Patent ID: 12226743

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

As used in the specification and appended claims, directional terms, such as “top,” “bottom,” “left,” “right,” “up,” “down,” “upper,” “lower,” “proximal,” “distal” and the like are used herein solely to indicate relative directions and are not otherwise intended to limit the scope of the invention or claims.

The present invention relates to systems and methods for mixing fluids such as solutions or suspensions. The systems can be commonly used as bioreactors or fermentors for culturing cells or microorganisms. By way of example and not by limitation, the inventive systems can be used in culturing bacteria, fungi, algae, plant cells, animal cells, protozoan, nematodes, and the like. The systems can accommodate cells and microorganisms that are aerobic or anaerobic and are adherent or non-adherent. The systems can also be used in association with the formation and/or treatment of solutions and/or suspensions that are for biological purposes, such as media, buffers, or reagents. For example, the systems can be used in the formation of media where sparging is used to control the pH of the media through adjustment of the carbonate/bicarbonate levels with controlled gaseous levels of carbon dioxide. The systems can also be used for mixing powders or other components into a liquid where sparging is not required and/or where the solution/suspension is not for biological purposes.

Depicted inFIGS.1-3is one embodiment of an inventive mixing system10incorporating features of the present invention. In general, mixing system10comprises a docking station12, a container station14that removably docks with docking station12, a container assembly16(FIG.2) that is supported by container station14, and a drive shaft17(FIG.3) that extends between docking station12and container assembly16. Container assembly16houses the fluid that is mixed. The various components of mixing system10will now be discussed in greater detail.

As depicted inFIG.2, container assembly16comprises a container18having a side20that extends from an upper end22to an opposing lower end24. Upper end22terminates at an upper end wall33while lower end24terminates at a lower end wall34. Container18also has an interior surface26that bounds a compartment28. Compartment28is configured to hold a fluid. In the embodiment depicted, container18comprises a flexible bag that is comprised of a flexible, water impermeable material such as a low-density polyethylene or other polymeric sheets or film having a thickness in a range between about 0.1 mm to about 5 mm with about 0.2 mm to about 2 mm being more common. Other thicknesses can also be used. The material can be comprised of a single ply material or can comprise two or more layers which are either sealed together or separated to form a double wall container. Where the layers are sealed together, the material can comprise a laminated or extruded material. The laminated material comprises two or more separately formed layers that are subsequently secured together by an adhesive. Examples of extruded material that can be used in the present invention include the HyQ CX3-9 and HyQ CX5-14 films available from HyClone Laboratories, Inc. out of Logan, Utah. The material can be approved for direct contact with living cells and be capable of maintaining a solution sterile. In such an embodiment, the material can also be sterilizable such as by ionizing radiation.

In one embodiment, container18can comprise a two-dimensional pillow style bag. In another embodiment, container18can be formed from a continuous tubular extrusion of polymeric material that is cut to length. The ends can be seamed closed or panels can be sealed over the open ends to form a three-dimensional bag. Three-dimensional bags not only have an annular side wall but also a two-dimensional top end wall and a two-dimensional bottom end wall. Three dimensional containers can comprise a plurality of discrete panels, typically three or more, and more commonly four or six. Each panel is substantially identical and comprises a portion of the side wall, top end wall, and bottom end wall of the container. Corresponding perimeter edges of each panel are seamed together. The seams are typically formed using methods known in the art such as heat energies, RF energies, sonics, or other sealing energies.

In alternative embodiments, the panels can be formed in a variety of different patterns. Further disclosure with regard to one method of manufacturing three-dimensional bags is disclosed in United States Patent Publication No. US 2002-0131654 A1, published Sep. 19, 2002, which is incorporated herein by specific reference in its entirety.

It is appreciated that container18can be manufactured to have virtually any desired size, shape, and configuration. For example, container18can be formed having a compartment sized to 10 liters, 30 liters, 100 liters, 250 liters, 500 liters, 750 liters, 1,000 liters, 1,500 liters, 3,000 liters, 5,000 liters, 10,000 liters or other desired volumes. The size of the compartment can also be in the range between any two of the above volumes. Although container18can be any shape, in one embodiment container18is specifically configured to be generally complementary to the chamber on container station14in which container18is received so that container18is properly supported within the chamber.

Although in the above discussed embodiment container18is depicted as a flexible bag, in alternative embodiments it is appreciated that container18can comprise any form of collapsible container or semi-rigid container. Container18can also be transparent or opaque.

Continuing withFIG.2, formed on container18are a plurality of ports30at upper end22, a plurality of ports31on opposing sides of side20at lower end24and a port32on lower end wall34. Each of ports30-32communicate with compartment28. Although only a few ports30-32are shown, it is appreciated that container18can be formed with any desired number of ports30-32and that ports30-32can be formed at any desired location on container18. Ports30-32can be the same configuration or different configurations and can be used for a variety of different purposes. For example, ports30can be coupled with fluid lines for delivering media, cell cultures, and/or other components into container18and withdrawing fluid from container18. Ports30can also be used for delivering gas to container18, such as through a sparger, and withdrawing gas from container18.

Ports30-32can also be used for coupling probes and/or sensors to container18. For example, when container18is used as a bioreactor or fermentor for growing cells or microorganisms, ports30-32can be used for coupling probes such as temperature probes, pH probes, dissolved oxygen probes, and the like. Various optical sensors and other types of sensors can also be attached to ports30-32. Examples of ports30-32and how various probes, sensors, and lines can be coupled thereto is disclosed in United States Patent Publication No. 2006-0270036, published Nov. 30, 2006, and United States Patent Publication No. 2006-0240546, published Oct. 26, 2006, which are incorporated herein by specific reference in their entirety. Ports30-32can also be used for coupling container18to secondary containers, to condenser systems, and to other desired fittings.

Container assembly16further comprises an impeller assembly40. Impeller assembly40comprises a first rotational assembly42A mounted on upper end wall33, a second rotational assembly42B mounted on lower end wall34, a flexible drive line44that extends between rotational assemblies42A and42B, and an impeller46coupled to drive line44. Drive line44has a longitudinal axis48that extends along the length thereof and can centrally extend therethrough.

As depicted inFIG.4, rotational assembly42A comprises an outer casing50having an outwardly projecting annular sealing flange52and an outwardly projecting annular mounting flange53. A hub54is rotatably disposed within outer casing50. One or more bearing assemblies55can be disposed between outer casing50and hub54to permit free and easy rotation of hub54relative to casing50. Likewise, one or more seals56can be formed between outer casing50and hub54so that during use an aseptic seal can be maintained between outer casing50and hub54as hub54rotates relative to outer casing50. Second end60of hub54is coupled with a first end70of drive line44. This coupling can be by overmolding, clamp, fastener, or other conventional techniques. Other configurations can also be used.

