Impeller system for use with a bioreactor

Abstract

The present disclosure relates to an impeller system (1) for use with a bioreactor (2), the impeller system having a drive shaft (3) configured to rotate in a rotational direction (R) about the longitudinal axis (X) of the drive shaft by a drive motor (4) of the bioreactor, and at least two impeller blades (5) connected to the drive shaft and configured to rotate with the drive shaft when the drive shaft rotates, the at least two impeller blades being configured to transition from a folded state to an unfolded state for performing agitation. 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 a liquid (7) within the bioreactor when agitation is performed.

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 manufacturing such an impeller system.

Background Art

[0002] WO 2013 / 151733 discloses a fluid mixing system including a container such as a flexible bag that bounds a compartment. A flexible drive line is disposed within the compartment, and the drive line has a first end rotatably connected to a first end of the container and an opposing 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. Rotation of the drive line facilitates rotation of the impeller within the container. The impeller may comprise pivotable or foldable blades. By folding the blades (the blades bend about a position between the shaft and the blade tip), the container can be folded more completely around the impeller while minimizing the risk of damaging the container and the blades, for example during transport. Each of the blades can automatically move from a folded (folded) position that captures and mixes fluid to an extended (deployed) position.

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

[0004] Furthermore, a relatively complex mechanical system is required to deploy the foldable blades to the extended position in order to initiate agitation.

[0005] Accordingly, an object of the present disclosure is to provide an impeller system for use with a bioreactor, wherein in a folded state, the blades are folded towards each other and do not occupy much space around the drive line.

[0006] A further object of the present disclosure is to provide an impeller system for use with a bioreactor, wherein a mechanical system that is not relatively complex is required to move the folded blades to an unfolded position in order to initiate agitation.

Prior Art Documents

Patent Documents

[0007]

Patent Document 1

Summary of the Invention

[0008] According to an embodiment of the present disclosure, there is provided an impeller system for use with a bioreactor, the impeller system comprising: - a drive shaft configured to rotate in a rotational direction around the longitudinal axis of the drive shaft by a drive motor of the bioreactor; - at least two impeller blades connected to the drive shaft and configured to rotate with the drive shaft when the drive shaft rotates, the at least two impeller blades being configured to transition from a folded state in which at least two impeller blades are not axially symmetrically arranged around the drive shaft, such as being aligned along the longitudinal axis, to an unfolded state in which at least two impeller blades are axially symmetrically arranged around the drive shaft for performing agitation. At least one of at least two impeller blades is configured to transition from a folded state to an unfolded state by rotating along the circumference of the drive shaft due to resistance from the liquid within the bioreactor when agitation is performed, and includes at least two impeller blades.

[0009] Since at least two impeller blades, such as three, four, five, six, or more blades, preferably all blades, are not arranged axially symmetrically around the drive shaft, for example, being aligned along the longitudinal axis in the folded state, the space occupied around the drive shaft in the folded state is much less. For example, when a bioreactor bag or a similar flexible container for bioreaction is used, that is, when the flexible container for bioreaction is folded around the impeller system, easier transportation and a significantly reduced size of the impeller system become possible.

[0010] In the context of this patent application, "aligned" means "substantially radially aligned", that is, the angle formed between similar radially extending features of a first article (such as a blade) and a second article (such as an adjacent blade arranged radially) is less than 60 degrees, more preferably less than 45 degrees, even more preferably less than 30 degrees, even more preferably less than 20 degrees, even more preferably less than 15 degrees with respect to each other around the common axis of rotation of the drive shaft, particularly the longitudinal axis of the drive shaft, such as the portion of the drive shaft to which the blade is connected or engages in another manner.

[0011] Furthermore, at least one of the at least two impeller blades transitions from a folded state (e.g., along a circumferential arc) to an unfolded state along the circumference of the drive shaft by rotating along the circumference of the drive shaft due to the resistance from the liquid in the bioreactor when agitation is performed. Among them, at least one of the two (or more) impeller blades gradually "automatically" shifts to its own individual / unique position along the circumference of the drive shaft in the final axisymmetric configuration of the unfolded impeller blade in a basically very natural way. That is, the hydrodynamic force exerted by the liquid on at least one of the at least two impeller blades, for example, slides (e.g., rotationally slides) at least one of the at least two impeller blades along the circumference (or circumferential arc) of the drive shaft / allows sliding, thereby pushing at least one of the impeller blades into its unique location in the final axisymmetric configuration of the unfolded impeller blade. Therefore, the use of a complex mechanical system for deploying the impeller blades can be avoided.

