Device and method for handling biological entities

Abstract

A device for handling biological entities (1) placed in a liquid (2) in a culture vessel (3), comprising a culture vessel mount (4), a main mount (5), a drive unit (6) and a control unit (16), wherein a damping unit (7) is arranged between the culture vessel mount (4) and the main mount (5), wherein the damping unit (7) comprises at least one compliant element (8, 9), wherein the drive unit (6) is configured to move the culture vessel mount (4) relative to the main mount (5), and wherein the control unit (16) is configured to control the drive unit (6) such that the culture vessel mount (4) moves relative to the main mount (5) such that the biological entities (1) are dispersed throughout the liquid (2) in the culture vessel (3). Further, a method for handling biological entities (1) placed in a liquid (2) in a culture vessel (3), preferably by using a device according to any one of claims 1 to 12, wherein at least one culture vessel (3) is placed in a culture vessel mount (4) being arranged on a main mount (5), wherein a damping unit (7) is arranged between the culture vessel mount (4) and the main mount (5), and wherein the culture vessel mount (4) is driven by a drive unit (6) such that a movement is applied to the at least one culture vessel (3) for dispersing the biological entities (1) within the liquid (2).

Description

[0001] Device and method for handling biological entities

[0002] The present invention relates to a device for handling biological entities placed in a liquid in a culture vessel.

[0003] Further, the present invention relates to a method for handling biological entities placed in a liquid in a culture vessel.

[0004] Biological entities are usually kept in a liquid culture medium in a culture vessel and may also be processed in this culture vessel, for example pipetted, microscoped, etc. In culturing biological entities, dispersing the biological entities evenly across the entire area of a culture vessel and centralizing them in the center of the culture vessel serve different purposes, each important for specific experimental designs and objectives.

[0005] Even dispersion of the biological entities ensures that all biological entities have equal access to nutrients and growth factors in the culture medium. This can lead to more uniform growth and behavior. Further, it is easier to analyze and image biological entities when they are evenly spread out. This distribution minimizes cell clumping and overlapping, providing clearer results for microscopy and other imaging techniques.

[0006] Furthermore, in experiments involving genetic manipulation or infection with viruses or other agents, an even dispersion can ensure that all biological entities have an equal chance of exposure, leading to more consistent results. Moreover, evenly dispersed biological entities are necessary for certain types of assays, such as wound healing assays, where a clear area is created for cells to migrate into. The initial even dispersion ensures that the migration observed is due to the experimental conditions, not pre-existing density variations.

[0007] Centralizing cells is often used in 3D culture systems to promote the formation of spheroids or organoids. This can be crucial for studies that aim to mimic in vivo tissue environments, as spheroids can better replicate the three-dimensional structures of tissues.Bringing biological entities together in the center of the culture vessel can enhance cell-cell interactions, which is important in studying processes like stem cell differentiation, tissue development, and cancer cell behavior in a more physiologically relevant context.

[0008] Further, centralizing biological entities can lead to high-density cultures that may be necessary for certain experimental conditions, such as those requiring intense cellcell communication or those aiming to achieve certain physiological conditions not replicable in sparsely populated cultures. For experiments aiming to observe the effects of gradients of substances (e.g., drugs, growth factors), centralizing biological entities can create a scenario where the diffusion of the substance can be studied in relation to distance from a central point.

[0009] Each of these techniques requires careful handling and specific conditions to ensure the health and viability of the biological entities. The choice between dispersing biological entities evenly and centralizing them depends on the experimental goals and the specific requirements of the type of biological entity being cultured.

[0010] Further, DE 4 334 323 A1 relates to a method and a device for a more uniform distribution of the dry content of one or more finished bags during its packaging operation, the said distribution being achieved by vibrating or shaking the bag.

[0011] Moreover, the company Adolf Kuhner AG, Switzerland distributes and sells laboratory grade shaker with internal or external controller, for example the Lab Shaker ES-X.

[0012] The problem with the dispersion of biological entities is that this has to be done manually and is therefore extremely time-consuming.

[0013] One of the objectives of the present invention is therefore to provide a device and a method for specifically influencing the distribution of biological entities in the liquid of a culture vessel with easy means.