Rotational assembly42A is secured to container18so that second end60of hub54communicates with compartment28. Specifically, in the depicted embodiment container18has an opening74extending through upper end wall33. Sealing flange52of outer casing50is sealed, such as by welding or adhesive, around the perimeter bounding opening74so that hub54communicates with compartment28. Flange52can be welded on the interior or exterior surface of container18. In this configuration, outer casing50is fixed to container18but hub54, and thus also drive line44and impeller46, can freely rotate relative to outer casing50and container18. As a result of rotational assembly42A sealing opening74, compartment28is sealed closed so that it can be used in processing sterile fluids.

Turning toFIG.2, rotational assembly42B can have the same configuration as rotational assembly42A and can be mounted to lower end wall34of container18in the same manner that rotational assembly42A is mounted to container18. Like elements between rotational assemblies42A and42B are identified by like reference characters. Second end72of drive line44can be mounted to hub54of rotational assembly42B in the same way that drive line44is connected to hub54of rotational assembly42A. As will be discussed below in greater detail, a drive shaft is used to engage and rotate hub54of rotational assembly42A. In the above configuration, a separate drive shaft could also be used to engage and rotate hub54of rotational assembly42B. In other embodiments, hub54of rotational assembly42B need not be directly engaged and rotated by a separate drive shaft and thus opening62on hub54of rotational assembly42B can be eliminated.

Impeller46comprises a central hub76having a plurality of blades78radially outwardly projecting therefrom. It is appreciated that a variety of different numbers and configurations of blades78can be mounted on hub76. Hub76can be tubular so that hub76is slid over drive line44and then secured in the desired location by crimping, welding, adhesive or using a set screw, clamp, fastener or other securing technique. In other embodiments, hub76can comprise two or more separate members that are secured about drive line44. In yet other embodiments, drive line44can comprise two or more separate members where an end of two of the members can be secured using any desired method on opposing ends of hub76. Although only one impeller46is shown, it is appreciated that impeller46can be positioned at any position along drive line44and that any number of impellers, such as 2, 3, 4, or more, can be positioned along drive line44. The impellers disclosed herein and the alternatives discussed relative thereto are examples of mixing elements. Mixing elements, however, also include other structures that can be mounted on drive line44that can function to mix fluid when rotated but which would not normally be considered an impeller.

Drive line44can be made from a variety of different flexible materials. By way of example and not be limitation, in one embodiment drive line44can be made from a braided material such as cable, cord or rope. The braided material can be made from strands that are comprised of metal, polymer or other materials that have desired strength and flexibility properties and can be sterilized. For example, the strands can be made from stainless steel. In other embodiments, drive line44can be made from a flexible tube, a single solid core line, a linkage, such as a chain or a linkage of universal joints, or other flexible or hinged members.

As depicted inFIG.3, impeller assembly40is used in conjunction with drive shaft17. Drive shaft17has a first end84and an opposing second end86. Formed at first end84is a frustoconical engaging portion88that terminates at a circular plate90. Notches92are formed on the perimeter edge of circular plate90and are used for engaging drive shaft17with a drive motor assembly as will be discussed below.

Formed at second end86of drive shaft362is driver portion68. Driver portion68has a non-circular transverse cross section complementary to engaging portion66of hub54(FIG.4) so that it can facilitate locking engagement within engaging portion66of hub54. In the embodiment depicted, driver portion68has a polygonal transverse cross section. However, other non-circular shapes can also be used. It is also appreciated that other releasable locking mechanisms can be used to engage drive shaft362with hub54. For example, a bayonet connection, threaded connection, clamp, or fastener could be used.

Returning toFIG.1, container station14comprises a support housing100supported on a cart102. Support housing100has a substantially cylindrical sidewall104that extends between an upper end106and an opposing lower end108. Lower end108has a floor110mounted thereto. As a result, support housing14has an interior surface112that bounds a chamber114. An annular lip116is formed at upper end106and bounds an opening118to chamber114. As discussed above, chamber114is configured to receive container assembly16so that container18is supported therein.

Although support housing100is shown as having a substantially cylindrical configuration, in alternative embodiments support housing100can have any desired shape capable of at least partially bounding a compartment. For example, sidewall104need not be cylindrical but can have a variety of other transverse, cross sectional configurations such as square, rectangular, polygonal, elliptical, or irregular. Furthermore, it is appreciated that support housing100can be scaled to any desired size. For example, it is envisioned that support housing100can be sized so that chamber114can hold a volume of less than 50 liters, more than 1,000 liters or any of the other volumes or range of volumes as discussed above with regard to container18. Support housing100is typically made of metal, such as stainless steel, but can also be made of other materials capable of withstanding the applied loads of the present invention.

With continued reference toFIG.1, sidewall104of support housing100has an enlarged access120at lower end108so as to extend through sidewall104. A door122is hingedly mounted to sidewall104and can selectively pivot to open and close access120. A latch assembly124is used to lock door122in the closed position. An opening126, which is depicted in the form of an elongated slot, extends through door122. Opening126is configured to align with ports31(FIG.2) of container assembly16when container assembly16is received within chamber114so that ports31project into or can otherwise be accessed through opening126. In some embodiments, a line for carrying fluid or gas will be couple with port31and can extend out of chamber114through opening126. As previously mentioned, any number of ports31can be formed on container18and thus any number of separated lines may pass out through opening126or through other openings formed on support housing100. Alternatively, different types of probes, inserts, connectors, or the like may be coupled with ports31which can be accessed through opening126or other openings.

In one embodiment of the present invention means are provided for regulating the temperature of the fluid that is contained within container18when container18is disposed within support housing100. By way of example and not by limitation, sidewall104can be jacketed so as to bound one or more fluid channels that encircle sidewall104and that communicate with an inlet port130and an outlet port132. A fluid, such as water or propylene glycol, can be pumped into the fluid channel through inlet port130. The fluid then flows in a pattern around sidewall104and then exits out through outlet port132.

By heating or otherwise controlling the temperature of the fluid that is passed into the fluid channel, the temperature of support housing100can be regulated which in turn regulates the temperature of the fluid within container18when container18is disposed within support housing100. In an alternative embodiment, electrical heating elements can be mounted on or within support housing100. The heat from the heating elements is transferred either directly or indirectly to container18. Alternatively, other conventional means can also be used such as by applying gas burners to support housing100or pumping the fluid out of container18, heating the fluid and then pumping the fluid back into container18. When using container18as part of a bioreactor or fermentor, the means for heating can be used to heat the culture within container18to a temperature in a range between about 30° C. to about 40° C. Other temperatures can also be used.

