EP1919625A1

EP1919625A1 - Device and method for the elimination of magnetic particles from a liquid

Info

Publication number: EP1919625A1
Application number: EP06792895A
Authority: EP
Inventors: Thomas Rothmann; Thomas Deutschmann; Christian Lenz; Cordula Leurs
Original assignee: Qiagen GmbH
Current assignee: Qiagen GmbH
Priority date: 2005-08-18
Filing date: 2006-08-18
Publication date: 2008-05-14
Anticipated expiration: 2026-08-18
Also published as: JP2009505090A; EP1919625B1; JP5027128B2; US8323507B2; US20090206039A1; DE102005039175A1; WO2007020294A1

Abstract

Disclosed is a device for eliminating magnetic particles from a liquid. Said device comprises a first vessel (10), a second vessel (20), a joining area (11, 21, 30; 200) extending from the interior of the first vessel (10) to the interior of the second vessel (20), at least one magnet (40) for supplying a magnetic field, and a guiding means (50), with the aid of which the magnetic field can be directed along one side of the joining area (11, 21, 30; 200).

Description

Apparatus and method for separating magnetic particles from a liquid

The present invention relates to a device for separating magnetic particles from a liquid and to a method for separating magnetic particles from a liquid. The device and method are suitable for applications in biochemistry, molecular genetics, microbiology, medical diagnostics or forensic medicine, for example.

Methods based on magnetic separation using specific and / or unspecific binding magnetic particles are becoming increasingly important in the field of sample preparation for diagnostic or analytical studies, in particular for the isolation of nucleic acids. This is especially true for automated processes, since in this way a large number of samples can be prepared within a short time and can be dispensed laborious Zentrifugationsschritte. This will create the conditions for efficient screening with high sample throughput. This is of tremendous importance, since a purely manual handling of very large sample numbers is practically unmanageable. Another important application of magnetic particles are pharmaceutical screening methods for the identification of potential drugs.

The basic principle of the magnetic separation of substances from complex mixtures is based on the fact that magnetic particles, for example by chemical treatment of their surface with specific binding properties are equipped for the target substances to be separated. The size of such magnetic particles is generally in the range of about 0.05 to 500 microns so as to provide a large surface area for the binding reaction. Furthermore, the magnetic particles may have a density similar to the density of the liquid in which they are suspended. In this case, sedimentation of the magnetic particles can take several hours. In known separation processes, the magnetic particles are immobilized by applying magnetic forces or a magnetic field, for example by means of a permanent magnet, at one point. This accumulation of magnetic particles is also referred to as pellet. Subsequently, the liquid supernatant is separated, for example, by suction or decantation and discarded. Since the magnetic particles are immobilized by the magnetic forces, it is largely prevented that magnetic particles are separated together with the supernatant.

Typically, the immobilized magnetic particles are then resuspended. In this case, an elution liquid or an elution buffer is used, which is suitable for dissolving the bond between the target substance and the magnetic particles, so that the target substance molecules are released from the magnetic particles. The target substance molecules can then be separated together with the elution liquid, while the magnetic particles are immobilized by the action of a magnetic field. Before the elution step, one or more washing steps can be carried out.

Various devices have been described for carrying out such magnetic particle separation processes. This is how US describes

2001/0022948 a device in which a magnetic rod in a first

Submerged reaction vessel containing suspended in liquid magnetic particles.

There, the magnetic rod attracts the magnetic particles, so that the

Magnetic particles adhere to the rod. The magnetic rod is then pulled out of the first reaction vessel together with the magnetic particles adhering thereto and introduced into a second reaction vessel. There will then be the

Magnetic force of the rod is reduced or switched off, so that the magnetic

Dissolve particles from the rod and in a second reaction vessel

Liquid to be suspended. Similar methods are also known from US 6,065,605 and WO 2005/005049.

On the other hand, EP 0 965 842 discloses a device in which the magnetic particles are mixed with the liquid in which they are suspended be pulled up with a pipette. The pipette tip has a special separation area, which can be acted upon by a magnet with a magnetic field. As a result, the magnetic particles are immobilized as a pellet on the inside of the pipette tip. Subsequently, the pipetted liquid is removed from the pipette tip by the pipetting function. Thereafter, the magnetic field in the separation region can be removed again, whereby the immobilized in the pellet magnetic particles are released again. A similar method and apparatus are described in US 6,187,270.

Another principle for the separation of magnetic particles is described in EP 0 905 520. The magnetic particles remain in the same reaction vessel while the liquid in this vessel is exchanged. In this case, the pellets for adaptation to a respective process step in a desired height at the

Side wall of the reaction vessel to be immobilized. This is done by

Provision of magnets which are arranged on different arms of a rotatably mounted carrier at respectively different distances from the axis of rotation.

By rotating the carrier, a particular arm can be brought into the vicinity of the side wall of the reaction vessel, and thus a specific magnet. At this point, the magnetic particles are then immobilized as a pellet.