[0014] In a first aspect, the present invention may solve the objective by a device for handling biological entities placed in a liquid in a culture vessel, comprising a culture vesselmount, a main mount, a drive unit and a control unit, wherein a damping unit is arranged between the culture vessel mount and the main mount, wherein the damping unit comprises at least one compliant element, wherein the drive unit is configured to move the culture vessel mount relative to the main mount, and wherein the control unit is configured to control the drive unit such that the culture vessel mount moves relative to the main mount such that the biological entities are dispersed throughout the liquid in the culture vessel.

[0015] In a second aspect, the present invention may solve the objective with a method for handling biological entities placed in a liquid in a culture vessel, preferably by using a device according to the first aspect, wherein at least one culture vessel is placed in a culture vessel mount being arranged on a main mount, wherein a damping unit is arranged between the culture vessel mount and the main mount, and wherein the culture vessel mount is driven by a drive unit such that a movement is applied to the at least one culture vessel for dispersing the biological entities within the liquid.

[0016] One of the advantages may be that the distribution of biological entities placed in a liquid can be influenced automatically by moving the culture vessel mount and therefore the at least one culture vessel via the drive unit that is controlled by the control unit. Preferably, the culture vessel is a circular culture vessel. Depending on the movement being applied to the culture vessel the biological entities can be dispersed, preferably distributed at least substantially equally over the entire area of the culture vessel, within the liquid of the culture level. By arranging a damping unit between the main mount and the culture vessel mount, the movement of the culture vessel mount generated by the drive unit is controlled and thus the movement necessary for the dispersion of the biological entities is realized with simple means. Preferably, the movement of the culture vessel is a two-dimensional movement. Moreover, the main mount may allow the fixation of the device to a variety of holders or machines.

[0017] A further advantage may be that the dispersion of the biological entities in the liquid can be performed in a repeatable manner, i.e. the degree of dispersion of the biological entities is at least substantially replicable.The term "control unit" is to be understood in its broadest sense and refers in particular in the claims, preferably in the specification to a controller, computer, integrated circuit or similar device. For instance, the control unit may comprise machine-readable instructions, i.e. , a computer program, which may prompt one or more processors to execute a method. Further, the method according to the second aspect, or aspects thereof, may be performed by the control unit.

[0018] Further features, advantages and preferred embodiments are disclosed or may become apparent in the following.

[0019] According to a preferred embodiment of the invention, said biological entities are single cells, a monolayer of cells or multicellular biological entities, for example selected from the group consisting of: cell aggregates; organoids; spheroids; zebrafish eggs; zebrafish larvae; C. elegans; tissue sections; biopsy tissue; and assembloids, or combinations thereof.

[0020] According to a further preferred embodiment of the invention, said control unit is configured to control the drive unit such that an interrupted circular back and forth movement, and / or an interrupted elliptical back and forth movement and / or a crossshaped movement is applied to the at least one culture vessel being arranged in the culture vessel mount for dispersing the biological entities throughout the liquid in the culture vessel. An advantage may be that an interrupted circular back and forth movement and an interrupted elliptical back and forth movement can be realized with simple constructive means, for example with a drive unit comprising a motor that may be controlled by the control unit. The term “interrupted circular back and forth movement” is to be understood in the claims, preferably in the description, in its broadest sense and also includes movements that are smaller or larger than a circle, for example a semi-circle, a quarter circle or a three-quarter circle. This also applies to the term “half-elliptical”. An advantage of a cross-shaped movement may be that the dispersion of the biological entities is achieved rapidly. Alternatively or additionally, said control unit is configured to control the drive unit such that the drive unit comprises a rotation speed of 150 rpm (“revolution per minute”) or more, preferably of 200 rpm (“revolution per minute”) or more. Alternatively or additionally, said control unit is configured to control the drive unit such that the drive unit applies the movement to the at least one culture vessel being arranged in the culture vesselmount for a short time (less than 6 complete revolutions, preferably less than 3 complete revolutions, and / or roughly less than 2 s, preferably less than 1 s) and / or with a mean characteristic diameter of 2 cm or smaller, preferably of 1 cm or smaller, so as to be able to spread / disperse the biological entities away from each other. If considered for instance a circular movement with a trajectory of 3 mm radius, the involved centrifugal acceleration of the sample might be: a = (2TI*4HZ)2* 3 mm ~ 1.9 m / s2

[0021] According to a further preferred embodiment of the invention, the control unit is further configured to control the drive unit such that the biological entities are centralized throughout the liquid in the culture vessel. This may have the advantage that further handling of the biological entities is possible, where the biological entities should be centralized.

