Container, mixing device and method of using a mixing device
Patent Information
- Application Number
- EP2023711046
- Authority / Receiving Office
- EP · EP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2023-03-13
- Publication Date
- 2026-01-21
AI Technical Summary
Existing mixing devices for biological and chemical substances, such as bioreactors, do not ensure efficient or complete mixing and are prone to liquid leakage during the mixing process, which can lead to inconsistent concentrations of particles or components in the fluid.
A container with a closure element featuring movable sealing surfaces that allow for controlled access and movement, enabling the container to be moved along a path to induce mixing while preventing uncontrolled leakage, using a movement device connected to the container to create a mixing movement within the fluid.
This solution allows for rapid, complete, and efficient mixing of contents, ensuring a reproducible concentration of particles or components in the fluid, preventing leakage during the mixing process and maintaining the integrity of the contents.
Smart Images

Figure EP2023056379_19092024_PF_FP_ABST
Abstract
Description
[0001] Hombrechtikon Systems Engineering AG, Garstliqweq 6, CH-8634
[0002] Hombrechtikon
[0003] Container, mixing device and method for using a mixing device
[0004] The invention relates to a container for a mixing device, a mixing device and a method for using a mixing device according to the preamble of the independent claims.
[0005] Many methods for purifying and processing cells, DNA, and other biomolecules are known in the art. One type of purification is DNA extraction, in which the DNA is precipitated in a nonpolar environment. DNA can also be purified by centrifugation, e.g., after cell disruption, or by electrophoretic methods.
[0006] Biomolecules can also be synthesized and purified by immobilizing them on an insoluble support. Common substrates for immobilizing biomolecules include glass, as well as other, less common substrates such as gold, platinum, oxides, semiconductors, and various polymer substrates.
[0007] Since manual purification and processing in numerous steps is too time-consuming, these processes are now fully automated. Magnetic beads (magnetic particles) play a key role in the automation of laboratory methods.
[0008] Magnetic bead-based cleanup and magnetic bead-based normalization are widely used methods for the immobilization, purification, and concentration adjustment of nucleic acids. Typical applications of these methods include sample preparation in the context of DNA sequencing or DNA detection (e.g., using PCR, or polymerase chain reaction). The magnetic particles were developed in 1995 at the Whitehead Institute for the purification of PCR products. The magnetic particles are usually paramagnetic and can consist, for example, of polystyrene coated with iron. Various molecules with carboxyl groups can then be attached to the iron. These carboxyl groups can reversibly bind the DNA molecules, thus immobilizing the DNA molecules.
[0009] Methods using magnetic particles, for example, include the following steps. First, the PCR products are bound to the magnetic particles. This typically involves mixing the liquid and the magnetic particles contained therein. The magnetic particles with the attached PCR products are then separated from impurities (this step can be achieved, for example, by pipetting the solution from the solid / from the container). The magnetic particles with the attached PCR products are then washed. After washing, the PCR products are eluted from the magnetic particles and transferred to a new plate.
[0010] In fully automated processes, the necessary reagents are automatically pipetted into the sample after the starting material has been introduced in an isolation process and then removed again. The magnetic particle-bound nucleic acids are collected at the bottom and edges of the containers and, depending on the routine, are redissolved by optimized pipetting. Finally, the DNA or RNA is eluted into separate, capped containers for immediate storage or further use.
[0011] One of the most important methods for synthesizing, normalizing, and purifying biomolecules is the method using magnetic particles. In this method, the biomolecules are bound to the surface of the magnetic particles. The magnetic particles are then immobilized using a magnet, and the solution, which contains byproducts and impurities, can be easily separated. This allows the biomolecules to be purified and isolated quickly and easily. The advantage of magnetic beads is that the beads can move freely within the experimental setup, which is important for the binding steps. If you want to remove the liquid from the container, for example, in a washing step, you simply hold a magnet to the container and the liquid can then be separated.
[0012] The magnetic particles are small paramagnetic or ferromagnetic spheres coated with various materials that impart the required properties. Nickel particles coated with a plastic are often used.
[0013] In the current state of the art, the aforementioned steps are usually carried out in bioreactors, in which the magnetic particles and the liquid are mixed with biomolecules to ensure the most complete binding of the biomolecules to the magnetic particles. However, such bioreactors or mixing devices can also be used for the processing and mixing of other biological or chemical substances, such as cells.
