • DE 296 14 623 U1 discloses a magnetic separator equipped with movable permanent magnets.
  • the magnetic particles containing reaction vessel by mechanical drive means to move relative to a permanently installed permanent magnet.
  • DE 100 63 984 A1 described device having a movable magnetic holder and a movable reaction vessel holder.
  • the magnetic particles are immobilized or collected on the inner wall or at the bottom of a reaction vessel as a "pellet".
  • these devices are not suitable for removing the magnetic particles from a reaction vessel. Therefore, to separate the liquid from the magnetic particles in each case the liquid must be sucked from the individual reaction vessels. This is disadvantageous because it involves a high material consumption (disposable pipette tips). Furthermore, it can not be prevented that individual magnetic particles are sucked with; This results in a high error rate. Further errors can be caused by dripping liquids, which lead to cross contamination.
  • a magnetic separator having a plurality of rotatable rods magnetized by an electromagnetic excitation coil can.
  • the magnetic particles By immersing the rod in the magnetic particles containing liquid and pulling out the rod in the magnetized state, the magnetic particles can be removed from the liquid and optionally transferred to another reaction vessel. There they can be released by switching off the excitation coil back into a liquid, for example in a washing or elution liquid.
  • a disadvantage of this device is that the magnetic field generated by the excitation coil is not sufficiently homogeneous, so that the individual rods - depending on their position within the annular exciter coil - are magnetized differently strong. This disadvantage occurs especially when a large number of rods is needed.
  • the exciter coil has a relatively large amount of space, resulting in constructive restrictions.
  • the known devices are not suitable for the simultaneous treatment of larger numbers of samples, as required for high-throughput applications (eg 364 or 1536 well plates).
  • the invention therefore an object of the invention to provide devices and methods with which the separation of magnetic particles from liquids and the transfer of magnetic particles from a liquid is made possible in another liquid, without causing the aforementioned disadvantages occur.
  • the devices and methods should be suitable for use in high throughput processes.
  • the two legs are made of a soft magnetic magnetic material, for example of soft iron (especially Fe-Ni alloys) or magnetizable steel.
  • Their cross section may be, for example, square, rectangular, circular or oval; The size of the cross-sectional area depends on the desired cross-sectional area of the magnetic field and may be 20 to 100 cm 2 , for example. It is also possible, the legs on a frame or attach housing made of non-magnetizable material.
  • the two legs are generally stacked with the leg bearing the head over that portion of the other leg intended to receive the liquid containers (i.e., the sample cups).
  • the header may be detachably arranged, thereby enabling, for example, the replacement of headers having different numbers or types (length, diameter, fixed or movable) of magnetizable bars.
  • the number of rods depends on the number of samples or fluid containers to be treated simultaneously.
  • Microtiter plates, in particular with 96, 384 or 1536 depressions ("wells") are preferably used as containers, so that corresponding head pieces with, for example, 96, 384 or 1536 magnetizable bars are provided for these cases.
  • sample tubes or reaction vessels having a volume of, for example, 0.015 to 100 ml, which can be treated individually or in groups, in each case in combination with magnetizable bars adapted thereto.
  • the rods are also made of a soft magnetic material, as described above. Their length and diameter depend on the intended application, in particular on the dimensions of the containers and the volumes of liquid, and can be varied accordingly. It is further provided that on the rods in each case a strippable, replaceable sheath is plugged in order to avoid cross-contamination between different liquid samples. This is preferably a special Device provided which allows the automatic discarding of used cases and the provision and installation of new cases.
  • a substantially homogeneous magnetic field is generated between the poles of the legs. This allows the arrangement of a larger number of rods, for example in several rows, with the magnetic field at each of the rods being approximately equal; This is particularly advantageous with regard to high throughput methods.
  • the devices according to the invention have the further advantage that the magnetic particles - when switched on - ansanneln substantially at the top of the rods.
  • the permanent magnets are / are movably arranged relative to the magnetic circuit of the device, so that the magnetic field between the poles can be alternately switched on and off by movement of the magnet (s).
  • the magnet (s) is / are in the magnetic circuit or in this in or out of the magnetic circuit out. That is, the magnetic field between the poles is turned on when the permanent magnet (s) are in a first position, and that the magnetic field between the poles is turned off when the permanent magnet (s) in a second position is / are located. In the said second position, the magnet (s) is / are preferably located outside the magnetic circuit.
  • the magnetic field may preferably be switched on and off in such a way that the magnet (s) are moved within the iron circle (magnetic circuit) (eg by rotation) or that the magnet (s) of outside is moved into the magnetic circuit ("turn on") and then moved back outward (“turn off”).
  • the device can be used to remove magnetic particles using the magnetizable rods of a first liquid and to transfer in a second or more liquid and release there again. Furthermore, this makes it possible to additionally use the rods for other functions, for example as stirring rods.
  • all hard magnetic materials known to the person skilled in the art can be used for producing the permanent magnets, in particular ferrites, Al-Ni-Co alloys and rare earth magnets (preferably NdFeB); Such magnetic materials and magnets are commercially available from various manufacturers.
  • the region of the device in which the movable magnet (s) is / are arranged in the iron circle is at least partially surrounded by a material shielding the magnetic field.
  • a material shielding the magnetic field As a shielding material, a soft magnetic material may be used and / or a person skilled in the art, magnetic fields shielding material such. Tinplate or mumetal.
  • This shielding material is arranged around the movable magnet (s) in such a way that when it is turned off no magnetic forces can act on the sample liquid reservoir located in the air gap of the magnetic circuit.
  • a shield which completely surrounds the region in which the permanent magnet (s) are arranged. In particular, this may be formed a short-circuit ring.
  • the device is preferably arranged so that that portion of the device in which the movable magnet (s) are / are arranged in the iron circle, in the case of a movement of the magnet (s) in the iron or at least partially of the magnetic Field shielding material is surrounded.
  • the two legs of the device are connected to each other at the two poles side by a likewise magnetizable (soft magnetic) material, so that a magnetic circuit or a magnetizing ring is formed, which - with the exception of the air gap between the poles - is completely closed.
  • the movable permanent magnet (s) is / are preferably disposed between the two legs and at the other end (i.e., opposite the poles). If the two legs are interconnected as described, then the permanent magnet (s) is / are preferably mounted in or on the region connecting the two legs. Preferably, the magnet (s) are movably installed in a recess provided in one of the legs or in the part connecting the two legs.
  • the magnet In order to enable movement of the permanent magnet (s) for switching the magnetic field on and off, the magnet, or a group of several magnets, can be arranged to be rotatable or tiltable in a recess provided therefor. By turning or tilting the magnet can be brought into a position in which its poles or its magnetic field in the direction of the magnetic circuit or in the direction of the legs have (switched state, maximum field strength between the poles of the legs), or the magnet can be moved to another position, in the magnetic field emanating from it is substantially perpendicular to the said direction (switched-off state).
  • the magnet (s) may also be rotated or tilted to intermediate positions to cause the field strength between the poles of the legs to be less than the maximum value.
  • the movement can be done either directly or indirectly by hand or by means of one or more electric motors, or by pneumatic or hydraulic means; also combinations of the mentioned means are possible.
  • the drive means may further, known in the art means such.
  • B. linkage or gear include.
  • the extent of movement of the / the permanent magnet is predictable.
  • the magnetic field strength depending on the particular application, set to a specific value. This can be achieved in particular by predetermining and adhering to a specific tilting or rotation angle or a specific displacement distance.
  • the head carrying the magnetizable rods is movably mounted.
  • the head piece may be movable in the horizontal plane.
  • drive means eg., Electric, pneumatic, hydraulic
  • the said magnetizable rod (s) are rotatably mounted (about their longitudinal axis) on the respective header and can be rotated during the treatment of a liquid containing magnetic particles to effect mixing to accelerate the detachment of the particles from the rods.
  • the rotation is preferably carried out by electromotive means.
  • liquids containing such particles are introduced into the air gap of the device, below the magnetizable rods, wherein containers of the type mentioned above can be used.
  • at least one holding device is provided which can be positioned below the bars, so that the bars are aligned with the openings of the container.
  • This holding device can be configured for example in the form of a holding plate.
  • the holding device is movable in a substantially horizontal plane in one or more directions; Alternatively or additionally, the holding device may be movable in the vertical direction.
  • the movement is preferably carried out by electromotive drive or by pneumatic or hydraulic means, or by combinations of these means.
  • the holding devices can also be designed in such a way that they are suitable for carrying out shaking movements.
  • the design measures required for this purpose are generally known to the person skilled in the art. It is further provided that both the head piece and the holding device can be moved and used to carry out shaking movements. In this way, a particularly effective mixing of the sample liquid is possible if the rods are immersed therein.
  • a control or regulating device is provided, by means of which the vertical movement of the holding device (s) is adjustable or controllable in such a way that, upon an upward movement, the rods (7) are immersed in the liquid-filled containers (10). is effected.
  • the said holding device may be part of a program-controlled laboratory robot system, wherein it is preferably arranged so that a plurality of individual said containers or groups of such containers, in particular microtiter plates, alternately placed in a position below said rods and then after a predetermined time interval is again brought into a position which is outside the area located below the bars. In this way, a high sample throughput is possible.
  • the devices of the invention may be advantageously combined with other devices for the automated treatment of sample material. Furthermore, two or more of the devices according to the invention can be arranged side by side and combined.
  • the particles into the liquid after step d may be advantageous to release the particles into the liquid after step d by switching off the magnetic field, to mix them, and then by switching them on of the magnetic field to collect again at the bars.
  • the mixing can be effected for example by rotation of the rods or by shaking the holding device and / or the head part.
  • the said methods can be carried out in a particularly simple and rapid manner.
  • the devices and methods of the invention are particularly suitable for the application areas mentioned above, in particular for high-throughput methods.
  • Fig. 1A and 1B show an embodiment of a device according to the invention in a side view.
  • the device (1) has two magnetizable legs (2, 3) of a magnetic circuit, the legs being connected to one another in the region (6). At the opposite end of the legs are the two poles (4,5) with an intermediate air gap (12).
  • the pole (4) of the upper leg (2) carries a head piece (8) with magnetizable bars (7) attached thereto.
  • a holding device (11) which is connected to the pole (5) of the other leg (3) or at least in contact therewith.
  • a sample container (9) is arranged with a plurality of recesses (10) for receiving liquid samples, for example removably fixed on the holding device (11).
  • a rod or cuboid permanent magnet (15) is rotatably arranged.
  • a short-circuit ring (20) is arranged (this is shown broken through in the region of the rotatable magnet).
  • Fig. 1A shows the device in the off state; the position of the permanent magnet (15) is substantially perpendicular to the direction of the magnetic circuit; The magnetic field of the permanent magnet is passed into the short-circuit ring (20).
  • Fig. 1B shows the same device in the on state.
  • the position of the permanent magnet (15) points substantially in the direction of the magnetic circuit.
  • between the poles (4,5) and thus also at the ends of Rods (7) generates a magnetic field that can be used to attract magnetic particles.
  • Fig. 1C shows a sectional view of the in the Fig. 1A / B device, in which by the dashed line a ( Fig. 1B ) indicated level.
  • the arrows (17) show schematically the direction of the magnetic field in the on state.
  • Fig. 1D and 1E show, also in a schematic side view, a further embodiment of the inventive devices, wherein the magnet used has a flat cuboid shape and the poles are located on the two large side surfaces.
  • Fig. 1D is the switched-on state (the magnetic field runs in the direction of the iron circle)
  • Fig. 1E the switched-off state is shown.
  • the position of the short-circuit ring (20) is merely indicated.
  • the others, in Fig. 1A, 1B The elements shown have been omitted for simplicity of illustration.
  • Fig. 2 and Fig. 3 show, also in side view, further construction variants of the devices according to the invention.
  • Fig. 4 shows the device (1) of Fig. 1A / B in plan view; thereby, the annular shape of the short-circuit ring (20) can be seen.
  • the short-circuit ring (20) is designed so that it does not fully abut the magnetic circuit, but a cavity (22) is present. This facilitates access to the rotatable magnet (15).
  • the shorting ring (20) may be composed of two halves (20a, 20b) or multiple parts as indicated by the dashed line 21 to facilitate assembly and disassembly.
  • Fig. 5 shows an embodiment of the device according to the invention (also in side view), in which in the recess (16) a displaceable (double arrow) permanent magnet (15) is provided.
  • Fig. 5 shows the on state in which the permanent magnet causes between the poles (4,5) creates a magnetic field. To turn off the magnet is moved out of the magnetic circuit of the device (1) to the outside.
  • Fig. 6 shows a modification of the in Fig. 1A / B device shown, wherein the two legs (3,4) are of different lengths.
  • Figs. 7A to 7D show various views of a particularly preferred embodiment in which a magnet (15) on a pad (40) is arranged, which is rotatable in a horizontal plane about the axis Y.
  • the magnet (15) can be brought into the magnetic circuit (iron circle) by rotation of the support (40) (switched-on state, Figs. 7C, 7D ) or moved out of the area of the magnetic circuit ( Fig. 7A, 7B ).
  • the pad (40) is preferably in the form of a turntable or as a rotatable arm which is moved by means of known drive devices.
  • two or more magnets may be mounted on the base.
  • Figs. 7A, 7C show a sectional view in the surface of the axis of rotation Y; the Fig. 7B, 7D each show the same device in plan view.
  • Fig. 8 shows an embodiment of the device (1) according to the invention in side view; In this case, the two legs (2,3) are not connected to each other by a common area (6).
  • the rotatable magnet (15) is arranged between the two legs (2, 3), on the side opposite the air gap.
  • the short-circuit ring (20) is shown in sectional view.
  • Fig. 9 shows the front view of the upper leg (4) of a device according to the invention with the head piece (8) and attached rods (7).
  • a holding device (8) is positioned, on which several containers (10) are arranged in rows.
  • the holding device can be moved in the horizontal plane in different directions as well as up and down (arrows).
  • Fig. 10 shows in longitudinal section examples of different forms of magnetizable rods (7).
  • the particles attracted under the influence of the magnetic field are designated by (30).
  • Fig. 9d shows a rod provided with a replaceable sleeve (25).

