Apparatus and method for agitating fluids

Abstract

A vessel (24) includes an interior volume (25) containing a liquid, a helical shaft (28) located within the interior volume, and a rotatable impeller (30). The impeller has an aperture (38) that receives the screw shaft and allows the impeller to travel bidirectionally along the screw shaft. When the impeller travels along the screw shaft, the impeller rotates axially about the screw shaft to agitate the liquid in the interior volume.

Description

Technical Field

[0001] Embodiments of the present invention generally relate to bioprocessing apparatus, systems and methods, and more particularly, to impellers for agitating fluids in mixers or bioreactor bags. Background Art

[0002] Mixers and bioreactors are often used to carry out biochemical and / or biological processes and / or process liquids and other products of such processes. Such mixers often include flexible or collapsible single-use disposable bags, which are supported by external rigid structures (such as stainless steel shells or housings). The bag is made of a thin flexible plastic film sheet, and is located in a rigid housing and filled with the desired fluid to be processed. The fluid in the bag needs to be mixed or stirred to prevent particles from settling at the bottom of the bag.

[0003] Known mixing devices typically include a rotatable agitator or impeller fixedly mounted at the bottom of a disposable bag, which is held in a rigid canister or support structure. Such an impeller typically has a base portion that contains permanent magnets that are magnetically coupled to and driven by permanent magnets of a motor. In use, the motor magnets rotate, which causes the base portion of the impeller to rotate about an axis, thereby causing agitation of the fluid within the bag.

[0004] However, in known systems, the fixed impeller must be replaced together with a single-use disposable bag. As will be appreciated, the magnets in the base portion of the impeller are also located within the bag and are therefore single-use, resulting in high consumable costs.

[0005] Furthermore, the fixed position of the impeller within the bag may result in inefficient mixing. Specifically, the impeller only stirs a small portion of the total liquid, which contributes to the sedimentation of particles from the liquid, typically to a location below the impeller. Modifying the impeller to act on more liquid (e.g., by increasing its size) requires a larger magnet, which is prohibitively expensive.

[0006] In view of the foregoing, there is a need for an apparatus and system for agitating fluids in a bioreactor bag that provides efficient mixing, prevents particle settling, and has low manufacturing costs. Summary of the invention

[0007] Some embodiments commensurate with the scope of the initially claimed subject matter are summarized below. These embodiments are not intended to limit the scope of the claimed subject matter, but these embodiments are only intended to provide a brief overview of possible embodiments. In fact, the present disclosure can encompass various forms that may be similar or different from the embodiments set forth below.

[0008] In one embodiment, a vessel includes an interior volume for containing liquid, a spiral shaft located within the interior volume, and a rotatable impeller. The impeller has an orifice that receives the spiral shaft and allows the impeller to travel bidirectionally along the spiral shaft. When the impeller travels along the spiral shaft, the impeller rotates axially around the spiral shaft to agitate the liquid in the interior volume.

[0009] In another embodiment of the present invention, a bioreactor system includes a vessel having an interior volume for containing a liquid, a screw shaft located within the interior volume, a rotatable impeller, and a drive assembly that controls the impeller to travel bidirectionally along the screw shaft. The impeller has an orifice that receives the screw shaft and allows the impeller to travel bidirectionally along the screw shaft. When the impeller travels along the screw shaft, the impeller rotates axially around the screw shaft to agitate the liquid in the interior volume of the vessel.

[0010] In yet another embodiment, a method of agitating a fluid in a vessel includes moving a rotatable impeller along a screw axis in a first direction. The screw axis is located within an interior volume of the vessel. When the impeller moves along the screw axis in the first direction, the impeller rotates axially around the screw axis to agitate the liquid in the interior volume. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The present invention will be better understood by reading the following description of non-limiting embodiments with reference to the accompanying drawings, in which:

[0012] Figure 1 is an enlarged cross-sectional view of a mixer showing a known drive assembly and stationary impeller.

[0013] Figure 2 is a front cross-sectional view of a mixer including a rotatable impeller according to an embodiment of the present invention.