[0014] A corresponding mixing device is known from US 2022 / 0135924 A1. The mixing device of US 2022 / 0135924 A1 is intended to provide optimal conditions for mixing a reaction liquid. The mixing is based on a change in the internal volume of the reaction vessel, which triggers movement of the liquid. The change in the internal volume is based in particular on a change in the shape of the reaction vessel, for which the reaction vessel has at least one flexible area / region. The flexible area is a flexible base, which is moved by a magnetic drive element connected to the base. This creates a mixing movement. However, such mixing devices do not guarantee efficient or complete mixing.In addition, the container of the mixing device must be attached to a surface and leakage of the liquid during mixing cannot be prevented.
[0015] The object of the invention is therefore to provide a container, a mixing device, and a method for using a mixing device that avoid the adverse effects known from the prior art, in particular enabling rapid, complete, and efficient mixing. Specifically, it should be possible for a withdrawn volume of fluid / liquid to always contain a reproducible concentration / amount of, in particular, cells, magnetic particles, molecules, or other particles or components, while preventing any leakage of fluid / liquid during mixing and withdrawal.
[0016] The object is achieved by a container, by a mixing device and by a method for using a mixing device having the features of the independent claims.
[0017] According to the invention, a mixing device is proposed which comprises a container with an interior space for accommodating a content. The container comprises an opening and a closure element arranged at the opening for closing the opening. The mixing device further comprises a movement device which is connected to the container in such a way that the container can be moved along a movement path by the movement device.
[0018] The closure element comprises a first sealing element with a first sealing surface and a second sealing element with a second sealing surface opposite the first sealing surface. The first sealing surface and the second sealing surface extend along the movement path, and the first and / or second sealing element are movable such that the opening can be opened and closed by a relative movement of the sealing surfaces to one another.
[0019] Because the first sealing surface and the second sealing surface extend along the movement path (or movement axis), it is possible to access the interior of the container through the opening while the container is being moved by the movement device, without risking uncontrolled leakage of the contents. For this purpose, a suitable device, such as a pipette or syringe, can be inserted between the sealing surfaces to access the contents. Because the sealing surfaces extend along the movement path, the corresponding device can remain static while the container is moving. The sealing elements can act as a type of splash guard.
[0020] By moving the container by means of the movement device, a movement of the contents, in particular of the fluid / liquid, is generated, such that a mixing movement / a flow is induced in the fluid / liquid, which leads to mixing. By moving back and forth, the flow in the container is generated, which results in a homogeneous mixing of the contents. The movement path can be a linear path / straight line. Alternatively or additionally, the movement path can be curved, i.e. form a curve (or comprise differently shaped sections). The movement takes place in particular in at least one direction of the movement path, particularly preferably in both directions, such that the container is moved back and forth along the movement path, preferably shaken along the movement path.The movement path can have a length tailored to the length of the sealing surfaces. In particular, the movement path can have a length of up to 50 cm, particularly preferably 1 to 25 cm, especially 5 to 15 cm. The length of the sealing surfaces can be 0.5 to 4 times as long as the length of the movement path, in particular 1 to 3 times as long, particularly preferably 1.5 to 2.5 times as long. The fact that the first and / or second sealing element are movable in such a way that the opening can be opened and closed by a relative movement of the sealing surfaces means in particular that the opening can be closed by the sealing surfaces moving towards one another and can be opened by the sealing surfaces moving away from one another. The opening can be opened / closed by one of the two sealing surfaces (e.g. the first) moving and the other sealing surface (e.g. the second) remaining stationary.During opening, the moving sealing surface can move toward the container wall to which it is attached and away from the opposite sealing surface (and vice versa during closing). Alternatively, and preferably, both sealing surfaces can move.
[0021] The sealing surfaces can be moved by a drive. However, the sealing surfaces are particularly preferably moved apart by a force acting on the sealing elements / sealing surfaces.
[0022] Within the scope of the invention, "closed / sealed" with reference to the opening can be understood in particular as follows: The opening is closed when the sealing surfaces are arranged in such a way that no or hardly any contents can escape from the interior, or no corresponding device is inserted between the sealing surfaces that forces the sealing surfaces apart. For this purpose, the sealing surfaces can abut one another (the opening could therefore be closed by placing the first sealing surface against the second sealing surface), but the sealing surfaces can also be spaced apart to prevent escape. A small distance can mean, in particular, 0 to 10 mm, specifically 1 to 5 mm.