The said conventional devices and methods all have the common feature that they are designed as so-called open systems, since according to their respective principle of action magnetic rods or pipettes must be inserted one or more times in the reaction vessel. As a result, these conventional devices and methods run the risk of cross-contamination of other reaction vessels by aerosol and / or droplet formation. As a result, examination results can be falsified or even rendered unusable.

It is therefore an object of the present invention to at least partially overcome the above-described problems in the prior art.

This object is achieved by an apparatus according to claim 1 and a method according to claim 29. Further details, advantages and aspects of The present invention will become apparent from the dependent claims, the description and the accompanying drawings.

According to an embodiment of the present invention, there is provided an apparatus for separating magnetic particles from a liquid comprising a first vessel, a second vessel, a bonding surface connecting the interior of the first vessel to the interior of the second vessel, at least one magnet for providing a magnetic field, and a guide means by means of which the magnetic field is guided along one side of the connection surface, provided.

By such a device, magnetic particles suspended in a liquid in the first vessel can be separated from this liquid without having to insert a magnetic rod or a pipette tip into the first vessel. Rather, the magnetic particles can be formed into a pellet by the magnetic field, and this pellet can be transferred to the second vessel along the joint surface by the guide means located outside the vessel. In this way, the risk of cross-contamination, for example, by dripping the liquid from the magnetic rod or the pipette tip, significantly reduced or even excluded. Furthermore, the device can be provided as a closed system, further reducing the risk of cross-contamination.

Depending on the application, the length of the connection surface can be chosen so that an influence of the particles, for example, the drying of the particles, is supported or reduced.

According to a further exemplary embodiment of the present invention, the connecting surface is formed by a first side wall of the first vessel, a second side wall of the second vessel and a connecting region connecting the first and the second side wall. This eliminates the need to provide a separate interface.

In particular, the first and the second vessel could thus be formed as depressions (wells) in a microtiter plate. As an alternative to this embodiment, of course, the first and the second vessel as well as the bonding surface can be provided as separate elements. In this case, for example, the connection surface could be formed as a bridge or hose.

According to another embodiment of the present invention, a permanent magnet is used. In this way, the magnetic field can be provided inexpensively. The guide means would then be designed such that the magnet could be guided mechanically along the connection surface. Alternatively, the at least one magnet could also be designed as an electromagnet. Also in this case, the electromagnet can be guided mechanically along the connection surface. In addition, however, a plurality of electromagnets, for example, on an underside of the connecting surface, be arranged one behind the other. The guide means would then sequentially energize and turn the electromagnets on and off so that the magnetic field generated by the electromagnets travels along the interface from the first to the second vessel.

According to another embodiment of the present invention is

Guide means is designed so that the at least one magnet can be guided in a fixed predetermined distance from the connection surface. In particular, the fixed predetermined distance may be zero so that the magnet is in contact with the bonding surface as it is passed past it.

In this way, it can be ensured that a substantially constant magnetic force is always exerted on the magnetic particles formed into a pellet along the path from the first vessel to the second vessel. In this way, it is possible to effectively prevent magnetic particles from being released from the pellet due to a weakening of the magnetic force.

According to another exemplary embodiment of the present invention, at least one heating and / or cooling element, for example, is at the connecting surface Heating wire and / or Peltier element provided. By using heating and / or cooling elements, the magnetic particles can be kept on their way to a predetermined temperature.

According to another embodiment of the present invention, the connection surface along the path of the at least one magnet is formed as a circular arc. Typically, then, the guide means is formed so that the at least one magnet is guidable on a circular path, the radius of the circular path being less than or equal to the radius of the arc formed by the connection surface.

In this way, a particularly simple form of the guide can be done by the magnet is guided on a circular path or along a circular arc with a constant radius. The guide means can be mounted on a rotation axis, whereby the drive and the control of the guide means can be designed particularly simple. This also allows easy automation of the machining operations.

According to yet another embodiment of the present invention, at least a third vessel is further provided, which is connected via a second connection surface with the first and the second vessel, and a second guide means on which at least one further magnet is arranged. In this case, the first and the second vessel together with the third vessel, the second connection surface, the second guide means and the further magnet form a further device for separating magnetic particles as described above.

In this way, after the first separation of the magnetic particles from the liquid in the first vessel one or, if several vessels and

Guide devices are interposed, several washes of the magnetic particles take place before the magnetic particles in a

Be transferred elution solution. According to yet another exemplary embodiment of the present invention, at least one of the vessels has a functional element, in particular an outlet opening and / or a filter. With this functional element, for example, subsequent analysis steps, such as a PCR step (Polymerase Chain Reaction), can be prepared. In this case, the outlet opening preferably has fastening possibilities with the aid of which, for example, reaction stubs can be fastened to the outlet opening.

According to yet another embodiment of the present invention, the vessels are formed in a cartridge. This allows a compact design, in particular, a so-called lab-on-a-chip can be realized in this way. In such a lab-on-a-chip, all devices necessary for carrying out an examination are integrated on a chip or a cartridge.

