Impeller system for use with bioreactor

Abstract

The present disclosure relates to an impeller system (1) for use with a bioreactor (2), having: a drive shaft (3) configured to be rotated about a longitudinal axis (X) of the drive shaft in a direction of rotation (R) by a drive motor (4) of the bioreactor; at least two impeller blades (5) connected to the drive shaft, configured to rotate with the drive shaft when the drive shaft rotates, where the at least two impeller blades are configured to transition from a folded state to an unfolded state to perform stirring. When stirring is performed, at least one of the at least two impeller blades transitions from a folded state to an unfolded state by rotating along a circumference (6) of the drive shaft due to resistance from a liquid (7) from the bioreactor.

Description

Technical Field

[0001] The present disclosure relates to an impeller system for use with a bioreactor, a method of using such an impeller system, and a method of making such an impeller system. Background Art

[0002] WO 2013 / 151733 A1 discloses a fluid mixing system, which includes a container, such as a flexible bag, defining a compartment. A flexible drive line is arranged in the compartment, the drive line having a first end rotatably connected to a first end of the container and an opposite second end rotatably connected to a second end of the container. At least one mixing element, such as an impeller, is coupled to the flexible drive line. The rotation of the drive line facilitates the rotation of the impeller in the container. The impeller may include pivotable or foldable blades. By folding the blades (where the blades are bent about a portion between an axis and a blade tip), the container can be more completely folded around the impeller while minimizing the risk of damaging the container and the blades, for example, during transportation. Each of the blades can capture a fluid and automatically move from a folded (folded) position to an unfolded (unfolded) position for mixing the fluid.

[0003] However, a problem with the fluid mixing system of WO 2013 / 151733 A1 is that, in the folded state, the foldable blades still occupy a considerable space around the drive line.

[0004] Furthermore, a relatively complex mechanical system is required to open the foldable blades to the deployed position in order to initiate stirring. Summary of the invention

[0005] It is therefore an object of the present disclosure to provide an impeller system for use with a bioreactor wherein in a folded state the blades fold towards each other to occupy less space around the drive line.

[0006] It is another object of the present disclosure to provide an impeller system for use with a bioreactor in which a relatively less complex mechanical system is required to transition the folded blades to an unfolded position to initiate agitation.

[0007] According to an embodiment of the present disclosure, there is provided an impeller system for use with a bioreactor, comprising:

[0008] - a drive shaft configured to be rotated in a rotational direction about a longitudinal axis of the drive shaft by a drive motor of the bioreactor;

[0009] - At least two impeller blades connected to the drive shaft and configured to rotate with the drive shaft when the drive shaft rotates, wherein the at least two impeller blades are configured to transition from a collapsed state to an unfolded state to perform agitation, wherein in the collapsed state the at least two impeller blades are not positioned symmetrically around the drive shaft axis, but rather are aligned, such as along a longitudinal axis, wherein in the unfolded state the at least two impeller blades are positioned symmetrically around the drive shaft axis, wherein when agitation is performed, at least one of the at least two impeller blades transitions from the collapsed state to the unfolded state by rotating along the circumference of the drive shaft due to resistance from liquid in the bioreactor.

[0010] Since at least two impeller blades, such as three, four, five, six or more blades, preferably all blades, are not positioned axially symmetrically around the drive shaft in the folded state, but are aligned, such as along the longitudinal axis, they take up much less space around the drive shaft in the folded state, thereby enabling easier transportation and the size of the impeller system is greatly reduced when, for example, a bioreactor bag or a similar flexible container for bioreactors is used, i.e. when the flexible container for bioreactors is folded around the impeller system.

[0011] In the context of the present patent application, "aligned" means "substantially radially aligned", i.e., the angles formed between similar radially extending features of a first item (such as a blade) and a second item (such as a blade arranged adjacent to the drive shaft) are less than 60 degrees, more preferably less than 45 degrees, and even more preferably less than 30 degrees, and even more preferably less than 20 degrees, and even more preferably less than 15 degrees, relative to a common rotation axis of the drive shaft, such as the longitudinal axis of the drive shaft, and in particular the portion of the drive shaft where the blades are connected or otherwise engaged with the drive shaft.