[0023] According to the invention, the container, in particular a
[0024] A storage container for a mixing device (i.e. in particular for introduction into and / or use with) is proposed, wherein the container comprises the interior for accommodating the contents such as the fluid, in particular the liquid. In addition, the container comprises the opening (through which contents can be added and removed) and the closure element arranged at the opening for closing the opening. The closure element comprises the first sealing element with the first sealing surface and the second sealing element with the second sealing surface opposite the first sealing surface. The first sealing surface and the second sealing surface extend (in particular parallel) opposite one another, and the first and / or second sealing element is movable such that the opening can be opened and closed by the relative movement of the sealing surfaces to one another.
[0025] By moving the container, the contents of the container can be mixed flexibly and efficiently, with the opening with the sealing surfaces allowing access to the interior of the container during movement of the container.
[0026] As mentioned above, the first sealing surface and the second sealing surface can run parallel to the movement path, in particular, the first sealing surface and the second sealing surface can extend parallel to each other along the movement path. In this case, "running parallel" can refer to an open and / or closed state of the opening, preferably at least to the closed state.
[0027] In an embodiment of the invention, the opening can form a slit when the closure element is closed, with the slit running parallel to the movement path. Furthermore, the closure element can be a valve, in particular a lip-shaped check valve. If the closure element is designed as a lip-shaped check valve, the first and second sealing elements serve as check valves, in particular in the form of lips that taper in a beak-like manner (preferably into the interior of the container). The lips prevent the contents from escaping from the container, while the corresponding device, such as the pipette, can easily penetrate the interior.
[0028] The first sealing element can be designed as a first closure wall and the second sealing element can be designed as a second closure wall, wherein the first closure wall and / or the second closure wall can be movable. In this case, the first and second closure walls can each have a first and second end and can each be fastened with the first end to a container wall of the container (preferably to opposite container walls) and have the first sealing surface or the second sealing surface at their second end. In this case, the closure walls can converge from their first ends (preferably into the interior of the container), so that the first sealing surface and the second sealing surface converge towards each other and bear against each other / the slight
[0029] In practice, the thickness of the closure walls may decrease from the first to the second end. Furthermore, the sealing surfaces may have a substantially rectangular area.
[0030] In a particularly preferred embodiment, the first sealing element and the second sealing element abut one another (or are only slightly spaced apart), i.e. in particular the first sealing surface and the second sealing surface, so that the opening is closed, and the first sealing element and / or second sealing element are elastic and / or bendable such that the opening can be opened by bending the first sealing element and / or second sealing element. By bending the sealing elements from a rest position (in particular due to a force applied by the corresponding device such as the pipette), the sealing surfaces can be moved away from one another, thereby opening the opening.Due to the bending, the sealing elements are under tension, so that the sealing elements move towards each other again (after removing the corresponding device such as the pipette between the sealing surfaces), so that the sealing surfaces lie against each other again / or have the small distance.
[0031] Deformation / bending of the sealing elements is therefore preferably achieved by a force exerted by the corresponding device. The deformation / bending of the sealing elements changes the shape of the sealing elements in such a way that the opening is opened. "Deformable" or "deformable" means, in particular, that the shape (of at least a section) of at least one sealing element can be changed. For this purpose, one or all of the sealing elements can be elastic enough that their shape can be reversibly changed by an applied force.
[0032] In an embodiment of the invention, the mixing device can comprise an instrument / device for supplying and / or removing the contents (i.e., the corresponding device), which can be moved between the first and second sealing surfaces such that the opening can be opened (by pushing the sealing surfaces apart) and the contents can be supplied and / or removed. The instrument can be a pipette or a syringe, i.e., an instrument for removing the liquid, which can in particular also be designed as a robot and can comprise a plurality of pipettes and / or syringes.
[0033] The container or the mixing device can comprise a support element with which the container can be connected to the movement device so that the container can be moved by the movement device. For this purpose, the movement device can comprise a drive, in particular a motor (such as an electric motor, in particular a servo motor), which is coupled to the container. The mixing device can comprise a rail in which the container is arranged, so that a movement of the container (and thus also the movement distance) is predetermined by the rail. Alternatively, the container can be arranged on an element / support / holder which is moved by the drive.In practice, the container can be designed, in particular, as a consumable, i.e., as a consumable that is introduced into the mixing device and can be disposed of after a corresponding process or procedure has been performed. A new container can then be inserted into the mixing device. The container is therefore preferably replaceable.