[0022] According to a further embodiment of the invention, the control unit is further configured to control the drive unit such that a continuous circular movement and / or a continuous elliptical movement is applied to the at least one culture vessel being arranged in the culture vessel mount for centralizing the biological entities within the culture vessel. This may have the advantage, that the movement of the culture vessel can be implemented easily, whereas a high degree of centralization of the biological entities is achieved.

[0023] According to a further preferred embodiment of the invention, the control unit is configured to control the drive unit such that the movement of the culture vessel is slower during centralization than during dispersion. This may enhance the centralization as well as the dispersion of the biological entities.

[0024] According to a further preferred embodiment of the invention, said culture vessel mount comprises a tray and a tray holder, wherein the tray comprises at least one receptacle for a culture vessel. This may have the advantage that the tray can be selected depending on the culture vessel used, so that the device can be easily adapted to different culture vessels without having to change the basic design of the device.According to a further preferred embodiment of the invention, said tray is detachable from the tray holder. This may enhance the handling of the device since the at least one culture vessel can be arranged on the tray being detached from the tray holder. Once the culture vessel or culture vessel are positioned on the tray, the tray may be attached to the tray holder, for example via a form-fit and / or force-ft connection.

[0025] According to a further preferred embodiment of the invention, said drive unit comprises a motor, preferably an electric motor, and / or a rotatably driven element, for example a gear being driven by a motor. A drive motor, preferably an electric motor, more preferably a single stepper motor, may have the advantage that due to the rotation of the rotor a predefined two-dimensional movement of the culture vessel mount can be easily achieved, especially a circular, half-circular, elliptical or halfelliptical movement. Additionally or alternatively a rotatably driven element may be arranged, which may have the advantage that the movement of the culture vessel mount can be further influenced, for example regarding the torque.

[0026] According to a further preferred embodiment of the invention, said drive unit, preferably a motor, for example an electric motor, of the drive unit, and the damping unit are arranged on a same side of the culture vessel mount, or wherein the drive unit, preferably a motor, for example an electric motor, of the drive unit, and the damping unit are arranged on opposite sides of the culture vessel mount. Arranging the drive unit and the damping unit on opposite sides of the culture vessel mount may have the advantage that the installation space is optimally utilized. Arranging the drive unit and the damping unit on a same side of the culture vessel mount may enhance the excitation of a circular or elliptical movement of the culture vessel mount. Additionally or alternatively the drive unit may be arranged eccentric in relation to the culture vessel mount. This may enhance the translation of the rotational movement of the motor into a two-dimensional circular and / or elliptical movement of the culture vessel mount.

[0027] According to a further preferred embodiment of the invention, at least one, preferably two, first compliant element extends in a first direction and wherein at least one, preferably two, second compliant element extends in a second direction, wherein the first direction and the second direction differ from each other. Dampening the movement of the culture vessel mount in two distinct directions may enhance theexcitation of a circular or elliptical movement of the same. Further, arranging two first compliant elements and two second compliant elements may enhance the stability and damping of the culture vessel mount, thereby improving the generation of the movement required for centralization and dispersion of the biological entities.

[0028] According to a further preferred embodiment of the invention, said first direction and said second direction extend in a common plane. This may have the advantage that the movement of the culture vessel mount can be dampened in said common plane. Additionally, the culture vessel mount may be movable by the drive unit within said common plane or within a plane being at least substantially parallel to said common plane. Hence, a predefined two-dimensional movement of the culture vessel mount can be induced which may enhance the centralization and / or dispersion of the biological entities.

[0029] According to a further preferred embodiment of the invention, said first direction and said second direction intersect at an angle in the region of 45° to 135°, preferable 80° to 100°, more preferably 88° to 92°, for example 90°. This may enhance the excitation of a two-dimensional circular or elliptical movement of the culture vessel mount being driven by the drive unit, especially by a drive unit comprising an electric motor, preferably a single step motor.

[0030] According to a further preferred embodiment of the invention, said at least one compliant element is provided in the form of a blade, preferably wherein the at least one compliant element comprises three dimensions, wherein two dimensions, e.g. length and / or width are much larger than the third dimension, e.g. thickness, e.g. at least by a factor of 2.

[0031] According to a further preferred embodiment of the invention, said at least one compliant element comprises a plastic and / or a metal, for example stainless steel, brass and / or copper.