According to another aspect of the present invention, there is provided a method of separating magnetic particles from a liquid comprising the steps of:

(A) providing a first vessel, a second vessel, a connection surface, which connects the interior of the first vessel with the interior of the second vessel, and a guide means for guiding at least one magnetic field;

(b) providing a suspension of magnetic particles in a first liquid in the first vessel;

(c) providing the at least one magnetic field by means of the guide means to a region of the connection surface arranged in the interior of the first vessel, so that a pellet of magnetic particles is formed at this area;

(D) guiding the at least one magnetic field by means of the guide means along one side of the connection surface to one inside the second region of the bonding surface, so that the magnetic particle pellet is guided along the bonding surface to a region of the bonding surface located inside the second vessel;

(e) removing the at least one magnetic field by means of the

Guiding means of the arranged in the interior of the second vessel portion of the connecting surface, so that the pellets forming magnetic particles are released again.

Such a method can, for example, in a device according to a

Embodiment of the present invention can be carried out in a simple manner in an automated form. With such a separation method, the risk of cross-contamination compared to the prior art is considerably reduced, since it is not necessary to introduce a magnetic rod or a pipette tip into the vessel. Therefore, here the risk of dripping liquid from the magnetic rod or the pipette tip is excluded.

In the following, the details of the invention will be explained with reference to various embodiments with reference to the accompanying drawings. It shows:

FIGS. IA to IE a schematic representation of a device and a

Method according to an embodiment of the present

Invention.

FIGS. 2A to 2E a schematic representation of a device and a

Method according to another embodiment of the present invention.

FIGS. 3A to 3C a schematic representation of a device and a

Method according to yet another embodiment of the present invention. FIGS. 4A and 4B is a schematic illustration of a washing process according to an embodiment of the present invention.

5 shows a guide means according to an exemplary embodiment of the present invention.

Fig. 6 shows a guide means according to another embodiment of the present invention.

7 is a cross-sectional view of a connection portion according to an embodiment of the present invention.

8 shows another embodiment of the present invention,

Fig. 9 shows another embodiment of the present invention.

Fig. 10 is a schematic representation of another embodiment of the present invention, in which the invention is implemented in a cartridge.

FIGS. IIA to HF a schematic representation, as an inventive

Method is performed in the embodiment shown in Fig. 10.

Fig. 12 is a schematic representation of a variant of the embodiment of the present invention shown in Fig. 10.

FIG. 13 shows a schematic illustration of a variant of the embodiment shown in FIG.

10 of the present invention.

Fig. 14 is a schematic representation of another variant of in

Fig. 10 embodiment shown. Fig. 15 is a schematic representation of a development of the in Fig.

10 shown embodiment of the present invention.

In the following description of various exemplary embodiments of the present invention, functionally identical features of the various embodiments are provided with the same reference numerals.

Fig. IA shows a schematic representation of a device according to an embodiment of the present invention. In a first vessel 10 is a liquid 15 in which magnetic particles 60 are suspended. Furthermore, a second vessel 20 is shown in which a second liquid 25, e.g. a wash solution or an elution solution. The first vessel 10 has a first side wall 11, which is connected to a second side wall 21 of the second vessel 20 via a connection region 30. In this embodiment, the first side wall 11, the second side wall 21 and the connection portion 30 form a connection surface extending from the interior of the first vessel 10 to the inside of the second vessel 20. However, such a connection surface could also be provided as a bridge formed in the form of a reverse Us separately from the first and the second vessel, which is inserted into the first and the second vessel. Furthermore, the connection surface could also be formed by a tube, one end of which is arranged in the interior of the first vessel and the other end is arranged in the interior of the second vessel.

Furthermore, a magnet 40 is provided, which may be embodied for example as a neodymium permanent magnet or as an electromagnet. The magnet 40 is arranged on a guide means 50. The guide means 50 is arranged so that it can guide the magnet 40, and thus the magnetic field generated by it, along the connection surface from the interior of the first vessel 10 into the interior of the second vessel 20. In the present exemplary embodiment, this means that the guide means 50 can guide the magnet 40 along the first side wall 11 and along an underside of the connection region 30 to the second side wall 21. As a guide means 50, for example, a cylindrical roller or a rotary arm can be used, as will be explained later in this application. However, it is also possible, for example, the magnet 40 on a flexible band, which is guided along the side walls 11, 21 and the underside of the connecting portion 30. The guide means 50 is designed to hold the magnet 40 at a fixed predetermined distance from the connecting surface, ie the side walls 11, 21 and the underside of the connecting region 30. In this case, the fixed predetermined distance is selected so that the magnetic attraction, the magnet 40 exerts on the suspended magnetic particles 60 when it is guided to the side wall 11, sufficient that the suspended particles are immobilized in a pellet 61 on the side wall 11 (see Fig. IB). In particular, the distance between the magnet 40 and the side walls 11, 21 and the underside of the connection region 30 may be zero. In this case, the magnet 40 is in contact with the sidewalls 11, 21 as well as the underside of the connecting portion 30 when it is passed therethrough.