[0034] The container according to the invention is particularly preferably chemically resistant, pH-stable, and temperature-resistant. Furthermore, the container can be designed to hold at least 10 ml of liquid / contents, preferably 10 ml to 500 ml or 20 ml to 100 ml, particularly preferably 20 ml to 50 ml of liquid / contents. The container can, in particular, comprise a polymer, particularly preferably consist of a polymer. Examples of polymers are polyethylene, polypropylene, polyethylene terephthalate, and / or polyetheretherketone.
[0035] In addition, the liquid and a large number of magnetic particles / cells / molecules, other particles or components that sink in a liquid can be arranged as contents in the interior of the container. The liquid and the large number of magnetic particles / cells / molecules, other particles or sinking components can be mixed by the movement of the container. A container pre-filled in this way can in particular be provided and sold as a "consumable". The mixability ensures in particular that the concentration of magnetic particles / cells / molecules, other particles or sinking components is the same for each volume of liquid / contents withdrawn, which can then be used in further steps or methods for processing, for example, biomolecules.The mixing device / container can in particular be a mixing device / container for providing a liquid with magnetic particles / cells / molecules, other particles or sinking components.
[0036] In one embodiment, the mixing device can further comprise a magnet, wherein the magnet can be arranged on the container in such a way that magnetic particles that can be introduced into the interior can be fixed in the container. This allows the liquid to be drained off and new liquid to be added without removing the magnetic particles from the interior. The magnet can be a permanent magnet and / or an electromagnet. To drain (or add) the liquid, an instrument for removing the liquid, such as a pipette, can be used so that the liquid can be removed from the container after molecules have been immobilized on the surface of the magnetic particles. This can be done via the opening of the container. The instrument for removing the liquid can also be a syringe or another suitable instrument.
[0037] In practice, the container and mixing device according to the invention are preferably used to provide liquid containing magnetic particles for other processes, such as biomolecule processing (whereby a consistent / reproducible concentration of magnetic particles can be provided for each withdrawn volume of liquid). Alternatively, the container according to the invention can be a reaction vessel and the mixing device a bioreactor in which biomolecules are processed with magnetic particles.
[0038] When used as a reaction container, the magnet can be movably mounted on the container / in the mixing device such that the magnetic particles are freely movable in the container during a reaction step and are fixed in the container during a washing step by changing the magnet position. In particular, the magnet can be movable such that the magnet is arranged in a first position on the container, fixing the magnetic particles, and by moving the magnet to a second position, the magnetic particles become movable. Of course, the container can also be moved relative to the magnet, for example, in an automated device, to achieve the same effect.
[0039] According to the invention, a method for using the mixing device is further proposed. The method comprises the following steps: The container is moved along the movement path by means of the movement device, wherein a portion of the contents is removed from the container during the movement of the container along the movement path.
[0040] To remove a portion of the contents, the device / instrument for supplying and / or removing the contents can be moved between the first and second sealing surfaces, thereby opening the opening. Furthermore, the first sealing element and the second sealing element can be in contact with each other (with a small gap) so that the opening is closed, and the first sealing element and / or second sealing element can be bent by the device for supplying and / or removing the contents in such a way that the opening is opened.
[0041] In the method according to the invention, the contents can also optionally be introduced into the interior of the container first. The contents can, for example, comprise magnetic particles and the liquid, and the magnetic particles and the liquid can be mixed in the interior by the movement of the container, thus preventing the magnetic particles from sinking.
[0042] In particular, the method can be a method for providing a liquid with magnetic particles / cells / molecules, other particles, or sinking components, in which magnetic particles / cells / molecules, other particles, or sinking components and the liquid (as contents) are introduced into the interior of the mixing device, and the liquid and magnetic particles / cells / molecules, other particles, or sinking components are thoroughly mixed in the interior. A predeterminable volume of liquid / contents can be withdrawn from the container, particularly preferably while the mixing / movement of the container is taking place.
[0043] Alternatively, the method can be a method for processing biomolecules in a mixing device according to the invention, in which magnetic particles and a liquid containing biomolecules (as contents) are introduced into the interior of the mixing device, and the liquid and magnetic particles are mixed in the interior. Furthermore, the method can comprise securing the magnetic particles in the container by arranging a magnet on the container and / or removing the liquid containing magnetic particles from the interior using the liquid removal instrument.
[0044] In the method according to the invention, in particular, the magnetic particles (also magnetic particles) / cells / molecules, other particles or sinking components and the liquid are mixed by interaction of the container and the movement device in order to obtain a liquid with magnetic particles / cells / molecules, other particles or sinking components, which has a uniform concentration of magnetic particles / cells / molecules, other particles or sinking components.