Landscapes

  • Physical Or Chemical Processes And Apparatus (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Soft Magnetic Materials (AREA)
  • Magnetic Treatment Devices (AREA)

Abstract

A device is provided to separate magnetic or magnetizable particles from a liquid by using a magnetic field. The device includes two limbs made of a soft-magnetic material. An air gap is provided between be two poles of the limbs. The air gap can receive one or more liquid containers. A head piece is arranged in a fixed or detachable manner on one of the two poles. One or more magnetizable bars are disposed in a fixed or movable manner on the head piece, in the vertical direction. One or more permanent magnets are arranged in a movable manner on at least one point of the device, such that a magnetic field can be produced between the two poles and the magnetic field can be activated or deactivated by moving the magnet(s). The region of the device where the movable magnet(s) are arranged is at least partially surrounded by a material that screens the magnetic field.

Description

Die Erfindung betrifft Vorrichtungen zum Abtrennen von magnetischen oder magnetisierbaren Partikeln aus Flüssigkeiten mittels eines Magnetfeldes, das durch einen oder mehrere Permanentmagneten erzeugt wird.
Die Erfindung betrifft ferner Verfahren zum Abtrennen von magnetischen oder magnetisierbaren Partikeln aus Flüssigkeiten mittels eines Magnetfeldes, das durch einen oder mehrere Permanentmagneten erzeugt wird. Die Vorrichtungen und Verfahren sind beispielsweise für Anwendungszwecke in der Biochemie, Molekulargenetik, Mikrobiologie, medizinischen Diagnostik und forensischen Medizin geeignet.The invention relates to devices for separating magnetic or magnetizable particles from liquids by means of a magnetic field generated by one or more permanent magnets.
The invention further relates to methods for separating magnetic or magnetizable particles from liquids by means of a magnetic field generated by one or more permanent magnets. The devices and methods are suitable for, for example, applications in biochemistry, molecular genetics, microbiology, medical diagnostics and forensic medicine.

Verfahren, die auf der magnetischen Abtrennung unter Verwendung von spezifisch bindenden, magnetisch anziehbaren Partikeln beruhen, erlangen im Bereich der Probenvorbereitung für diagnostische oder analytische Untersuchungen zunehmende Bedeutung. Dies gilt insbesondere für automatisierte Verfahren, da auf diese weise eine große Anzahl von Proben innerhalb kurzer Zeit analysiert werden können und auf arbeitsaufwendige Zentrifugationsschritte verzichtet werden kann. Dadurch werden die Voraussetzungen für ein effizientes Screening mit einem hohen Proben-Durchsatz geschaffen. Dies ist beispielsweise für Anwendungen bei molekulargenetischen Studien oder auf dem Gebiet der medizinischen Diagnostik von enormer Bedeutung, da eine rein manuelle Handhabung von sehr großen Probenzahlen praktisch nicht zu bewältigen ist. Weitere wichtige Anwendungsgebiete betreffen pharmazeutische Screening-Methoden zur Identifizierung potentieller Arzneimittel-Wirkstoffe.Methods based on magnetic separation using specific binding, magnetically attractable particles are becoming increasingly important in the field of sample preparation for diagnostic or analytical studies. This is especially true for automated procedures, since in this way a large number of samples can be analyzed within a short time and can be dispensed with laborious Zentrifugationsschritte. This will create the conditions for efficient screening with high sample throughput. This is of great importance, for example, for applications in molecular genetic studies or in the field of medical diagnostics, since a purely manual handling of very large numbers of samples is practically unmanageable. Further important fields of application concern pharmaceutical screening methods for the identification of potential active pharmaceutical ingredients.

Das Grundprinzip der magnetischen Abtrennung von Substanzen aus komplexen Gemischen beruht darauf, daß magnetische Partikel (magnetisierbare bzw. magnetisch anziehbare Partikel) in spezifischer Weise für den beabsichtigten Separationsprozeß funktionalisiert werden, d. h. sie werden durch chemische Behandlung mit spezifischen Bindungseigenschaften für die abzutrennenden Zielsubstanzen ausgestattet. Die Größe solcher Magnetpartikel liegt im allgemeinen im Bereich von ca. 0,05 bis 500 µm.
Magnetpartikel, die spezifische Bindungseigenschaften für bestimmte Substanzen aufweisen und sich zur Abtrennung dieser Substanzen aus komplexen Gemischen eignen, sind beispielsweise in DE 195 28 029 A1 beschrieben worden und sind kommerziell erhältlich (z. B. chemagen Biopolymer-Technologie AG, DE-52499 Baesweiler).The basic principle of the magnetic separation of substances from complex mixtures is based on the fact that magnetic particles (magnetizable or magnetically attractable particles) are specifically functionalized for the intended separation process, ie they are equipped by chemical treatment with specific binding properties 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.
Magnetic particles which have specific binding properties for certain substances and are suitable for separating these substances from complex mixtures are described, for example, in US Pat DE 195 28 029 A1 and are commercially available (eg, Chemagen Biopolymer-Technologie AG, DE-52499 Baesweiler).

Bei bekannten Trennverfahren werden die funktionalisierten Magnetpartikel in einem ersten Schritt ("Bindungs-Schritt") zu einem aufzureinigenden Gemisch hinzugegeben, das die Zielsubstanz(en) in einer Flüssigkeit enthält, welche die Bindung der Zielsubstanz-Moleküle an die Magnetpartikel begünstigt (Bindungspuffer). Dadurch kommt es zu einer selektiven Bindung der im Gemisch vorhandenen Zielsubstanz(en) an die Magnetpartikel. Anschließend werden diese Magnetpartikel durch Anwendung magnetischer Kräfte bzw. eines Magnetfeldes, beispielsweise mittels eines Permanentmagneten, an einer Stelle der Reaktionsgefäß-Innenwand immobilisiert ("Pellet"). Nachfolgend wird der flüssige Überstand abgetrennt und verworfen, beispielsweise durch Absaugen oder Dekantieren. Da die Magnetpartikel auf die genannte Weise immobilisiert sind, wird weitgehend verhindert, daß diese Partikel mit dem Überstand abgetrennt werden.In known separation processes, the functionalized magnetic particles are added in a first step ("binding step") to a mixture to be purified, which contains the target substance (s) in a liquid which favors the binding of the target substance molecules to the magnetic particles (binding buffer). This results in a selective binding of the target substance (s) present in the mixture to the magnetic particles. Subsequently, these magnetic particles are immobilized by application of magnetic forces or a magnetic field, for example by means of a permanent magnet, at a location of the reaction vessel inner wall ("pellet"). Subsequently, the liquid supernatant is separated and discarded, for example by suction or decantation. Since the magnetic particles are immobilized in the aforementioned manner, it is largely prevented that these particles are separated with the supernatant.

Anschließend werden die immobilisierten Magnetpartikel erneut resuspendiert. Dabei wird eine Elutionsflüssigkeit bzw. ein Elutionspuffer verwendet, der geeignet ist, die Bindung zwischen der/den Zielsubstanz(en) und den Magnetpartikeln zu lösen, so daß die Zielsubstanz-Moleküle von den Magnetpartikeln freigesetzt werden und mit der Elutionsflüssigkeit abgetrennt werden können, während die Magnetpartikel durch Einwirkung eines Magnetfeldes immobilisiert werden. Vor dem Elutionsschritt können ein oder mehrere Waschschritte durchgeführt werden.Subsequently, the immobilized magnetic particles are resuspended again. In this case, an elution liquid or an elution buffer is used, which is suitable to dissolve the bond between the target substance (s) and the magnetic particles, so that the target substance molecules of the magnetic particles are released and can be separated with the elution liquid, while the magnetic particles are immobilized by the action of a magnetic field. Before the elution step, one or more washing steps can be carried out.

Für die Durchführung von Trennverfahren mittels magnetischer Partikel sind verschiedenartige Vorrichtungen beschrieben worden. DE 296 14 623 U1 offenbart einen Magnetseparator, der mit beweglichen Dauermagneten ausgestattet ist. Alternativ wird vorgeschlagen, daß die Magnetpartikel enthaltende Reaktionsgefäß durch mechanische Antriebseinrichtungen relativ zu einem fest installierten Dauermagneten zu bewegen. Nach einem ähnlichen Prinzip arbeitet auch die in DE 100 63 984 A1 beschriebene Vorrichtung, die eine bewegliche Magnethalterung und eine bewegliche Reaktionsgefäßhalterung aufweist.Various devices have been described for performing magnetic particle separation processes. DE 296 14 623 U1 discloses a magnetic separator equipped with movable permanent magnets. Alternatively, it is proposed that the magnetic particles containing reaction vessel by mechanical drive means to move relative to a permanently installed permanent magnet. After a similar principle also works in DE 100 63 984 A1 described device having a movable magnetic holder and a movable reaction vessel holder.

Mit den vorstehend genannten Vorrichtungen läßt sich erreichen, daß die Magnetpartikel an der Innenwand oder am Boden eines Reaktionsgefäßes als "Pellet" immobilisiert oder gesammelt werden. Diese Vorrichtungen sind jedoch nicht dafür geeignet, um die Magnetpartikel aus einem Reaktionsgefäß zu entfernen. Deshalb muß zur Abtrennung der Flüssigkeit von den Magnetpartikeln jeweils die Flüssigkeit aus den einzelnen Reaktionsgefäßen abgesaugt werden. Dies ist nachteilig, weil es mit einem hohen Materialverbrauch einhergeht (Einmal-Pipettenspitzen). Ferner läßt sich nicht verhindern, daß einzelne Magnetpartikel mit abgesaugt werden; hieraus resultiert eine hohe Fehlerquote. Weitere Fehler können durch herabtropfende Flüssigkeiten verursacht werden, die zu Kreuzkontaminationen führen.With the above-mentioned devices can be achieved that the magnetic particles are immobilized or collected on the inner wall or at the bottom of a reaction vessel as a "pellet". However, these devices are not suitable for removing the magnetic particles from a reaction vessel. Therefore, to separate the liquid from the magnetic particles in each case the liquid must be sucked from the individual reaction vessels. This is disadvantageous because it involves a high material consumption (disposable pipette tips). Furthermore, it can not be prevented that individual magnetic particles are sucked with; This results in a high error rate. Further errors can be caused by dripping liquids, which lead to cross contamination.