[0012] Furthermore, when agitation is performed, at least one of the at least two impeller blades is transformed from a folded state to an unfolded state along the circumference of the drive shaft (e.g., along a circumferential arc) by rotating along the circumference of the drive shaft due to resistance from the liquid in the bioreactor. Therein, at least one of the two (or more) impeller blades is substantially "automatically" and gradually transformed along the circumference of the drive shaft to its own individual / unique position in the final axisymmetric configuration of the impeller blade in the unfolded state in a very natural manner: the fluid dynamic force exerted by the liquid on at least one of the at least two impeller blades pushes at least one of the impeller blades into its unique position in the final axisymmetric configuration of the impeller blade in the unfolded state, for example by causing / making at least one of the at least two impeller blades slide (e.g., rotationally slide) along the circumference (or circumferential arc) of the drive shaft. Thus, the use of a complex mechanical system for unfolding the impeller blades can be avoided.

[0013] Another advantage of the above-mentioned impeller system is that, in the folded state, when the flexible container for bioreactor is folded around the impeller system, at least two impeller blades are less likely to damage the flexible container for bioreactor (e.g., a soft bag) because at least two impeller blades are aligned along the longitudinal axis, thereby dispersing any pressure applied to the inner side (of the corresponding side) of the flexible container for bioreactor to multiple impeller blades, thereby preventing puncture or tearing of the flexible container for bioreactor.

[0014] One embodiment relates to an impeller system as described above, wherein at least two impeller blades are each independently connected to the drive shaft. Thus, at least one individual impeller blade can be moved to the corresponding impeller blade's final position in the folded state independently of the other impeller blades, thereby increasing the reliability of the impeller system. Furthermore, the foregoing enables "tuning" of the impeller system by removing or adding impeller blades, which also facilitates manufacturing.

[0015] One embodiment of the present disclosure relates to an impeller system as previously described, wherein at least one of the at least two impeller blades is independently attached to the drive shaft using a ring configured to rotate about the drive shaft, wherein the ring is configured to rotate from a first orientation on the drive shaft in a folded state to a separate second orientation on the drive shaft in an unfolded state, such that the at least two impeller blades are positioned symmetrically about the drive shaft axis. The use of such a rotatable ring enables at least one of the at least two impeller blades to naturally move to its final position in the unfolded state. Removal or addition of impeller blades is also further simplified.

[0016] One embodiment relates to an impeller system as described above, wherein the ring or the drive shaft is provided with a joint on one side of a partial circumference at an axial portion of the ring, and the ring or the partial circumference is provided with a joint member on the other side, wherein the joint and the joint member are configured to engage with each other when the ring has reached a second orientation, thereby preventing the ring from rotating beyond the second orientation.

[0017] One embodiment relates to an impeller system as previously described, wherein at least two impeller blades are adjacent to each other along the longitudinal axis in the folded state. Thus, by spacing the at least two impeller blades closely together, such as by stacking them onto each other along the longitudinal axis, the chances of local pressure points occurring are further reduced, thereby further preventing puncture or tearing of the flexible container for bioreactor.

[0018] One embodiment relates to an impeller system as described above, wherein, in the folded state, at least two impeller blades are adjacent to each other along the longitudinal axis in such a way that, when viewed along the longitudinal axis, the contours of the at least two impeller blades are aligned or otherwise accessible to each other. Thus, a compact "packaging" of the impeller blades is achieved, wherein, due to the alignment of the contours of the impeller blades in the longitudinal direction, at least two impellers are prevented from protruding relative to each other in a direction perpendicular to the longitudinal axis, thereby further preventing local puncture of the flexible container for bioreactors.

[0019] One embodiment relates to an impeller system as described above, wherein the radial outer edges of two or more impeller blades are rounded in the main plane of the impeller blades, so that, for example when transporting or storing the flexible container for bioreactor and the impeller system, the bioreactor folds smoothly onto the impeller blades, further reducing the risk of damage to the flexible container for bioreactor.

[0020] One embodiment relates to an impeller system as described above, wherein the rounded radial outer edges of two or more impeller blades have a constant radius of curvature to further facilitate smooth placement of the flexible container for bioreactor onto the radial outer edges of the impeller blades in a folded state.

[0021] One embodiment relates to an impeller system as described above, wherein the radially outer edges of two or more impeller blades are rounded in a plane transverse to the radially outer edges and the main plane of the impeller blades. Thus, the impeller blades are less "sharp" to further prevent puncture or cutting of the flexible container for bioreactors in the folded state.

[0022] One embodiment is directed to an impeller system as previously described, wherein at least two impeller blades are aligned along the longitudinal axis in the folded state, thereby providing a compact impeller blade packaging.