According to a further exemplary embodiment of the present invention, the connection surface can be channel-shaped. FIG. 7 shows a cross-section of the connecting region 30, which is formed on its upper side between the first vessel 10 and the second vessel 20 in the form of a groove-shaped depression. In this way, it is possible to prevent the first liquid 15, which possibly adheres to the pellet 61, from detaching laterally in the upper region of the connection region 30 and possibly leading to cross contamination. Should liquid actually detach on movement of the pellet 61 from the first to the second vessel, this liquid is returned via the channel into the first or the second vessel.

In the following, reference will now be made to FIGS. IA to IE describes a method according to an embodiment of the present invention. In Fig. IA, the initial state is seen in which the magnetic particles 60 are suspended in the liquid 15 in the first vessel 10. The magnet 40 is arranged outside the region of the side wall 11 of the first vessel 10. As shown in Fig. IB, the magnet 40 is then brought by the guide means 50 to the side wall 11 of the first vessel 10. There he attracts the magnetic particles 60, which are immobilized as a pellet 61 on the side wall 11. Subsequently, the magnet 40 is guided by the guide means 50 along the side wall 11 via the connecting portion 30 to the side wall 21 of the second vessel 20, see Fign. IC and ID. The magnetic particles formed by the magnetic force to the pellet 61 follow due to the magnetic attraction of the movement of the magnet 40. In this way, the pellet 61 along the connecting surface, ie along the inside of the side wall 11 over the top of the connecting portion 30 to the inside of the side wall 21 of the second vessel 20, out. Finally, as shown in FIG. IE, the magnet 40 is led away from the side wall 21 of the second vessel 20, so that the magnetic particles forming the pellet 61 are released again. The magnetic particles 60 resuspend in the liquid 25 in the second vessel 20, eg a washing or elution solution.

Another embodiment of the present invention will now be described with reference to FIGS. 2 A to 2E described. Again, a first and a second vessel 10,

20 are provided, which are connected to each other via a connecting surface 11, 21, 30. The connection surface is in turn formed by a first side wall 11, a second side wall 21 and a connection region 30. It is the

Bonding surface, i. Here, the first side wall 11, the second side wall 21 and the connecting portion 30, formed so that it forms a circular arc with radius R. Typically, the side walls 11, 21 and the connecting portion 30 are integrally formed as a connecting surface. However, as already stated above, the first and the second vessel as well as the connection surface can also be provided as separate elements. The guide means 50 is formed as a four-armed turnstile, as shown enlarged in Fig. 5.

In Fig. 5, the guide means on four rotating arms 51, 52, 53, 54, which are rotatably mounted about an axis 55. At the ends remote from the axis of rotation 55 of the pivot arms 51, 52, 53, 54 are each magnets 40, 41, 42, 43 are arranged. The total length r of the rotating arms 51, 52, 53, 54 including the magnets 40, 41, 42, 43 is less than or equal to the radius R of the circular arc, so that the magnets 40, 41, 42, 43 at a distance Rr on the side walls 11th , 21 and the connection area 30 can be passed. If the total length r is equal to the circular arc radius R, the magnets 40, 41, 42, 43 with the side walls 11, 21 and the connecting portion 30 in contact when they are passed by it. In this case, it is advantageous if the surfaces of the magnets 40, 41, 42, 43, which are in contact with the side walls 11, 21 and the connection region 30, are advantageous are curved, wherein the radius of curvature is smaller than the circular arc radius R.

According to Fig. 5, the four pivot arms are integrally formed, but they could also be formed as a single pivot arms and individually secured to the axis of rotation 55. Furthermore, the number of four rotating arms is merely exemplary, because depending on the application, fewer or more rotating arms can be provided. In particular, it is possible to provide only a single rotary arm. Furthermore, the four pivot arms in Fig. 5 are each offset by 90 °, i. evenly distributed over the circumference covered by the turnstile 2 π r. Depending on the application, however, the two or more rotating arms can also be arranged offset to one another in arbitrarily adjustable angular distances.

Another embodiment of a guide means 50 usable in the apparatus shown in Fig. 2A is shown in Fig. 6. Therein, the guide means 50 is formed as a cylindrical roller or wheel with a radius r, which is less than or equal to the circular arc radius R. According to FIG. 6, three magnets 40, 41, 42 are each offset by 120 ° in receptacles 56, 57, 58. However, it would also be conceivable that the magnets are arranged on the surface of the cylindrical guide means, in which case the radius r together with the thickness of the magnets must be less than or equal to the circular arc radius R. Again, of course, the number and mutual position of the magnets can be varied according to the requirements of a particular application accordingly. In particular, it is conceivable that the magnets 40, 41, 42 can be removed from the receptacles 56, 57, 58, so that the number of magnets between one and the number of receptacles can be varied.