In DE 100 57 396 C1 wird ein Magnetseparator vorgeschlagen, der eine Vielzahl von drehbaren Stäben aufweist, die durch eine elektromagnetische Erregerspule magnetisiert werden können. Durch Eintauchen des Stabes in die Magnetpartikel enthaltende Flüssigkeit und Herausziehen des Stabes im magnetisierten Zustand können die Magnetpartikel aus der Flüssigkeit entfernt werden und gegebenenfalls in ein weiteres Reaktionsgefäß überführt werden. Dort können sie durch Abschalten der Erregerspule wieder in eine Flüssigkeit freigesetzt werden, beispielsweise in eine Wasch- oder Elutionsflüssigkeit.
Nachteilig ist bei dieser Vorrichtung, daß das von der Erregerspule erzeugte magnetische Feld nicht ausreichend homogen ist, so daß die einzelnen Stäbe - abhängig von ihrer Position innerhalb der ringförmigen Erregerspule - unterschiedlich stark magnetisiert werden. Dieser Nachteil tritt insbesondere dann hervor, wenn eine große Anzahl von Stäben benötigt wird. Außerdem hat die Erregerspule einen relativ hohen Platzbedarf, woraus sich konstruktive Einschränkungen ergeben.In DE 100 57 396 C1 there is proposed a magnetic separator having a plurality of rotatable rods magnetized by an electromagnetic excitation coil can. By immersing the rod in the magnetic particles containing liquid and pulling out the rod in the magnetized state, the magnetic particles can be removed from the liquid and optionally transferred to another reaction vessel. There they can be released by switching off the excitation coil back into a liquid, for example in a washing or elution liquid.
A disadvantage of this device is that the magnetic field generated by the excitation coil is not sufficiently homogeneous, so that the individual rods - depending on their position within the annular exciter coil - are magnetized differently strong. This disadvantage occurs especially when a large number of rods is needed. In addition, the exciter coil has a relatively large amount of space, resulting in constructive restrictions.

Die bekannten Vorrichtungen sind vor allem nicht für die gleichzeitige Behandlung von größeren Anzahlen von Proben geeignet, wie dies für Hochdurchsatz-Anwendungen erforderlich ist (z. B. Mikrotiterplatten mit 364 oder 1536 wells).Above all, the known devices are not suitable for the simultaneous treatment of larger numbers of samples, as required for high-throughput applications (eg 364 or 1536 well plates).

Der Erfindung lag deshalb die Aufgabe zugrunde, Vorrichtungen und Verfahren bereitzustellen, mit denen die Abtrennung von Magnetpartikeln aus Flüssigkeiten und das Überführen von Magnetpartikeln aus einer Flüssigkeit in eine andere Flüssigkeit ermöglicht wird, ohne daß dabei die vorstehend genannten Nachteile auftreten. Insbesondere sollen die Vorrichtungen und Verfahren für die Anwendung bei Hochdurchsatzverfahren geeignet sein.The invention therefore an object of the invention to provide devices and methods with which the separation of magnetic particles from liquids and the transfer of magnetic particles from a liquid is made possible in another liquid, without causing the aforementioned disadvantages occur. In particular, the devices and methods should be suitable for use in high throughput processes.

Diese und weitere Aufgaben werden überraschenderweise durch eine Vorrichtung gemäß Hauptanspruch sowie durch Verfahren gemäß Anspruch 24-27 gelöst, sowie durch die in den abhängigen Ansprüchen beschriebenen Ausführungsformen.These and other objects are surprisingly achieved by a device according to the main claim and by methods according to claims 24-27, and by the embodiments described in the dependent claims.

Demnach zeichnen sich die erfindungsgemäßen Vorrichtungen zum Abtrennen von magnetischen oder magnetisierbaren Partikeln aus einer Flüssigkeit durch folgende Merkmale aus:

  • die Vorrichtungen weisen zwei Schenkel aus einem weichmagnetischen werkstoff auf; diese bilden - gegebenenfalls zusammen mit weiteren Komponenten - einen magnetischen Kreis;
  • zwischen den beiden Polen der Schenkel ist ein Luftspalt vorhanden, der zur Aufnahme eines Behälters oder einer Vielzahl von Behältern geeignet ist;
  • an dem einen der beiden Pole ist ein Kopfstück fest oder lösbar angeordnet; an dem Kopfstück ist/sind in vertikaler Richtung ein magnetisierbarer Stab oder eine Vielzahl derartiger Stäbe fest oder beweglich angebracht;
  • an mindestens einer Stelle der Vorrichtung ist ein Permanentmagnet, oder eine Gruppe von mindestens zwei Permanentmagneten, beweglich angeordnet; die Anordnung ist dergestalt, daß ein Magnetfeld zwischen den beiden Polen erzeugbar ist und das Magnetfeld durch Bewegung des/der Magneten eingeschaltet oder ausgeschaltet werden kann;
  • derjenige Bereich der Vorrichtung, in welchem der/die bewegliche(n) Magnet(e) im magnetischen Kreis (Eisenkreis) angeordnet ist/sind, ist zumindest teilweise von einem das magnetische Feld abschirmenden Material umgeben.
Accordingly, the devices according to the invention for separating magnetic or magnetizable particles from a liquid are characterized by the following features:
  • the devices have two legs of a soft magnetic material; these form - optionally together with other components - a magnetic circuit;
  • between the two poles of the legs an air gap is provided, which is suitable for receiving a container or a plurality of containers;
  • on the one of the two poles, a head piece is arranged fixed or detachable; a magnetizable rod or a plurality of such rods is fixedly or movably mounted on the head piece in the vertical direction;
  • at least one location of the device, a permanent magnet, or a group of at least two permanent magnets, is movably arranged; the arrangement is such that a magnetic field can be generated between the two poles and the magnetic field can be switched on or off by movement of the magnet (s);
  • that portion of the device in which the movable magnet (s) is / are located in the magnetic circuit (iron circle) is at least partially surrounded by a material shielding the magnetic field.

Die beiden Schenkel sind aus einem weichmagnetischen Magnetwerkstoff, beispielsweise aus Weicheisen (insbesondere Fe-Ni-Legierungen) oder magnetisierbarem Stahl hergestellt. Ihr Querschnitt kann beispielsweise quadratisch, rechteckig, kreisrund oder oval sein; die Größe der Querschnittsfläche hängt von der gewünschten Querschnittsfläche des Magnetfeldes ab und kann beispielsweise 20 bis 100 cm2 betragen. Ferner ist es möglich, die Schenkel an einem Rahmen oder Gehäuse aus nichtmagnetisierbarem Material zu befestigen.The two legs are made of a soft magnetic magnetic material, for example of soft iron (especially Fe-Ni alloys) or magnetizable steel. Their cross section may be, for example, square, rectangular, circular or oval; The size of the cross-sectional area depends on the desired cross-sectional area of the magnetic field and may be 20 to 100 cm 2 , for example. It is also possible, the legs on a frame or attach housing made of non-magnetizable material.

Die beiden Schenkel sind im allgemeinen übereinander angeordnet, wobei sich der das Kopfstück tragende Schenkel sich über demjenigen Bereich des anderen Schenkels befindet, der für die Aufnahme der Flüssigkeitsbehälter (d. h. der Probengefäße) bestimmt ist.The two legs are generally stacked with the leg bearing the head over that portion of the other leg intended to receive the liquid containers (i.e., the sample cups).

Das Kopfstück kann lösbar angeordnet sein, wodurch beispielsweise das Auswechseln von Kopfstücken mit unterschiedlichen Anzahlen oder Arten (Länge, Durchmesser; fest oder beweglich) von magnetisierbaren Stäben ermöglicht wird. Die Anzahl der Stäbe hängt von der Anzahl der Proben bzw. Flüssigkeitsbehälter ab, die gleichzeitig behandelt werden sollen. Bevorzugt werden als Behälter Mikrotiterplatten, insbesondere mit 96, 384 oder 1536 Vertiefungen ("wells") verwendet, so daß für diese Fälle entsprechende Kopfstücke mit beispielsweise 96, 384 oder 1536 magnetisierbaren Stäben vorgesehen sind. Weiterhin kommen als Behälter auch Probenröhrchen oder Reaktionsgefäße mit einem Volumen von beispielsweise 0,015 bis 100 ml in Betracht, die einzeln oder in Gruppen behandelt werden können, jeweils in Kombination mit daran angepaßten magnetisierbaren Stäben.The header may be detachably arranged, thereby enabling, for example, the replacement of headers having different numbers or types (length, diameter, fixed or movable) of magnetizable bars. The number of rods depends on the number of samples or fluid containers to be treated simultaneously. Microtiter plates, in particular with 96, 384 or 1536 depressions ("wells") are preferably used as containers, so that corresponding head pieces with, for example, 96, 384 or 1536 magnetizable bars are provided for these cases. Also suitable as containers are sample tubes or reaction vessels having a volume of, for example, 0.015 to 100 ml, which can be treated individually or in groups, in each case in combination with magnetizable bars adapted thereto.

Die Stäbe, wahlweise auch das Kopfstück, sind ebenfalls aus einem weichmagnetischen Material gefertigt, wie oben beschrieben. Ihre Länge und ihr Durchmesser richten sich nach dem beabsichtigten Anwendungszweck, insbesondere nach den Dimensionen der Behälter und den Flüssigkeitsvolumina, und können entsprechend variiert werden.
Ferner ist vorgesehen, daß über die Stäbe jeweils eine abstreifbare, auswechselbare Umhüllung aufgesteckt wird, um Kreuzkontaminationen zwischen verschiedenen Flüssigkeitsproben zu vermeiden. Hierfür wird vorzugsweise eine besondere Vorrichtung vorgesehen, welche das automatische Abwerfen der gebrauchten Hüllen und die Bereitstellung und das Anbringen neuer Hüllen ermöglicht.The rods, optionally also the head piece, are also made of a soft magnetic material, as described above. Their length and diameter depend on the intended application, in particular on the dimensions of the containers and the volumes of liquid, and can be varied accordingly.
It is further provided that on the rods in each case a strippable, replaceable sheath is plugged in order to avoid cross-contamination between different liquid samples. This is preferably a special Device provided which allows the automatic discarding of used cases and the provision and installation of new cases.

Durch die Anordnung eines Permanentmagneten, der auch aus mehreren einzelnen Magneten zusammengesetzt sein kann, wird zwischen den Polen der Schenkel ein im wesentlichen homogenes Magnetfeld erzeugt. Dadurch wird die Anordnung einer größeren Anzahl von Stäben, beispielsweise in mehreren Reihen, ermöglicht, wobei das magnetische Feld an jedem der Stäbe annähernd gleich groß ist; dies ist dies insbesondere im Hinblick auf Hochdurchsatzverfahren von Vorteil. Die erfindungsgemäßen Vorrichtungen haben des weiteren den Vorteil, daß sich die Magnetpartikel - im eingeschalteten Zustand - im wesentlichen an der Spitze der Stäbe ansamaneln.The arrangement of a permanent magnet, which may also be composed of a plurality of individual magnets, a substantially homogeneous magnetic field is generated between the poles of the legs. This allows the arrangement of a larger number of rods, for example in several rows, with the magnetic field at each of the rods being approximately equal; This is particularly advantageous with regard to high throughput methods. The devices according to the invention have the further advantage that the magnetic particles - when switched on - ansanneln substantially at the top of the rods.