[0032] According to a further preferred embodiment of the invention, said culture vessel mount is driven by the drive unit such that an interrupted circular back and forth movement, an interrupted elliptical back and forth movement and / or a cross-shaped movement is applied to the at least one culture vessel for dispersing the biologicalentities within the liquid. Alternatively or additionally, said drive unit is driven with a rotation speed of 150 rpm (“revolution per minute”) or more, preferably of 200 rpm (“revolution per minute”) or more. Alternatively or additionally, said drive unit applies the movement to the at least one culture vessel being arranged in the culture vessel mount for a short time (less than 6 complete revolutions, preferably less than 3 complete revolutions, and / or roughly less than 2 s, preferably less than 1 s) and / or with a mean characteristic diameter of 2 cm or smaller, preferably of 1 cm or smaller, so as to be able to spread / disperse the biological entities away from each other. If considered for instance a circular movement with a trajectory of 3 mm radius, the involved centrifugal acceleration of the sample might be: a = (2TI*4HZ)2* 3 mm ~ 1.9 m / s2

[0033] According to a further preferred embodiment of the invention, before and / or after dispersing the biological entities, the culture vessel mount is driven by the drive unit such that a continuous circular movement and / or a continuous elliptical movement is applied to the at least one culture vessel for centralizing the biological entities within the liquid. Additionally, the movement of the culture vessel may be slower during centralization than during dispersion.

[0034] There are several ways how to design and further develop the teaching of the present invention in an advantageous way. To this end, it is to be referred to the patent claims subordinate to the main claims on the one hand and to the following explanation of preferred examples of embodiments of the invention, illustrated by the drawing on the other hand. In connection with the explanation of the preferred embodiments of the invention by the aid of the drawing, generally preferred embodiments and further developments of the teaching will be explained.

[0035] In the drawing

[0036] Fig. 1 shows centralized and dispersed biological entities in a culture vessel in a side view;

[0037] Fig. 2 shows centralized and dispersed biological entities in a culture vessel in a top view;Fig. 3 shows a device according to an embodiment of the invention in a top view;

[0038] Fig. 4 shows a device according to a further embodiment of the invention in a top view; and

[0039] Fig. 5 shows steps of a method according to an embodiment of the present invention.

[0040] Figures 1 and 2 show in a side view and in a top view biological entities 1 placed in a liquid 2, for example a liquid culture medium, in a culture vessel 3. On the left-hand side of figures 1 and 2 the biological entities 1 are dispersed within the liquid 2, whereas on the right-hand side, the biological entities 1 are centralized in the middle of the culture vessel 3. Further, the culture vessel 3 comprises a circular shape which is advantageous for using the culture vessel 3 in a device according to an embodiment of the invention and / or for using it with a method according to an embodiment of the invention.

[0041] Figure 3 shows a device for handling biological entities 1 placed in a liquid 2 in a culture vessel 3 according to an embodiment of the invention. The device comprises a culture vessel mount 4 for holding the culture vessels 3, a main mount 5, a drive unit 6 and a control unit 16. In this embodiment the culture vessel mount 4 holds four culture vessels 3, whereas it is possible that the culture vessel mount 4 is designed to hold less or more than four culture vessels 3.

[0042] Further, figure 3 shows that a damping unit 7 is arranged between the culture vessel mount 4 and the main mount 5. The damping unit 7 comprises two first compliant elements 8 and two second compliant elements 9. The first compliant elements 8 extend in a first direction 10, whereas the second compliant elements 9 extend in a second direction 11. The first and second direction 10, 11 extend in a common plane and intersect at an angle 12 of 90°. It is noted that the first and second direction 10, 11 could also intersect at an angle 12 in the region of 45° to 135°, preferable 80° to 100°, more preferably 88° to 92°. The common plane of the first and second direction 10, 11 is at least substantially parallel to the plane in which the culture vessel mount3 is moving due to the drive unit 6. Figure 3 further shows that the compliant elements 8, 9 are provided in the form of a blade.

[0043] The drive unit 6 may comprise a motor, preferably an electric motor, for example a stepper motor. The drive unit 6 and the damping unit 7 are arranged on the same side of the culture vessel mount 4. Further, the drive unit 6 is arranged eccentric in relation to the culture vessel mount 4. Hence, the rotational movement of the drive unit 6 is translated into a circular or elliptical movement of the culture vessel 3. The translation into a circular or an elliptical movement is further enhanced by the first compliant elements 8 and the second compliant elements 9 of the damping unit 7.