[0045] Additionally or alternatively, the movement of the container is designed to keep the particles, cells, molecules, or sinking components contained in the interior suspended in such a way that sedimentation at the bottom of the container can be prevented. Furthermore, a mixing or swirling process is improved by keeping the particles suspended in the vessel and / or by preventing or reducing coagulation of beads. Allowing the magnetic particles to float freely and / or preventing sedimentation of the magnetic particles advantageously improves biochemical reactions in the mixing device, namely biomolecule immobilization.
[0046] In the context of the present invention, the term "biomolecule" can be understood to mean DNA, RNA, nucleic acids, proteins, start sequences, monomers, or other biologically active molecules. Such biomolecules can be processed in the mixing device according to the invention and introduced into the container according to the invention (preferably in a liquid). The processing can include, among other things, washing steps and / or reaction steps and can be carried out with magnetic particles. A washing step in the context of the invention is a process step in which the liquid is removed from the container after thorough mixing, and in particular the impurities are separated from the magnetic particles with the attached biomolecules. A washing step can also include rinsing with a rinsing fluid.Within the scope of the invention, a reaction step is a process step in which the biomolecules bound to the magnetic particles are converted, bound to the particles, or extended (chain extension, e.g., PCR "polymerase chain reaction"). A contaminant is understood in particular to be a substance that has not fully reacted or is not bound to the magnetic particles, the solvent, byproducts, and contaminants, as well as a mixture of two or more of the above-described substances.
[0047] Within the scope of the invention, a liquid or the content can be a solution or suspension, in particular a mixture of liquid and magnetic particles or a reaction mixture of biomolecules and / or reagents and / or impurities.
[0048] For the purposes of the invention, “magnetic particle” (also “magnetic bead”) can be understood to mean a particle in the micrometer or millimeter range. Furthermore, the magnetic particles can be porous. A biomolecule can be bound to the surface of the magnetic particles in particular via thiol groups and / or amino groups and / or hydroxyl groups and / or carboxyl groups and / or carbonyl groups and / or ester groups and / or nitrile groups and / or amine groups and / or any other functional groups or other interactions. Magnetic particles can also be coated nickel particles or any other ferro- or paramagnetic particles. Magnetic particles typically have a diameter of approximately 1 micrometer. For the purposes of the invention, approximately 1 micrometer is understood to mean 0.5 to 1.5 micrometers, in particular 0.7 to 1.3 micrometers, particularly preferably 0.9 to 1.1 micrometers.
[0049] The aforementioned magnetic particles can therefore be functionalized magnetic particles that bind biomolecules such as DNA in a sample material. They can then be immobilized using magnetic force and thus separated from a reagent liquid. This is removed, and the biomolecules can then be detached from the particles. The magnetic particles should preferably be added in a precise amount. This is made possible by the devices and method according to the invention. The mixing device can be used for the preparation of or in any enzymatic process involving nucleic acids (e.g., polymerase chain reaction (PCR), isothermal DNA amplification, reverse transcription). The biomolecules bound to the magnetic particles can be detached from the surface of the magnetic particles and subsequently reused.
[0050] In the following, the invention is explained in more detail using exemplary embodiments with reference to the drawings.
[0051] Fig. 1 is a schematic representation of a first embodiment of a container according to the invention; Fig. 2A is a schematic representation of a first embodiment of a closure element according to the invention;
[0052] Fig. 2B is a schematic representation of a second embodiment of a closure element according to the invention;
[0053] Fig. 3 is a perspective view of a first embodiment of a mixing device according to the invention;
[0054] Fig. 4 is a representation of an embodiment of a container according to the invention with a lip check valve;
[0055] Fig. 5 is a side view of an embodiment of a container according to the invention;
[0056] Fig. 6 is a side view of an embodiment of a container according to the invention with bulges;
[0057] Fig. 7 is a schematic representation of a pipetting process according to the invention;
[0058] Fig. 8 is a perspective view of a second embodiment of a mixing device according to the invention;
[0059] Fig. 9 is a schematic representation of an embodiment of a mixing device according to the invention with an instrument for removing the liquid and a magnet.
[0060] A mixing device is, in particular, a device with a container in which liquids containing magnetic particles can be provided under adjustable and thus optimal conditions. The operation of a mixing device is therefore, in particular, an application in chemistry, biochemistry, or biotechnology, which enables chemical and biological processes or provides reactants for them.