As will be discussed below in greater detail, a yoke140is centrally mounted on the interior surface of floor110of support housing100. Yoke140has a U-shaped slot142that is bounded by an inwardly projecting U-shaped catch lip144. Yoke140is configured so that when container assembly16is received within chamber114of support housing100, second rotational assembly42B can be manually slid into slot142(FIG.3) so that mounting flange53of second rotational assembly42B is captured within slot142below catch lip144, thereby securing second rotational assembly42B to yoke140and preventing rotational assembly42B from being raised vertically relative to yoke140. It is appreciated that the function of yoke140is to releasably engage second rotational assembly42B and as such, yoke140can be in the form of a variety of different slots, clamps, ties, fasteners or the like. It is likewise appreciated that second rotational assembly42B can be attached to yoke140by reaching in through access120on sidewall104of support housing100.

As depicted inFIG.1, docking station12comprises a stand134, an adjustable arm assembly136coupled to stand134and a drive motor assembly300mounted on arm assembly136. Drive motor assembly300is used in conjunction with drive shaft17(FIG.3) and can be used for mixing and/or suspending a culture, solution, suspension, or other liquid within container18(FIG.2). Turning toFIG.3, drive motor assembly300comprises a housing304having a front face305that extends from a top surface306to an opposing bottom surface308. An opening310extends through housing304from top surface306to bottom surface308. A tubular motor mount312is rotatably secured within opening310of housing304. Upstanding from motor mount312is a locking pin316. A drive motor314is mounted to housing304and engages with motor mount312so as to facilitate select rotation of motor mount312relative to housing304. Drive shaft17is configured to pass through motor mount312so that engaging portion88of drive shaft17is retained within motor mount312and locking pin316of motor mount312is received within notch92of drive shaft17. As a result, rotation of motor mount312by drive motor314facilitates rotation of drive shaft17. Further discussion of drive motor assembly300and how it engages with drive shaft17and alternative designs of drive motor assembly300are discussed in US Patent Publication No. 2011/0188928, published Aug. 4, 2011, which is incorporated herein in its entirety by specific reference.

Arm assembly136is used to adjust the position of drive motor assembly300and thereby also adjust the position of drive shaft17. As depicted inFIG.5, arm assembly136comprises a first arm320mounted to stand134that vertically raises and lowers, a second arm322mounted to the first arm320that slides horizontally back and forth, and a third arm324mounted to second arm322that rotates about a horizontal axis326. Drive motor assembly300is mounted to third arm324. Accordingly, by movements of arms320,322, and/or324, drive motor assembly300can be positioned in any desired location or orientation relative to support housing100and container assembly16. For example, drive motor assembly300can be positioned so that drive shaft17is centered and vertically oriented when connected with container assembly16. In other embodiments, drive shaft17can be oriented at an angle, such as in a range between 10° to 30° from vertical when connected with container assembly16. Further discussion and alternative embodiments with regard to docking station12, arm assembly136, and container station14is provided in US Patent Publication No. 2011/0310696, published Dec. 22, 2011, which is incorporated herein in its entirety by specific reference.

During use, container station14and docking station12are removably coupled together as shown inFIG.1. One example of how docking station12and container assembly16can be coupled together is disclosed in US Patent Publication No. 2011/0310696 which was previously incorporated by reference. Other methods can also be used. Either before or after coupling together container station14and docking station12, container assembly16is positioned within chamber114of support housing100and second rotational assembly42B is secured to yoke140as discussed above.

In this position, arm assembly136is used to properly position drive motor assembly300so that first rotational assembly42A can be coupled with drive motor assembly300. Specifically, as depicted inFIG.3, housing304of drive motor assembly300has a U-shaped receiving slot330that is recessed on a front face305and bottom surface308so as to communicate with opening310extending through housing304. Receiving slot330is bounded by an inside face332on which a U-shaped catch slot334is recessed. As shown inFIG.1, a door336is hingedly mounted to housing304and selectively closes the opening to receiving slot330from front face305. As depicted inFIG.3, to facilitate attachment of rotational assembly42A to housing304, with door336rotated to an open position, rotational assembly42A is horizontally slid into receiving slot330from front face305of housing304so that mounting flange53that is radially outwardly extending from the upper end of rotational assembly42A is received and secured within catch slot334. First rotational assembly42A is advanced into receiving slot330so that opening62of rotational assembly42A aligns with the passage extending through motor mount312. Door336(FIG.1) is then moved to the closed position and secured in place by a latch or other locking mechanism so that first rotational assembly42A is locked to drive motor assembly300.

Rotational assemblies42A and42B are now secured to drive motor assembly300and yoke140, respectively, as shown inFIG.6. Arm assembly136(FIG.5) can now be used to remove any slack from or to tension flexible drive line44by raising drive motor assembly300to which rotational assembly42A is coupled. Likewise, arm assembly136can be used to adjust the orientation of drive line44. For example, by adjusting the position of drive motor assembly300, drive line44can be adjusted so as to be centered within support housing100and vertically oriented or drive line44can be oriented at an angle, such as in a range between 10° to 30° from vertical. Other positions and orientations can also be used.

Once first rotational assembly42A is secured to drive motor assembly300, drive shaft17can be advanced down through motor mount312of drive motor assembly300and into opening62of rotational assembly42A so that drive shaft17engages with hub54. Fluid and other components can be delivered into container18. Drive motor324can be activated so as to rotate drive shaft17which in turn begins to rotate hub54, drive line44and impeller46. Where container18is functioning as a bioreactor or fermentor, cells or microorganisms along with nutrients and other standard components can be added to container18. Rotation of impeller46facilitates mixing and/or suspension of the fluid and components contained within container18. Where drive line44is made of a material that flexes under torsion, such as a flexible cable, cord, solid core line or the like, drive line44will typically be able to axially twist along the length thereof. That is, first end70will begin to rotate concurrently with the rotation of hub54of first rotational assembly42A but second end72and hub54of second rotational assembly42A will not begin to rotate until drive line44has sufficiently twisted along its length so that second end72produces a torsion force on hub54of second rotational assembly42A sufficient to overcome the frictional resistance on hub54. Impeller46also produces resistance against the fluid within container18which results in twisting of drive line44during rotation. In other embodiments, such as where drive line44is a type of linkage, axle twisting of drive line44may be negligible.