Erfindungsgemäß ist/sind die Permanentmagneten relativ zum magnetischen Kreis der Vorrichtung beweglich angeordnet, so daß das Magnetfeld zwischen den Polen durch Bewegung des/der Magneten abwechselnd ein- bzw. ausgeschaltet werden kann. Der/die Magnet(e) wird/werden dazu im Magnetkreis oder in diesen hinein bzw. wieder aus dem Magnetkreis heraus bewegt.
Das heißt, daß das Magnetfeld zwischen den Polen eingeschaltet ist, wenn sich der/die Permanentmagnet(e) in einer ersten Position befindet/befinden, und daß das Magnetfeld zwischen den Polen abgeschaltet ist, wenn sich der/die Permanentmagnet(e) in einer zweiten Position befindet/ befinden. In der genannten zweiten Position befindet/befinden sich der/die Magnet(e) vorzugsweise außerhalb des magnetischen Kreises.According to the invention, the permanent magnets are / are movably arranged relative to the magnetic circuit of the device, so that the magnetic field between the poles can be alternately switched on and off by movement of the magnet (s). The magnet (s) is / are in the magnetic circuit or in this in or out of the magnetic circuit out.
That is, the magnetic field between the poles is turned on when the permanent magnet (s) are in a first position, and that the magnetic field between the poles is turned off when the permanent magnet (s) in a second position is / are located. In the said second position, the magnet (s) is / are preferably located outside the magnetic circuit.

Das Magnetfeld kann vorzugsweise in der Weise ein- bzw. ausgeschaltet werden, daß der/die Magnet(e) innerhalb des Eisenkreises (magnetischen Kreises) bewegt werden (z. B. durch Rotation), oder daß der/die Magnet(e) von außen her in den magnetischen Kreis hineinbewegt wird/werden ("Einschalten") und danach wieder nach außen bewegt wird/werden ("Ausschalten").The magnetic field may preferably be switched on and off in such a way that the magnet (s) are moved within the iron circle (magnetic circuit) (eg by rotation) or that the magnet (s) of outside is moved into the magnetic circuit ("turn on") and then moved back outward ("turn off").

Durch die Möglichkeit, das Magnetfeld ein- bzw. auszuschalten, kann die Vorrichtung dazu verwendet werden, magnetische Partikel mit Hilfe der magnetisierbaren Stäbe aus einer ersten Flüssigkeit zu entfernen und in eine zweite oder weitere Flüssigkeit zu überführen und dort wieder freizusetzen. Ferner wird es dadurch ermöglicht, die Stäbe zusätzlich für andere Funktionen zu nutzen, beispielsweise als Rührstäbe.The possibility of switching the magnetic field on and off, the device can be used to remove magnetic particles using the magnetizable rods of a first liquid and to transfer in a second or more liquid and release there again. Furthermore, this makes it possible to additionally use the rods for other functions, for example as stirring rods.

Zur Herstellung der Permanentmagnete können grundsätzlich alle dem Fachmann bekannten hartmagnetischen Materialien verwendet werden, insbesondere Ferrite, Al-Ni-Co-Legierungen und Seltenerd-Magnete (vorzugsweise NdFeB); derartige Magnetwerkstoffe und Magnete sind von verschiedenen Herstellern kommerziell erhältlich.In principle, all hard magnetic materials known to the person skilled in the art can be used for producing the permanent magnets, in particular ferrites, Al-Ni-Co alloys and rare earth magnets (preferably NdFeB); Such magnetic materials and magnets are commercially available from various manufacturers.

Derjenige Bereich der Vorrichtung, in welchem der/die beweglichen Magnet(e) im Eisenkreis angeordnet ist/sind, ist zumindest teilweise von einem das magnetische Feld abschirmenden Material umgeben.
Als abschirmendes Material kann ein weichmagnetisches Material verwendet werden oder/und ein dem Fachmann bekanntes, magnetische Felder abschirmendes Material, wie z. B. Weißblech oder Mumetall. Dieses abschirmende Material wird in der Weise um den/die beweglichen Magneten herum angeordnet, daß im ausgeschalteten Zustand keine magnetischen Kräfte auf die im Luftspalt des Magnetkreises befindlichen Probenflüssigkeitsbehälter wirken können.
Besonders bevorzugt ist eine Abschirmung, die den Bereich, in dem der/die Permanentmagnet(e) angeordnet sind, vollständig umgibt. Insbesondere kann hierfür ein Kurzschlußring ausgebildet sein.The region of the device in which the movable magnet (s) is / are arranged in the iron circle is at least partially surrounded by a material shielding the magnetic field.
As a shielding material, a soft magnetic material may be used and / or a person skilled in the art, magnetic fields shielding material such. Tinplate or mumetal. This shielding material is arranged around the movable magnet (s) in such a way that when it is turned off no magnetic forces can act on the sample liquid reservoir located in the air gap of the magnetic circuit.
Particularly preferred is a shield which completely surrounds the region in which the permanent magnet (s) are arranged. In particular, this may be formed a short-circuit ring.

Die Vorrichtung ist vorzugsweise so eingerichtet, daß derjenige Bereich der Vorrichtung, in welchem der/die beweglichen Magnet(e) im Eisenkreis angeordnet ist/sind, im Falle einer Bewegung des/der Magneten im Eisenkreis oder in diesen hinein zumindest teilweise von einem das magnetische Feld abschirmenden Material umgeben ist.The device is preferably arranged so that that portion of the device in which the movable magnet (s) are / are arranged in the iron circle, in the case of a movement of the magnet (s) in the iron or at least partially of the magnetic Field shielding material is surrounded.

Gemäß einer besonders bevorzugten Ausführungsform sind die beiden Schenkel der Vorrichtung an der den beiden Polen gegenüberliegenden Seite durch ein ebenfalls magnetisierbares (weichmagnetisches) Material miteinander verbunden, so daß ein magnetischer Kreis oder ein Magnetisierungsring gebildet wird, der - mit Ausnahme des Luftspaltes zwischen den Polen - vollständig geschlossen ist.According to a particularly preferred embodiment, the two legs of the device are connected to each other at the two poles side by a likewise magnetizable (soft magnetic) material, so that a magnetic circuit or a magnetizing ring is formed, which - with the exception of the air gap between the poles - is completely closed.

Der/die bewegliche(n) Permanentmagnet(e) ist/sind vorzugsweise zwischen den beiden Schenkeln und an deren anderem Ende (d. h. den Polen gegenüberliegend) angeordnet. Falls die beiden Schenkel, wie beschrieben, miteinander verbundnen sind, dann wird/werden der/die Permanentmagnet(e) vorzugsweise in oder an dem die beiden Schenkel verbindenden Bereich angebracht. Bevorzugt ist/sind der/die Magnet(e) in einer dafür vorgesehenen Aussparung in einem der Schenkel oder in dem die beiden Schenkel verbindenden Teilstück beweglich eingebaut.The movable permanent magnet (s) is / are preferably disposed between the two legs and at the other end (i.e., opposite the poles). If the two legs are interconnected as described, then the permanent magnet (s) is / are preferably mounted in or on the region connecting the two legs. Preferably, the magnet (s) are movably installed in a recess provided in one of the legs or in the part connecting the two legs.

Um eine Bewegung des/der Permanentmagneten zum Ein- und Ausschalten des Magnetfeldes zu ermöglichen, kann der Magnet, oder eine Gruppe von mehreren Magneten, drehbar oder kippbar in einer dafür vorgesehenen Aussparung angeordnet werden. Durch Drehen oder Kippen kann der Magnet in eine Position gebracht werden, in der seine Pole bzw. sein Magnetfeld in Richtung des magnetischen Kreises bzw. in Richtung auf die Schenkel weisen (eingeschalteter Zustand, maximale Feldstärke zwischen den Polen der Schenkel), oder der Magnet kann in eine andere Position gebracht werden, in der das von ihm ausgehende Magnetfeld im wesentlichen senkrecht zu der genannten Richtung steht (ausgeschalteter Zustand). Der Magnet/die Magnete kann/können auch in dazwischenliegende Positionen gedreht oder gekippt werden, um zu erreichen, daß die Feldstärke zwischen den Polen der Schenkel einen geringeren als den maximalen Wert hat.In order to enable movement of the permanent magnet (s) for switching the magnetic field on and off, the magnet, or a group of several magnets, can be arranged to be rotatable or tiltable in a recess provided therefor. By turning or tilting the magnet can be brought into a position in which its poles or its magnetic field in the direction of the magnetic circuit or in the direction of the legs have (switched state, maximum field strength between the poles of the legs), or the magnet can be moved to another position, in the magnetic field emanating from it is substantially perpendicular to the said direction (switched-off state). The magnet (s) may also be rotated or tilted to intermediate positions to cause the field strength between the poles of the legs to be less than the maximum value.

Alternativ ist es auch möglich, den/die Magnet(en) verschiebbar anzubringen, so daß der/die Magnet(e) durch Verschieben in den Magnetkreis hineingebracht werden können (Einschalten) oder wieder aus diesem entfernt werden können (Ausschalten).Alternatively, it is also possible to slidably mount the magnet (s) so that the magnet (s) can be moved into the magnetic circuit by shifting it (turning it on) or removing it again (turning it off).

Die Bewegung (z. B. Kippen, Drehen, Verschieben) kann entweder direkt oder indirekt von Hand oder mittels einem oder mehrerer Elektromotoren erfolgen, oder durch pneumatische oder hydraulische Mittel; auch Kombinationen der genannten Mittel sind möglich. Die Antriebseinrichtungen können weitere, dem Fachmann bekannte Mittel, wie z. B. Gestänge oder Getriebe umfassen.The movement (eg tilting, turning, shifting) can be done either directly or indirectly by hand or by means of one or more electric motors, or by pneumatic or hydraulic means; also combinations of the mentioned means are possible. The drive means may further, known in the art means such. B. linkage or gear include.

Nach einer bevorzugten Ausführungsform ist vorgesehen, daß das Ausmaß der Bewegung des/der Permanentmagneten vorherbestimmbar ist. Auf diese Weise läßt sich die magnetische Feldstärke, abhängig vom jeweiligen Anwendungszweck, auf einen bestimmten Wert einstellen. Dies kann insbesondere dadurch erreicht werden, daß ein bestimmter Kipp- oder Drehwinkel oder eine bestimmte Verschiebungsstrecke vorgegeben und eingehalten wird.According to a preferred embodiment it is provided that the extent of movement of the / the permanent magnet is predictable. In this way, the magnetic field strength, depending on the particular application, set to a specific value. This can be achieved in particular by predetermining and adhering to a specific tilting or rotation angle or a specific displacement distance.

Gemäß einer weiteren Ausführungsform ist vorgesehen, daß das die magnetisierbaren Stäbe tragende Kopfstück bewegbar angebracht ist. Insbesondere kann das Kopfstück in der horizontalen Ebene bewegbar sein. Vorzugsweise sind dann Antriebsmittel (z. B. elektrisch, pneumatisch, hydraulisch), Getriebe, Gestänge und dgl. mit dem Kopfstück verbunden, so daß das Kopfstück zur steuerbaren Ausführung von Schüttelbewegungen geeignet ist (z. B. kreisförmige Bewegungen oder Bewegungen nach Art eines Orbitalschüttlers).According to a further embodiment it is provided that the head carrying the magnetizable rods is movably mounted. In particular, the head piece may be movable in the horizontal plane. Preferably, then drive means (eg., Electric, pneumatic, hydraulic), gearbox, linkage and the like are connected to the head piece, so in that the head piece is suitable for controllably performing shaking movements (eg circular movements or orbital shaker movements).

Ferner wird bevorzugt, daß der/die genannte(n) magnetisierbare(n) Stab/Stäbe drehbar (um ihre Längsachse) an dem jeweiligen Kopfstück angebracht sind und während der Behandlung einer magnetpartikelhaltigen Flüssigkeit in Rotation versetzt werden können, um eine Durchmischung zu bewirken oder um das Ablösen der Partikel von den Stäben zu beschleunigen. Die Rotation erfolgt vorzugsweise durch elektromotorische Mittel.It is further preferred that the said magnetizable rod (s) are rotatably mounted (about their longitudinal axis) on the respective header and can be rotated during the treatment of a liquid containing magnetic particles to effect mixing to accelerate the detachment of the particles from the rods. The rotation is preferably carried out by electromotive means.