[0012] A further advantage of the above impeller system is that in the folded state, since at least two impeller blades are aligned along the longitudinal axis, when a flexible container for bioreaction is folded around the impeller system, the flexible container for bioreaction (e.g., a flexible bag) is less likely to be damaged, whereby the pressure applied to the inside (each side) of the flexible container for bioreaction is distributed over the plurality of impeller blades, thereby preventing puncture or tearing of the flexible container for bioreaction.

[0013] One embodiment relates to the impeller system described above, where at least two impeller blades are each independently connected to a drive shaft. Thus, at least one individual impeller blade can move to the final position of each impeller blade in the unfolded state independently of the other impeller blades, enhancing the reliability of the impeller system. Further, the above enables "adjustment" of the impeller system, for example, by removing or adding impeller blades, which also facilitates manufacturing.

[0014] One embodiment of the present disclosure relates to the impeller system described above, where at least one of at least two impeller blades is independently attached to a drive shaft using a ring configured to rotate around the drive shaft. The ring is configured to rotate from a first orientation on the folded drive shaft to a second individual orientation on the unfolded drive shaft such that at least two impeller blades are arranged axially symmetrically around the drive shaft. By using such a rotatable ring, at least one of at least two impeller blades can naturally move to the final position in the unfolded state. Removal or addition of impeller blades is also further simplified.

[0015] One embodiment relates to the impeller system described above, where an engaging portion is provided on one of the ring or the local circumference of the drive shaft at the axial position of the ring, and an engaging member is provided on the other of the ring or the local circumference. The engaging portion and the engaging member are configured to engage with each other when the ring reaches the second orientation, thereby preventing the ring from rotating beyond the second orientation.

[0016] One embodiment relates to the impeller system described above. In the folded state, at least two impeller blades are adjacent to each other along the longitudinal axis. Thus, by closely spacing at least two impeller blades from each other, such as by stacking them on top of each other along the longitudinal axis, the possibility of local pressure points is further reduced, and thus, puncturing or tearing of the flexible container for bioreaction is further prevented.

[0017] One embodiment relates to the impeller system described above. In the folded state, at least two impeller blades are adjacent to each other along the longitudinal axis such that the contours of at least two impeller blades are aligned or can otherwise approach each other when viewed along the longitudinal axis. Thus, a compact "package" of impeller blades is achieved, and at least two impellers are prevented from protruding relative to each other in a direction perpendicular to the longitudinal axis because the contours of the impeller blades are longitudinally aligned, and thus, local puncturing of the flexible container for bioreaction is further prevented.

[0018] One embodiment relates to the impeller system described above. The radially outer edges of two or more impeller blades are rounded in the main plane of the impeller blade, for example, when transporting or storing the flexible container for bioreaction and the impeller system, it enables the bioreactor to be smoothly folded onto the impeller blade, further reducing the risk of damage to the flexible container for bioreaction.

[0019] One embodiment relates to the impeller system described above. The rounded radially outer edges of two or more impeller blades have a constant radius of curvature, further facilitating the smooth placement of the flexible container for bioreaction that covers the radially outer edges of the impeller blades in the folded state.

[0020] One embodiment relates to the impeller system described above, wherein the radially outer edges of two or more impeller blades are rounded in a plane transverse to the main plane and the radially outer edges of the impeller blades. Thus, the impeller blades are not "sharp" in order to further prevent piercing or cutting of the flexible container for bioreaction in the folded state.

[0021] One embodiment relates to the impeller system described above, wherein at least two impeller blades in the folded state are aligned along the longitudinal axis, providing a compact impeller blade package.

[0022] One embodiment relates to the impeller system described above, wherein at least two impeller blades in the folded state establish a rotational angle relative to each other around the longitudinal axis of less than 45 degrees, more preferably less than 30 degrees, even more preferably less than 15 degrees, and most preferably about 0 degrees, such that the impeller blades are close to each other in the rotational direction in the folded state.