In one embodiment, at least a portion of drive line44is sufficiently flexible so that the flexible portion of drive line44can be twisted under torsion about longitudinal axis48of drive line44over an angle of at least 15°, 25°, 45°, 90°, 180°, 360°, 720° or more without plastic deformation of drive line44. In other embodiments, at least a portion of drive line44is sufficiently flexible so that the flexible portion of drive line44can be bent or folded relative to a linear longitudinal axis48(FIG.2) of drive line44over an angle α (FIG.3) of at least 15°, 25°, 45°, 90°, 135°, 180° or more without plastic deformation of drive line44. Expressed in other terms, drive line44or the flexible portion of drive line44can have a bend radius wrapped 180° without plastic deformation in a range between about 2 cm to about 100 cm with about 6 cm to about 80 cm, about 10 cm to about 60 cm, or about 10 cm to about 40 cm being more common. Other flexibilities can also be used. It is appreciated that the entire length of drive line44need not be flexible. For example, a percentage of the entire length of drive shaft44, such as at least or not to exceed 30%, 40%, 50%, 60%, 70%, 80% or more of drive shaft44, could be flexible while the remainder is rigid or at least more rigid.

In an alternative method of use as previously mentioned, a second drive shaft could be coupled with hub54of second rotational assembly42B though a hole formed in floor110of support housing100. In this embodiment, both ends70and72of drive line44could be concurrently rotated although there may still be some twisting of drive line44along a central length or adjacent to impeller46.

In mixing system10, docking station12is used which includes arm assembly136. In this design, docking station12can be coupled with any number of different container stations14having a container assembly16therein. In an alternative embodiment, however, docking station12can be eliminated and arm assembly136can be mounted directly onto support housing100. Alternative examples of arm assembles and how they can be mounted onto support housing100is disclosed in U.S. patent application Ser. No. 13/659,616, filed Oct. 24, 2012 (US Patent Publication No. 2013/0101982, published Apr. 25, 2013), which is incorporate herein in its entirety by specific reference.

In the above discussed embodiment depicted inFIG.1, yoke140is mounted on the interior surface of floor110of support housing100for engaging with second rotational assembly42B (FIG.2). In an alternative embodiment as depicted inFIG.7. A yoke140A can be mounted on the exterior surface of floor110of support housing100. A hole148centrally extends through floor100so as to communicate with chamber114. In this embodiment, yoke140A has an opening149that is bounded between a body150and a locking arm152hingedly mounted thereto. During use, with locking arm152in an open position, the free end of second rotational assembly42B (FIG.2) is passed down through hole148so as to be received within opening149. Locking arm152is then moved to the closed position, as shown inFIG.7, and secured in place by a latch154. In this configuration, the end of second rotational assembly42B is secured to yoke140A. It is appreciated that yokes140and140A can come in a variety of other configurations and need only be able to releasably engage the second rotational assembly. In still other embodiments, the yoke need not be secured to support housing100but can be located on a separate structure at a position below support housing100. Second rotational assembly42B can be configured to pass down through hole148and engage with the yoke.

In one embodiment of the present invention, means are provided for holding the lower end24of container18stationary while flexible drive line44is rotated within compartment28of container18. Examples of this means includes yoke140mounted on the interior surface of floor110, yoke140A mounted on the exterior surface of floor110and yoke140A mounted on a separate structure located below floor110.

Depicted inFIG.8is an alternative embodiment of an impeller assembly40A. Like elements between impeller assemblies40and40A are identified by like reference characters. Impeller assembly40A comprises a first rotational assembly160A and a second rotational assembly160B with drive line44extending therebetween. First rotational assembly160A has substantially the same configuration as first rotational assembly42A and includes outer casing50having sealing flange52for securing to container18and mounting flange53. First rotational assembly160A has a hub162that rotates relative to casing50. However, in contrast to having an opening62(FIG.4) located at the end thereof, hub162includes an outwardly projecting stem164. Stem164has a non-circular transverse cross section, such as polygonal, so that a drive shaft17A having a complementary socket166, that replaces driver portion68(FIG.3), can securely engage with and rotate hub162.

As depicted inFIG.9, second rotational assembly160B comprises an outer casing168that includes a cylindrical base170having one or more mounting flanges171radially outwardly projecting from a lower end thereof and an enlarged annular sealing flange172radially outwardly projecting from the upper end thereof. Base170and mounting flanges171are configured to be engaged by yoke140A (FIG.8). Sealing flange172is configured to secure to container18, such as by welding, in the same manner as sealing flange52(FIG.2). Outer casing168has a top surface174on which a cylindrical blind pocket176is formed.

Second rotational assembly160B also includes a hub178having a base180to which second end72of drive line44is secured. Hub178also includes an annular flange182encircling and radially outwardly projecting from a lower end of base180. Flange182is configured so that it can be rotatably received within blind pocket176. Annular bearings184A and184B, such as roller thrust bearings, are also received within pocket176on opposing sides of flange184so that hub178can freely rotate relative to outer casing168. A cover plate186encircles hub178and/or drive line44and is positioned over bearing184A. Cover plate186is secured in place by engaging with locking fingers188that project from top surface174at spaced apart locations around pocket176. In this configuration, cover plate186retains hub178within outer casing168. It is appreciated that because pocket176is blind, it is not necessary to position a seal between hub178and outer casing168, although a seal can be used if desired. It is also appreciated that the rotational assemblies can have a variety of other configurations.

Returning toFIG.8, disposed at an upper end of drive line44is a foam breaker156. Foam breaker156includes a hub157secured to drive line44and a bar158that outwardly projects from opposing sides of hub157. Foam breaker156rotates concurrently with drive line44to break up foam that is formed at the upper end of container18. It is appreciated that foam breaker156can come in a variety of different configurations.

Also disposed along drive line44are a plurality of spaced apart impellers190A-D. As depicted inFIG.10, each impeller190comprises a tubular hub192which can be advanced over drive line44and secured in place such as by crimping, clamp, fastener, welding, set screw or the like. As depicted inFIG.11, a flange194encircles and radially outwardly projects from hub192. Flange194has a first side face196and an opposing second side face198with a plurality of openings200A extending therethrough adjacent to a perimeter edge of flange194. Outwardly projecting from first side face196are a plurality of spaced apart stops202with each stop202being disposed adjacent to a corresponding opening200A. Outwardly projecting from the end of each stop202is a key204.

