METHOD AND ARRANGEMENT FOR MIXING A LIQUID

Description

Changed description

[0001] The present invention relates to a method for mixing a liquid which is present in several closed containers and to an arrangement comprising a device for mixing a liquid present in several closed containers and the containers with the liquid.

[0002] Methods and devices for mixing liquids are disclosed in the following publications: GB 816960 A, WO 98 / 37955 A1, DE 102013107935 A1, US 6299344 B1, EP 0569214 A2 and US 7195394 B2.

[0003] EP 0569214A2 discloses a method and an arrangement for mixing a liquid which is present in several closed containers, each having at least one axis of symmetry, wherein several stacking surfaces arranged one above the other are used and the containers are placed on the stacking surfaces.

[0004] Flexible, single-use containers for liquids are increasingly used in pharmaceutical and biotechnology production processes. These flexible, single-use containers are also known as single-use bags. Compared to rigid containers, such as those made of stainless steel, these flexible, single-use containers offer many advantages: Firstly, they are delivered clean and sterile, meaning they do not need to be cleaned and sterilized. Secondly, they can be disposed of after use and therefore do not require cleaning. Furthermore, the complex validation steps for sterility and cleaning that are necessary for rigid containers are eliminated.

[0005] One challenge with flexible single-use containers is preventing the mixing of liquids within the sealed container. Opening the container to mix the contents is obviously undesirable, as this would negate the sterility benefits of flexible single-use containers.

[0006] Rotating shafts, which drive high-performance mixers, can therefore only be inserted into flexible containers with considerable effort. Sealing the shaft presents a major problem here.

[0007] Magnetically driven stirrers can be inserted into the flexible container during the manufacturing process before sterilization. However, the mixing power they can impart to the liquid remains limited.

[0008] The methods described above are mechanically very complex, technically demanding, and require a large amount of space. Especially in applications such as fractionation, where many fractions need to be mixed, the mixing systems described above do not offer an acceptable solution due to their large space requirements and complex technical effort.

[0009] Other devices known for mixing liquids in closed containers use the principle of inertia to induce movement of the liquid within the container by moving the container itself. In principle, these devices can be divided into those that, when viewed from above on a horizontal plane, produce linear trajectories of the container, and those that produce more complex trajectories. The former are naturally preferred in practice, since the simpler, linear trajectory can be achieved with simpler designs, which are therefore lower maintenance-intensive and more durable.

[0010] Examples of such designs include rockers and similar devices, which are intended to generate waves that promote mixing (see, for example, US 7195394 B2 or WO 2009 / 114442 A1).

[0011] However, mixing would be more effective if a vortex (also called a eddy) could be induced in the liquid instead of waves. This was proposed in US 2010 / 0172203 A1. However, this proposal relied on asymmetrically designed containers to generate the vortices. Manufacturing these asymmetrical containers is, of course, more difficult than manufacturing symmetrical ones, which is why this system ultimately failed to gain widespread acceptance due to its uneconomical nature. Against this background, the object of the present invention is to provide a method and an arrangement for mixing liquids contained in closed containers, wherein both symmetrical containers and vortices in the liquid can be used for mixing.

[0012] With regard to the method, this problem is solved by the features of claim 1.

[0013] With regard to the arrangement, the problem is solved by the features of claim 7.

[0014] To induce a vortex in the liquid, an asymmetrical situation must ultimately be created within the containers. A key insight of the invention is that the symmetry of the containers and the symmetry of the device for moving the containers along the path of motion need not be broken by making the containers or the device themselves asymmetrical. Rather, the skillful alignment or arrangement of the containers relative to the device can be used to induce a vortex in the liquid.

[0015] The invention thus combines particularly good mixing of the liquid within the closed containers with a particularly simple method. In other words, the invention combines particularly good mixing of the liquid within the closed containers with a particularly simple design of the device for moving the containers.

[0016] The method according to the invention is carried out with several containers simultaneously.

[0017] According to the invention, the containers are moved in a linear oscillation when viewed from above.