[0023] One embodiment relates to the impeller system described above, wherein at least two impeller blades are each independently connected to a drive shaft, enabling optimal design and operational flexibility.

[0024] Another aspect of the present disclosure relates to a flexible container for bioreaction comprising the impeller system described above, wherein the impeller system is disposed inside the flexible container for bioreaction.

[0025] One embodiment relates to the flexible container for bioreaction described above, wherein at least two impeller blades are in a folded state.

[0026] One embodiment relates to the flexible container for bioreaction described above, wherein the interior of the flexible container for bioreaction is sterile up to a sterility assurance level of at least 10-3 SAL.

[0027] One embodiment relates to the flexible container for bioreaction described above, which further comprises a sterile barrier for enclosing the flexible container. The sterile barrier is optionally configured as a bag, a pouch, or a tab having a sealed lid.

[0028] Another aspect of the present disclosure relates to a bioreactor comprising a drive motor and the above-described impeller system or the above-described flexible container for bioreaction, wherein a drive shaft is connected to the drive motor.

[0029] Another aspect of the present disclosure relates to a method of using the above-described impeller system, the method comprising: - connecting a drive shaft to a drive motor of a bioreactor; and - rotating the drive shaft about the longitudinal axis of the drive shaft by the drive motor of the bioreactor, wherein at least one of the at least two impeller blades rotates along the circumference of the drive shaft due to resistance from the liquid in the bioreactor to perform stirring of the liquid, thereby transitioning from a folded state to an unfolded state.

[0030] Another aspect of the present disclosure relates to a method of manufacturing the above-described impeller system, the method comprising: - manufacturing a drive shaft configured to rotate in a rotational direction about the longitudinal axis of the drive shaft by a drive motor of a bioreactor; and - manufacturing at least two impeller blades connected to the drive shaft and configured to rotate with the drive shaft, wherein at least one of the at least two impeller blades is configured to transition from a folded state in which the at least two impeller blades are not axially symmetrically arranged around the drive shaft to an unfolded state in which the at least two impeller blades are axially symmetrically arranged around the drive shaft for performing stirring. At least one of at least two impeller blades rotates along the circumference of the drive shaft by the resistance from the liquid in the bioreactor when agitation is performed, thereby transitioning from a folded state to an unfolded state, and a step of manufacturing; - A step of connecting at least two impeller blades to the drive shaft. One embodiment relates to the manufacturing method described above. The step of manufacturing at least two impeller blades includes the step of 3D printing at least one, for example, two of the at least two impeller blades. 3D printing is any of various processes in which materials are added together (such as liquid molecules or powder particles being fused together) and the materials are joined or solidified to create a three-dimensional object. 3D printing is often used in both rapid prototyping and additive manufacturing (AM). The object can have almost any shape or geometry and is typically generated (usually in continuous layers) using another electronic data source such as digital model data from a 3D model or a file in additive manufacturing file (AMF) format. There are many different technologies such as stereolithography (SLA) or fused deposition modeling (FDM). Thus, unlike materials removed from stock in conventional machining processes, 3D printing or AM typically constructs a three-dimensional object from a computer-aided design (CAD) model or AMF file by continuously adding materials layer by layer.

[0031] In one embodiment related to the manufacturing method described above, in the folded state, at least two impeller blades are aligned along the longitudinal axis.

Brief Description of the Drawings

[0032] Embodiments of the present disclosure will be described in more detail below with reference to the exemplary embodiments shown in the drawings.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Mode for Carrying Out the Invention

[0033] FIG. 1 shows an exemplary embodiment of a bioreactor 2 comprising a drive motor 4 and an impeller system 1, wherein a drive shaft 3 is connected to the drive motor 4. The bioreactor 2 may be a single-use or multi-use bioreactor 2. The bioreactor 2 may be configured to have an operating / work volume of 1 to 10,000 liters, preferably 10 to 5,000 liters, more preferably 50 to 3,000 liters, for example 40 to 60 liters. The bioreactor 2 generally relates to a manufactured or operated device or system that supports a biologically active environment. The bioreactor 2 may be cylindrical and may be made of glass and / or stainless steel. The bioreactor 2 may also relate to a device or system designed to grow cells or tissues in the context of cell culture.