[0044] By moving the culture vessel mount 4 with the drive unit 6 the culture vessels 3 are moved in two dimensions in such a way that the biological entities 1 within the culture vessel 3 are dispersed. In addition, the biological entities 1 may be centralized. For example, the control unit 16 is configured to control the drive unit 6 to apply an interrupted circular back and forth movement and / or an interrupted elliptical back and forth movement to the culture vessels 3 for dispersing the biological entities 1 within the culture vessel 3. Additionally, the drive unit 6 may be controlled by the control unit 16 to apply a continuous circular movement and / or a continuous elliptical movement to the culture vessels 3 for centralizing the biological entities 1 within the culture vessel 3.

[0045] Figure 4 shows a device for handling biological entities 1 placed in a liquid 2 in a culture vessel 3 according to a further embodiment of the invention. The device comprises a culture vessel mount 4 for holding the culture vessels 3, a main mount 5, a drive unit 6 and a control unit 16. In this embodiment the culture vessel mount 4 holds six culture vessels 3, whereas it is possible that the culture vessel mount 4 is designed to hold less or more than six culture vessels 3. Further, the culture vessel mount 4 comprises a tray 13 and a tray holder 14. The tray 13 is detachably attached to the tray holder 14 via clamps 15.

[0046] Further, the damping unit 7 comprises two first compliant elements 8 and two second compliant elements 9 each being provided in the form of a blade. The first compliant elements 8 extend in a first direction 10, whereas the second compliant elements 9 extend in a second direction 11. The first and second direction 10, 11 extend in acommon plane and intersect at an angle 12 of 90°. It is noted that the first and second direction 10, 11 could also intersect at an angle 12 in the region of 45° to 135°, preferable 80° to 100°, more preferably 88° to 92°. The common plane of the first and second direction 10, 11 is at least substantially parallel to the plane in which the culture vessel mount 3 is moving due to the drive unit 6.

[0047] The drive unit 6 may comprise a motor, preferably an electric motor, for example a stepper motor. The drive unit 6 and the damping unit 7 are arranged on opposite sides of the culture vessel mount 4. Further, the drive unit 6 is arranged eccentric in relation to the culture vessel mount 4. Hence, the rotational movement of the drive unit 6 is translated into a two dimensional circular or elliptical movement of the culture vessel 3. The translation into a circular or an elliptical movement is further enhanced by the first compliant elements 8 and the second compliant elements 9 of the damping unit 7.

[0048] By moving the culture vessel mount 4 with the drive unit 6 the culture vessels 3 are moved in such a way that the biological entities 1 within the culture vessel 3 are dispersed. In addition, the biological entities may be centralized. For example, the control unit 16 is configured to control the drive unit 6 to apply an interrupted circular back and forth movement and / or an interrupted elliptical back and forth movement to the culture vessels 3 for dispersing the biological entities 1 within the culture vessel 3. Additionally, the drive unit 6 may be controlled by the control unit 16 to apply a continuous circular movement and / or a continuous elliptical movement to the culture vessels 3 for centralizing the biological entities 1 within the culture vessel 3.

[0049] Figure 5 shows steps of a method according to an embodiment of the present invention.

[0050] The method comprises the steps of:

[0051] - placing S1 at least one culture vessel in a culture vessel mount being arranged on a main mount, wherein a damping unit is arranged between the culture vessel mount and the main mount,

[0052] - driving S2 the culture vessel mount is by a drive unit such that a movement is applied to the at least one culture vessel for dispersing the biological entities within the liquid.Add itional ly , the method may comprise the further step of driving S3 the culture vessel mount by the drive unit such that a continuous circular movement and / or a continuous elliptical movement is applied to the at least one culture vessel for centralizing the biological entities within the liquid. Figure 5 shows that step S3 is carried out after step S2, whereas step S3 could be alternatively or additionally carried before step S2.

[0053] Many modifications and other embodiments of the invention set forth herein will come to mind to the one skilled in the art to which the invention pertains having the benefit of the teachings presented in the foregoing description and the associated drawings. Therefore, it is to be understood that the invention is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.