Impeller190also includes a plurality of blades206. Each blade206comprises of an elongated arm208having an enlarged blade head210located at one end and an axle212disposed at the opposing end. Axle212has a first end214and an opposing second end216that project from opposing sides of arm208. First end214of axle212is configured to be received within a corresponding opening200A so that axle212can rotate within opening200A. An annular retainer220has a central passage222through which hub192can be advanced. A plurality of spaced apart openings200B that are sized to receive second end216of axle212extend between opposing sides of retainer220. A plurality of spaced apart keyways224are recessed on an outer edge of retainer220. Retainer220is configured to be advanced over hub192so that each key204is received within a corresponding keyway224, and second end216of each axle212is received within a corresponding opening200B. Retainer220can be secured to keys204such as by press fit connection, adhesive, welding, fasteners, or the like. Hub192, flange194and retainer220combine to form an impeller body to which blades206are attached.

In the assembled configuration, axle212is free to rotate within openings200A and200B so that blades206are movable between a collapsed position, such as where a blade206A is folded toward flange194inFIG.12, and an extended position, such as where blade206A is folded away from flange194inFIG.11. In the extended position, arm208hits against stop202to prevent further rotation away from the collapsed position. Blades206typically radially outwardly project from hub102when in the extended position but can project at angles relative to hub102. In most embodiments, however, an outer tip223of blades206is spaced farther from hub192when in the extended position than when in the collapsed position.

In alternative embodiments, it is appreciated that there are a wide variety of different ways in which blades206can be rotatably connected to hub192. For example, axles212could be rigidly fixed to flange194and/or retainer220. Arms208could then pivot about axles212. In another embodiment, axles212could be hingedly secured to flange194so as to eliminate the need for retainer220. In addition, both flange194and retainer220could be integrally formed as a unitary member with hub192and blades206could be snap fit or otherwise secured therebetween. Other alternatives also exist.

During sterilization, transport, storage, and at other times, in can be desirable to fold up or roll up container18into a more compact structure so that it is easier to handle and occupies less space. By making drive line44out of a flexible material, this enables drive line44to be concurrently folded up or rolled up with container18. Use of the flexible drive line also eliminates the need for an elongated drive shaft which can be expensive to make and difficult to attach, particularly in low ceiling environments. Furthermore, by making blades206movable between the collapsed and extended position, some or all of the blades can be moved to the collapsed position during the folding or rolling up of container18. Collapsing of the blades enables container18to be folded smaller, helps prevents blades206from puncturing container18and can result in less stress being placed on blade206. However, as will be discussed below in greater detail, as each impeller190is rotated within the fluid contained within container18, each of blades206catch the fluid and automatically move to the expanded position which is a more optimal position for mixing the fluid.

Another benefit of the inventive impeller190is that it is a modular system that can be used within a variety of different blade configurations. For example, in the embodiment depicted inFIG.10, each blade206has a blade head210having a generally flat rectangular configuration. This configuration of blade is commonly referred to as a Rushton blade. Depicted inFIG.13is an impeller225with like elements between impeller190and impeller225being identified by like reference characters. The only difference between impellers225and190is that in impeller225, blades206have been replaced with blades226. Blades226include arm208and axle212but in contrast to having a flat rectangular blade head210, they have a blade head228having a curved surface. More specifically, blade head228has a length with an arched or substantially semi-circular transverse cross section along the length. Again, each of blades226can be moved from a collapsed position to an extended position. Depicted inFIG.14is still another embodiment of an impeller230having foldable blades232with a blade head234that slopes relative to the longitudinal axis of hub192.

In each of impellers190,225, and230, the same impeller body can be used with blades of any desired configuration or size. Furthermore, the exchangeable blades need not be rotatable but can be designed to be fixed in the extended position. Such, modular impellers provide greater flexibility in being able to easily produce impellers having a desired configuration and mixing properties while maintaining a minimum number of stock parts.

Depicted inFIG.15is an alternative embodiment of an impeller238that is hingedly mounted to drive line44. Like elements between impellers190and238are identified by like reference characters. Impeller238is substantially identical to impeller190except that in contrast to hub192(FIG.10) which is tubular and received over drive line44, impeller238includes an elongated hub240having a first end242with a U-shaped connecter244A formed thereat and an opposing second end246with a U-shape connector244B formed thereat. Each of connectors244A and B bound a slot248and have an opening250transversely extending therethrough. Flexible line44is comprised of line portion252A having connector254A mounted on the end thereof and line portion252B having a connector254B mounted on the end thereof. Each of connecters254A and B also have an opening256transversely extending therethrough. During assembly, connectors254A and B are received within slots248of U-shaped connectors244A and B, respectively, so that openings250and256are aligned. Hinge pins258are then received within aligned openings250and256and secured in place so that connectors254A and B can freely pivot relative to impeller238. Hinge pins258can be attached to connectors244A and B by being press fit, welded, threaded or using other conventional techniques. In alternative embodiments, it is appreciated that a variety of different unions, hinges, swivels, and the like can be used to hingedly connect line portions252A and B to opposing ends of hub240. Furthermore, although impeller238is shown having pivotably mounted blades206, in an alternative embodiment impeller238can be formed with fixed blades.

FIG.16again depicts impeller238. However, in contrast to being hingedly coupled to flexible drive line44, impeller238inFIG.16is hingedly coupled to line portions262A and B of a rigid drive line264. That is, line portions262A and B can have openings256extending therethrough and can be made of shafts, rods or tubes or the like that are comprised of or consist of metal, plastics, composites, or the like that are substantially rigid or have limited flexibility. For example, line portions262A and B can have a bend radius wrapped 90° that must be greater than 8 meters, 10 meters or 12 meters to prevent plastic deformation.

Depicted inFIG.17is a perspective view of an alternative embodiment of a container assembly16B that includes an alternative embodiment of a flexible drive line. Container assembly16B can be operated within support housing100(FIG.1) in substantially the same manner as the other container assemblies discussed herein. Specifically, container assembly16B comprises container18having an impeller assembly40B coupled thereto. Impeller assembly40B comprises a first rotational assembly270mounted to upper end wall33of container18and a second rotational assembly242mounted to lower end wall34of container18. As depicted inFIGS.18and19, upper rotational assembly270comprises outer casing50and hub162as previously discussed. Various bearing assemblies274can be positioned between outer casing50and hub162to facilitate ease of rotation of hub162. One or more seals276can also be positioned between outer casing50and hub162to form a liquid-tight seal therebetween. An adapter278is coupled with hub162and has a stem280that projects away from hub162. In an alternative embodiment, stem280can be integrally formed as a unitary structure with hub162.