[0023] One embodiment relates to an impeller system as described above, wherein at least two impeller blades form a rotation angle relative to each other about the longitudinal axis in a folded state, which is less than 45 degrees, more preferably less than 30 degrees, and even more preferably less than 15 degrees, and most preferably about 0 degrees, so that the impeller blades are close together in the rotation direction in the folded state.

[0024] One embodiment relates to an impeller system as previously described, wherein at least two impeller blades are each independently connected to the drive shaft, thereby enabling optimized design and operational flexibility.

[0025] Another aspect of the present disclosure relates to a flexible container for bioreactor, comprising the aforementioned impeller system, wherein the impeller system is disposed inside the flexible container for bioreactor.

[0026] One embodiment relates to the aforementioned flexible container for bioreactor, wherein at least two impeller blades are in a folded state.

[0027] One embodiment relates to the aforementioned flexible container for bioreactor, wherein the interior of the flexible container for bioreactor is aseptically processed to a sterility assurance level of at least 10-3 SAL.

[0028] One embodiment relates to the aforementioned flexible container for bioreactor, further comprising a sterile barrier enclosing the flexible container, wherein the sterile barrier is optionally configured as a bag, a pouch or a tub with a sealing lid.

[0029] Another aspect of the present disclosure relates to a bioreactor, comprising a drive motor and the aforementioned impeller system or the aforementioned flexible container for bioreactor, wherein a drive shaft is connected to the drive motor.

[0030] Another aspect of the present disclosure relates to a method of using the aforementioned impeller system, comprising the following steps:

[0031] - connecting the drive shaft to a drive motor of the bioreactor; and

[0032] The drive shaft is rotated about the longitudinal axis of the drive shaft by a drive motor of the bioreactor, wherein at least one of the at least two impeller blades is transformed from a folded state to an unfolded state by rotating along the circumference of the drive shaft due to resistance from the liquid in the bioreactor to perform agitation of the liquid.

[0033] Another aspect of the present disclosure relates to a method for manufacturing the aforementioned impeller system, comprising the following steps:

[0034] - manufacturing a drive shaft configured to be rotated in a rotational direction about a longitudinal axis of the drive shaft by a drive motor of the bioreactor;

[0035] - manufacturing at least two impeller blades for connection to a drive shaft and for rotation with the drive shaft, wherein at least one of the at least two impeller blades is configured for transitioning from a folded state to an unfolded state to perform agitation, wherein in the folded state the at least two impeller blades are not positioned symmetrically about the drive shaft axis, wherein in the unfolded state the at least two impeller blades are positioned symmetrically about the drive shaft axis, wherein when agitation is performed, at least one of the at least two impeller blades transitions from the folded state to the unfolded state by rotating along the circumference of the drive shaft due to resistance from liquid in the bioreactor; and

[0036] - Connect at least two impeller blades to the drive shaft.

[0037] One embodiment relates to a manufacturing method as described above, wherein manufacturing at least two impeller blades includes 3D printing at least one of the at least two impeller blades, such as both. 3D printing is any of a variety of processes in which materials are added together (such as fusing liquid molecules or powder particles together), combined or solidified to create a three-dimensional object. 3D printing is commonly used for both rapid prototyping and additive manufacturing (AM). Objects can be of almost any shape or geometry and are typically produced (usually in sequential layers) using digital model data from a 3D model or another electronic data source such as an additive manufacturing file (AMF) file. There are many different technologies, such as stereolithography (SLA) or fused deposition manufacturing (FDM). Therefore, unlike traditional machining processes in which material is removed from a blank, 3D printing or AM typically builds a three-dimensional object from a computer-aided design (CAD) model or AMF file by continuously adding material layer by layer.

[0038] One embodiment relates to an aforementioned production method, wherein in the folded state at least two impeller blades are aligned along the longitudinal axis. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Embodiments of the present disclosure will be explained in more detail below with reference to the illustrative embodiments shown in the accompanying drawings, wherein:

[0040] Figure 1 An exemplary embodiment of a bioreactor is shown, comprising a drive motor and a flexible container for bioreactor having an impeller system according to the present disclosure, wherein a drive shaft is connected to the drive motor;

[0041] Figure 2 An exemplary embodiment of an impeller system according to the present disclosure is shown, such as Figure 1 An impeller system, wherein the impeller blades are in a folded state;

[0042] Figure 3 An exemplary embodiment of an impeller system according to the present disclosure is shown, such as Figure 1 or Figure 2 An impeller system, wherein the impeller blades are in an unfolded state;

