Patent Description:
The present invention relates to fluid mixing systems and, more specifically, fluid mixing systems having an impeller having pivotable blades.

The biopharmaceutical industry uses a broad range of mixing systems for a variety of processes such as in the preparation of media and buffers and in the growing, mixing and suspension of cells and microorganisms. Some conventional mixing systems, including bioreactors and fermentors, comprise a flexible bag disposed within a rigid support housing. An impeller is disposed within the flexible bag and is coupled with the drive shaft. Rotation of the drive shaft and impeller facilitates mixing and/or suspension of the fluid contained within flexible bag.

Although the current mixing systems are useful, they have some limitations. For example, where the drive shaft is secured within the flexible bag during the manufacturing process, the rigid drive shaft limits the ability to collapse or fold the flexible bag so as to reduce its size for transportation, storage and/or further processing. Likewise, where it is intended to reuse the drive shaft, such as when it is made of metal, this system has the disadvantage of needing to clean and sterilize the drive shaft between different uses.

In an alternative conventional system, a rotatable tube extends into the flexible bag and has an impeller coupled at the end thereof. During use, the rigid drive shaft is passed down into the tube and couples with the impeller. In turn, rotation of the drive shaft facilitates rotation of the impeller for mixing the fluid within the flexible bag. In this design, with the drive shaft removed, the flexible bag with tube can be folded for ease of storage and transportation. In addition, because the drive shaft does not directly contact the fluid within the bag, the drive shaft does not need to be cleaned or sterilized between uses.

However, the flexible bag is typically secured within the support housing prior to insertion of the drive shaft. It is thus necessary during use to vertically position the drive shaft over the top of the bag for insertion into the tube. For large bags or elongated bags that require a long drive shaft, this can be difficult to accomplish. Furthermore, in situations where the mixing system is located in a room with a relatively low ceiling, it may be impossible to vertically lift the drive shaft over the bag. This type of system also requires increased training in user operation to ensure that the drive shaft is properly received within the tube and properly engaged with the impeller so that the system operates as intended.

Conventional systems also have the drawback that the rigid impellers located within the bags limit the extent to which the bags can be collapsed by folding or other manipulation. Likewise, there are potential concerns that the blades of the impellers can puncture or otherwise damage the bags when the bags are folded around the impeller. In addition, folding the bag around the impeller can place unwanted stress on the rigid impeller blades. <CIT> discloses an impeller with blades privotabily coupled to its body as can be seen in <FIG> and <FIG>. The impeller is rigidly coupled to the drive shaft. US 2552D57 discloses a fluid mixing system according to the preamble of claim <NUM>.

Accordingly, what is needed in the art are mixing systems that solve all or some of the above problems.

Various embodiments will now be discussed with reference to the appended drawings. It is appreciated that these drawings depict only typical embodiments and are therefore not to be considered limiting. <FIG>, <FIG> depict embodiments of the present invention.

The drive shaft (<NUM>) may be at least partially disposed within the sterile compartment; and have a dynamic seal sealing the drive shaft (<NUM>) to the container (<NUM>).

The invention further relates to a method of mixing a fluid, the method comprising:.

The flexible bag may be positioned within a support housing. In addition, the drive line (<NUM>) may be disposed within the flexible compartment and the drive line being flexible, the method further comprises coupling a drive shaft (<NUM>) to the drive line to facilitate rotation of the drive line.

In another embodiment of the inventive method the drive line (<NUM>) is disposed within the flexible compartment, the drive line comprising a flexible tube, the method further comprises removably inserting a drive shaft (<NUM>) within the flexible tube, the drive shaft (<NUM>) engaging with the tube or first impeller (<NUM>) such that rotation of the drive shaft (<NUM>) causes rotation of the impeller.

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 a fluid mixing system comprising:.

Additionally, the impeller body may comprise a hub coupled to the drive line (<NUM>) or drive shaft (<NUM>), the plurality of blades being pivotably coupled to the hub.

The impeller body can have a hub coupled to the drive line (<NUM>) or drive shaft (<NUM>) and a flange radially outwardly projecting from the hub, the plurality of blades being pivotably coupled to the flange.

In addition, a retainer at least partially encircling the hub and being secured to the flange may be present. In this embodiment the plurality of blades is pivotably secured between the flange and the retainer.

In another embodiment the plurality of blades are pivotable between a collapsed position and an expanded position, such that each of the blades has a terminal tip that is closer to the drive line (<NUM>) or drive shaft (<NUM>) when the blades are in the collapsed position than when in the expanded position.

In preferred embodiments the container (<NUM>) comprises a flexible bag.

The fluid mixing system of the present invention may further comprise:.

In this particular embodiment the drive line (<NUM>) may be comprised of a flexible cable, cord, or tube and/or may further comprise a second rotational assembly, the second rotational assembly including a second casing mounted to a second end of the container (<NUM>); and a second hub rotatably mounted to the second casing, the second hub being coupled to a second end of the drive line.

In another embodiment the fluid mixing system further comprises the drive line (<NUM>) comprising a tube; and a drive shaft (<NUM>) being removably positioned within the tube.