Second rotational assembly272includes outer casing168, bearings184A and B and cover plate186as previously discussed. Second rotational assembly272also includes a hub284having an upwardly extending stem286that passes through cover plate186and an outwardly projecting flange288that is positioned between bearings184A and B. Located between rotational assemblies270and272is an impeller290. Impeller290comprises a tubular hub291having a first end292and an opposing second end293. Flange194encircles and radially outwardly projects from hub291. Blades206hingedly mounted between flange194and retainer220as previously discussed. In an alternative embodiment, fixed blades can be secured to hub291or flange194.

Drive line assembly40B also includes a flexible drive line44B that includes a drive line portion294A and a drive line portion294B. Each of drive line portions294comprise a flexible tube that can be made of a resiliently flexible plastic or other material. In the depicted embodiments, although not required, the tubes are corrugated so as to increase flexibility. Drive line portions294can have the same flexibility as drive line44as previously discussed. Drive line portion294A has a first end295that is received over and coupled to stem280and an opposing second end296that is received within and secured to first end292of hub291. Similarly drive line portion294B has a first end297received over and secured to stem286and an opposing second end298received within and secured to second end293of hub291. In this configuration, rotation of hub162of first rotational assembly270facilitates rotation of drive line portions294A and B, impeller290, and hub284of second rotational assembly272.

Although the above discussed embodiments primarily disclose the use of impellers having pivotable blades with flexible drive lines, it is appreciated that the inventive impellers of the present invention can also be used with rigid drive shafts. For example, depicted inFIG.20is a container assembly16C that includes container18. A dynamic seal350is mounted on upper end wall33. A rigid drive shaft352passes through dynamic seal350and has a first end354disposed outside of container18and an opposing second end356disposed within container18. Dynamic seal350enables drive shaft352to freely rotate relative to container18while forming an aseptic seal between container18and drive shaft352. A driver portion358, which can have a polygonal or other noncircular transverse cross section or some other engaging surface, can be formed at first end354so that a drive motor can engage with and rotate drive shaft352.

Mounted on second end356of drive shaft352is impeller190as previously discussed herein. Rotation of drive shaft356causes blades206to move to the expanded position and mix the fluid within container18. Impeller190can be replaced with the other impellers discussed herein having pivotable blades and can incorporate other alternative configurations as discussed herein. Again, as a result of pivotable blades206, container18can be more fully collapsed around impeller190while minimizing risk of damage to container18and to blades206.

Depicted inFIG.21is another alternative embodiment of mixing system that incorporates an impeller with pivotable or foldable blades. The mixing system includes an impeller assembly40C that comprises an elongated tubular connector542having a rotational assembly548mounted at one end and an impeller564or other mixing element mounted on the opposing end. More specifically, tubular connector542has a first end544and an opposing second end546with a passage549that extends therebetween. In one embodiment, tubular connector542comprises a flexible tube, such as a polymeric tube, having the same flexibility as discussed above with regard to drive line44. As such, tubular connector542can comprise a flexible drive line as claimed herein. In other embodiments, tubular connector542can comprise a rigid tube or other tubular structure.

Rotational assembly548is mounted to first end544of tubular connector542. Rotational assembly548comprises outer casing50having an outwardly projecting annular sealing flange52and an outwardly projecting mounting flange53as previously discussed. A tubular hub454is rotatably disposed within outer casing50. One or more bearing assemblies, as previously discussed, can be disposed between outer casing50and hub554to permit free and easy rotation of hub554relative to casing50. Likewise, one or more seals, as previously discussed, can be formed between outer casing50and hub554so that during use an aseptic seal can be maintained between outer casing50and hub554.

Hub554has an interior surface556that bounds an opening558extending therethrough. Interior surface556includes an engaging portion having a polygonal or other non-circular transverse cross section so that driver portion68of drive shaft362, as also shown inFIG.21, passing through opening558can engage the engaging portion and facilitate rotation of hub554by rotation of drive shaft362. Hub554can also comprise a tubular stem560projecting away from outer casing50. Hub554can couple with first end544of tubular connector542by stem560being received within first end544. A pull tie, clamp, crimp or other fastener can then be used to further secure stem560to tubular connect542so that a liquid tight seal is formed therebetween. Other conventional connecting techniques can also be used.

Impeller564comprises a central hub566having blades206pivotably coupled thereto through the use of flange194and retainer220as previously discussed with regard toFIG.11. Alternative embodiments as discussed herein with regard to other impellers having pivotable blades can also be incorporated into impeller564. Hub566has a first end570with a blind socket572formed thereat. Socket572typically has a noncircular transverse cross section, such as polygonal, so that it can engage a driver portion378of drive shaft362. Accordingly, when driver portion378is received within socket572, driver portion378engages with impeller564such that rotation of drive shaft362facilities rotation of impeller564.

Impeller564can be attached to connector542by inserting first end570of hub566within connector542at second end546. A pull tie, clamp, crimp, or other type of fastener can then be cinched around second end546of connector542so as to form a liquid tight sealed engagement between impeller564and connector542.

Rotational assembly548is secured to container18in substantially the same manner that rotational assembly42was secured to container18, as previously discussed with regard toFIG.2, so that tubular connector542and impeller564extend into or are disposed within compartment28of container18.

In general drive shaft362comprises a head section364and a shaft section366that can be coupled together by threaded connection or other techniques. Head section364has substantially the same configuration as drive shaft17discussed with regard toFIG.3and thus like features head section364and drive shaft17will be identified by like reference characters. Alternatively, drive shaft362can be formed as a single piece member or from a plurality of attachable sections. Drive shaft362has a first end368and an opposing second end370. Formed at first end368is a frustoconical engaging portion88as previously discussed with regard toFIG.3. Formed at second end370of drive shaft362is driver portion378. Driver portion378has a non-circular transverse cross section so that it can facilitate locking engagement within hub466of impeller464. In the embodiment depicted, driver portion378has a polygonal transverse cross section. However, other non-circular shapes can also be used. Driver portion68is also formed along drive shaft362toward first end368. Driver portion68also has a non-circular transverse cross section and is positioned so that it can facilitate locking engagement within the engaging portion of rotational assembly448.

During use, container18having impeller assembly40C coupled thereto is received within support housing100(FIG.1) and rotational assembly is secured to drive motor assembly300as previously discussed with regard toFIG.3. Drive shaft362is advanced down through motor mount312, hub454of rotational assembly548, tubular connecter542and into hub566of impeller564. As a result of the interlocking engagement of driver portions378and68with hubs566and554, respectively, rotation of drive shaft362by drive motor assembly300facilitates rotation of hub554, tubular connecter542and impeller564relative to outer casing50of rotational assembly548and container18. The rotation of impeller564causes blades206to move to the expanded position and mix the fluid within container18.