Zur Abtrennung von Magnetpartikeln werden Flüssigkeiten, die solche Partikel enthalten, in den Luftspalt der Vorrichtung, unterhalb der magnetisierbaren Stäbe, eingebracht, wobei Behälter der eingangs erwähnten Art verwendet werden können. Vorzugsweise ist hierfür mindestens eine Haltevorrichtung vorgesehen, die unterhalb der Stäbe positionierbar ist, so daß die Stäbe auf die Öffnungen der Behälter hin ausgerichtet werden. Diese Haltevorrichtung kann beispielsweise in Form einer Halteplatte ausgestaltet sein.For the separation of magnetic particles, liquids containing such particles are introduced into the air gap of the device, below the magnetizable rods, wherein containers of the type mentioned above can be used. Preferably, for this purpose, at least one holding device is provided which can be positioned below the bars, so that the bars are aligned with the openings of the container. This holding device can be configured for example in the form of a holding plate.

Des weiteren werden Ausführungsformen bevorzugt, bei denen die Haltevorrichtung in einer im wesentlichen horizontalen Ebene in einer oder mehreren Richtungen bewegbar ist; alternativ oder zusätzlich kann die Haltevorrichtung in vertikaler Richtung bewegbar sein. Die Bewegung erfolgt vorzugsweise durch elektromotorischen Antrieb oder durch pneumatische oder hydraulische Mittel, oder durch Kombinationen dieser Mittel.Furthermore, embodiments are preferred in which the holding device is movable in a substantially horizontal plane in one or more directions; Alternatively or additionally, the holding device may be movable in the vertical direction. The movement is preferably carried out by electromotive drive or by pneumatic or hydraulic means, or by combinations of these means.

Insbesondere können die Haltevorrichtungen auch in der Weise ausgebildet sein, daß sie zur Durchführung von Schüttelbewegungen geeignet sind. Die hierfür erforderlichen konstruktiven Maßnahmen sind dem Fachmann grundsätzlich bekannt. Ferner ist vorgesehen, daß sowohl das Kopfstück als auch die Haltevorrichtung bewegbar und zur Durchführung von Schüttelbewegungen verwendet werden können. Auf diese Weise ist eine besonders wirksame Durchmischung der Probenflüssigkeit möglich, wenn die Stäbe darin eingetaucht sind.In particular, the holding devices can also be designed in such a way that they are suitable for carrying out shaking movements. The design measures required for this purpose are generally known to the person skilled in the art. It is further provided that both the head piece and the holding device can be moved and used to carry out shaking movements. In this way, a particularly effective mixing of the sample liquid is possible if the rods are immersed therein.

Des weiteren wird bevorzugt, daß eine Steuer- oder Regelvorrichtung vorhanden ist, durch welche die vertikale Bewegung der Haltevorrichtung(en) in der weise einstellbar oder steuerbar ist, daß bei einer Aufwärtsbewegung ein Eintauchen der Stäbe (7) in die flüssigkeitsgefüllten Behälter (10) bewirkt wird.Furthermore, it is preferred that a control or regulating device is provided, by means of which the vertical movement of the holding device (s) is adjustable or controllable in such a way that, upon an upward movement, the rods (7) are immersed in the liquid-filled containers (10). is effected.

Insbesondere kann die genannte Haltevorrichtung Bestandteil eines programmgesteuerten Laborroboter-Systems sein, wobei sie vorzugsweise so eingerichtet ist, daß eine Vielzahl von einzelnen der genannten Behälter oder von Gruppen solcher Behälter, insbesondere Mikrotiterplatten, abwechselnd in eine Position unterhalb der genannten Stäbe gebracht und anschließend nach einem vorherbestimmbaren Zeitintervall wieder in eine Position gebracht wird, die außerhalb des unterhalb der Stäbe befindlichen Bereiches liegt. Auf diese Weise wird ein hoher Probendurchsatz ermöglicht.In particular, the said holding device may be part of a program-controlled laboratory robot system, wherein it is preferably arranged so that a plurality of individual said containers or groups of such containers, in particular microtiter plates, alternately placed in a position below said rods and then after a predetermined time interval is again brought into a position which is outside the area located below the bars. In this way, a high sample throughput is possible.

Nach einer weiteren, besonders bevorzugten Ausführungsform der Erfindung ist vorgesehen, daß der Vorrichtung ein programmgesteuerter Rechner zugeordnet und mit ihr verbunden ist. Dadurch kann mindestens eine der nachfolgenden Funktionen der Vorrichtung gesteuert oder geregelt werden, oder es können mindestens zwei der nachfolgend genannten Funktionen miteinander koordiniert werden:

  • Bewegung des/der Permanentmagneten zum Ein- und Ausschalten des magnetische Feldes, insbesondere Zeitdauer der Einschalt- und Ausschaltphasen, sowie magnetische Feldstärke;
  • Rotationsgeschwindigkeit und -Dauer im Falle rotierbarer Stäbe;
  • Bewegung des Kopfes in horizontaler Ebene, insbesondere Dauer, Frequenz und Amplitude einer Schüttelbewegung;
  • Bewegung des/der Haltevorrichtung(en), um Behälter oder Gruppen von Behältern abwechselnd unterhalb der Stäbe zu positionieren und anschließend wieder aus dieser Position zu entfernen, insbesondere Geschwindigkeit und Frequenz der Bewegungen, sowie Verweildauer der Haltevorrichtung unterhalb der Stäbe;
  • vertikale Bewegung der Haltevorrichtung, um den Stab/die Stäbe in die Flüssigkeit des/der Behälter einzutauchen und wieder daraus zu entfernen; insbesondere Eintauchtiefe, Dauer und Frequenz;
  • sofern vorgesehen, Rotations- oder Schüttelbewegung der Haltevorrichtung(en), insbesondere Rotationsgeschwindigkeit, -Amplitude und Intervalle zwischen einzelnen Arbeitsphasen.
According to a further, particularly preferred embodiment of the invention it is provided that the device is associated with a program-controlled computer and connected to it. As a result, at least one of the following functions of the device can be controlled or regulated, or at least two of the following functions can be coordinated with one another:
  • Movement of the / of the permanent magnet for switching on and off of the magnetic field, in particular duration of the switch-on and switch-off, and magnetic field strength;
  • Rotation speed and duration in the case of rotatable rods;
  • Movement of the head in the horizontal plane, in particular duration, frequency and amplitude of a shaking motion;
  • Movement of the holding device (s) to position containers and groups of containers alternately below the bars and then remove them again from that position, in particular the speed and frequency of the movements, as well as residence time of the holding device below the bars;
  • vertical movement of the fixture to dip and remove the rod (s) into the liquid of the container (s); in particular immersion depth, duration and frequency;
  • if provided, rotational or shaking movement of the holding device (s), in particular rotational speed, amplitude and intervals between individual working phases.

Die erfindungsgemäßen Vorrichtungen können auf vorteilhafte Weise mit anderen Vorrichtungen zur automatisierten Behandlung von Probenmaterial kombiniert werden. Des weiteren können auch zwei oder mehrere der erfindungsgemäßen Vorrichtungen nebeneinander angeordnet und kombiniert werden.The devices of the invention may be advantageously combined with other devices for the automated treatment of sample material. Furthermore, two or more of the devices according to the invention can be arranged side by side and combined.

Die Erfindung erstreckt sich deshalb auch auf Vorrichtungen der vorstehend beschriebenen Art, welchen eine oder mehrere der nachfolgend genannten Einrichtungen zugeordnet sind, deren Funktionen durch eine gemeinsame Steuerung mit den Funktionen der Vorrichtung koordiniert werden:

  • eine oder mehrere thermostatisierbare Heiz- oder Kühleinrichtungen;
  • eine oder mehrere Pipettierstationen zum Hinzudosieren von Flüssigkeiten, insbesondere Reagenzien;
  • eine oder mehrere Saugeinrichtungen zum Absaugen von Flüssigkeit aus den Behältern;
  • eine oder mehrere Einrichtungen zum Schütteln oder Durchmischen der in den Behältern enthaltenen Flüssigkeiten;
  • analytische Geräte, insbesondere für photometrische Messungen oder Lumineszenzdetektion.
The invention therefore also extends to devices of the type described above, to which one or more of the following devices are assigned, the functions of which are coordinated by a common control with the functions of the device:
  • one or more thermostatable heating or cooling devices;
  • one or more pipetting stations for metering in liquids, in particular reagents;
  • one or more suction means for sucking liquid from the containers;
  • one or more means for shaking or mixing the liquids contained in the containers;
  • analytical apparatus, in particular for photometric measurements or luminescence detection.

Die Erfindung umfaßt ferner Verfahren zum Abtrennen einer Zielsubstanz aus einem in flüssiger Form vorliegenden Stoffgemisch. Diese Verfahren weisen im allgemeinen folgende Schritte auf:

  1. a) Zugabe von magnetischen oder magnetisierbaren Partikeln, welche spezifische Bindungseigenschaften in Bezug auf die Zielsubstanz aufweisen;
  2. b) Einbringen eines vorgegebenen Volumen des Gemisches in den Luftspalt zwischen den zwei Polen eines magnetischen Kreises und Eintauchen eines magnetisierbaren Stabes in das Gemisch, wobei der Stab mit einem der Pole des magnetischen Kreises verbunden ist und das magnetische Feld zunächst ausgeschaltet ist;
  3. c) Einschalten des magnetischen Feldes durch Veränderung der Position eines im oder am magnetischen Kreis angeordneten Dauermagneten, wodurch der Stab magnetisiert wird und die Partikel sich im wesentlichen am unteren Ende des Stabes ansammeln; anschließend wird der Stab mit den anhaftenden Partikeln aus dem ersten Flüssigkeitsgemisch herausgenommen;
  4. d) Eintauchen des Stabes mit den anhaftenden Partikeln in ein vorgegebenes Volumen einer Flüssigkeit, welche Elution der Zielsubstanz von den Partikeln bewirkt;
  5. e) Herausheben des Stabes aus der Elutionsflüssigkeit, wobei die Partikel an dem Stab haften bleiben und so aus der Flüssigkeit abgetrennt werden.
The invention further includes methods for separating a target substance from a mixture of substances present in liquid form. These methods generally have the following steps:
  1. a) addition of magnetic or magnetisable particles which have specific binding properties with respect to the target substance;
  2. b) introducing a predetermined volume of the mixture into the air gap between the two poles of a magnetic circuit and immersing a magnetizable rod in the mixture, wherein the rod is connected to one of the poles of the magnetic circuit and the magnetic field is initially switched off;
  3. c) switching on the magnetic field by changing the position of a permanent magnet arranged in or on the magnetic circuit, whereby the rod is magnetized and the particles accumulate substantially at the lower end of the rod; then the rod with the adhering particles is taken out of the first liquid mixture;
  4. d) immersing the rod with the adhering particles in a given volume of a liquid which causes elution of the target substance from the particles;
  5. e) lifting the rod out of the elution liquid, the particles sticking to the rod and thus being separated from the liquid.

Zur Verbesserung der Reinheit und Ausbeute kann es vorteilhaft sein, die Partikel im Anschluß an Schritt d durch Ausschalten des magnetischen Feldes in die Flüssigkeit freizusetzen, diese zu durchmischen, und anschließend durch Einschalten des Magnetfeldes wieder an den Stäben zu sammeln. Das Durchmischen kann beispielsweise durch Rotation der Stäbe oder durch Schütteln der Haltevorrichtung oder/und des Kopfteils bewirkt werden.To improve the purity and yield, it may be advantageous to release the particles into the liquid after step d by switching off the magnetic field, to mix them, and then by switching them on of the magnetic field to collect again at the bars. The mixing can be effected for example by rotation of the rods or by shaking the holding device and / or the head part.

Ferner kann das beschriebene Verfahren wahlweise einen oder mehrere Wasch-Vorgänge enthalten; ein solcher Wasch-Vorgang kann sich beispielsweise an Schritt c) anschließen und wie folgt ablaufen:

  • Eintauchen des Stabes mit den anhaftenden Partikeln in ein vorgegebenes Volumen einer Waschflüssigkeit;
  • Ausschalten des magnetischen Feldes durch entgegengesetzte Veränderung der Position des Dauermagneten, wodurch die Partikel in die Flüssigkeit freigesetzt werden;
  • Mischen;
  • Einschalten des magnetischen Feldes durch Veränderung der Position eines im oder am magnetischen Kreis angeordneten Dauermagneten, wodurch der Stab magnetisiert wird und die Partikel sich im wesentlichen am unteren Ende des Stabes ansammeln;
  • Herausheben des Stabes aus der Waschflüssigkeit;
  • Elution der Zielsubstanz, wie in den Schritten d) und e).
Furthermore, the described method may optionally include one or more washing operations; such a washing process may, for example, follow step c) and proceed as follows:
  • Immersing the stick with the adhering particles in a predetermined volume of a washing liquid;
  • Turning off the magnetic field by oppositely changing the position of the permanent magnet, thereby releasing the particles into the liquid;
  • Mix;
  • Switching on the magnetic field by changing the position of a permanent magnet disposed in or on the magnetic circuit, thereby magnetizing the rod and allowing the particles to collect substantially at the lower end of the rod;
  • Lifting the rod out of the washing liquid;
  • Elution of the target substance as in steps d) and e).