[0034] The impeller system 1 is disposed inside a flexible container 15 for bioreaction. The outer surface of the flexible container 15 for bioreaction, such as the bioreactor bag 15, is disposed with respect to the inner surface (i.e., the inner side wall) of the bioreactor 2, and preferably provides a proper fit without folding or the like. The flexible container 15 for bioreaction may be configured for single use. Such a single-use flexible container 15 has several advantages, in particular reducing the need for assembly / disassembly, cleaning, sterilization and calibration. The impeller system 1 includes a drive shaft 3 configured to rotate in the rotational direction R about the longitudinal axis X of the drive shaft 3 by a drive motor 4 of the bioreactor 2. The drive shaft 3 can have a length of, for example, 10 to 250 cm, for example, 10 to 100 cm, for example, 10 to 50 cm, depending on the design of the bioreactor 2. At least two, for example two, three, four, fixed, six, or more impeller blades 5 are connected to the drive shaft 3 and configured to rotate in the rotational direction R together with the drive shaft 3. At least two impeller blades 5 are preferably disposed at the free end of the drive shaft 3, although other arrangements are also conceivable (e.g., spaced apart from the free end of the drive shaft 3). The impeller blade 5 may have the form of a (flat) plate, although other shapes such as curved blades are also conceivable. The impeller blade 5 may also be disposed at an angle with respect to the longitudinal axis X (the plane crossing it). At least two impeller blades 5 are configured to transition from a folded state I in which at least two impeller blades 5 are adjacent to each other or can approach each other around the longitudinal axis X in other ways to an unfolded state II for performing stirring, and at least two impeller blades are arranged symmetrically about the drive shaft 3 and radially separated from each other in the rotational direction. When two impeller blades 5 are used, in the unfolded state, the blades are radially separated from each other by about 180 degrees around the axis X, and when three impeller blades 5 are used, in the unfolded state, the blades are radially separated from each other by about 120 degrees around the axis X. FIG. 1 shows the impeller blade 5 in the unfolded state II.At least one of the at least two impeller blades 5 rotates, i.e., moves, along the circumference 6 of the drive shaft 3 due to the resistance from the liquid 7 in the bioreactor 2 when stirring is performed, and thus transitions from the folded state I to the unfolded state II.

[0035] Figure 2 shows an exemplary embodiment of an impeller system 1 according to the present disclosure, such as the impeller system 1 of Figure 1, in which the impeller blades 5 are in the 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 may each be independently connected to the drive shaft 3, as will be more clearly described with reference to Figure 4. In the folded state I, at least two impeller blades 5 are preferably adjacent to each other along the longitudinal axis X such that the contours 17 of the at least two impeller blades 5 are aligned, or can be adjacent to each other in a contacting or non - contacting manner, to form a "package" of impeller blades 5. For example, radially adjacent blades can establish angles with each other that are 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 with respect to the longitudinal axis X, and, if geometrically feasible, can establish an angle of 0 degrees or about 0 degrees with each other. All of the above are subject to geometric constraints such as the thickness, shape, connection means to the drive shaft, and / or the longitudinal spacing along the drive shaft 3 of each blade, but are not limited thereto.

[0036] Figure 3 shows an exemplary embodiment of an impeller system 1 according to the present disclosure, such as the impeller system 1 of Figure 1 or Figure 2, in which the impeller blades 5 are in the unfolded state I. Here, the impeller blades 5 are axially symmetrically arranged around the drive shaft 3 for stirring and can establish angles of approximately 120 degrees with each other with respect to the longitudinal axis X, as shown using three blades.

[0037] FIG. 4 shows an exploded view of an exemplary embodiment of an impeller system 1 according to the present disclosure, such as the impeller system 1 of FIGS. 1, 2, or 3, in a state I where the impeller blades 5 are not folded. The radially outer edges 12 of two or more impeller blades 5 are preferably rounded in the main plane 13 of the impeller blades 5. The rounded radially outer edges 12 of two or more impeller blades 5 preferably have a constant radius of curvature r. The radius of curvature r can be 2 to 10 cm, for example 2 to 5 cm. At least one of at least two rotatable impeller blades 5 can be independently attached to the drive shaft 3 using a rotatable ring 8 having engagement portions 10 such as a lower rotatable ring 29 and an upper rotatable ring 30, as shown in FIG. 4.