It is appreciated that impeller assembly40C, drive shaft362and the discrete components thereof can have a variety of different configuration and can be made of a variety of different materials. Alternative embodiments of and further disclosure with respect to impeller assembly40C, drive shaft362, and the components thereof are disclosed in U.S. Pat. No. 7,384,783, issued Jun. 10, 2008, and US Patent Publication No. 2011/0188928, published Aug. 4, 2011, which are incorporated herein in their entirety by specific reference.

In the prior discussed embodiments incorporating the flexible drive line, the flexible drive line is supported by being secured to both the upper end wall and lower end wall of the container. In an alternative embodiment, the flexible drive line can be supported and stabilized by being secured to the upper end wall of the container and at one or more locations along the length of the flexible drive line. For example, depicted inFIG.22is an alternative embodiment of a fluid mixing system10A incorporating features of the present invention. Fluid mixing system10A comprises a container assembly16D at least partially disposed within the compartment of a support housing100A. Like elements between container assembly16and16A and between support housing100and100A are identified by like reference characters. Furthermore, disclosure and alternative embodiments as previously discussed with regard to container16and support housing100are also applicable to corresponding elements of container assembly16A and support housing100A.

As depicted inFIG.23, container assembly16A comprises container18having flexible drive line44disposed therein. First end70of flexible drive line44is secured to upper end wall33of container18by rotational assembly42A. Mounted on flexible drive line44as spaced apart locations are mixing elements400A-C. Each of mixing element400A-C can comprise a fixed blade impeller, such as previously discussed impeller46, a foldable impeller, such as previously discussed impellers190,225,230,238, or other types of mixing elements. In alternative embodiments, container assembly16A can comprise one, two, or four or more mixing elements400. In contrast to container assembly16where second end72of drive line44is secured to lower end wall34, container assembly16A has second end72of drive line44suspended above lower end wall34.

To stabilize drive line44within compartment28of container18, container assembly16A comprises lateral support assemblies402A-C coupled with flexible drive line44at space apart locations along the length thereof. Each lateral support assembly402A-C comprises a retention assembly404having a first end405secured to side20of container18and an opposing second end407secured to flexible drive line44. Lateral support assembly402also includes a support rod406that is selectively received and secured within corresponding retention assembly404. Each retention assembly404comprises a port fitting410at first end405that is coupled with side20of container18, a receiver408at second end407that is mounted to flexible drive line44, and a flexible tube412that extends between port fitting410and receiver408.

As depicted inFIG.24, receiver408comprises an inner housing414that is securely fixed to flexible drive line44such as by crimping, adhesive, clamps, fasteners, or the like. Receiver408also includes an outer housing416that encircles inner housing414. A bearing418, such as a ball thrust bearing, roller thrust bearing, or other type of bearing, is disposed between inner housing414and outer housing416. Bearing418enables inner housing414and drive line44to rotate concurrently relative to outer housing416. Outer housing416includes a body420having a tubular stem422outwardly projecting therefrom. Stem422can be integrally formed with or secured to body420. An annular barb423can encircle and outwardly project on the end of stem422for engaging with flexible tube412. Stem422has an interior surface424that bounds an opening426that can extend into body420. Formed on interior surface424of stem422and/or body420is an engaging thread428.

As also depicted inFIG.24, port fitting410comprises a tubular stem430having a first end432and an opposing second end434. An annular barb436can encircle and outwardly extending from second end434for engaging with flexible tube412. Radially outwardly projecting from first end432is a retention flange438. As will be discussed below in greater detail, retention flange438is used to secure port fitting410to rigid support housing100. Retention flange438need not encircle stem430and can have a variety of different configurations. Encircling and radially outwardly projecting from stem430at a location between opposing ends432and434is a mounting flange440. Mounting flange440is welded or otherwise secured to side20of container18so as to form a liquid tight seal therewith. As a result, first end432of port fitting410disposed outside of container18while second end434is disposed within container18. Stem430has an interior surface442that bounds a passageway444extending therethrough.

Flexible tube412can comprise any type of flexible tube, tubing, hose, pipe or the like and is typically comprised of an elastomeric polymer. By making tube412flexible, tube412can be folded or rolled when collapsing container18for shipping, storage, disposal or the like. In an alternative embodiment it is appreciated that tube412need not be flexible but can be rigid or semi-rigid. Tube412has an interior surface446that bounds a passageway448that longitudinally extends through tube412from a first end450to an opposing second end452. First end450of tube412is advanced over stem430of port fitting410so as to form a liquid tight seal therewith while second end452of tube412is received over stem422of receiver408so as to form a liquid tight seal therewith. A fastener454such as a pull tie, crimp, clamp, or similar structure can be secured around first end450and second end452so as to secure the engagement between tube412and stems422and430.

During use, as depicted inFIG.22, container assembly16D is received within chamber114of support housing100A. Support housing100A is substantially identical is support housing100as previously discussed with regard toFIG.1and like elements are identified by like reference characters. Support housing100A is distinguished from support housing100in that it does not include yoke140located on floor110(FIG.1). Rather, support housing100A includes a plurality of locking fittings460A-C mounted at spaced apart locations on sidewall104. As depicted inFIGS.25and26, each locking fitting460comprises a base462having a first end464and an opposing second end466. A passageway468centrally passes through base462between opposing ends464and466. A flange470can encircle and radially outwardly project from base462at a location between opposing ends464and466. During the manufacture of support housing100A, vertically spaced apart holes475(FIG.22) can be formed through sidewall104so as to extend to chamber114. Second end466of each locking fitting460is received within a corresponding hole475so that flange470hits against the exterior surface of sidewall104. Welding or other fastening techniques can then be used to secure each locking fitting460to support housing100A within the corresponding hole475.

Formed on the end face of base462at second end466is a catch472. Catch472is disposed adjacent to interior surface112of support housing100A and has a U-shaped body474with a U-shaped opening476passing therethrough. U-shaped opening476is aligned with passageway468passing through base462. Body474has an interior surface478that includes an undercut U-shaped channel480and a U-shaped catch lip482that radially inwardly projects adjacent to channel480. Catch472is configured so that retention flange438on port fitting410can be slidably received and captured within channel480so that passageway468of locking fitting460is aligned with passageway444of a corresponding port fitting410. It is appreciated that retention flange438and/or channel480can be tapered so that a releasable friction fit is formed therebetween. It is also appreciated that there are a variety of different fastening techniques that can be used to releasably secure port fitting410to locking fitting460.