Claims

C l a i m s1. Device for handling biological entities (1) placed in a liquid (2) in a culture vessel (3), comprising a culture vessel mount (4), a main mount (5), a drive unit (6) and a control unit (16), wherein a damping unit (7) is arranged between the culture vessel mount (4) and the main mount (5), wherein the damping unit (7) comprises at least one compliant element (8, 9), wherein the drive unit (6) is configured to move the culture vessel mount (4) relative to the main mount (5), and wherein the control unit (16) is configured to control the drive unit (6) such that the culture vessel mount (4) moves relative to the main mount (5) such that the biological entities (1) are dispersed throughout the liquid (2) in the culture vessel (3).

2. Device according to claim 1, characterized in that the control unit (16) is configured to control the drive unit (6) such that an interrupted circular back and forth movement, and / or an interrupted elliptical back and forth movement and / or a crossshaped movement is applied to the at least one culture vessel (3) being arranged in the culture vessel mount (4) for dispersing the biological entities (1) throughout the liquid (2) in the culture vessel (3).

3. Device according to claim 1 or claim 2, wherein the control unit (16) is further configured to control the drive unit (6) such that the biological entities (1) are centralized throughout the liquid (2) in the culture vessel (3).

4. Device according to claim 3, characterized in that the control unit (16) is further configured to control the drive unit (6) such that a continuous circular movement and / or a continuous elliptical movement is applied to the at least one culture vessel (3) being arranged in the culture vessel mount (4) for centralizing the biological entities (1) within the culture vessel (3).

5. Device according to any one of claims 1 to 4, characterized in that the culture vessel mount (4) comprises a tray (13) and a tray holder (14), wherein the tray (13) comprises at least one receptacle for a culture vessel (3),preferably wherein the tray (13) is detachable from the tray holder (14).

6. Device according to any one of claims 1 to 5, characterized in that the drive unit (6) comprises a motor, preferably an electric motor, and / or a rotatably driven element, for example a gear being driven by a motor.

7. Device according to any one of claims 1 to 6, characterized in that the drive unit (6) is arranged eccentric in relation to the culture vessel mount (4), preferably wherein the drive unit (6) and the damping unit (7) are arranged on a same side of the culture vessel mount (4), or wherein the drive unit (6) and the damping unit (7) are arranged on opposite sides of the culture vessel mount (4).

8. Device according to any one of claim 1 to 7, characterized in that at least one, preferably two, first compliant element (8) extends in a first direction (10) and wherein at least one, preferably two, second compliant element (9) extends in a second direction (11 ), wherein the first direction (10) and the second direction (11 ) differ from each other.

9. Device according to claim 8, characterized in that the first direction (10) and the second direction (11) extend in a common plane.

10. Device according to claim 9, characterized in that the first direction (10) and the second direction (11) intersect at an angle (12) in the region of 45° to 135°, preferable 80° to 100°, more preferably 88° to 92°, for example 90°.

11. Device according to any one of claims 1 to 9, characterized in that the at least one compliant element (8, 9) is provided in the form of a blade, preferably wherein the at least one compliant element (8, 9) comprises three dimensions, wherein two dimensions, e.g. length and / or width are much larger than the third dimension, e.g. thickness, e.g. at least by a factor of 2.

12. Device according to claim 11 , characterized in that the at least one compliant element (8, 9) comprises a plastic and / or a metal, for example stainless steel, brass and / or copper.

13. Method for handling biological entities (1) placed in a liquid (2) in a culture vessel (3), preferably by using a device according to any one of claims 1 to 12,wherein at least one culture vessel (3) is placed in a culture vessel mount (4) being arranged on a main mount (5), wherein a damping unit (7) is arranged between the culture vessel mount (4) and the main mount (5), and wherein the culture vessel mount (4) is driven by a drive unit (6) such that a movement is applied to the at least one culture vessel (3) for dispersing the biological entities (1 ) within the liquid (2).

14. Method according to claim 13, characterized in that the culture vessel mount (4) is driven by the drive unit (6) such that an interrupted circular back and forth movement, an interrupted elliptical back and forth movement and / or a cross-shaped movement is applied to the at least one culture vessel (3) for dispersing the biological entities (1) within the liquid (2).

15. Method according to claim 13 or 14, characterized in that before and / or after dispersing the biological entities (1 ), the culture vessel mount (4) is driven by the drive unit (6) such that a continuous circular movement and / or a continuous elliptical movement is applied to the at least one culture vessel (3) for centralizing the biological entities (1) within the liquid (2).

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