The operation of the embodiment shown in Fig. 2A is shown in Figs. 2A to 2E reproduced. First, the magnet 40 is moved to the side wall 11 of the first vessel 10, where then the magnetic particles form a pellet 61 (Figure 2B). The magnet 40 is then passed along the circular arc, followed by the pellet 61 (Figures 2C and 2D). The pellet 61 is then introduced into the second vessel 20 (FIG. 2E) and finally the magnet 40 is led away from the second side wall 21 so that the magnetic particles are in the second vessel Resuspend fluid (not shown). In this way, the pellet is guided from inside the first vessel along the bonding surface to the interior of the second vessel.

Another embodiment of the present invention is shown in FIGS. 3 A to 3C shown. In addition, a third vessel 70 is provided, which is connected to the second vessel 20 via a second connection region 80. In this case, the interconnected side walls of the second and the third vessel and the second connection region form a second connection surface, which is formed as a circular arc with radius R '. Typically, the circular arc radius R 'is equal to the circular arc radius R between the first and second vessels, but may be selected differently from R depending on the nature of the application. Furthermore, a second guide means 100 is arranged between each opposite side walls of the second and the third vessel, which has at least one further magnet 90. With the aid of the magnet 90 and the second guide means 100, the magnetic particles transferred from the first vessel 10 into the second vessel 20 and resuspended there can be combined in a second pellet 62 on the side wall of the second vessel. In the same way as between the first and the second vessel, the pellet 62 can now be transferred from the second vessel to the third vessel 70 via the second connecting surface. When the magnet 90 is led away from the side wall of the third vessel 70, the magnetic particles may be resuspended in the liquid 75 contained in the third vessel 70. For example, in this device, a washing solution can be provided in the second vessel and an elution solution in the third vessel. In this case, the eluted magnetic particles could be transported back by opposite rotation of the second guide means in the second vessel and disposed of there. Furthermore, of course, further vessels and interposed connecting surfaces and guide means may be provided with magnets, wherein in the respective vessels for a particular method required liquids are provided.

According to another embodiment of the present invention, the apparatus shown in Fig. 3A may also be used to carry out a washing process as follows. First, the first pellet 61 from the first vessel 10th in the filled with washing solution second Gelaß 20 transferred. There, the magnet 40 is then led away from the side wall of the second vessel along a first direction of rotation, so that the magnetic particles are resuspended in the washing solution. Then, the magnet 90 arranged on the second guide means 100 is guided along a first rotational direction to the opposite side wall of the second vessel, so that the magnetic particles form a second pellet 62 there. In this case, the first direction of rotation of the first guide means 50 is opposite to the first direction of rotation of the second guide means 100. Subsequently, the magnet 90 is then led away from the side wall of the second vessel again along a second direction of rotation. Now the second pellet 62 dissolves and the magnetic particles are resuspended in the wash solution. Then, the magnet 40 arranged on the first guide means 50 is guided along a second rotational direction to the opposite side wall of the second vessel, so that the magnetic particles again form a first pellet 61 there. In this case, the second direction of rotation of the first guide means 50 is opposite to the second direction of rotation of the second guide means 100. The first and second rotational direction of the first guide means may be the same or opposite. Also, the first and second rotational direction of the second guide means may be the same or opposite. The process can be repeated until the washing process is completed successfully.

Hereinafter, another embodiment of the present invention will be described with reference to FIG. 8. Therein, the first vessel 10 and the second vessel 20 are provided as separate vessels. A connection surface 200 is formed as a bridge in the form of an inverted Us, wherein a first end of the connection surface 200 is arranged in the first vessel 10 and a second end of the connection surface 200 in the second vessel 20 is arranged. Typically, the connecting surface 200 is formed on its upper side groove-shaped. In this case, a plurality of electromagnets 40 are arranged in the connection surface 200, arranged one behind the other from the first vessel 10 to the second vessel 20. For example, the connecting surface 200 could be formed as an injection molded part, in which the electromagnets are embedded. The electromagnets are individually controllable by a guide means 50, that is individually switched on and off. In this embodiment, the separation of the magnetic particles is as follows: First, all of the electromagnets 40 under the connection surface 200 are turned off, and the connection surface is placed in the first and second vessels as shown. Then, the guide means 50 controls the lowermost solenoid (s) at the first end of the interface located in the first vessel. There then forms a pellet of magnetic particles due to the magnetic attraction. Now adjacent electromagnets, which are arranged closer to the end located in the second vessel along the connection surface 200, are switched on one after the other and the electromagnets are switched off again from the first end of the connection surface. In this way, the magnetic field travels from the first end of the bonding surface to the second end of the bonding surface, and the pellet retraces this motion due to the magnetic attraction. When the pellet finally reaches the inside of the second vessel, the electromagnets are switched off and the magnetic particles forming the pellet resuspend in a liquid 25 in the second vessel 20. In this way separation of the magnetic particles can take place without the device moving parts must have. In this way, the device is particularly reliable and low maintenance.