Durch Verwendung einer der oben beschriebenen erfindungsgemäßen Vorrichtungen können die genannten Verfahren auf besonders einfache und schnelle Weise durchgeführt werden. Die erfindungsgemäßen Vorrichtungen und Verfahren eignen sich in besonders vorteilhafter Weise für die eingangs erwähnten Anwendungsgebiete, insbesondere für Hochdurchsatz-Methoden.By using one of the devices according to the invention described above, the said methods can be carried out in a particularly simple and rapid manner. The devices and methods of the invention are particularly suitable for the application areas mentioned above, in particular for high-throughput methods.

Die Erfindung wird nachfolgend anhand der beigefügten schematischen Zeichnungen beispielhaft erläutert. Die verwendeten Bezugszeichen haben in allen Zeichnungen dieselbe Bedeutung, sofern nicht anders angegeben. Da es sich lediglich um schematische Darstellungen handelt, können die tatsächlichen Größenverhältnisse hiervon abweichen.The invention will now be described by way of example with reference to the accompanying diagrammatic drawings. The reference numbers used have the same meaning in all drawings unless otherwise indicated. Since it is only are schematic representations, the actual size ratios may differ.

Fig. 1A und 1B zeigen eine Ausführungsform einer erfindungsgemäßen Vorrichtung in einer Seitenansicht. Die Vorrichtung (1) weist zwei magnetisierbare Schenkel (2,3) eines magnetischen Kreises auf, wobei die Schenkel im Bereich (6) miteinander verbunden sind. Am gegenüberliegenden Ende der Schenkel befinden sich die beiden Pole (4,5) mit einem dazwischen liegenden Luftspalt (12). Der Pol (4) des oberen Schenkels (2) trägt ein Kopfstück (8) mit daran angebrachten magnetisierbaren Stangen (7). Unterhalb der Stangen befindet sich eine Haltevorrichtung (11), die mit dem Pol (5) des anderen Schenkels (3) verbunden ist oder zumindest in Kontakt mit diesem steht. Auf der Haltevorrichtung ist ein Probenbehälter (9) mit mehreren Vertiefungen (10) zur Aufnahme von Flüssigkeitsproben angeordnet, beispielsweise wiederablösbar auf der Haltevorrichtung (11) fixiert. Fig. 1A and 1B show an embodiment of a device according to the invention in a side view. The device (1) has two magnetizable legs (2, 3) of a magnetic circuit, the legs being connected to one another in the region (6). At the opposite end of the legs are the two poles (4,5) with an intermediate air gap (12). The pole (4) of the upper leg (2) carries a head piece (8) with magnetizable bars (7) attached thereto. Below the bars is a holding device (11) which is connected to the pole (5) of the other leg (3) or at least in contact therewith. On the holding device, a sample container (9) is arranged with a plurality of recesses (10) for receiving liquid samples, for example removably fixed on the holding device (11).

Auf der dem Luftspalt (12) gegenüberliegenden Seite ist in dem die beiden Schenkel verbindenden Bereich (6) eine Aussparung (16) vorhanden, in der ein stab- oder quaderförmiger Dauermagnet (15) drehbar angeordnet ist. Um den Bereich des Dauermagneten ist ein Kurzschlußring (20) angeordnet (dieser ist im Bereich des drehbaren Magneten durchbrochen dargestellt). Fig. 1A zeigt die Vorrichtung im ausgeschalteten Zustand; die Lage des Dauermagneten (15) ist im wesentlichen senkrecht zur Richtung des magnetischen Kreises; das magnetische Feld des Dauermagneten wird in den Kurzschlußring (20) geleitet.On the opposite side of the air gap (12) is in the region connecting the two legs (6) has a recess (16) in which a rod or cuboid permanent magnet (15) is rotatably arranged. Around the region of the permanent magnet, a short-circuit ring (20) is arranged (this is shown broken through in the region of the rotatable magnet). Fig. 1A shows the device in the off state; the position of the permanent magnet (15) is substantially perpendicular to the direction of the magnetic circuit; The magnetic field of the permanent magnet is passed into the short-circuit ring (20).

Fig. 1B zeigt dieselbe Vorrichtung im eingeschalteten Zustand. Die Lage des Dauermagneten (15) zeigt im wesentlichen in die Richtung des magnetischen Kreises. Dadurch wird zwischen den Polen (4,5) und somit auch an den Enden der Stäbe (7) ein Magnetfeld erzeugt, das zur Anziehung von Magnetpartikeln verwendet werden kann. Fig. 1B shows the same device in the on state. The position of the permanent magnet (15) points substantially in the direction of the magnetic circuit. As a result, between the poles (4,5) and thus also at the ends of Rods (7) generates a magnetic field that can be used to attract magnetic particles.

Fig. 1C zeigt eine Schnittdarstellung der in den Fig. 1A/B gezeigten Vorrichtung, in der durch die gestrichelte Linie a (Fig. 1B) angedeuteten Ebene. Die Pfeile (17) zeigen schematisch die Richtung des Magnetfeldes im eingeschalteten Zustand an. Fig. 1C shows a sectional view of the in the Fig. 1A / B device, in which by the dashed line a ( Fig. 1B ) indicated level. The arrows (17) show schematically the direction of the magnetic field in the on state.

Die Fig. 1D und 1E zeigen, ebenfalls in schematischer Seitenansicht, eine weitere Ausführungsform der erfindungsgemäßen Vorrichtungen, wobei der verwendete Magnet eine flache Quader-Form aufweist und die Pole sich an den beiden großen Seitenflächen befinden. In Fig. 1D ist der eingeschaltete Zustand (das Magnetfeld verläuft in Richtung des Eisenkreises), in Fig. 1E der ausgeschaltete Zustand dargestellt. Die Position des Kurzschlußringes (20) ist lediglich angedeutet. Die weiteren, in Fig. 1A, 1B gezeigten Elemente sind zur Vereinfachung der Darstellung weggelassen worden.The Fig. 1D and 1E show, also in a schematic side view, a further embodiment of the inventive devices, wherein the magnet used has a flat cuboid shape and the poles are located on the two large side surfaces. In Fig. 1D is the switched-on state (the magnetic field runs in the direction of the iron circle), in Fig. 1E the switched-off state is shown. The position of the short-circuit ring (20) is merely indicated. The others, in Fig. 1A, 1B The elements shown have been omitted for simplicity of illustration.

Fig. 2 und Fig. 3 zeigen, ebenfalls in Seitenansicht, weitere Konstruktionsvarianten der erfindungsgemäßen Vorrichtungen. Fig. 2 and Fig. 3 show, also in side view, further construction variants of the devices according to the invention.

Fig. 4 zeigt die Vorrichtung (1) der Fig. 1A/B in Draufsicht; dadurch ist die ringförmige Gestalt des Kurzschlußringes (20) zu erkennen. Bei der gezeigten Ausführungsform ist der Kurzschlußring (20) so gestaltet, daß er nicht vollständig am Magnetkreis anliegt, sondern ein Hohlraum (22) vorhanden ist. Dadurch wird der Zugang zu dem drehbaren Magneten (15) erleichtert bzw. ermöglicht. Der Kurzschlußring (20) kann aus zwei Hälften (20a, 20b) oder mehreren Teilen zusammengesetzt sein, wie durch die gestrichelte Linie 21 angedeutet, um die Montage und Demontage zu erleichtern. Fig. 4 shows the device (1) of Fig. 1A / B in plan view; thereby, the annular shape of the short-circuit ring (20) can be seen. In the embodiment shown, the short-circuit ring (20) is designed so that it does not fully abut the magnetic circuit, but a cavity (22) is present. This facilitates access to the rotatable magnet (15). The shorting ring (20) may be composed of two halves (20a, 20b) or multiple parts as indicated by the dashed line 21 to facilitate assembly and disassembly.

Fig. 5 zeigt eine Ausführungsform der erfindungsgemäßen Vorrichtung (ebenfalls in Seitenansicht), bei der in der Aussparung (16) ein verschiebbarer (Doppelpfeil) Dauermagnet (15) vorgesehen ist. Fig. 5 zeigt den eingeschalteten Zustand, in welchem der Dauermagnet bewirkt, daß zwischen den Polen (4,5) ein Magnetfeld entsteht. Zum Ausschalten wird der Magnet aus dem magnetischen Kreis der Vorrichtung (1) nach außen verschoben. Fig. 5 shows an embodiment of the device according to the invention (also in side view), in which in the recess (16) a displaceable (double arrow) permanent magnet (15) is provided. Fig. 5 shows the on state in which the permanent magnet causes between the poles (4,5) creates a magnetic field. To turn off the magnet is moved out of the magnetic circuit of the device (1) to the outside.

Fig. 6 zeigt eine Abwandlung der in Fig. 1A/B dargestellten Vorrichtung, wobei die beiden Schenkel (3,4) unterschiedlich lang sind. Fig. 6 shows a modification of the in Fig. 1A / B device shown, wherein the two legs (3,4) are of different lengths.

Die Fig. 7A bis 7D zeigen verschiedene Ansichten einer besonders bevorzugten Ausführungsform, bei der ein Magnet (15) auf einer Unterlage (40) angeordnet ist, die in einer horizontalen Ebene um die Achse Y drehbar ist. Dadurch kann der Magnet (15) durch Rotation der Unterlage (40) in den magnetischen Kreis (Eisenkreis) hineingebracht werden (eingeschalteter Zustand, Fig. 7C, 7D) oder aus dem Bereich des magnetischen Kreises herausbewegt werden (Fig. 7A, 7B). Der in diesen Abbildungen (Fig. 7A bis 7D) nicht dargestellte Kurzschlußring (20) weist im Bereich der Unterlage (40) eine passende Aussparung auf, oder das abschirmende Material ist auf dieser Seite der Vorrichtung nicht vollständig ausgebildet. Die Unterlage (40) ist vorzugsweise in Form einer Drehscheibe oder auch als drehbarer Arm ausgebildet, die/der mittels bekannter Antriebsvorrichtungen bewegt wird. Auf der Unterlage können optional auch zwei oder mehrere Magnete angebracht sein.
Fig. 7A, 7C zeigen eine Schnittdarstellung in der Fläche der Drehachse Y; die Fig. 7B, 7D zeigen jeweils dieselbe Vorrichtung in Draufsicht.The Figs. 7A to 7D show various views of a particularly preferred embodiment in which a magnet (15) on a pad (40) is arranged, which is rotatable in a horizontal plane about the axis Y. As a result, the magnet (15) can be brought into the magnetic circuit (iron circle) by rotation of the support (40) (switched-on state, Figs. 7C, 7D ) or moved out of the area of the magnetic circuit ( Fig. 7A, 7B ). The one in these pictures ( Figs. 7A to 7D ), not shown, shorting ring (20) has in the area of the base (40) has a matching recess, or the shielding material is not completely formed on this side of the device. The pad (40) is preferably in the form of a turntable or as a rotatable arm which is moved by means of known drive devices. Optionally, two or more magnets may be mounted on the base.
Figs. 7A, 7C show a sectional view in the surface of the axis of rotation Y; the Fig. 7B, 7D each show the same device in plan view.