Locking fitting460also includes a locking slot486formed on first end464of base462and which is located outside of support housing100A. Locking slot486includes a first leg488that passes through base462to passageway468and runs parallel to passageway468. Locking slot486also includes a second leg490that extends normal to first leg488at the end thereof so as to extend around a portion of the perimeter of base462. Second leg490also extends to passageway468.

Returning toFIG.25, each support rod406comprises a linear shaft500that extends between a first end502and an opposing second end504. A locking thread506is formed on second end504. A locking arm508radially outwardly projects from shaft500as first end502. Locking arm508is sized to be received within locking slot486. Support rod406is typically comprised of metal but other rigid or semi-rigid materials can also be used.

During use, as previously discussed and depicted inFIG.22, container assembly16D is received within chamber114of support housing100A. Once inserted, each port fitting410is secured to a corresponding locking fitting460as previously discussed and depicted inFIG.27A. In this assembled configuration, second end504of each support rod406is advanced through passageway468of locking fitting460through passageway444of port fitting410and into passageway448of tube412. Each support rod406is continued to be advanced until locking thread506reach engaging thread428on retention assembly404. Concurrently, locking arm508is received within first leg488(FIG.26) of locking slot486. In this position, locking arm508can be rotated downward through second leg490of locking slot406so as to lock support rod406to locking fitting460. As locking arm508is rotated, shaft500with locking threads506thereon are rotated. As locking threads506are rotated they threadedly engage with engaging threads428on receiver408, thereby securing support rod406to receiver408. As a result, opposing ends of support rod406are secured to locking fitting460and receiver408which creates a lateral rigid support for flexible drive line44. It is appreciated that a variety of other connections can be used for securing one or both of opposing ends of support rod404such as a bayonet connection, luer-lock connection, clamp, separate fastener, or the like.

The lateral rigid support of flexible drive line44achieves a number of benefits. For example, where mixing element400is an impeller, the rotation of the impeller causes the impeller to tend to migrate laterally. Lateral movement of drive line44and mixing elements400can cause damage to container18and can produce irregular mixing within container14. Irregular mixing can be especially problematic where the mixing system is being used as a bioreactor or fermetor used for growing cells or microorganisms. In those cases, irregular mixing can apply unwanted shear forces on the cells or microorganisms or can result in irregular feeding or gas transfer to the cells or microorganisms. Use of the lateral support assemblies prevents unwanted lateral movement of drive line44and mixing elements400within container18and helps maintain uniform mixing. Although in the depicted embodiment three separate lateral support assemblies402are shown, in alternative embodiments, container assembly16D can be formed with only one or two lateral support assemblies. Alternatively, four or more lateral support assemblies can also be used based on the size or other operational conditions for container assembly16D.

Furthermore, as a result of the lateral support to drive line44, second end72of drive line44need not be connected to lower end wall34of container18. In some cases this is beneficial because it permits a more convenient folding of container18. That is, in some designs for container18, the most compact folding of container18requires that the center of opposing end walls33and34be pulled away from each other. Where drive line44is secured to the opposing end walls33and34, the end walls cannot be pulled away from each other and thus container18cannot be folded in the most compact manner.

In addition, where the opposing ends of drive line44are connected to the top and bottom of container18, as inFIG.2, drive line44is tensioned to help prevent lateral walking of the impeller. As previously discussed, to facilitate the tension of drive line44, the second end of container18is secured to the floor or relative to the floor of the support housing. In contrast, by using the lateral support assemblies, drive line44does not need to be tensioned and it is not necessary to secure the second end of container18to the floor of the support housing.

Depicted inFIG.28is a container assembly16E disposed within support housing100A. Container assembly16E includes lateral support assemblies402A-C. However, in contrast to being connected to flexible drive line44, container assembly16E includes a rigid drive shaft516such as drive shaft352as depicted inFIG.20. Lateral support assemblies402facilitate the lateral support of drive shaft516along the length thereof. Again, any number of lateral support assemblies402can be used and any number of mixing elements400can be mounted thereon. Other alternative embodiments as previously discussed with regard to like elements of container assembly16D are also applicable container assembly16D.

In another alternative embodiment, a container assembly can be formed that includes impeller assembly40C as depicted and previously discussed with regard toFIG.21. One or more lateral support assemblies402can extend between the side of container18and tubular connector442. The container assembly can be housed within support housing100A.

Depicted inFIG.29is another alternative embodiment of a container assembly16F disposed within support housing100A. Container assembly16F is used where greater stability of drive line44is required, such as for long containers18. Container assembly16F comprises container18housing drive line44on which one or more mixing elements400are disposed. First end70of drive line44is secured to upper end wall33by first rotational assembly42A and second end72of drive line44is secured to lower end wall34by second rotational assembly42B in the same manner as previously discussed with regard to container assembly16depicted inFIGS.2and3. In turn, second rotational assembly42B can be secured to floor110of support housing100A using one of the yokes previously discussed or can be otherwise secured in place. Container assembly16F also includes one or more lateral support assemblies402extending between side20of container18and flexible drive line44as previously discussed with regard to container assembly16D depicted inFIGS.22-24. Thus, in this embodiment flexible drive line44is supported both at opposing ends and at one or more locations along its length. Use and alternative embodiments as discussed with the other container assemblies are also applicable to container assembly16F.

Finally, depicted inFIG.30is another alternative embodiment of a container assembly16G disposed within support housing100A. Container assembly16G is substantially the same as container assembly16D and thus the prior disclosure, alternative embodiments and reference characters for container assembly16D are also applicable to container assembly16E. Container18has a central longitudinal axis520that extends between upper end wall33and lower end wall34. In container assembly16D, rotational assembly42A is mounted on upper end wall33in alignment with central longitudinal axis520and drive line44extends along central longitudinal axis520. In contrast, container assembly16G has rotational assembly42A disposed on upper end wall33at a location spaced apart from central longitudinal axis520and, more specifically, adjacent to sidewall104of support housing100A. However, lateral support assemblies402hold the portion of drive line44on which mixing elements400are disposed, along central longitudinal axis520.

Container assembly16G has the advantage that mixing elements400are still centrally disposed within container18so that the fluid within container18can have uniform mixing but the central area of upper end wall33is now openly exposed. As such, ports, fitting, probes, sample tubes and the like can now be centrally mounted on upper end wall33, which is often considered a valuable location. Furthermore, placing rotational assembly42A closer to sidewall104of support housing100A can make it easier to connect rotational assembly42A to drive motor assembly300(FIG.1). Thus, because of the flexible nature of drive line44and the rigid lateral support produced by lateral support assemblies402, rotational assembly42A can be located at any position on upper end wall33and even at the upper end of side20of container18.

The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.