Below is another embodiment of the present invention

Invention described with reference to FIG. 9. Again, a first and a second vessel 10, 20 are provided, which are connected to each other via a connecting surface 11, 21, 30. The connection surface is in turn formed by a first side wall 11, a second side wall 21 and a connection region 30. Furthermore, heating elements 110 are provided on the connecting surface 11, 21, 30. Through these heating elements, the temperature of the magnetic particles can be increased, so that, for example, the drying of the particles is supported.

However, instead of heating elements, cooling elements, for example Peltier elements, can also be provided on the connecting surface 11, 21, 30 in order to provide a

Cooling of the magnetic particles and adhering to the magnetic particles

Effect substances. In this way, for example, a drying of

Particles are reduced, if required by the analysis. Furthermore, in the embodiment shown in FIG. 9, the vessel 20 has additional functional elements 120, 130 which serve to prepare subsequent analysis steps. The vessel 20 has at the bottom of the vessel an outlet opening 120, on the inside of a filter 130 is attached.

Of course, various aspects of the embodiment just described can also be combined with the exemplary embodiments described above. Thus, e.g. Also be arranged along a first side wall, a connecting region and a second side wall individually controllable electromagnets. Likewise, a mechanical guide, e.g. a roller or pivot arms, are guided along a connecting surface formed separately as a bridge.

In all embodiments described above, the connecting surfaces may be designed channel-shaped. Furthermore, in all described embodiments, the guide means may be formed so that the

The speed with which they lead the magnetic field or along the connecting surfaces, is controllable. In particular, the speed can be set to zero so that the pellet can be immobilized at the current position. Furthermore, in all described embodiments, the guide means may be formed so that the direction in which they or the magnetic fields to the

Run along connecting surfaces, is controllable. In particular, then one

Direction reversal possible during the movement of the pellets. Furthermore, all embodiments mentioned above can be designed as closed systems.

In Fig. 10, yet another embodiment of the present invention is shown schematically. This is a so-called lab-on-a-chip, in which a first and a second vessel 1010, 1020 are integrated in a cartridge 1000. The first and second vessels 1010, 1020 are interconnected by a connection area 1030. Both vessels 1010, 1020 are formed as chambers in the cartridge 1000 and filled with liquid. Typically, the second passage 1020 could contain an elution liquid. In this context, it should be noted that Fig. 10 is merely a schematic representation in which the first and the second vessel are the same size. Of course, the sizes of the individual vessels may differ. In particular, typically the volume of an elution vessel will be less than that of a wash vessel.

A closure 1100 prevents mixing of the liquids. However, closure 1100 may be removed using the cartridge. Optionally closure 1100 is designed so that it can be brought into the closed position after removal and again serves as a closure. Typically, the cartridge 1000 is provided with a lid in which two access openings 1012, 1022 are located. The access openings 1012, 1022 serve to bring magnetic particles into and out of the vessels. The access openings 1012, 1022 may be provided with lids. Finally, the cartridge has a magnet 1040 which can be moved by a guide means 1050 along a wall of the first vessel 1010, the connection region 1030 to a wall of the second vessel 1020. In particular, the magnet 1040 may not only be attached to a sidewall but also along the ceiling wall, i. the lid, or the bottom of the cartridge 1000 be feasible.

In the following, with reference to FIGS. 1A to 1 IF briefly describe the operation of the embodiment of the present invention shown in FIG. 10. As shown in FIG. 1A, magnetic particles 1060 are first introduced into the first vessel 1010 through the access opening 1012. If these particles 1060 are now to be removed from the liquid present in the first vessel 1010, then the magnet 1040 is brought in by means of the guide means 1050. This forms a pellet 1061 immobilized on the sidewall of the first vessel 1010 (see FIG. 1B). Pellet 1061 is then fed to closure 1100 (see Figure 1 IC). Now, the shutter 1100 is opened and the path for the pellet 1061 is released into the connection area 1030 (see Fig. HD). The pellet 1061 is then inserted into the second vessel 1020 by means of the magnet 1040 (see Fig. HE), where it can subsequently be released (see Fig. HF). Should the magnetic particles 1060 from the second vessel 1020 through the second Access opening 1022 are removed, it is advisable to form the magnetic particles 1060 again by means of the magnet 1040 into a compact pellet 1061, which can be easily seen through opening 1022. Via the second access opening 1022 it is likewise possible to remove the liquid without the magnetic particles 1060. Typically, the magnet 1040 would hold the pellet 1061 at a distance from the access port 1022 during liquid withdrawal, thus allowing removal of the liquid without entrainment of the magnetic particles.

Another embodiment of the present invention is shown in FIG. In essence, the structure is the same as that shown in Fig. 10, but a magnet arrangement similar to the embodiment shown in Fig. 8 is provided. In this case, a plurality of electromagnets 1040 - from the first vessel 1010 to the second vessel 1020 extending successively arranged - in the cartridge

1000 integrated. For example, the cartridge 1000 could be formed as an injection-molded part, in which the electromagnets 1040 are embedded. The

Electromagnets are individually controllable by a guide means 1050, i. individually switched on and off. In this way, a magnetic field extending from the first vessel 1010 via the connection region 1030 to the second vessel 1020 can be generated. Pelleting and transport of the pellet from the first vessel 1010 to the second vessel 1020 is then similar to that shown in FIG

Ausiührungsbeispiel why a more detailed explanation is omitted here.