Fig. 8 zeigt eine Ausführungsform der erfindungsgemäßen Vorrichtung (1) in Seitenansicht; in diesem Fall sind die beiden Schenkel (2,3) nicht durch einen gemeinsamen Bereich (6) miteinander verbunden. Der drehbare Magnet (15) ist zwischen den beiden Schenkeln (2,3) angeordnet, auf der dem Luftspalt gegenüberliegenden Seite. Der Kurzschlußring (20) ist in Schnittdarstellung abgebildet. Fig. 8 shows an embodiment of the device (1) according to the invention in side view; In this case, the two legs (2,3) are not connected to each other by a common area (6). The rotatable magnet (15) is arranged between the two legs (2, 3), on the side opposite the air gap. The short-circuit ring (20) is shown in sectional view.

Fig. 9 zeigt die Vorderansicht des oberen Schenkels (4) einer erfindungsgemäßen Vorrichtung mit dem Kopfstück (8) und daran angebrachten Stäben (7). Unterhalb der Stäbe ist eine Haltevorrichtung (8) positioniert, auf der mehrere Behälter (10) in Reihen angeordnet sind. Die Haltevorrichtung läßt sich in der horizontalen Ebene in verschiedene Richtungen sowie nach oben und unten bewegen (Pfeile). Fig. 9 shows the front view of the upper leg (4) of a device according to the invention with the head piece (8) and attached rods (7). Below the bars, a holding device (8) is positioned, on which several containers (10) are arranged in rows. The holding device can be moved in the horizontal plane in different directions as well as up and down (arrows).

Fig. 10 (a-d) zeigt im Längsschnitt Beispiele für verschiedene Formen der magnetisierbaren Stäbe (7). Die unter dem Einfluß des Magnetfeldes angezogenen Partikel sind mit (30) bezeichnet. Fig. 9d zeigt einen Stab, der mit einer auswechselbaren Hülle (25) versehen ist. Fig. 10 (ad) shows in longitudinal section examples of different forms of magnetizable rods (7). The particles attracted under the influence of the magnetic field are designated by (30). Fig. 9d shows a rod provided with a replaceable sleeve (25).

Claims (27)

  1. Device for separating magnetic or magnetizable particles (30) from a liquid by using a magnetic field, wherein
    - said device (1) comprises two limbs (2, 3) made of a soft-magnetic material;
    - between the two poles (4, 5) of the limbs (2, 3) there is an air gap (12) which is suitable for receiving a container or a plurality of containers (9, 10);
    - a head piece (8) is arranged in a fixed or detachable manner on one of the two poles (4), and a magnetizable bar or a plurality of magnetizable bars (7) is/are disposed in a fixed or movable manner on said head piece, in the vertical direction;
    - a permanent magnet (15) or a group of at least two permanent magnets is movably arranged on at least one point of the device, such that a magnetic field (17) can be produced between the two poles (4, 5) and the magnetic field can be activated or deactivated by moving the magnet(s) (15), and wherein
    - that region of the device wherein the movable magnet(s) is/are arranged is at least partially surrounded by a material (20) which screens the magnetic field.
  2. Device according to claim 1, characterized in that the two limbs (2, 3) are connected with each other at the side (6) opposite the poles (4, 5) and thereby form a magnetic circuit (iron circuit).
  3. Device according to claim 1 or 2, characterized in that the magnet(s) is/are arranged within the iron circuit such that they are movable, particularly rotatable, or that the magnet(s) is/are arranged such that it/they can be moved into the magnetic circuit from the outside and then again out of the said circuit.
  4. Device according to any one of the preceding claims, characterized in that the region of the device wherein the movable magnet(s) is/are arranged within the iron circuit is at least partially surrounded by a material which screens the magnetic field.
  5. Device according to any one of the preceding claims, characterized in that in the case of the magnet(s) moving within or into the iron circuit, the region of the device wherein the movable magnet(s) is/are arranged within the iron circuit is at least partially surrounded by a material which screens the magnetic field.
  6. Device according to any one of the preceding claims, characterized in that the permanent magnet(s) is/are arranged such that they are rotatable or tiltable, in a recess (16) provided for that purpose.
  7. Device according to any one of the preceding claims, characterized in that the permanent magnet(s) is/are provided in a displaceable manner, in a recess (16) provided for that purpose.
  8. Device according to any one of the preceding claims, characterized in that the permanent magnet(s) is/are arranged on a rotatable support (40) by means of which the said permanent magnet(s) can be moved into the magnetic circuit and then again out of the said circuit.
  9. Device according to any one of the preceding claims, characterized in that the movement of the permanent magnet(s) is accomplished by means of an electric motor or by pneumatic or hydraulic means.
  10. Device according to any one of the preceding claims, characterized in that the extent of the movement, particularly the rotation angle or the distance of displacement, of the permanent magnet(s) can be predetermined in order to set the magnetic field strength to a desired value.
  11. Device according to any one of the preceding claims, characterized in that the region of the magnetic circuit wherein the movable magnet(s) is/are arranged is completely surrounded by a material which screens the magnetic field, said screening preferably being provided in the form of a short circuit ring (20).
  12. Device according to any one of the preceding claims, characterized in that the said head piece (8) is movable in the horizontal plane, preferably for carrying out a shaking motion.
  13. Device according to any one of the preceding claims, characterized in that the said head piece (8) carries a plurality of bars (7) arranged in rows.
  14. Device according to any one of the preceding claims, characterized in that the head piece (8) is attached in a replaceable manner.
  15. Device according to any one of the preceding claims, characterized in that the said bar(s) (7) are arranged in a rotatable manner and can preferably be rotated around the longitudinal axis by means of an electromotive drive.
  16. Device according to any one of the preceding claims, characterized in that the said bar(s) (7) are each covered with a strippable, replaceable envelope (25).
  17. Device according to any one of the preceding claims, characterized in that at least one holding device (11) for the said container(s) (9, 10) is associated to said device, which holding device (11) is suitable for positioning the container(s) below the said head piece and the bars arranged thereon.
  18. Device according to claim 17, characterized in that the said holding device(s) can be moved in the horizontal plane and/or vertically, preferably by electromotive drive or by pneumatic or hydraulic means.
  19. Device according to claim 18, characterized in that the holding device(s) is/are adapted for carrying out shaking movements.
  20. Device according to any one of claims 17 to 19, characterized in that the holding device(s) is/are a component of a program-controlled laboratory robot system and is/are adapted such that a plurality of individual ones of the said containers or of groups of such containers, particularly microtitre plates, are alternately moved into a position below the said bars and subsequently, after a predeterminable time interval, again into a position which is outside the region below the bars.
  21. Device according to any one of claims 17 to 20, characterized in that the vertical motion of the holding device(s) (11) can be open-loop controlled or closed-loop controlled by an open-loop control unit or a closed-loop control unit, in such a manner that in the case of an upward movement an immersion of the bars (7) into the liquid-filled containers (10) is caused.
  22. Device according to any one of the preceding claims, characterized in that a program-controlled processor is associated to the device and is connected therewith, by means of which at least one of the following functions of the device can be open-loop controlled or closed-loop controlled, or by means of which at least two of the functions mentioned below can be coordinated with one another:
    - movement of the permanent magnet(s) to activate and deactivate the magnetic field, particularly the duration of the activated and deactivated phases, as well as magnetic field strength;
    - rotation speed and duration of rotation in the case of rotatable bars;
    - movement of the head in a horizontal plane, particularly duration, frequency and amplitude of a shaking motion;
    - movement of the holding device(s) to position the container(s) or groups of containers alternately below the bars and subsequently to remove them from that position, particularly the velocity and frequency of the movements, as well as the dwell time of the holding device below the bars;
    - vertical movement of the holding device to immerse the bar/the bars into the liquid of the container(s) and remove the same therefrom; particularly immersion depth, duration and frequency;
    - if provided, rotation or shaking motion of the holding device(s), particularly rotation speed, rotation amplitude and intervals between the individual operation phases.
  23. Device according to one or more of the preceding claims, characterized in that one or more of the below-mentioned means are associated to the said device, the functions of said means being coordinated with the functions of the said device by means of a common control:
    - one or more thermostattable heating or cooling means;
    - one or more pipetting stations for metered addition of liquids, especially reagents;
    - one or more suction means for exhausting liquid from the containers by suction;
    - one or more means for shaking or intermixing the liquids contained in the containers;
    - analytic apparatuses, particularly for photometric measuring or luminescence detection.
  24. Device for separating a target substance from a mixture of substances which is present in liquid form, comprising the following steps:
    a) addition of magnetic or magnetizable particles that have specific binding properties in relation to the target substance;
    b) placing a pre-determined volume of the mixture in the air gap between the two poles of a magnetic circuit and immersing a magnetizable bar into the mixture, said bar being connected with one of the said poles of the magnetic circuit, and the magnetic field being initially deactivated;
    c) activating the magnetic field by changing the position of a permanent magnet arranged in or on the magnetic circuit, whereby the bar is magnetized and the particles accumulate substantially at the lower end of the bar;
    d) immersing the bar, together with the particles adhering thereto, into a predetermined volume of a liquid that causes the elution of the target substance from the particles;
    e) lifting the bar out of the elution liquid.
  25. Process according to claim 24, characterized in that, following step d), the following steps are performed:
    f) deactivating the magnetic field by an opposite change of the position of the permanent magnet, whereby the particles are released into the liquid;
    g) mixing;
    h) activating the magnetic field by changing the position of a permanent magnet arranged in or on the magnetic circuit, whereby the bar is magnetized and the particles accumulate substantially at the lower end of the bar;
    i) lifting the bar out of the elution liquid.
  26. Process according to claim 24 or 25, characterized in that, following step c), the following steps are performed:
    k) immersing the bar, together with the particles adhering thereto, into a pre-determined volume of a wash liquid;
    l) deactivating the magnetic field by an opposite change of the position of the permanent magnet, whereby the particles are released into the liquid;
    m) mixing;
    h) activating the magnetic field by changing the position of a permanent magnet arranged in or on the magnetic circuit, whereby the bar is magnetized and the particles accumulate substantially at the lower end of the bar;
    l) lifting the bar out of the elution liquid;
    m) elution of the target substance, as in steps d) and e) of claims 24, or according to claim 25.
  27. Process according to any one of claims 24 to 26, characterized in that it is carried out by using a device according to any one of claims 1 to 23.
EP04740646A 2003-07-10 2004-07-05 Device and method for removing magnetic or magnetisable particles from a liquid Active EP1644120B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10331254A DE10331254B4 (en) 2003-07-10 2003-07-10 Apparatus and method for separating magnetic or magnetizable particles from a liquid
PCT/EP2004/007308 WO2005005049A1 (en) 2003-07-10 2004-07-05 Device and method for removing magnetic or magnetisable particles from a liquid

Publications (2)

Publication Number Publication Date
EP1644120A1 EP1644120A1 (en) 2006-04-12
EP1644120B1 true EP1644120B1 (en) 2011-11-30

Family

ID=34041761

Family Applications (1)

Application Number Title Priority Date Filing Date
EP04740646A Active EP1644120B1 (en) 2003-07-10 2004-07-05 Device and method for removing magnetic or magnetisable particles from a liquid

Country Status (9)