[0018] According to the invention, it is also provided that the containers are moved exclusively in the horizontal plane. This does not mean that the containers must be arranged entirely in the plane (that would be impossible because the containers are three-dimensional objects). Rather, movement in the horizontal plane means that the (imaginary) trajectory of the containers lies in the respective (imaginary) horizontal plane.

[0019] According to the invention, an exclusively linear movement is used, which takes place exclusively within the horizontal plane.

[0020] The execution of the inventive method with several containers simultaneously is achieved according to the invention by having several stacked storage surfaces and placing several containers, at least partially filled with a liquid to be mixed, on the storage surfaces (aligned according to the invention). This measure is also particularly advantageous with regard to the space requirements of the device.

[0021] The device for moving the containers and thus for mixing the liquid can therefore be accommodated even in a relatively small installation space / space.

[0022] For the purposes of this invention, "liquids" means all substances or mixtures of substances that have a liquid component, including, for example, suspensions or emulsions.

[0023] The axis of symmetry of the containers, lying in the horizontal plane, is an axis with respect to which mirror symmetry exists when viewed from above onto the horizontal plane. Of course, other symmetries of the containers may also exist.

[0024] According to the invention, it is preferably provided that, in the top view onto the horizontal plane, there are no axes of symmetry of the containers that coincide at least partially – preferably completely – with the projection of the path of motion onto the horizontal plane (pure points of intersection are of course excluded). In other words, according to the invention, the containers are to be oriented such that they are asymmetrical with respect to the path of motion.

[0025] The alignment or arrangement of the containers according to the invention creates "slanted" boundaries within the containers, which deflect the liquid from the direction of the path of movement and thereby generate the vortex.

[0026] An oscillating motion is understood to be an essentially repeating movement that follows the path of motion.

[0027] A simple example would be a linear movement that goes back and forth between two points in the horizontal plane. However, certain rocking movements around a horizontal axis also naturally repeat themselves and appear linear when viewed from above.

[0028] The fact that the path of motion appears horizontal in the top view can be understood, for example, to mean that the projection of the path of motion onto the horizontal plane is linear.

[0029] In addition to the movement that appears linear in the top view, other movements may be superimposed, as long as at least part of the path of movement appears linear in the top view on the horizontal plane.

[0030] The containers may contain additional functional elements, such as connectors and / or handles. The presence of the axis of symmetry according to the invention naturally refers only to the liquid-holding (inner) part of the containers. For externally arranged additional elements of the containers, there are of course no restrictions within the scope of the invention, as long as the orientation or arrangement according to the invention is possible on the device.

[0031] According to the invention, the containers are arranged such that the axes of symmetry lie in the horizontal plane or lie substantially in the horizontal plane. The deviation must not be so large that no vortex is induced in the liquid.

[0032] Further advantageous embodiments of the invention are defined in the dependent claims.

[0033] It can be provided that the containers are aligned such that the axes of symmetry and the path of motion, viewed from above on the horizontal plane, form an angle between 5° and 85°, preferably between 10° and 60°, and particularly preferably between 20° and 40°. Most preferably, the containers can be aligned such that the axes of symmetry and the path of motion, viewed from above on the horizontal plane, form an angle of 30°.

[0034] If the containers have more than one axis of symmetry in the top view, the preferred angular relationship in the top view on the horizontal plane between the path of motion and the axis of symmetry along which the containers have a longer, in particular the longest, extent.

[0035] The containers can have a basic shape of a rectangle, an isosceles trapezoid, or a combination of a rectangle and an isosceles trapezoid when viewed from above.

[0036] It is particularly preferred that the containers are used only partially filled, so that in addition to the liquid in the containers a gas cushion – in particular an air cushion – is present. This allows both the inventive effect of at least one vortex in the liquid and the interlocking wave motions of the liquid in the air cushion to be used for mixing the liquid, which can ensure optimal mixing in a short time.