[0038] The rotatable ring 8 may be configured to rotate around the drive shaft 3, and the rotatable ring 8 is folded 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 arranged axially symmetrically around the drive shaft 3 and each of the impeller blades 5 has a unique axially symmetric position. As shown in FIG. 4, the lower rotatable ring 29 may be provided with a lower circumferential recess 27, and the upper rotatable ring 30 may be provided with an upper circumferential recess 28. The circumferential length of the lower circumferential recess 27 is different from the circumferential length of the upper circumferential recess 28. An engagement member 11 in the form of a notch or a protrusion is provided on the local circumference 9 of the drive shaft 3.

[0039] Essentially, the ring 8 acts on the drive shaft 3 as a keyed slot mechanism. The keyed slot is typically designed with little or no "slope" to prevent rotation due to similar dimensions of the key width and slot width. However, in the embodiment shown in FIG. 4, a relatively large keyway width, i.e., the circumferential length of the lower and upper circumferential recesses 27, 28, is used to create a large "slope" to allow additional rotation, and since the keyway equivalents of the lower and upper rings 29, 30, i.e., the lengths of the lower and upper circumferential recesses 27, 28, are of different sizes for each ring 8, the amount of rotation allowed is different. The "key" equivalent in the embodiment shown in FIG. 4 is essentially the engagement member 11.

[0040] Each ring 8, i.e., each of the lower ring 29 and the upper ring 30, has a "keyway" (i.e., the circumferential length of each of the lower circumferential recess 27 and the upper circumferential recess 28) that is significantly larger than the key (engagement member 11) such that the second impeller blade 5 associated with the lower ring 29 rotates around the drive shaft 3 along the circumferential recess 27 (counting upward from the lower end of the impeller system 2 in FIG. 4) and stops rotating when it contacts the engagement member 11 on one side of the engagement portion 10 at the engagement portion 10, and the third impeller blade 5 associated with the upper ring 30 rotates around the drive shaft 3 along the circumferential recess 28 and also stops rotating when the engagement portion 10 of the upper ring 30 contacts the same key, i.e., the engagement member 11.

[0041] The lower ring 29 has a very large keyway (length of the circumferential recess 27) that allows rotation up to 120 degrees or about 120 degrees, and the upper ring 30 has a very large keyway (length of the circumferential recess 28) that allows rotation up to 240 degrees or about 240 degrees. As a result, when three impeller blades 5 are used, they are arranged with a phase shift of 120 degrees or about 120 degrees relative to each other around the axis of rotation X.

[0042] Rings 8, such as the two rings 8 shown in FIG. 4, can be held in their longitudinal positions by using a lower ring 20 and an upper ring 19. The ring 8 is then firmly "locked" (i.e., in the longitudinal direction) between the upper ring 19 and the lower ring 20. As can be seen from FIG. 4, the lower ring 20 may be provided with an impeller blade 5 fixedly attached to the drive shaft 3, for example integrally formed with the drive shaft 3, i.e., non-movable relative to the local circumference 9 of the drive shaft 3. In contrast, other impeller blades 5, as shown in FIG. 4, are configured to rotate relative to the drive shaft 3 due to the resistance of the liquid (i.e., in a direction opposite to the direction of the rotation direction R, as will be understood by those skilled in the art).

[0043] The radially outer edges 12 of two or more impeller blades 5 are preferably rounded in the main plane 13 of the impeller blade and in a plane 14 transverse to the radially outer edge 12.

[0044] FIGS. 5-7 show exemplary embodiments of the impeller system 1 according to the present disclosure and include a connection mechanism for connecting a lower drive shaft portion 23 of the drive shaft 3 (in use, as clearly shown in FIG. 7) to an upper drive shaft portion 24 of the drive shaft 3. Two or more impeller blades 5 are connected to the lower drive shaft portion 23. FIG. 5 shows a first variant of the connection mechanism, in which one or more longitudinal guide grooves 21, such as one, two, three, four or more guide grooves 21, are provided at the longitudinal upper end of the lower drive shaft portion 23. The guide grooves 21 are configured to receive one or more elongated guide members 26, as shown in FIG. 7. Thereby, 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. The first variant of the connection mechanism shown in FIG. 5 comprises relatively short guide grooves 21 compared to the second variant of the connection mechanism shown in FIGS. 6 and 7, which shows relatively long guide grooves 21.