Fig. 13 shows a perspective view of another embodiment of the present invention. The interior of the cartridge 1000 corresponds substantially to the construction shown in FIG. However, the magnet 1040 is disposed outside of the cartridge 1000. It can be guided along the surface of the cartridge 1000 by means of a guide means 1050 such that a pellet moves under the influence of the magnetic force from the first vessel via the connection region to the second vessel. Furthermore, the magnet 1040 may be directed away from or toward the surface by the guide means 1050. In this way, for example, a pellet may be formed by lowering the magnet 1040 above the first vessel onto the surface of the cartridge. Likewise, those in a pellet bonded magnetic particles are released by the magnet 1040 is lifted off the surface of the cartridge again.

Another embodiment of the present invention is shown in FIG. Therein, the cartridge 1000 is arranged on a guide means 1050, which is designed as a movable support. The carrier 1050 is movable in its plane, but preferably also perpendicular thereto, so that it can move the cartridge 1000 mounted thereon along a predeterminable path. A magnet 1040 is held substantially stationary by a retaining means 1045. By raising or lowering the carrier 1050, the surface of the cartridge 1000 can be brought to the magnet 1040. By moving the carrier 1050 in its plane, the cartridge 1000 is then moved on a predeterminable path under the magnet 1040. In essence, therefore, the embodiment shown in Fig. 14 represents a reversal of the principle shown in Fig. 13.

FIG. 15 shows a development of that shown in FIG

Embodiment. In this case, in addition to the first and the second vessel 1010, 1020 still a third vessel 1070 on the cartridge 1000 is arranged. This third vessel 1070 is separated from the third vessel 1070 by a second closure 1200. In this case, the second vessel 1020 could contain a washing liquid and the third vessel 1070 an elution solution. It should be understood that, of course, any number of other vessels can be integrated on a cartridge and the exact number of vessels and the liquids contained in them are tailored to the specific application.

By the embodiments of the present invention described above

The invention enables a separation of magnetic particles from a liquid which significantly reduces or even eliminates the risk of cross-contamination. In particular, the devices according to the above embodiments of the present invention may be configured and operated as closed systems. The devices and methods according to the embodiments of the present invention are simple and to a considerable extent automation friendly.

Claims

claims

An apparatus for separating magnetic particles from a liquid, comprising

a first vessel (10; 1010),

a second vessel (20; 1020),

a connecting surface (11, 21, 30; 200) extending from the interior of the first vessel (10) to the interior of the second vessel (20),

at least one magnet (40) for providing a magnetic field,

and a guide means (50) by means of which the magnetic field along one side of the connecting surface (11, 21, 30, 200) is feasible.

2. Apparatus according to claim 1, wherein the connecting surface is formed by a first side wall (11) of the first vessel, a second side wall (21) of the second vessel and a connecting region (30) connecting the first and second side walls.

3. Device according to claim 1 or 2, wherein the at least one magnet (40) is a permanent magnet.

4. Apparatus according to claim 1 or 2, wherein the at least one magnet (40) is an electromagnet.

5. Device according to one of the preceding claims, wherein the guide means (50) is formed so that the at least one magnet (40) at a fixed predetermined distance to the side of the connecting surface (11, 21,

30; 200) is feasible.

A device according to claim 5, wherein said fixed predetermined distance is zero so that the magnet is in contact with said side joining surface (11, 21, 30, 200) when it is passed therethrough.

7. Device according to one of the preceding claims, wherein the guide means (50) at least one further magnet (41, 42, 43) which is spaced from the first magnet (40).

8. Device according to one of the preceding claims, wherein at least one heating and / or cooling element (110) is provided on the connecting surface (11, 21, 30;

9. Device according to one of the preceding claims, wherein the connecting surface (11, 21, 30, 200) is formed as a circular arc.

10. The apparatus of claim 9, wherein the guide means (50) is formed so that the at least one magnet (40) can be guided on a circular path, wherein the radius (r) of the circular path is less than or equal to the radius (R) of Circular arc, which is formed by the connecting surface (11, 21, 30, 200).

11. The device according to claim 10, wherein the guide means (50) has at least one first pivot arm (51), whose one end is arranged on a rotation axis (55) and at the other end of the at least one magnet (40) is arranged.

12. The apparatus of claim 11, wherein the guide means (50) one or more further rotation arms (52, 53, 54), in which one end to the axis of rotation (55) is arranged and at the respective other end of the another magnet (41, 42, 43) is arranged.

13. The apparatus of claim 12, wherein the rotating arms (51, 52, 53, 54) are integrally formed.

14. Device according to one of claim 10, wherein the guide means (50) is cylindrical, which is rotatably mounted about an axis (55).