[0043] Figure 4 An exemplary embodiment of an impeller system according to the present disclosure is shown, such as Figure 1 , Figure 2 or Figure 3 An exploded view of an impeller system of FIG. 1 , wherein the impeller blades are in an unfolded state; and

[0044] Figures 5 to 7 An exemplary embodiment of an impeller system according to the present disclosure is shown including a connection mechanism for connecting a lower drive shaft portion to an upper drive shaft portion. DETAILED DESCRIPTION

[0045] Figure 1 An exemplary embodiment of a bioreactor 2 is shown, which includes an impeller system 1 and a drive motor 4 according to an exemplary embodiment of the present disclosure, wherein a drive shaft 3 is connected to the drive motor 4. The bioreactor 2 can be a single-use or multiple-use bioreactor 2. The bioreactor 2 can be configured for an operating / working volume of 1 to 10,000 liters, preferably 10 to 5,000 liters, more preferably 50 to 3,000 liters, such as 40 to 60 liters. The bioreactor 2 generally relates to a manufactured or modified device or system that supports a biologically active environment. The bioreactor 2 can be cylindrical and can be made of glass and / or stainless steel. The bioreactor 2 can also relate to a device or system designed to grow cells or tissues in the case of cell culture.

[0046] The impeller system 1 is configured inside a flexible container 15 for bioreactor. The outer surface of the flexible container 15 for bioreactor, such as a bioreactor bag 15, is positioned against the inner surface (i.e., the inner side wall) of the bioreactor 2 to provide a suitable fit, preferably without folding, etc. The flexible container 15 for bioreactor can be configured for single use. This single-use flexible container 15 has several advantages, especially reducing assembly / disassembly, cleaning, disinfection and calibration requirements. The impeller system 1 includes a drive shaft 3, which is configured to rotate around the longitudinal axis X of the drive shaft 3 along the rotation direction R by the drive motor 4 of the bioreactor 2. The drive shaft 3 can have a length of, for example, 10 to 250 cm, such as 10 to 100 cm, for example 10 to 50 cm, depending on the design of the bioreactor 2. At least two impeller blades 5, such as two, three, four, five, six or even more impeller blades are connected to the drive shaft 3 and are configured to rotate along the rotation direction R with the drive shaft 3. At least two impeller blades 5 are preferably arranged at the free end of the drive shaft 3, but other arrangements are also conceivable (e.g., such as being spaced apart from the free end of the drive shaft 3). The impeller blades 5 may have the form of a (flat) plate, but other shapes, such as curved blades, are also conceivable. The impeller blades 5 may also be arranged at an angle relative to the longitudinal axis X (a plane transverse to the longitudinal axis X). The at least two impeller blades 5 are configured to be used for transitioning from a folded state I, in which the at least two impeller blades 5 are adjacent to each other or otherwise accessible to each other about the longitudinal axis X, to an unfolded state II to perform stirring, wherein in the folded state I the at least two impeller blades 5 are adjacent to each other or otherwise accessible to each other about the longitudinal axis X, wherein in the unfolded state II the at least two impeller blades are rotationally positioned away from each other axle-symmetrically around the drive shaft 3. If two impeller blades 5 are used, in the unfolded state the blades will be radially spaced about the axis X by about 180 degrees from each other, wherein if three impeller blades 5 are used, in the unfolded state the blades will be radially spaced about the axis X by about 120 degrees. Figure 1 The impeller blades 5 are shown in an unfolded state II. When agitation is performed, at least one of the at least two impeller blades 5 is transformed from the folded state I to the unfolded state II by rotating, i.e. moving, along the circumference 6 of the drive shaft 3 due to resistance from the liquid 7 in the bioreactor 2.

[0047] Figure 2 An exemplary embodiment of an impeller system 1 according to the present disclosure is shown, such as Figure 1 The impeller system 1 of the present invention comprises an impeller blade 5 in a folded state I. At least two impeller blades 5 are in the folded state I, for example for storage or transportation. At least two impeller blades 5 can each be independently connected to the drive shaft 3, as will be described with reference to Figure 4More clearly explained. In the folded state I, at least two impeller blades 5 may be adjacent to each other 16 along the longitudinal axis X, preferably forming a "packaging" of the impeller blades 5 in such a way that the profiles 17 of at least two impeller blades 5 are aligned or otherwise adjacent to each other in a contacting or non-contacting manner when viewed along the longitudinal axis X. For example, radially adjacent blades may form an angle with respect to the longitudinal axis X that is less than 90 degrees, more preferably less than 60 degrees or 45 degrees, more preferably less than 40 degrees, preferably less than 30 degrees, preferably less than 15 degrees, preferably less than 10 degrees, preferably less than 5 degrees, and if geometrically feasible, may form an angle of 0 degrees or about 0 degrees with each other, all of the foregoing being subject to geometrical constraints such as, but not limited to, their respective blade thickness, shape, means of connection to the drive shaft and / or longitudinal spacing along the drive shaft 3.