Generally disclosed are 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 in <FIG> is one mixing system <NUM> incorporating features of the present invention. In general, mixing system <NUM> comprises a docking station <NUM>, a container station <NUM> that removably docks with docking station <NUM>, a container assembly <NUM> (<FIG>) that is supported by container station <NUM>, and a drive shaft <NUM> (<FIG>) that extends between docking station <NUM> and container assembly <NUM>. Container assembly <NUM> houses the fluid that is mixed. The various components of mixing system <NUM> will now be discussed in greater detail.

As depicted in <FIG>, container assembly <NUM> comprises a container <NUM> having a side <NUM> that extends from an upper end <NUM> to an opposing lower end <NUM>. Upper end <NUM> terminates at an upper end wall <NUM> while lower end <NUM> terminates at a lower end wall <NUM>. Container <NUM> also has an interior surface <NUM> that bounds a compartment <NUM>. Compartment <NUM> is configured to hold a fluid. In the embodiment depicted, container <NUM> comprises 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 <NUM> to about <NUM> with about <NUM> to about <NUM> 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-<NUM> and HyQ CX5-<NUM> 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, container <NUM> can comprise a two-dimensional pillow style bag. In another embodiment, container <NUM> can 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. <CIT>.

It is appreciated that container <NUM> can be manufactured to have virtually any desired size, shape, and configuration. For example, container <NUM> can be formed having a compartment sized to <NUM> liters, <NUM> liters, <NUM> liters, <NUM> liters, <NUM> liters, <NUM> liters, <NUM>,<NUM> liters, <NUM>,<NUM> liters, <NUM>,<NUM> liters, <NUM>,<NUM> liters, <NUM>,<NUM> liters or other desired volumes. The size of the compartment can also be in the range between any two of the above volumes. Although container <NUM> can be any shape, in one embodiment container <NUM> is specifically configured to be generally complementary to the chamber on container station <NUM> in which container <NUM> is received so that container <NUM> is properly supported within the chamber.

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

Continuing with <FIG>, formed on container <NUM> are a plurality of ports <NUM> at upper end <NUM>, a plurality of ports <NUM> on opposing sides of side <NUM> at lower end <NUM> and a port <NUM> on lower end wall <NUM>. Each of ports <NUM>-<NUM> communicate with compartment <NUM>. Although only a few ports <NUM>-<NUM> are shown, it is appreciated that container <NUM> can be formed with any desired number of ports <NUM>-<NUM> and that ports <NUM>-<NUM> can be formed at any desired location on container <NUM>. Ports <NUM>-<NUM> can be the same configuration or different configurations and can be used for a variety of different purposes. For example, ports <NUM> can be coupled with fluid lines for delivering media, cell cultures, and/or other components into container <NUM> and withdrawing fluid from container <NUM>. Ports <NUM> can also be used for delivering gas to container <NUM>, such as through a sparger, and withdrawing gas from container <NUM>.

Ports <NUM>-<NUM> can also be used for coupling probes and/or sensors to container <NUM>. For example, when container <NUM> is used as a bioreactor or fermentor for growing cells or microorganisms, ports <NUM>-<NUM> can be used for coupling probes such as temperatures probes, pH probes, dissolved oxygen probes, and the like. Various optical sensors and other types of sensors can also be attached to ports <NUM>-<NUM>. Examples of ports <NUM>-<NUM> and how various probes, sensors, and lines can be coupled thereto is disclosed in <CIT> and <CIT>. Ports <NUM>-<NUM> can also be used for coupling container <NUM> to secondary containers, to condenser systems, and to other desired fittings.

Container assembly <NUM> further comprises an impeller assembly <NUM>. Impeller assembly <NUM> comprises a first rotational assembly 42A mounted on upper end wall <NUM>, a second rotational assembly 42B mounted on lower end wall <NUM>, a flexible drive line <NUM> that extends between rotational assemblies 42A and 42B, and an impeller <NUM> coupled to drive line <NUM>. Drive line <NUM> has a longitudinal axis <NUM> that extends along the length thereof and can centrally extend therethrough.

As depicted in <FIG>, rotational assembly 42A comprises an outer casing <NUM> having an outwardly projecting annular sealing flange <NUM> and an outwardly projecting annular mounting flange <NUM>. A hub <NUM> is rotatably disposed within outer casing <NUM>. One or more bearing assemblies <NUM> can be disposed between outer casing <NUM> and hub <NUM> to permit free and easy rotation of hub <NUM> relative to casing <NUM>. Likewise, one or more seals <NUM> can be formed between outer casing <NUM> and hub <NUM> so that during use an aseptic seal can be maintained between outer casing <NUM> and hub <NUM> as hub <NUM> rotates relative to outer casing <NUM>. Second end <NUM> of hub <NUM> is coupled with a first end <NUM> of drive line <NUM>. This coupling can be by overmolding, clamp, fastener, or other conventional techniques. Other configurations can also be used.