[0014] Figure 3 According to an embodiment of the present invention Figure 2 A perspective view of a screw shaft and a portion of a rotatable impeller.

[0015] Figure 4 According to an embodiment of the present invention Figure 3 Bottom view of the screw shaft and rotatable impeller.

[0016] Figure 5 is a cross-sectional view of a mixer including a screw shaft and a rotatable impeller, depicting an electromagnet and a magnetic impeller housing in a repelling state, according to an embodiment of the present invention.

[0017] Figure 6 According to an embodiment of the present invention Figure 5 A cross-sectional view of a mixer depicting the electromagnet and magnetic impeller housing in an attracted state.

[0018] Figure 7 is a perspective view of a mixer according to an embodiment of the present invention including another embodiment of a rotatable impeller that utilizes a linear actuator for axial movement.

[0019] Figures 8A-8C is used with a linear actuator according to an embodiment of the present invention Figure 7 Various views of the rotatable impeller and casing. DETAILED DESCRIPTION

[0020] Reference will now be made in detail to exemplary embodiments of the present invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference symbols are used throughout the drawings to refer to the same or like parts.

[0021] As used herein, the terms "flexible" or "collapsible" refer to structures or materials that are pliable or capable of bending without breaking, and may also refer to compressible or expandable materials. An example of a flexible structure is a bag formed from a polyethylene film. The terms "rigid" and "semi-rigid" are used interchangeably herein to describe a "non-collapsible" structure, i.e., a structure that will not fold, collapse, or otherwise deform to significantly reduce its elongated dimensions under normal forces. Depending on the context, "semi-rigid" may also refer to a structure that is more flexible than a "rigid" element, such as a bendable tube or catheter, but is still a structure that will not collapse longitudinally under normal conditions and forces.

[0022] "Vessel" as that term is used herein refers to a flexible bag, a flexible container, a semi-rigid container, or a rigid container, as the case may be. The term "vessel" as used herein is intended to include, but is not limited to, mixer or bioreactor vessels having flexible or semi-rigid walls or wall portions, single-use flexible bags, and other containers or conduits commonly used in biological or biochemical processes, including, for example, cell culture / purification systems, fermentation systems, media / buffer preparation systems, and filtration / purification systems.

[0023] As used herein, the term "bag" refers to a flexible or semi-rigid container or vessel that is used, for example, as a mixer or bioreactor for the contents therein. Although the embodiments are described in conjunction with a single-use stirred tank mixer system, they are not limited thereto and may be used with a variety of vessels and related equipment used in biological or biochemical processing. In addition, the embodiments may be applicable to mixing or agitating fluids in other non-biological / biochemical environments.

[0024] Reference now Figure 1, depicting a known rotatable agitator or impeller 10. The impeller 10 has a base portion 12 mounted in a shaft 24. The bottom surface 14 of the disposable bag is held within a rigid tank or support structure 16, which may be formed of, for example, stainless steel, polymers, composite materials, glass or other metals and may be cylindrical, although other shapes may be used as long as it is capable of supporting a single-use flexible mixer or bioprocessing / bioreactor bag.

[0025] The base portion 12 includes one or more blades 13 and also contains a permanent magnet 18 which, in use, is magnetically coupled to and driven by a permanent magnet 20 of a motor 22. In use, the motor magnet 20 rotates which causes the base portion 12 of the impeller 10 to rotate about the axis 24, resulting in agitation of the fluid within the bag.

[0026] As mentioned, the fixed impeller 10 contains a plurality of magnets 18 that must be replaced along with the single-use disposable bag (i.e., the single-use disposable bag must be replaced after multiple uses, which requires that the fixed impeller 10 also be replaced). In addition, the fixed position of the impeller 10 within the bag may result in inefficient mixing and only agitation of a small volume of the total liquid, which may cause particles to settle out of the liquid, typically to a location below the impeller 10. Modifying the impeller 10 to act on more liquid (e.g., by increasing its size) requires larger magnets, which is prohibitively expensive.