[0048] Figure 3 An exemplary embodiment of an impeller system 1 according to the present disclosure is shown, such as Figure 1 or Figure 2 1, wherein the impeller blades 5 are in an unfolded state I. The impeller blades 5 are now arranged axisymmetrically around the drive shaft 3 for performing stirring and, as shown with three blades, can form an angle of about 120 degrees with respect to the longitudinal axis X.

[0049] Figure 4 An exemplary embodiment of an impeller system 1 according to the present disclosure is shown, such as Figure 1 , Figure 2 or Figure 3 Exploded view of an impeller system 1 of FIG. 1 , wherein the impeller blades 5 are in an unfolded state I. The radially outer edges 12 of two or more impeller blades 5 are preferably rounded in a main plane 13 of the impeller blades 5. The rounded, radially outer edges 12 of the two or more impeller blades 5 preferably have a constant radius of curvature r. The radius of curvature r may be 2 to 10 cm, such as 2 to 5 cm. At least one of the at least two rotatable impeller blades 5 may be independently attached to the drive shaft 3 by means of a rotatable ring 8 provided with a joint 10, such as a lower rotatable ring 29 and an upper rotatable ring 30, respectively, as shown in FIG. Figure 4 shown.

[0050] The rotatable ring 8 may be configured to rotate around the drive shaft 3, wherein the rotatable ring 8 is configured to rotate from a first orientation (i.e., a first angular position) on the drive shaft 3 in the folded state I to a second orientation (i.e., a second angular position) on the drive shaft 3 in the unfolded state II, such that at least two rotatable impeller blades 5 are positioned axially symmetrically around the drive shaft 3, wherein each of the impeller blades 5 has a unique axially symmetrical position. Figure 4As shown, the lower rotatable ring 29 may be provided with a lower circumferential recess 27, while the upper rotatable ring 30 may be provided with an upper circumferential recess 28. The partial circumference 9 of the drive shaft 3 is provided with an engagement member 11 in the form of a notch, a protrusion, etc. The circumferential length of the lower circumferential recess 27 is different from the circumferential length of the upper circumferential recess 28.

[0051] Basically, the ring 8 acts as a keyed slot mechanism relative to the drive shaft 3. Since the key width and slot width are similar in size, the keyed slot is usually designed to have little to no "slop" to prevent rotation. Figure 4 In the embodiment shown, a relatively large keyway width, i.e., the circumferential length of the lower circumferential recess 27 and the upper circumferential recess 28, is used to induce a large degree of "ramp" to enable additional rotation, and because the keyway equivalents of the lower ring 29 and the upper ring 30, i.e., the length of the lower circumferential recess 27 and the upper circumferential recess 28, are different in size for each ring 8, the amount of rotation that can be achieved is different. Figure 4 The "key" equivalent of the embodiment shown is essentially the engagement member 11.

[0052] Each ring 8, i.e. each of the lower ring 29 and the upper ring 30, has a "keyway" (i.e. the respective circumferential length of the lower circumferential recess 27 and the upper circumferential recess 28) which is significantly longer than the key (engagement member 11) so that when the second impeller blade 5 (from the lower ring 29) associated with the lower ring 29 is engaged, the second impeller blade 5 (from the upper ring 30) is engaged. Figure 4 When the lower end of the impeller system 2 (counting upward) rotates about the drive shaft 3 along the circumferential recess 27 and contacts the engaging member 11 at one side of the engaging portion 10 at the engaging portion 10, it stops rotating, and when the third impeller blade 5 associated with the upper ring 30 rotates about the drive shaft 3 along the upper circumferential recess 28 and the engaging portion 10 of the upper ring 30 contacts the same key, i.e. the engaging member 11, it also stops rotating.