[0061] Factors that can be controlled or regulated in mixing devices include the composition of the contents, the gas supply, temperature, pH, sterility, and others. The mixing device can be used to provide a liquid with a predefined concentration of magnetic particles / cells / molecules / other particles and / or sinking components, or for the extraction and processing of biomolecules. The processing and degradation of chemical compounds can also take place in mixing devices.
[0062] Fig. 1 shows a schematic representation of a first embodiment of a container 2 according to the invention for a mixing device. The container 2 comprises an interior space 3 suitable for receiving a content such as a fluid 31. The container 2 further comprises an opening 4 and a closure element arranged at the opening 4 for closing the opening 4.
[0063] The closure element comprises a first sealing element 10 with a first sealing surface 11 and a second sealing element 20 with a second sealing surface 21 opposite the first sealing surface 11. The first sealing surface 11 and the second sealing surface 21 extend parallel to each other. The first sealing element 10 and the second sealing element 20 are movable, so that the opening 4 can be opened or closed by moving the sealing surfaces 11, 21.
[0064] On the right-hand side of Fig. 1, the opening 4 is closed and forms a slot 4, since the sealing surfaces 11, 21 abut one another or are slightly spaced apart. On the left-hand side of Fig. 1, the sealing surfaces 11, 21 are further apart, thus opening 4 is open. Fig. 2A shows a schematic representation of a first embodiment of the closure element 100 according to the invention. The closure element 100 comprises the first sealing element 10 with the first sealing surface 11 and the second sealing element 20 with the second sealing surface 21 opposite the first sealing surface 11. The first sealing surface 11 and the second sealing surface 21 extend on the left-hand side of Fig. 2, i.e. when the opening 4 is closed, parallel to one another and parallel to a linear / straight movement path S.
[0065] Since the first sealing surface 11 and the second sealing surface 21 extend along the movement path S, the interior of the container can be accessed via the opening 4 while the container is moved back and forth / shaken along the movement path S by a movement device (not shown here).
[0066] On the right-hand side of Fig. 2A, the opening 4 is open because a corresponding device 8, such as a pipette or syringe, is arranged between the sealing surfaces 11, 21. When a force is applied by the corresponding device 8 to the sealing elements 10, 20, these are bent apart and consequently the sealing surfaces 11, 21 are moved apart. Since the sealing surfaces 11, 21 run along the movement path S, the corresponding device 8 can remain static while the container moves, with the corresponding device 8 sliding along the sealing surfaces 11, 21 and pressing them apart. The sealing elements 10, 20 are elastic in such a way that the sealing surfaces 11, 21 are only completely pressed apart in the area in which the corresponding device 8 is currently located.
[0067] Fig. 2B shows a schematic representation of a second embodiment of the closure element 100 according to the invention. The closure element 100 comprises the first sealing element 10 with the first sealing surface 11 and the second sealing element 20 with the second sealing surface 21 opposite the first sealing surface 11. The first sealing surface 11 and the second sealing surface 21 extend in the closed state (left side of Fig. 2B) and in an open state (right side of Fig. 2B) of the opening 4, parallel to each other and parallel to a curved / curved movement path S.
[0068] Since the first sealing surface 11 and the second sealing surface 21 extend along the movement path S, the interior of the container can be accessed via the opening 4 while the container is moved back and forth / shaken along the movement path S by a movement device (not shown here).
[0069] On the right-hand side of Fig. 2B, the opening 4 is open because the corresponding device 8, such as the pipette or syringe, is arranged between the sealing surfaces 11, 21. The force exerted by the corresponding device 8 on the sealing elements 10, 20 bends them apart and consequently the sealing surfaces 11, 21 are moved apart. Since the sealing surfaces 11, 21 run along the movement path S, the corresponding device 8 can remain static while the container moves, with the corresponding device 8 sliding along the sealing surfaces 11, 21 and pressing them apart. The sealing surfaces 11, 21 are thereby completely pressed apart over their entire length as long as the corresponding device 8 is arranged between the sealing surfaces 11, 21.
[0070] Fig. 3 shows a perspective view of a first embodiment of a mixing device 1 according to the invention, which comprises the container 2, which is shown here without a closure element. The mixing device 1 further comprises the movement device 5, which is fastened to the container 2 via a fastening element 6 such that the container 2 can be moved by the movement device 5 along the movement path S. The movement device 5 is designed as a roller 5, which rolls over the surface 51 and thus moves the container 2 back and forth in a rail 50.