[0027] Reference now Figure 2 , a vessel 24 according to an embodiment of the present invention includes an internal volume 25 configured to receive and hold fluids for processing / mixing. The vessel 24 has a total height H and a minimum working volume level or height V. The internal volume 25 of the vessel 24 also includes a screw shaft 28 and a rotatable impeller 30. In an embodiment, the screw shaft 28 has a height that is approximately the same as or greater than the minimum working volume height V. The impeller travels an axial height controlled by the drive assembly 56 according to the height of the liquid. This height ensures that the impeller 30 will remain immersed in the fluid in the internal volume 25 during use. As will be appreciated, in certain embodiments, the height of the screw shaft 28 may deviate from (e.g., be lower than) the minimum working volume height V without departing from the present invention.

[0028] As described in more detail below, as impeller 30 travels along screw axis 28, impeller 30 rotates axially about screw axis 28 to mix or otherwise agitate the liquid in interior volume 25. Impeller 30 rotates as it moves linearly along screw axis 28, which is characterized by a helical profile that converts the linear motion along screw axis 28 into rotational motion of impeller 30.

[0029] More specifically, in Figure 3 and 4In the embodiment shown in , the impeller 30 includes a generally circular base portion 34 that includes one or more blades 36. In the depicted embodiment, there are four blades, but as will be appreciated, other numbers, shapes and sizes of blades may be used without departing from the invention.

[0030] like Figure 4 , base portion 34 includes an aperture 38 that receives screw shaft 28 and allows bi-directional travel of impeller 30 along screw shaft 28. Aperture 38 is defined by an inner aperture edge 40 that defines the shape of aperture 38 and is substantially complementary in shape to the cross-section of screw shaft 28.

[0031] refer to Figure 4 , in an embodiment, the screw shaft 28 has a substantially rectangular cross-section 42, and similarly, the orifice 38 has a complementary rectangular shape. The shaft 28 is twisted or rotated so that the shaft 28 has an overall spiral or twisted profile. Specifically, the cross-section 42 of the screw shaft 28 rotates about the longitudinal axis A, moving from one end of the screw shaft 28 to the other end along the longitudinal axis A. Although the screw shaft 28 is shown as having a substantially rectangular cross-section, other shapes are possible without departing from the invention.

[0032] The helical profile of shaft 28 and the complementary shape of aperture 38 cause impeller 30 to rotate about longitudinal axis A as it travels along helical shaft 28. Specifically, impeller aperture 38 engages the cross-sectional profile of helical shaft 28, causing impeller 30 to rotate axially as impeller 30 moves linearly along shaft 28. As will be appreciated, a change in the direction of travel of impeller 30 on shaft 28 reverses the direction of rotation of impeller 30.

[0033] The screw shaft 28 and the impeller 30 can be made of a variety of materials, including but not limited to plastics and metals. In an embodiment, the shaft 28 and / or the impeller 30 can include a coating to reduce particle emissions caused by contact between the orifice 38 and the shaft 28 during use. In an embodiment, a ceramic coating, such as a titanium-based coating, can be used. In other embodiments, a polymer coating or a composite material can be used. The coating can be located on the shaft 28 and / or the impeller 30 and can be applied via known techniques, including but not limited to additive manufacturing.

[0034] As will be appreciated, the number of turns or twists per unit linear measurement (eg, centimeters or inches) of the shaft 28 may vary without departing from the invention.

[0035] The mixing efficiency of the rotatable impeller 30 disclosed herein is significantly better than that of a fixed impeller because the impeller 30 moves bi-directionally up and down along the screw shaft 28. This linear motion of the impeller 30 removes particulate sediment that may occur at the bottom of the vessel 24 (typically below the fixed impeller in known systems) by creating an up and down pumping motion with the rotatable impeller 30. This motion of the impeller 30 also allows a single impeller 30 to perform the work of multiple stages of fixed position impellers (not depicted), where multiple impellers are stacked axially around the shaft at the bottom of the interior of the vessel.