[0037] Flexible bags – preferably made of plastic – can be used as containers. In particular, so-called single-use bags can be used. These can be made, for example, from two films that are sealed along one edge.

[0038] Such bags are essentially flat when empty. Of course, other containers that have a significant height even when empty can also be used within the scope of the invention.

[0039] A transport tray can be positioned between the containers – in particular single-use bags – and the storage surface. Preferably, the transport trays can be designed to form the storage surface for the container to be placed or already placed above them. In other words, the containers – preferably by means of transport trays – can be stacked for mixing according to the invention.

[0040] Particularly preferably, in the process according to the invention, a pharmaceutical or a precursor and / or intermediate product occurring in a pharmaceutical or biotechnological production process can be used as a liquid. In other words, the process according to the invention can be applied to pharmaceuticals or, more generally, to a pharmaceutical or biotechnological production process.

[0041] Examples of specific applications of the inventions would be the homogenization of buffer solutions and the mixing of precipitated material in the liquid.

[0042] Further advantages and details of the invention will become apparent from the figures and the accompanying figure description. These show: Fig. 1a a schematic top view arrangement, Fig. 1b the arrangement of Fig. 1a In a schematic sectional view, Fig. 2a, an arrangement according to the invention with stacked containers; in a schematic side view, Fig. 2b, a top view of the arrangement according to Fig. 2a , Fig. 3 a schematic top view of an arrangement and Fig. 4 an arrangement according to the invention for mixing liquids present in several containers.

[0043] In Fig. 1a und 1b is an arrangement consisting of a device 10 for mixing a liquid 1 present in a container 2 in a schematic top view ( Fig. 1a ) and in a schematic sectional view ( Fig. 1b ) shown.

[0044] The top view is directed towards a horizontal plane 3 (essentially the drawing plane), which also forms the storage area for the container 2.

[0045] Container 2 (in this embodiment a single-use bag) has a rectangular interior combined with a flat isosceles trapezoid as its basic shape for the liquid 1 holding the interior. Container 2 also has several functional elements on the outside, such as hose connectors and a retaining eyelet.

[0046] Essentially, the container 2 holding the liquid 1 is mirror-symmetrical with respect to an axis of symmetry A in the horizontal plane 3.

[0047] The device 10 is designed to move the container 2, thereby mixing the liquid 1. The path of movement B is indicated by an arrow. This is a purely linear oscillating movement within the horizontal plane 3. Alternatively, the indicated movement could also be achieved, for example, by means of a seesaw or the like.

[0048] To generate purely linear motion, devices known in the prior art can, in principle, be used. These can include rails and a (e.g., electric) drive with an eccentric. An example is given in Fig. 4 hinted at.

[0049] The drive and / or its control system can be designed to repeat the motion along path B 5 to 120 times per minute. This speed can be adjustable.

[0050] As can be easily seen from the top view, the axis of symmetry A and the path of motion B form an acute angle between 20° and 40° (30° in this embodiment). The action of the boundaries holding the liquid 1 and their oblique arrangement with respect to the path of motion B creates a deflection effect, resulting in the formation of a vortex within the liquid 1. Both the deflection effect of the container boundaries and the vortex are shown in Fig. 1a Indicated graphically.

[0051] As can be seen from the sectional view of the Fig. 1b As can be seen, container 2 is only partially filled, so that a gas cushion 6 – in this embodiment, air – is present inside the container alongside the liquid 1. This allows for wave formation (schematically shown in Fig. 1b to create (as shown) in container 2. The mixing effect of the vortex is further enhanced by the waves, which overlap depending on the intensity of the movement generated by the device. For clarity, the device 10 is shown in Fig. 1b not shown.

[0052] In the Figuren 2a und 2b Figure 1 shows an embodiment of an arrangement according to the invention, wherein the containers 2 are arranged inside transport trays 5. The transport trays 5 are stackable. By stacking several containers 2, at least partially filled with liquid 1, in transport trays, a device 10 (e.g., as shown in Figure 10) can be used to transport the liquid. Fig. 1a ) Liquid 1 is mixed simultaneously in several containers 2.