[0053] The lower ring 29 has a keyway (circumferential recess 27 length) that is large enough to enable a rotation of 120 degrees or approximately 120 degrees, and the upper ring 30 has a keyway (circumferential recess 28 length) that is large enough to enable a rotation of 240 degrees or approximately 240 degrees, so that if three impeller blades 5 are used, they are placed 120 degrees or approximately 120 degrees out of phase with each other about the rotation axis X.

[0054] Ring 8, such as Figure 4 The two rings 8 shown in the figure can be maintained in their longitudinal position by using the lower end ring 20 and the upper end ring 19. The ring 8 is then securely "locked" (i.e. longitudinally) between the upper end ring 19 and the lower end ring 20. Figure 4 As can be seen in FIG. 1 , the lower end ring 20 can be provided with impeller blades 5 which are fixedly attached to the drive shaft 3, for example formed integrally therewith, i.e. cannot move relative to the local circumference 9 of the drive shaft 3. Figure 4 The other impeller blades 5 shown in FIG. 5 are configured to rotate relative to the drive shaft 3 due to the resistance of the liquid (ie, in a direction opposite to the direction of rotation R, as will be appreciated by the skilled person).

[0055] The radially outer edge 12 of two or more impeller blades 5 is preferably rounded in a plane 14 transverse to the radially outer edge 12 and to the main plane 13 of the impeller blade.

[0056] Figures 5 to 7 An exemplary embodiment of an impeller system 1 according to the present disclosure is shown, comprising a connection mechanism (such as in FIG. 1 ) for connecting a lower drive shaft portion 23 of a drive shaft 3 (during use) to an upper drive shaft portion 24 of a drive shaft 3. Figure 7 Two or more impeller blades 5 are connected to the lower drive shaft portion 23. Figure 5 A first variant of the connection mechanism is shown, in which one or more longitudinal guide slots 21, such as one, two, three, four or more guide slots 21, are provided in the lower drive shaft portion 23 at its upper longitudinal end. The guide slots 21 are configured to receive one or more elongated guide members 26, such as Figure 7 Therefore, the torque of the drive motor connected to the upper drive shaft portion 24 can be properly transmitted to the lower drive shaft portion 23. Figure 6 and Figure 7 The connecting mechanism shown in the figure shows a second variant of a relatively long guide groove 21, as shown in FIG. Figure 5 The first variant of the connecting mechanism shown comprises a relatively short guide groove 21 .

[0057] like Figure 5 The first variant shown comprises one or more (radial) resilient locking members 22 arranged below the relatively short guide slot 21 to lock onto one or more corresponding protrusions (not shown) on the upper drive shaft portion 24. The upper drive shaft portion 24 may be hollow, such as Figure 7 As shown, for receiving the lower drive shaft portion 23. One or more protrusions can be configured on the inner side of the circumferential wall of such a hollow upper drive shaft portion 24. In order to facilitate locking "behind" such a protrusion, one or more radially outwardly extending connecting edges 25 can be provided on the longitudinal upper end of the elastic locking member 22.

[0058] like Figure 6 and Figure 7The second variant shown also comprises one or more (radial) resilient locking members 22 (although now arranged between the relatively long guide grooves 21 in the rotational / circumferential direction R) for locking to one or more corresponding protrusions (not shown) on the upper drive shaft part 24. The upper drive shaft part 24 may be hollow for receiving the lower drive shaft part 23, as mentioned above, such as Figure 7 As shown. In a second variant, the elastic locking members 22 substantially alternate with the guide grooves 21 in the rotational / circumferential direction R. One or more projections may again be arranged on the inner side of the circumferential wall of such a hollow upper drive shaft portion 24. In order to facilitate locking behind the projections, one or more radially outwardly extending connecting edges 25 may be provided on the longitudinal upper end of the elastic locking members 22. The skilled person will understand that the features of the first and second variants may be combined or mixed if desired.

[0059] As mentioned above, another aspect of the present disclosure relates to a method of using the aforementioned impeller system 1, which comprises the following steps:

[0060] - a drive motor 4 connecting the drive shaft 3 to the bioreactor 2; and

[0061] - The drive shaft 3 is rotated around the longitudinal axis X of the drive shaft 3 by the drive motor 4 of the bioreactor 2, wherein at least one of the at least two impeller blades 5 is transformed from a folded state I to an unfolded state II by rotating along the circumference 6 of the drive shaft 3 due to the resistance from the liquid 7 in the bioreactor to perform stirring of the liquid 7.