[0036] While the embodiments present an alternative to a plurality of stacked stationary impellers, in aspects, a plurality of rotatable impellers 30 may travel along the screw shaft 28 without departing from the scope of the present invention.

[0037] In an embodiment, the impeller 30 includes a housing 48, 148 (see Figure 5 , 6 8A-8C). The housing 48, 148 facilitates bidirectional travel of the impeller 30 on the shaft 28 and protects the bottom surface 14 of the bag from being scratched or otherwise punctured by the blades 36 during transport or use. Figure 5 and 6 In the embodiment shown in FIG. 4 , the housing 48, 148 is a substantially rectangular box-like structure having one or more open sides / faces. The housing 48, 148 has an upper surface and a lower surface (relative to the top and bottom of the vessel / bag) that include a hole through which the shaft 28 is received. Specifically, the housing 48 has an upper housing aperture 52 and a lower housing aperture 54. As shown, the impeller 30 fits within the housing 48.

[0038] Now turn to Figure 5 and Figure 6 , the assembled housing 48 and impeller 30 can be raised and / or lowered around the shaft 28 via the use of magnets. In an embodiment, the impeller 30 is operably connected to at least one impeller magnet 50 located within the housing 48. The magnet 50 can be permanent or temporary and can be made of steel, iron, cobalt, nickel, and alloys thereof. The magnet 50 can have a variety of shapes, sizes, and locations. In an embodiment, the magnet is located near (e.g., surrounding) a lower housing aperture 54 through which the shaft 28 passes.

[0039] In an embodiment, bi-directional travel of the impeller 30 and the housing 48 along the screw shaft 28 is achieved via a drive assembly 56. The drive assembly 56 may include an electromagnet 58 that can selectively change polarity to cause bi-directional movement of the impeller 30 along the screw shaft 28. In an alternative embodiment, the magnet 50 may be integrated directly into the impeller 30 (e.g., into the base portion 34 and / or the blades 36).

[0040] More specifically, in Figure 5, drive assembly 56 changes the polarity of electromagnet 58 to match the polarity of impeller magnet 50 to produce an SS polarity repulsion state, thereby magnetically urging impeller 30 in direction D1 away from drive assembly 56. This causes housing 48 to rise upward along shaft 28, thereby urging impeller 30 upward, causing impeller 30 to rotate as it travels linearly upward along screw shaft 28.

[0041] exist Figure 6 , drive assembly 56 changes the polarity of electromagnet 58 to be opposite to the polarity of impeller magnet 50 to produce an NS attraction state, thereby magnetically pulling impeller 30 toward drive assembly 56. As will be appreciated, this lowers impeller 30 and housing 48 along shaft 28 in direction D2, resulting in reverse rotation of impeller 30.

[0042] In embodiments, an electromagnet of sufficient strength may be used to raise and / or lower the impeller 30 without departing from the invention. Specifically, the current strength may vary depending on, for example, the agitation torque / RPM requirements of the vessel.

[0043] In an embodiment, the polarity of the electromagnet 58 can be reversed at predetermined automatic intervals. In this way, the shaft 28 does not require a mechanical stop (although it is within the scope of the present invention to include a mechanical stop at the top of the shaft 28), but when the housing 48 and impeller 30 approach the top of the shaft 28, the polarity can be automatically reversed to prevent the housing and impeller from leaving the shaft 28. In other embodiments, the electromagnet 58 can be activated in response to a detected condition within the fluid or vessel to agitate / mix the fluid. In yet other embodiments, when the impeller 30 and housing 48 are close to the top of the shaft 28, the electromagnet 58 can simply be turned off, so that the impeller 30 and housing 48 return to their starting position via gravity.

[0044] Reference now Figure 7 In an alternative embodiment, the impeller 30 may be raised or lowered via an electric linear actuator 60. The linear actuator 60 includes a motor 63 that extends and retracts a piston-like rod portion 64 that includes an arm 62 and a housing connector 66. The housing connector 66 is substantially parallel to the rod portion 64 and is raised or lowered with the rod portion 64.