[0053] The arrangement of the containers 2 on the respective storage surface (which forms the horizontal plane 3) according to the embodiment shown in the Figuren 2a und 2b is analogous to that from Fig. 1a . That is, the axis of symmetry A of the containers forms an angle with the path of motion B (indicated by an arrow).

[0054] Fig. 3 Figure 2 schematically shows an embodiment in which the container 2 has two different axes of symmetry A in the horizontal plane 3. The path of movement B is arranged at an angle to both axes of symmetry A in the top view of the horizontal plane 3. In particular, the angle between the path of movement B and that axis of symmetry A is shown. Fig. 3 The angle along which the container has the greater extent is between 20° and 40°.

[0055] In Fig. 4 Figure 1 shows an embodiment of the invention with several containers 2 arranged one above the other. The containers are arranged in transport trays 7 (the containers 2 themselves are therefore not clearly visible). A rail system with a drive is visible (below the transport trays 7), which achieves the alignment between the path of movement B and the axis of symmetry A according to the invention.

[0056] The execution according Fig. 4 It is designed as a mobile cart with wheels.

[0057] Supports are provided that can be used to hold the cart still while the liquid is being mixed.

Claims

1. Method for mixing a liquid which is present in several closed containers (2) each having at least one axis of symmetry (A), wherein - the containers (2) are arranged such that the axes of symmetry each lie substantially in a horizontal plane (3), - the containers (2) are moved in an oscillating manner along a movement path (B) that appears linear when the horizontal plane (3) is viewed from above, - in order to generate at least one vortex in the liquid (1) the containers (2) are oriented such that the movement path (B) and the axes of symmetry (A) each are different when the respective horizontal plane (3) is viewed from above - when viewed from above the containers (2) are moved exclusively linearly in an oscillating manner, - the containers (2) are moved exclusively in the respective horizontal plane, and - several shelves disposed above each other are used and the containers (2) are placed on the shelves.

2. Method according to claim 1, characterized in that the containers (2) are oriented such that the axes of symmetry (A) and the movement path (B) form an angle (α) of between 5° and 85°, preferably between 10° and 60° and particularly preferably between 20° and 40°, when the horizontal plane (3) is viewed from above.

3. Method according to claim 1 or 2, characterized in that, when viewed from above the containers (2) have a basic shape of a rectangle, an isosceles trapezium or a combination of a rectangle and an isosceles trapezium.

4. Method according to one of claims 1 to 3, characterized in that the containers (2) are used only partly filled, with the result that a gas cushion (6) - in particular an air cushion - is present in the containers (2) in addition to the liquid (1).

5. Method according to one of claims 1 to 4, characterized in that flexible bags - preferably made of plastic - are used as containers (2).

6. Method according to one of claims 1 to 5, characterized in that a medicinal product or a precursor and / or intermediate occurring in a pharmaceutical or biotechnology production process is used as liquid (1).

7. Arrangement consisting of a device (10) for mixing a liquid (1) present in several closed containers (2) and of the containers (2) with the liquid (1), in particular for carrying out a method according to one of claims 1 to 6, wherein the containers (2) each have at least one axis of symmetry (A) and are each arranged on the device (10) such that the axes of symmetry (A) each lie substantially in a horizontal plane (3), and wherein the device is designed to move the containers (2) in an oscillating manner along a movement path (B) that appears linear when the respective horizontal plane (3) is viewed from above, characterized in that the containers (2) are oriented such that the movement path (B) and the axes of symmetry (A) are different when the respective horizontal plane (3) is viewed from above, wherein the apparatus is configured to - move the containers (2) exclusively linearly in an oscillating manner when viewed from above and - move the containers (2) exclusively in the respective horizontal plane and wherein the containers (2) are placed on several shelves disposed above each other.

8. Arrangement according to claim 7, characterized in that a transport shell (5) is located between the containers and the shelf.