[0071] The interior space 3 can contain, for example, a liquid and a plurality of magnetic particles, wherein the liquid and the plurality of magnetic particles can be mixed by the reciprocating movement of the container 2. The closure element, not shown here, serves to prevent the contents from spilling during the movement of the container 2 along the movement path S.
[0072] Fig. 4 shows an illustration of an embodiment of a container 2 according to the invention with the closure element 100, which is designed as a lip check valve 100.
[0073] The first sealing element 10 and the second sealing element 20 serve as non-return valves in the form of lips, which taper into the interior 3 of the container 2 in a beak-like manner. The lips 10, 20 touch each other at the sealing surfaces 11, 21.
[0074] Fig. 5 shows a side view of an embodiment of the container 2 according to the invention. In the interior 3 of the container 2, the liquid 31 is arranged, which is mixed by the movement of the container 2 indicated in the left and right illustration of Fig. 5 with the arrows F1, F2.
[0075] The closure element 100 prevents the liquid 31 from escaping from the container 2 while it is being mixed by the movement of the container 2. The closure element 100 is a separate element from the container 2, which is plugged onto the container 2 and thus arranged on a container wall of the container 2. Fig. 6 shows a side view of an embodiment of the container 2 according to the invention with bulges 30. These bulges 30 reduce the rippling of the liquid 31 during the movement indicated by the arrow F1, since the bulges 30 act as a type of breakwater, the curved edges of which reflect the liquid 31 back to the center.
[0076] Fig. 7 shows a schematic representation of a pipetting process according to the invention and thus a method for using the mixing device.
[0077] In the three illustrations of Fig. 7, the container is being moved. During the movement of the container 2, the pipette 8 is pressed into the lip-type check valve 100, causing the sealing surfaces 11, 21 to move apart as the sealing elements 10, 20 bend outward. This opens the opening 4, allowing the pipette 8 to penetrate the interior 3 and access the liquid 31.
[0078] The pipette 8 takes up a portion of the liquid 31 from the container 2, which can then be discharged from the interior 3.
[0079] The insertion of the pipette 8 is coordinated with the movement of the container 2 in such a way that the pipette 8 is not inserted into the closure element 100 at the point marked by the cross (left side of Fig. 7 and also shown in Fig. 5 on the right side).
[0080] Fig. 8 shows a perspective view of a second embodiment of the mixing device 1 according to the invention, which comprises the container 2 with the closure element 100. The mixing device 1 further comprises the movement device 5, which is connected to the container 2 via a fastening element in the form of the container holder 52 such that the container 2 can be moved back and forth by the movement device 5. The movement device 5 is a motor 5, which sets the container holder 52 in motion via a gear 53.
[0081] Fig. 9 shows a schematic representation of an embodiment of a mixing device 1 according to the invention with the pipette 8 and a magnet 7.
[0082] The mixing device 1 comprises the magnet 7, wherein the magnet 7 is arranged on the container 2 such that magnetic particles 32 are fixed in the container 2. This allows the liquid 31 to be removed by means of a pipette 8 without magnetic particles 22 after the pipette 8 has been inserted via the closure element 100 into the interior 3 of the container 2. If no magnet 7 is used, the liquid 31 can be removed with a predeterminable concentration of magnetic particles 32.
[0083] While the invention has been shown and described in detail in the drawings and foregoing description, such illustration and description are to be regarded as illustrative or exemplary and not restrictive.
[0084] The invention is not limited to the disclosed embodiments. Other variations of the disclosed embodiments may be understood and effected by those skilled in the art in practicing a claimed invention from a study of the drawings, the disclosure, and the dependent claims. In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. The mere fact that certain measures are repeated in mutually different dependent claims does not mean that a combination of those measures cannot be advantageously used. Any reference signs in the claims should not be construed as limiting the scope.
Claims
1. Mixing device comprising a container (2) with an interior space (3) for receiving a content (31, 32), wherein the container (2) comprises an opening (4) and a closure element (100) arranged at the opening (4) for closing the opening (4);and a movement device (5) which is connected to the container (2) in such a way that the container (2) can be moved along a movement path (S) by the movement device (5), characterized in that the closure element (100) comprises a first sealing element (10) with a first sealing surface (11) and a second sealing element (20) with a second sealing surface (21) opposite the first sealing surface (11), wherein the first sealing surface (11) and the second sealing surface (21) run along the movement path (S) and the first sealing element (10) and / or second sealing element (20) can be moved in such a way that the opening (4) can be opened and closed by a relative movement of the sealing surfaces (10, 20) to one another.