[0045] refer to Figure 7 , the housing connector 66 of the linear actuator 60 is connected to the housing 148. The connector 66 can be attached to the housing 148 at the surface 160, although other attachment areas are possible. In an embodiment, the connector 66 can be integral with the housing 148. In other embodiments, it can be detachable from the housing 148.

[0046] In this embodiment, the housing 148 is a generally U-shaped bracket having a first aperture 150 and a second aperture 152, the first aperture 150 and the second aperture 152 being sized and shaped to allow the shaft 28 to pass therethrough. In use, the impeller 30 fits within the housing 148, and when the connector 60 is raised or lowered, the housing 148 contacts the impeller 30 and causes the impeller 30 to move up and down along the screw shaft 28, resulting in rotation of the impeller 30.

[0047] In embodiments, the speed of the linear actuator can be selectively varied. As will be appreciated, in these embodiments, the speed can be increased or decreased to change the RPM of the impeller.

[0048] The housing 148 eliminates the need for magnets because it is moved directly by the linear actuator 60. This significantly reduces the cost of the impeller 30. In an embodiment, the linear actuator 60 is located outside the vessel and may extend into the vessel interior volume 25 to engage the impeller 30 and housing 148 through a sealed port.

[0049] Also disclosed herein is a method of agitating a fluid in a vessel 24. The method includes moving a rotatable impeller 30 along a screw axis 28 in a first direction D1. The screw axis 28 is located within an interior volume 25 of the vessel 24. When the impeller 30 moves along the screw axis 28 in the first direction, the impeller 30 rotates axially around the screw axis 28 to agitate the liquid in the interior volume 25.

[0050] In some embodiments, the method further includes moving the rotatable impeller 30 in a second direction D2 opposite to the first direction along the screw axis 28. Moving the impeller 30 in the first direction along the screw axis 28 rotates the impeller 30 in the first direction, while moving the impeller 30 in the second direction rotates the impeller 30 in the second direction opposite to the first direction.

[0051] refer to Figure 5-6 In embodiments where rotatable impeller 30 is moved along screw shaft 28 via drive assembly 56 including electromagnet 58, the method further includes changing the polarity of electromagnet 58 to move rotatable impeller 30 in a second direction opposite to the first direction along screw shaft 28. In some embodiments, the method includes changing the strength of electromagnet 58 to change the RPM of rotatable impeller 30.

[0052] refer to Figure 7 and 8A -8C, in embodiments where the rotatable impeller 30 is moved along the screw shaft 28 via the linear actuator 60 , the method further includes varying the speed of the linear actuator 60 to vary the RPM of the rotatable impeller 30 .

[0053] As used herein, elements or steps stated in the singular and preceded by the word "a" or "an" should be understood not to exclude the plural number of the elements or steps, unless such exclusion is explicitly stated. In addition, reference to "one embodiment" of the present invention is not intended to be interpreted as excluding the existence of additional embodiments that also incorporate the described features. In addition, unless explicitly stated to the contrary, embodiments that "comprise," "include," or "have" an element or multiple elements having a particular property may include additional such elements that do not have that property.

[0054] Although the dimensions and types of materials described herein are intended to define the parameters of the invention, they are by no means limiting, but rather exemplary embodiments. Many other embodiments will be apparent to those skilled in the art upon reviewing the above description. Therefore, the scope of the invention should be determined with reference to the appended claims and the full scope of equivalents to which such claims are entitled. In the appended claims, the terms "including" and "wherein" are used as the colloquial language equivalents of the corresponding terms "comprising" and "wherein". Furthermore, in the appended claims, terms such as "first", "second", "upper", "lower", "bottom", "top", etc. are used merely as labels and are not intended to impose numerical or positional requirements on their objects. Furthermore, the limitations of the appended claims are not written in the form of means plus function and are not intended to be interpreted as such unless and until such claim limitations expressly use the phrase "means for" followed by a functional statement without further structure.