15. The apparatus of claim 14, wherein the at least one magnet (40) and / or the further magnets (41, 42) on the surface of the cylindrical guide means (50) are arranged.

16. The apparatus of claim 14, wherein the at least one magnet (40) and / or the further magnets (41, 42) each in a in the cylindrical guide means (50) formed receptacle (56, 57, 58) are arranged.

17. Device according to one of claims 12, 13, 15 or 16, wherein the at least one magnet (40) and the one or more further magnets (41, 42, 43) are each offset by the same angle to each other.

18. Device according to one of the preceding claims, wherein the guide means (50) is formed so that the speed at which the magnetic field of the one (40) and / or the plurality of further magnets (41, 42, 43) along the connecting surface (11, 21, 30, 200) leads, is controllable.

19. Device according to one of the preceding claims, wherein the guide means (50) is formed so that the direction in which the magnetic field of the one (40) and / or the plurality of further magnets (41, 42, 43) along the connecting surface (11, 21, 30, 200) leads, is controllable.

20. Device according to one of the preceding claims, further comprising

at least a third vessel (70) which is connected via a second connection surface with the first and the second vessel, and

a second guide means (100) for guiding at least one further magnetic field, wherein the first and the second pass (10, 20) together with the third

Container (70), the second connection surface, the second guide means (100) and the further magnetic field form a device according to one of claims 1 to 18.

The apparatus of claim 20, wherein the first and second guide means (50, 100) are disposed on opposite sides of the second vessel (20).

22. Device according to claim 20 or 21, wherein the second vessel (20) contains a washing solution and the third vessel contains an elution solution.

23. Device according to one of the preceding claims, wherein at least one of the vessels (10, 20, 70) has a functional element, in particular an outlet opening and / or a filter.

24. Device according to one of the preceding claims, wherein the connecting surface (30) is channel-shaped.

25. Device according to one of the preceding claims, wherein the first and the second vessel (1010, 1020) and / or the third vessel (1070) in a

Cartridge (1000) are formed.

The apparatus of claim 25, wherein each adjacent vessel (1010, 1020; 1020, 1070) is separated from each other by a removable closure (1100, 1200).

The apparatus of claim 25 or 26, wherein the cartridge (1000) comprises a cover having a first access opening (1012) to a first vessel (1010) and a second access opening (1022, 1072) to a second vessel.

The apparatus of any one of claims 25 to 27, wherein the guide means (1050) is adapted to guide the cartridge (1000) along a magnet (1040).

29. A method of separating magnetic particles from a liquid, comprising the steps of:

(a) providing a first vessel (10), a second vessel (20), a bonding surface (11, 21, 30; 200) connecting the interior of the first vessel with the interior of the second vessel (20), and a guide means (50) for guiding at least one magnetic field (40);

(b) providing a suspension of magnetic particles (60) in a first liquid (70) in the first vessel (10);

(c) providing the at least one magnetic field by means of the

Guiding means (50) to a region (11) of the connecting surface arranged in the interior of the first vessel (10) so that a pellet (61) of magnetic particles is formed on this region (11);

(d) guiding the at least one magnetic field by means of the guide means (50) along one side of the connection surface (11, 21, 30; 200) such that the magnetic particle pellet (61) is disposed along an opposite side of the connection surface (11, 21, 30, 200) is guided to a region (21) of the connection surface arranged in the interior of the second vessel (20);

(E) removing the at least one magnetic field by means of the guide means (50) from the interior of the second vessel (20) arranged region (21) of the connection surface, so that the

Pellet (60) forming magnetic particles (60) are released again.

30. The method of claim 29, further comprising providing at least a third vessel connected to the second vessel via a second interface, and second guide means for guiding at least one further magnetic field.

wherein the magnetic particles (60) after step (e) in the second vessel

(20), and

the magnetic particles (60) are then transferred analogously to the steps (a) to (e) by means of the second guide means and the further magnetic field from the second vessel (20) into the third vessel.

31. The method of claim 30, wherein the step of washing the magnetic particles in the second vessel comprises the substeps of:

Releasing the magnetic particle (60) forming a pellet (61)

Removing the at least one magnetic field by the first guide means (50),

Forming a pellet (62) by providing the at least one further magnetic field by the second guide means,

Releasing the magnetic particles (60) forming a pellet (62) by removing the at least one further magnetic field by the second guide means,

Forming a pellet (61) by providing the at least one magnetic field through the first guide means (50).

32. The method of claim 31, wherein providing the at least one magnetic field or the at least one further magnetic field by rotating the first and the second guide means in a first rotational direction, wherein the first direction of rotation of the first guide means opposite to the first direction of rotation of the second guide means is and wherein the removal of the at least one magnetic field or the at least one further magnetic field by turning the first and the second guide means in a direction opposite to the first rotational direction second rotational direction, wherein the second rotational direction of the first guide means is opposite to the second rotational direction of the second guide means.

33. The method of claim 29, wherein in step (d), the guide means (1050) guides the vessels (1010, 1020) along the magnet (1040).