[0062] Yet another aspect of the present disclosure relates to a method for manufacturing the aforementioned impeller system 1, comprising the following steps:

[0063] - manufacturing a drive shaft 3 which is configured to be rotated in a rotation direction R about a longitudinal axis X of the drive shaft 3 by a drive motor 4 of the bioreactor 2;

[0064] - manufacturing at least two impeller blades 5, which are used to be connected to the drive shaft 3 and to rotate with the drive shaft 3, wherein at least one of the at least two impeller blades 5 is constructed to transform from a folded state I to an unfolded state II to perform agitation, wherein in the folded state I, the at least two impeller blades 5 are not positioned symmetrically around the drive shaft 3 axis, but are aligned such as along the longitudinal axis X of the drive shaft 3, wherein in the unfolded state II, the at least two impeller blades 5 are positioned symmetrically around the drive shaft 3 axis, wherein when performing agitation, at least one of the at least two impeller blades 5 transforms from the folded state I to the unfolded state II by rotating along the circumference 6 of the drive shaft 3 due to the resistance of the liquid 7 in the bioreactor 2; and

[0065] At least two impeller blades 5 are connected to the drive shaft 3 .

[0066] Manufacturing the at least two impeller blades 5 may include 3D printing at least one of the at least two impeller blades 5 .

[0067] It should be noted that in a preferred embodiment, if desired, at least one of the impeller blades 5, in particular the non-transforming impeller blades 5 (i.e., the impeller blades 5 that do not rotate along the circumference of the drive shaft) can be rigidly connected or secured to the drive shaft 3 during its manufacture, or optionally formed integrally with the drive shaft 3.

[0068] Description of Reference Numerals

[0069] 1. Impeller system

[0070] 2. Bioreactor

[0071] 3. Drive shaft

[0072] 4. Drive motor

[0073] 5. Impeller blades

[0074] 6. Circumference of drive shaft

[0075] 7. Liquid

[0076] 8. Ring

[0077] 9. Partial Circumference

[0078] 10. Joint

[0079] 11.Jointing components

[0080] 12. Radial outer edge

[0081] 13. Main plane of impeller blades

[0082] 14. Plane transverse to the main plane and radial outer edge

[0083] 15. Bioreactor bags

[0084] 16. Stacked impeller blades

[0085] 17. Impeller blade profile

[0086] 18. Pivot

[0087] 19. Upper end ring

[0088] 20.Lower end ring

[0089] 21. Boot slot

[0090] 22. Elastic locking member

[0091] 23. Lower drive shaft

[0092] 24. Upper drive shaft

[0093] 25. Connecting edge of elastic locking member

[0094] 26. Guide component

[0095] 27. Circumferential recess of the lower rotatable ring

[0096] 28. Circumferential recess of upper rotatable ring

[0097] 29. Lower rotatable ring

[0098] 30.Upper rotatable ring

[0099] R = Direction of rotation

[0100] X = longitudinal axis

[0101] I=folded / folded state

[0102] II=Unfolded state

[0103] r = radius of curvature

Claims

1. An impeller system (1) for use with a bioreactor (2), comprising: - a drive shaft (3) configured to be rotated in a rotational direction (R) about a longitudinal axis (X) of the drive shaft by a drive motor (4) of the bioreactor; - At least two impeller blades (5) connected to the drive shaft and configured to rotate with the drive shaft when the drive shaft rotates, wherein the at least two impeller blades are configured to transition from a first folded state (I) to an unfolded state (II) to perform agitation, wherein in the folded state the at least two impeller blades are not positioned symmetrically around the drive shaft axis, wherein in the unfolded state the at least two impeller blades are positioned symmetrically around the drive shaft axis, wherein when agitation is performed, at least one of the at least two impeller blades transitions from the folded state to the unfolded state by rotating along the circumference (6) of the drive shaft due to resistance from the liquid (7) in the bioreactor.

2. The impeller system (1) according to claim 1, wherein the at least two impeller blades (5) are each independently connected to the drive shaft (3).

3. An impeller system (1) according to claim 2, wherein at least one of the at least two impeller blades (5) is independently attached to the drive shaft (3) using a ring (8, 29, 30) configured to rotate around the drive shaft, wherein the ring is configured to rotate from a first orientation on the drive shaft in the folded state (I) to a second orientation on the drive shaft in the unfolded state (II), so that the at least two impeller blades are positioned symmetrically around the drive shaft.

4. The impeller system (1) according to claim 3, wherein one of the ring (8, 29, 30) or the drive shaft (3) is provided with a joint (10) on a partial circumference (9) at an axial portion of the ring, and the other of the ring or the partial circumference is provided with a joint member (11), wherein the joint portion and the joint member are configured to engage with each other when the ring has reached the second orientation, thereby preventing the ring from rotating beyond the second orientation.