2. Mixing device according to claim 1, wherein the first sealing surface (11) and the second sealing surface (21) extend parallel to the movement path (S), in particular the first sealing surface (11) and the second sealing surface (21) extend parallel opposite one another along the movement path (S).
3. Mixing device according to claim 1 or 2, wherein the opening (4) forms a slot in the closed state of the closure element (100), the slot running parallel to the movement path (S).
4. Mixing device according to one of the preceding claims, wherein the closure element (100) is a valve (100), in particular a lip check valve (100).
5. Mixing device according to one of the preceding claims, wherein the first sealing element (10) is designed as a first closure wall and the second sealing element (20) is designed as a second closure wall.
6. Mixing device according to claim 5, wherein the first and second closure walls each have a first and second end and are each attached at the first end to a container wall of the container (2) and have at their second end the first sealing surface (11) and the second sealing surface (21) respectively, wherein the closure walls converge from their first ends so that the first sealing surface (11) and the second sealing surface (21) abut one another.
7. The mixing device of claim 6, wherein a thickness of the closure walls decreases from the first to the second end.
8. Mixing device according to one of the preceding claims, wherein the sealing surfaces (11, 21) have a substantially rectangular surface.
9. Mixing device according to one of the preceding claims, wherein the first sealing element (10) and the second sealing element (20) abut one another so that the opening (4) is closed and the first sealing element (10) and / or second sealing elements (20) are bendable such that the opening (4) can be opened by bending the first sealing element (10) and / or second sealing element (20).
10. Mixing device according to one of the preceding claims, comprising a device for supplying and / or removing the contents (8), which is movable between the first sealing surface (11) and the second sealing surface (21) in such a way that the opening (4) can be opened and the contents (31, 32) can be supplied and / or removed.
11. Mixing device according to one of the preceding claims comprising a magnet (7), wherein the magnet (7) can be arranged on the container (2) in such a way that magnetic particles (32) which can be introduced into the interior (3) can be fixed in the container (2).
12. Mixing device according to claim 11, wherein the magnet (7) is a permanent magnet and / or an electromagnet.
13. Container for a mixing device according to one of the preceding claims, comprising an interior space (3) for receiving a content (31, 32); an opening (4); and a closure element (100) arranged at the opening (4) for closing the opening (4), wherein the closure element (100) comprises a first sealing element (10) with a first sealing surface (11) and a second sealing element (20) with a second sealing surface opposite the first sealing surface (11). (20), wherein the first sealing surface (11) and the second sealing surface (21) extend opposite one another and the first sealing element (10) and / or second sealing element (20) is movable such that the opening (4) can be opened and closed by a relative movement of the sealing surfaces (10, 20) to one another.
14. Container according to claim 13, wherein the first sealing element (10) and / or the second sealing element (20) are bendable such that the opening (4) can be opened by bending the first sealing element (10) and / or the second sealing element (20).
15. Container according to claim 13 or 14, wherein the closure element (100) is a valve (100), in particular a lip check valve (100).
16. Container according to one of claims 13 to 15 comprising a holding element (6, 52) with which the container (2) can be connected to a movement device (5).
17. Container according to one of claims 13 to 16, wherein a liquid (31) and a plurality of magnetic particles (32) or cells are arranged in the interior (3).
18. A method for using a mixing device (1) according to any one of claims 1 to 12, wherein the method comprises the following steps: a) moving the container (2) by means of the movement device (5) along the movement path (S); b) removing a portion of the contents (31, 32) during the movement of the container (2) along the movement path (S).
19. The method according to claim 18, wherein, in order to remove the part of the contents (31, 32), a device for supplying and / or removing the contents (31, 32) is moved between the first sealing surface (11) and the second sealing surface (21) so that the opening (4) is opened.
20. The method according to claim 19, wherein the first sealing element (10) and the second sealing element (20) abut one another, so that the opening (4) is closed and the first sealing element (10) and / or second Sealing elements (20) are bent by the device for supply and / or removal (8) in such a way that the opening (4) is opened.
21. Method according to one of claims 18 to 20, wherein the content (31, 32) comprises magnetic particles (32) and a liquid (31) and the magnetic particles (32) and the liquid (31) are mixed in the interior space (3).