Country Link
US (1) US7776221B2 (en)
EP (1) EP1644120B1 (en)
JP (1) JP4762139B2 (en)
AT (1) ATE535305T1 (en)
CA (1) CA2531399C (en)
DE (1) DE10331254B4 (en)
DK (1) DK1644120T3 (en)
ES (1) ES2377733T3 (en)
WO (1) WO2005005049A1 (en)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101229997B1 (en) * 2004-12-22 2013-02-06 톰 헨닝 요한센 Method for Forming a High-Gradient Magnetic Field and a substance Separation Device Based Thereon
DE102005004664B4 (en) * 2005-02-02 2007-06-21 Chemagen Biopolymer-Technologie Aktiengesellschaft Apparatus and method and use for separating magnetic or magnetizable particles from a liquid and their uses
EP1748295A1 (en) 2005-07-28 2007-01-31 Nederlandse Organisatie voor toegepast-natuurwetenschappelijk Onderzoek TNO System for manipulating magnetic particles
AU2006294433B2 (en) * 2005-09-26 2011-06-09 Magswitch Technology Worldwide Pty Ltd Magnet arrays
WO2007033437A1 (en) * 2005-09-26 2007-03-29 Magswitch Technology Worldwide Pty Ltd Magnet arrays
CN101426664B (en) 2006-03-13 2013-02-13 磁转换技术全球控股有限公司 Magnetic wheel
AU2007278425B2 (en) * 2006-07-28 2011-11-17 Qiagen Gmbh Device for processing samples
DE502007004200D1 (en) 2007-08-14 2010-08-05 Qiagen Gmbh A method for suspending or resuspending particles in a solution and apparatus adapted thereto
DE102007045474A1 (en) 2007-09-21 2009-04-02 Qiagen Gmbh Apparatus and method for treating liquids with magnetic particles
DE102008047855A1 (en) * 2008-09-18 2010-04-22 Siemens Aktiengesellschaft Separating device for separating magnetizable and non-magnetizable particles transported in a suspension flowing through a separation channel
WO2011007310A1 (en) * 2009-07-17 2011-01-20 Koninklijke Philips Electronics N.V. Apparatus for the enrichment of magnetic particles
US9660267B2 (en) 2009-09-18 2017-05-23 A123 Systems, LLC High power electrode materials
US9174846B2 (en) * 2009-09-18 2015-11-03 A123 Systems Llc Ferric phosphate and methods of preparation thereof
US8512558B2 (en) * 2010-02-19 2013-08-20 Roche Molecular Systems, Inc. Magnetic separation system comprising flexible magnetic pins
CN104122127A (en) * 2014-07-18 2014-10-29 东南大学 Biological sample treatment device
DE102015218010A1 (en) 2015-09-18 2017-03-23 Hamilton Bonaduz Ag Magnetic isolator with magnetic activation and deactivation
JP6841630B2 (en) 2015-10-15 2021-03-10 キヤノンメディカルシステムズ株式会社 Specimen testing device
US20190022667A1 (en) * 2016-01-19 2019-01-24 Shanxi Zdgsy Bio-Scientific Co., Ltd. Multifunctional biological substance separation device
JP6461869B2 (en) 2016-03-30 2019-01-30 Ckd株式会社 Flow path switching valve and manufacturing method thereof
GB2549496B (en) * 2016-04-19 2020-12-30 Adey Holdings 2008 Ltd Monitoring magnetite buildup in a magnetic filter
SG11201901233SA (en) * 2016-10-31 2019-03-28 Amgen Inc Purification systems and methods
US10399048B2 (en) 2017-08-03 2019-09-03 Agilent Technologies, Inc. Sample processing apparatus with integrated heater, shaker and magnet
DK3692307T3 (en) 2017-10-02 2021-11-15 Adey Holdings 2008 Ltd Measurement of magnetic waste accumulation in a magnetic filter
CN107731446A (en) * 2017-11-16 2018-02-23 北京中科三环高技术股份有限公司 A kind of open type permanent magnetic device
JP6955436B2 (en) 2017-12-25 2021-10-27 Ckd株式会社 Electromagnetic actuator
USD917063S1 (en) 2019-11-20 2021-04-20 Agilent Technologies, Inc. Sample processing apparatus
USD914231S1 (en) 2019-11-20 2021-03-23 Agilent Technologies, Inc. Sample processing apparatus

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE932621C (en) 1936-10-11 1955-09-05 Max Baermann Magnetic holding device with a permanent magnet and soft iron pole pieces
US2904178A (en) * 1956-03-13 1959-09-15 Research Corp Apparatus for collecting magnetic susceptible material
GB1006763A (en) * 1964-04-23 1965-10-06 Mullard Ltd Improvements in and relating to magnetic filters
US3533928A (en) * 1969-04-21 1970-10-13 Inoue K Method of and apparatus for the deburring of workpieces
US3904956A (en) * 1973-02-26 1975-09-09 Brien Kevin C O Alternating force magnetometer
US4272510A (en) * 1976-04-26 1981-06-09 Smith Kendall O Magnetic attraction transfer process for use in solid phase radioimmunoassays and in other assay methods
SE409954B (en) * 1976-06-11 1979-09-17 Mineral Processing Dev MAGNETIC SEPARATOR
JPS6048215B2 (en) * 1981-01-16 1985-10-25 株式会社井上ジャパックス研究所 magnetic filter
US4444398A (en) * 1983-02-22 1984-04-24 Ferrofluidics Corporation Self-activating ferrofluid seal apparatus and method
US4988618A (en) * 1987-11-16 1991-01-29 Gene-Trak Systems Magnetic separation device and methods for use in heterogeneous assays
US4939121A (en) * 1988-10-20 1990-07-03 General Dynamics Corporation, Electronics Division Method and apparatus for inducing grain orientation by magnetic and electric field ordering during bulk superconductor synthesis
DE69515675T2 (en) * 1994-05-11 2000-07-20 Genera Technologies Ltd Process for capturing a ligand from a liquid and device for carrying it out
DE4421058A1 (en) * 1994-06-16 1995-12-21 Boehringer Mannheim Gmbh Process for the magnetic separation of liquid components
US5567326A (en) * 1994-09-19 1996-10-22 Promega Corporation Multisample magnetic separation device
DE19528029B4 (en) 1995-07-31 2008-01-10 Chemagen Biopolymer-Technologie Aktiengesellschaft Magnetic polymer particles based on polyvinyl alcohol, process for their preparation and use
JPH09248483A (en) * 1996-03-14 1997-09-22 Inaba Eiko Magnetic flocculation treatment apparatus of impurities in liquid
DE29614623U1 (en) 1996-08-23 1996-12-19 Agowa Ges Fuer Molekularbiolog Magnetic separator for separating and washing paramagnetic particles and for eluting substances that have been bound to the paramagnetic particles
IL123210A0 (en) * 1998-02-06 1998-09-24 Gombinsky Moshe A device and system for the collection of magnetic particles
IT1313206B1 (en) * 1998-07-14 2002-06-17 Toushin Keisoku Corp MAGNETIC TREATMENT EQUIPMENT FOR FLUIDS AND PROCEDURE FOR ITS USE.
FI20000583A0 (en) * 2000-03-14 2000-03-14 Labsystems Oy Dish and rod
DE10057396C1 (en) 2000-11-18 2002-04-04 Karlsruhe Forschzent Separation of e.g. biomolecules from dispersion or solution, employs magnetic particles onto which substance is sorbed, and electromagnet for their extraction
DE10063984A1 (en) * 2000-12-19 2002-06-20 Bilatec Ges Zur Entwicklung Bi Laboratory separator for magnetic particles employed in molecular biology, employs a moving magnet holder contacting reaction vessel to draw particles against its wall
DE10117659C2 (en) 2001-04-09 2003-07-17 Steinert Gmbh Elektromagnetbau High gradient magnetic filter and method for separating weakly magnetizable particles from liquid media

Also Published As

Publication number Publication date
JP2009513318A (en) 2009-04-02
EP1644120A1 (en) 2006-04-12
US7776221B2 (en) 2010-08-17
WO2005005049A1 (en) 2005-01-20
US20070175830A1 (en) 2007-08-02
CA2531399A1 (en) 2005-01-20
ATE535305T1 (en) 2011-12-15
JP4762139B2 (en) 2011-08-31
DE10331254B4 (en) 2006-05-04
DE10331254A1 (en) 2005-02-10
DK1644120T3 (en) 2012-03-19
ES2377733T3 (en) 2012-03-30
CA2531399C (en) 2012-01-31

Similar Documents

Publication Publication Date Title
EP1644120B1 (en) Device and method for removing magnetic or magnetisable particles from a liquid
EP1843854B1 (en) Device and method for the elimination of magnetic or magnetizable particles from a liquid
EP1446668B1 (en) Device and method for treating magnetic particles
EP1919625B1 (en) Device and method for the separation of magnetic particles from a liquid
EP2033715B1 (en) Method for suspending or re-suspending particles in a solution and device adapted therefor
EP0644425B1 (en) Analyser having a device for separating magnetic microparticles
EP0774123B1 (en) Measurement process and arrangement for carrying out luminometric series analyses and multiple vessel for receiving liquid samples therefor
DE10057396C1 (en) Separation of e.g. biomolecules from dispersion or solution, employs magnetic particles onto which substance is sorbed, and electromagnet for their extraction
DE60023185T2 (en) APPARATUS AND METHOD FOR MIXING AND DISCONNECTING USING MAGNETIC PARTICLES
DE19823719A1 (en) Method and device for processing small quantities of substances
EP1420888A1 (en) System for separating magnetically attractable particles
EP2030689A1 (en) Microplate support with magnets
EP0988536A1 (en) Method and device for isolating and/or analyzing charged biomolecules
EP2192987B1 (en) Apparatus and method for the treatment of liquids with magnetic particles
DE19854003A1 (en) Simultaneous magnetic particle handling in a two-dimensional arrangement
EP2810704B1 (en) Agitator for mixing liquid samples in micro- and millilitre reaction vessels
EP1291647B1 (en) Magnetic gripping device for changing elongated probes in an X-ray analyser
DE102020209001B4 (en) Lysis of a sample using magnetic elements and rotary relative movement
EP1291648B1 (en) Space-saving housing for an X-ray apparatus with sample changer
DE19955169A1 (en) Solenoids with air gap to influence magnetic particles in fluid in a titration plate, is useful for mixing, vibration, precipitation and filtration
DE102013006235B4 (en) Device for mixing liquids in a microchannel

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20060105

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PL PT RO SE SI SK TR

DAX Request for extension of the european patent (deleted)
GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PL PT RO SE SI SK TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

Free format text: NOT ENGLISH

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

Free format text: LANGUAGE OF EP DOCUMENT: GERMAN

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 502004013115

Country of ref document: DE

Effective date: 20120301

REG Reference to a national code

Ref country code: SE

Ref legal event code: TRGR

RAP2 Party data changed (patent owner data changed or rights of a patent transferred)

Owner name: PERKINELMER CHEMAGEN TECHNOLOGIE GMBH

REG Reference to a national code

Ref country code: NL

Ref legal event code: T3

REG Reference to a national code

Ref country code: NL

Ref legal event code: SD

Effective date: 20120308

REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2377733

Country of ref document: ES

Kind code of ref document: T3

Effective date: 20120330

REG Reference to a national code

Ref country code: DE

Ref legal event code: R081

Ref document number: 502004013115

Country of ref document: DE

Owner name: PERKINELMER CHEMAGEN TECHNOLOGIE GMBH, DE

Free format text: FORMER OWNER: CHEMAGEN BIOPOLYMER-TECHNOLOGIE AKTIENGESELLSCHAFT, 52499 BAESWEILER, DE

Effective date: 20120213

Ref country code: DE

Ref legal event code: R081

Ref document number: 502004013115

Country of ref document: DE

Owner name: PERKINELMER CHEMAGEN TECHNOLOGIE GMBH, DE

Free format text: FORMER OWNER: CHEMAGEN BIOPOLYMER-TECHNOLOGIE AKTIENGESELLSCHAFT, 52499 BAESWEILER, DE

Effective date: 20120105

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20120330

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20120301

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111130

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111130

REG Reference to a national code

Ref country code: GB

Ref legal event code: 732E

Free format text: REGISTERED BETWEEN 20120607 AND 20120613

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111130

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111130

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111130

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20120229

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111130

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111130

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20120831

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 502004013115

Country of ref document: DE

Effective date: 20120831

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20120731

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130201

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 502004013115

Country of ref document: DE

Effective date: 20130201

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111130

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20120705

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20040705

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 13

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 14

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 15

P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20230425

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 20230525

Year of fee payment: 20

Ref country code: IT

Payment date: 20230612

Year of fee payment: 20

Ref country code: IE

Payment date: 20230524

Year of fee payment: 20

Ref country code: FR

Payment date: 20230523

Year of fee payment: 20

Ref country code: DK

Payment date: 20230627

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: SE

Payment date: 20230526

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: BE

Payment date: 20230616

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20230518

Year of fee payment: 20

Ref country code: FI

Payment date: 20230712

Year of fee payment: 20

Ref country code: ES

Payment date: 20230809

Year of fee payment: 20

Ref country code: CH

Payment date: 20230801

Year of fee payment: 20

Ref country code: AT

Payment date: 20230626

Year of fee payment: 20