[0055] This written description uses examples to disclose several embodiments of the invention, including the best mode, and also to enable a person skilled in the art to practice the embodiments of the invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to a person skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal language of the claims.

Claims

1. A vessel (24), comprising: an interior volume (25) configured to contain a liquid; a screw shaft (28) located within the interior volume (25); A rotatable impeller (30); The rotatable impeller (30) has an aperture (38) configured to receive the screw shaft (28) and allow bidirectional travel of the rotatable impeller (30) along the screw shaft (28); and Wherein, when the rotatable impeller (30) travels along the screw axis (28), the rotatable impeller (30) rotates axially around the screw axis (28) to agitate the liquid in the internal volume (25).

2. The vessel (24) according to claim 1, further comprising: A housing (48, 148) in which the rotatable impeller (30) is located, the housing (48, 148) including a housing aperture (52, 54, 150, 152) configured to receive the screw shaft (28).

3. The vessel (24) according to claim 1, wherein: The rotatable impeller (30) is operably connected to at least one impeller magnet (50) that allows the bi-directional travel of the rotatable impeller (30) along the screw shaft (28) to be controlled via a drive assembly (56).

4. The vessel (24) according to claim 3, wherein: The drive assembly (56) includes an electromagnet (58) that is selectively capable of changing polarity to cause the rotatable impeller (30) to move bi-directionally along the screw shaft (28).

5. The vessel (24) according to claim 1, wherein: The rotatable impeller (30) is configured to be operably attached to the linear actuator (60), and the linear actuator (60) can be used to control the bidirectional travel of the rotatable impeller (30) along the screw shaft (28).

6. The vessel (24) according to claim 1, wherein: The impeller aperture (38) is a slot configured to engage a cross-sectional profile of the screw shaft (28) to cause axial rotation of the rotatable impeller (30) as the rotatable impeller (30) moves linearly along the screw shaft (28).

7. The vessel (24) according to claim 1, wherein: The screw shaft (28) has a length substantially equal to or less than the minimum working volume height of the vessel (24).

8. The vessel (24) according to claim 1, wherein: The vessel is a collapsible bag.

9. The vessel (24) according to claim 1, wherein: The vessel is a bioreactor bag.

10. A bioreactor system comprising: a vessel (24) having an interior volume (25) configured to contain a liquid; a screw shaft (28) located within the interior volume (25); A rotatable impeller (30); The rotatable impeller (30) has an aperture (38) configured to receive the screw shaft (28) and allow the rotatable impeller (30) to travel bidirectionally along the screw shaft (28); a drive assembly (56) configured to control bidirectional travel of the rotatable impeller (30) along the screw shaft (28); and Wherein, when the rotatable impeller (30) travels along the screw axis (28), the rotatable impeller (30) rotates axially around the screw axis (28) to agitate the liquid in the interior volume (25) of the vessel (24).

11. The bioreactor system according to claim 10, wherein: The rotatable impeller (30) is operably connected to at least one impeller magnet (50) that allows the bi-directional travel of the rotatable impeller (30) along the screw shaft (28) to be controlled via the drive assembly (56).

12. The bioreactor system according to claim 11, wherein: The drive assembly (56) includes an electromagnet (58) that is selectively capable of changing polarity to cause the rotatable impeller (30) to move bi-directionally along the screw shaft (28).

13. The bioreactor system according to claim 10, wherein: The drive assembly (56) includes a linear actuator (60) operable to control the bi-directional travel of the housing (48, 148) and rotatable impeller (30) along the screw shaft (28).

14. The bioreactor system according to claim 10, wherein: The impeller bore (38) is a notch configured to engage a cross-sectional profile of the screw shaft (28) to cause axial rotation of the rotatable impeller (30) as the rotatable impeller (30) moves linearly along the screw shaft (28).

15. The bioreactor system according to claim 10, wherein: The screw shaft (28) has a length substantially equal to or less than the minimum working volume height of the vessel (24).

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