[0045] As shown in FIG. 5, the first modification is provided below the relatively short guide groove 21 and includes one or more (radial) elastic locking members 22 for locking to one or more corresponding protrusions (not shown) on the upper drive shaft portion 24. The upper drive shaft portion 24 may be hollow as shown in FIG. 7 to receive the lower drive shaft portion 23. One or more protrusions may be arranged inside the peripheral wall of such a hollow upper drive shaft portion 24. In order to facilitate locking behind such protrusions, one or more connecting edges 25 extending radially outward can be provided at the longitudinal upper end of the elastic locking member 22.

[0046] As shown in FIGS. 6 and 7, the second modification also includes one or more (radial) elastic locking members 22, which are arranged here 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 portion 24. The upper drive shaft portion 24 may be hollow as shown in FIG. 7 to receive the lower drive shaft portion 23 as described above. In the second modification, the elastic locking members 22 are basically alternating with the guide grooves 21 in the rotational / circumferential direction R. One or more protrusions may also be arranged inside the peripheral wall of such a hollow upper drive shaft portion 24. In order to facilitate locking behind the protrusions, one or more connecting edges 25 extending radially outward can be provided at the longitudinal upper end of the elastic locking member 22. Those skilled in the art will understand that they can combine or mix the features of the first and second modifications as needed.

[0047] As described above, another aspect of the present disclosure is a method of using the impeller system 1 described above, the method comprising: - connecting the drive shaft 3 to the drive motor 4 of the bioreactor 2; - A step of rotating the drive shaft 3 around the longitudinal axis X of the drive shaft 3 by the drive motor 4 of the bioreactor 2, wherein at least one of at least two impeller blades 5 rotates along the circumference 6 of the drive shaft 3 due to the resistance from the liquid 7 in the bioreactor to execute stirring of the liquid 7, thereby transitioning from the folded state I to the unfolded state II. Yet another aspect of the present disclosure relates to a method of manufacturing the impeller system 1 described above, the method comprising: - A step of manufacturing a drive shaft 3 configured to rotate in the rotational direction R around the longitudinal axis X of the drive shaft 3 by the drive motor 4 of the bioreactor 2; - A step of manufacturing at least two impeller blades 5 connected to the drive shaft 3 and configured to rotate with the drive shaft 3, wherein at least one of the at least two impeller blades 5 is not axially symmetrically arranged around the drive shaft 3, such as being aligned along the longitudinal axis X of the drive shaft 3, from the folded state I to the unfolded state II for stirring, in which at least two impeller blades 5 are axially symmetrically arranged around the drive shaft 3, wherein at least one of the at least two impeller blades 5 rotates, i.e., moves, along the circumference 6 of the drive shaft 3 due to the resistance from the liquid 7 in the bioreactor 2 when stirring is executed, thereby transitioning from the folded state I to the unfolded state II. - A step of connecting at least two impeller blades 5 to the drive shaft 3. The step of manufacturing at least two impeller blades 5 can include a step of 3D printing at least one of the at least two impeller blades 5. In a preferred embodiment, it should be noted that at least one of the impeller blades 5, in particular the non-transitional impeller blades 5 (i.e., the impeller blades 5 that do not rotate along the circumference of the drive shaft), may be firmly connected or fixed to the drive shaft 3 during its manufacture, if necessary, or alternatively may be integrally formed with the drive shaft 3.

Explanation of Signs

[0048] 1. Impeller system 2. Bioreactor 3. Drive shaft 4. Drive motor 5. Impeller blade 6. Circumference of the drive shaft 7. Liquid 8. Ring 9. Local circumference 10. Engagement part 11. Engagement member 12. Radial outer edge 13. Main surface of the impeller blade 14. Plane transverse to the main plane and the radial outer edge 15. Bioreactor bag 16. Stacked impeller blades 17. Contour of the impeller blade 18. Swivel 19. Upper end ring 20. Lower end ring 21. Guide groove 22. Elastic locking member 23. Lower drive shaft part 24. Upper drive shaft part 25. Connection edge of the elastic locking member 26. Guide member 27. Circumferential recess of the lower rotating ring 28. Circumferential recess of the upper rotating ring 29. Lower rotating ring 30. Upper rotating ring R = Rotation direction X = Longitudinal axis I = Folded / Folded state II = Unfolded state r = Radius of curvature