5. Impeller system (1) according to any one of the preceding claims, wherein: In the folded state (I), the at least two impeller blades (5) are adjacent to each other (16) along the longitudinal axis (X).

6. The impeller system (1) according to claim 5, wherein: In the folded state (I), the at least two impeller blades (5) are adjacent to each other (16) along the longitudinal axis (X) in such a way that the contours (17) of the at least two impeller blades are aligned when viewed along the longitudinal axis.

7. Impeller system (1) according to any of the preceding claims, wherein the radially outer edges (12) of two or more impeller blades (5) are rounded in a main plane (13) of the impeller blades.

8. Impeller system (1) according to claim 7, wherein the rounded radially outer edges (12) of the two or more impeller blades (5) have a constant radius of curvature (r).

9. The impeller system (1) according to any of the preceding claims, wherein the radial outer edges (12) of two or more impeller blades (5) are rounded in a plane (14) transverse to the radial outer edges and to the main plane (13) of the impeller blades.

10. The impeller system (1) according to any of the preceding claims, wherein the at least two impeller blades (5) are aligned along the longitudinal axis in the folded state (I).

11. An impeller system (1) according to any of the preceding claims, wherein the at least two impeller blades (5) form a rotation angle relative to each other about the longitudinal axis (X) in the folded state (I), the rotation angle being less than 45 degrees, more preferably less than 30 degrees, and even more preferably less than 15 degrees, most preferably about 0 degrees.

12. Impeller system (1) according to any of the preceding claims, wherein the at least two impeller blades (5) are each independently connected to the drive shaft (3).

13. A flexible container (15) for bioreactors, comprising an impeller system (1) according to any one of the preceding claims, wherein the impeller system is arranged inside the flexible container for bioreactors.

14. A flexible container (15) for bioreactors according to claim 13, wherein the at least two impeller blades (5) are in the folded state (I).

15. The flexible container (15) for bioreactor according to claim 13 or 14, wherein the interior of the flexible container for bioreactor is aseptically processed to a sterility assurance level of at least 10-3 SAL.

16. A flexible container (15) for bioreactors according to any one of claims 13 to 15, further comprising a sterile barrier enclosing the flexible container, wherein the sterile barrier is optionally constructed as a bag, a pouch or a barrel with a sealing lid.

17. A bioreactor (2) comprising a drive motor (4) and an impeller system (1) according to any one of claims 1 to 12 or a flexible container (15) for bioreactors according to any one of claims 13 to 16, wherein the drive shaft (3) is connected to the drive motor (4).

18. A method of using an impeller system (1) according to any one of claims 1 to 12, comprising the following steps: - connecting the drive shaft (3) to the drive motor (4) of the bioreactor (2); as well as - The drive shaft is rotated around the longitudinal axis (X) of the drive shaft by the drive motor of the bioreactor, wherein at least one of the at least two impeller blades (5) is transformed from the folded state (I) to the unfolded state (II) by rotating along the circumference (6) of the drive shaft due to resistance from the liquid (7) in the bioreactor to perform stirring of the liquid.

19. A method for manufacturing an impeller system (1) according to any one of claims 1 to 12, comprising the following steps: - manufacturing a drive shaft (3) configured to be rotated in a rotational direction (R) about a longitudinal axis (X) of the drive shaft by a drive motor (4) of the bioreactor (2); - manufacturing at least two impeller blades (5) for connection to the drive shaft and for rotation with the drive shaft, wherein at least one of the at least two impeller blades is configured to transform from the folded state (I) to the unfolded state (II) for performing agitation, wherein in the folded state the at least two impeller blades are not positioned symmetrically around the drive shaft axis, wherein in the unfolded state the at least two impeller blades are positioned symmetrically around the drive shaft axis, wherein when performing agitation, at least one of the at least two impeller blades transforms from the folded state to the unfolded state by rotating along the circumference (6) of the drive shaft due to resistance from the liquid (7) in the bioreactor; as well as - Connecting said at least two impeller blades to said drive shaft.

20. The method of claim 19, wherein manufacturing the at least two impeller blades (5) comprises 3D printing at least one of the at least two impeller blades.

21. The method according to claim 19 or 20, wherein in the folded state (I) the at least two impeller blades (5) are aligned along the longitudinal axis (X).

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