Claims

1. An impeller system (1) for use with a bioreactor (2), comprising: - A drive shaft (3) configured to rotate in a rotational direction (R) about the 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: From a folded first state (I) in which the at least two impeller blades are not axially symmetrically arranged around the drive shaft; Configured to transition from the folded first state (I) to an unfolded state (II) in which the at least two impeller blades are axially symmetrically arranged around the drive shaft for performing agitation; At least two impeller blades (5), wherein 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 a liquid (7) in the bioreactor when agitation is performed. The impeller system (1) comprises:

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. The 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, and 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) such that the at least two impeller blades are axially symmetrically arranged around the drive shaft.

4. An engaging portion (10) is provided on one of the rings (8, 29, 30) or a local circumference (9) of the drive shaft (3) at the axial position of the ring, and an engaging member (11) is provided on the other of the ring or the local circumference, and the engaging portion and the engaging member are configured to engage with each other when the ring reaches the second direction, thereby preventing the ring from rotating beyond the second direction. The impeller system (1) according to claim 3.

5. In the folded state (I), the at least two impeller blades (5) are adjacent to each other along the longitudinal axis (X). The impeller system (1) according to any one of claims 1 to 4.

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

7. The radially outer edges (12) of the two or more impeller blades (5) are rounded on the main surface (13) of the impeller blade. The impeller system (1) according to any one of claims 1 to 6.

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

9. The radially outer edges (12) of the two or more impeller blades (5) are rounded on the main surface (13) of the impeller blade and a plane (14) transverse to the radially outer edge. The impeller system (1) according to any one of claims 1 to 8.

10. The at least two impeller blades (5) in the folded state (I) are aligned along the longitudinal axis. The impeller system (1) according to any one of claims 1 to 9.

11. The at least two impeller blades (5) in the folded state (I) establish a rotational angle relative to each other around the longitudinal axis (X) that is less than 45 degrees, more preferably less than 30 degrees, even more preferably less than 15 degrees, and most preferably approximately 0 degrees. The impeller system (1) according to any one of claims 1 to 10.

12. The impeller system (1) according to any one of claims 1 to 11, wherein each of the at least two impeller blades (5) is independently connected to the drive shaft (3).

13. A flexible container (15) for bioreaction, comprising the impeller system (1) according to any one of claims 1 to 12, disposed inside the flexible container for bioreaction.

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

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

16. The flexible container (15) for bioreaction according to any one of claims 13 to 15, further comprising a sterile barrier enclosing the flexible container, the sterile barrier being optionally configured as a bag, pouch, or tab having a sealed lid.

17. A bioreactor (2) comprising a drive motor (4) and the impeller system (1) according to any one of claims 1 to 12 or the flexible container (15) for bioreaction 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 the impeller system (1) according to any one of claims 1 to 12, comprising: - connecting the drive shaft (3) to the drive motor (4) of the bioreactor (2); - rotating the drive shaft about 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) rotates along the periphery (6) of the drive shaft due to the resistance from the liquid (7) in the bioreactor to perform stirring of the liquid, thereby transitioning from the folded state (I) to the unfolded state (II).

19. A method for manufacturing the impeller system (1) according to any one of claims 1 to 12, comprising: - manufacturing a drive shaft (3) configured to rotate in a rotational direction (R) about the longitudinal axis (X) of the drive shaft by a drive motor (4) of the bioreactor (2); - manufacturing at least two impeller blades (5) connected to the drive shaft and configured to rotate with the drive shaft, wherein at least one of the at least two impeller blades is configured to transition from a folded state (I) in which the at least two impeller blades are not axially symmetrically arranged around the drive shaft to an unfolded state (II) in which the at least two impeller blades are axially symmetrically arranged around the drive shaft for performing agitation; wherein at least one of the at least two impeller blades is configured to transition from the folded state to the unfolded state by rotating along the circumference (6) of the drive shaft due to resistance from a liquid (7) in the bioreactor when agitation is performed; and - connecting the at least two impeller blades to the drive shaft.

20. The method according to claim 19, wherein the step of 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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