Rotational assembly 42A is secured to container <NUM> so that second end <NUM> of hub <NUM> communicates with compartment <NUM>. Specifically, in the depicted embodiment container <NUM> has an opening <NUM> extending through upper end wall <NUM>. Sealing flange <NUM> of outer casing <NUM> is sealed, such as by welding or adhesive, around the perimeter bounding opening <NUM> so that hub <NUM> communicates with compartment <NUM>. Flange <NUM> can be welded on the interior or exterior surface of container <NUM>. In this configuration, outer casing <NUM> is fixed to container <NUM> but hub <NUM>, and thus also drive line <NUM> and impeller <NUM>, can freely rotate relative to outer casing <NUM> and container <NUM>. As a result of rotational assembly 42A sealing opening <NUM>, compartment <NUM> is sealed closed so that it can be used in processing sterile fluids.

Turning to <FIG>, rotational assembly 42B can have the same configuration as rotational assembly 42A and can be mounted to lower end wall <NUM> of container <NUM> in the same manner that rotational assembly 42A is mounted to container <NUM>. Like elements between rotational assemblies 42A and 42B are identified by like reference characters. Second end <NUM> of drive line <NUM> can be mounted to hub <NUM> of rotational assembly 42B in the same way that drive line <NUM> is connected to hub <NUM> of rotational assembly 42A. As will be discussed below in greater detail, a drive shaft is used to engage and rotate hub <NUM> of rotational assembly 42A. In the above configuration, a separate drive shaft could also be used to engage and rotate hub <NUM> of rotational assembly 42B. In other embodiments, hub <NUM> of rotational assembly 42B need not be directly engaged and rotated by a separate drive shaft and thus opening <NUM> on hub <NUM> of rotational assembly 42B can be eliminated.

Impeller <NUM> comprises a central hub <NUM> having a plurality of blades <NUM> radially outwardly projecting therefrom. It is appreciated that a variety of different numbers and configurations of blades <NUM> can be mounted on hub <NUM>. Hub <NUM> can be tubular so that hub <NUM> is slid over drive line <NUM> and then secured in the desired location by crimping, welding, adhesive or using a set screw, clamp, fastener or other securing technique. In other embodiments, hub <NUM> can comprise two or more separate members that are secured about drive line <NUM>. In yet other embodiments, drive line <NUM> can 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 hub <NUM>. Although only one impeller <NUM> is shown, it is appreciated that impeller <NUM> can be positioned at any position along drive line <NUM> and that any number of impellers, such as <NUM>, <NUM>, <NUM>, or more, can be positioned along drive line <NUM>. 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 line <NUM> that can function to mix fluid when rotated but which would not normally be considered an impeller.

Drive line <NUM> can be made from a variety of different flexible materials. By way of example and not be limitation, in one embodiment drive line <NUM> can be made from a braded material such as cable, cord or rope. The braded 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 line <NUM> can 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 in <FIG>, impeller assembly <NUM> is used in conjunction with drive shaft <NUM>. Drive shaft <NUM> has a first end <NUM> and an opposing second end <NUM>. Formed at first end <NUM> is a frustoconical engaging portion <NUM> that terminates at a circular plate <NUM>. Notches <NUM> are formed on the perimeter edge of circular plate <NUM> and are used for engaging drive shaft <NUM> with a drive motor assembly as will be discussed below.

Formed at second end <NUM> of drive shaft <NUM> is driver portion <NUM>. Driver portion <NUM> has a non-circular transverse cross section complementary to engaging portion <NUM> of hub <NUM> (<FIG>) so that it can facilitate locking engagement within engaging portion <NUM> of hub <NUM>. In the embodiment depicted, driver portion <NUM> has 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 shaft <NUM> with hub <NUM>. For example, a bayonet connection, threaded connection, clamp, or fastener could be used.

Returning to <FIG>, container station <NUM> comprises a support housing <NUM> supported on a cart <NUM>. Support housing <NUM> has a substantially cylindrical sidewall <NUM> that extends between an upper end <NUM> and an opposing lower end <NUM>. Lower end <NUM> has a floor <NUM> mounted thereto. As a result, support housing <NUM> has an interior surface <NUM> that bounds a chamber <NUM>. An annular lip <NUM> is formed at upper end <NUM> and bounds an opening <NUM> to chamber <NUM>. As discussed above, chamber <NUM> is configured to receive container assembly <NUM> so that container <NUM> is supported therein.

Although support housing <NUM> is shown as having a substantially cylindrical configuration, in alternative embodiments support housing <NUM> can have any desired shape capable of at least partially bounding a compartment. For example, sidewall <NUM> need 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 housing <NUM> can be scaled to any desired size. For example, it is envisioned that support housing <NUM> can be sized so that chamber <NUM> can hold a volume of less than <NUM> liters, more than <NUM>,<NUM> liters or any of the other volumes or range of volumes as discussed above with regard to container <NUM>. Support housing <NUM> is 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 to <FIG>, sidewall <NUM> of support housing <NUM> has an enlarged access <NUM> at lower end <NUM> so as to extend through sidewall <NUM>. A door <NUM> is hingedly mounted to sidewall <NUM> and can selectively pivot to open and close access <NUM>. A latch assembly <NUM> is used to lock door <NUM> in the closed position. An opening <NUM>, which is depicted in the form of an elongated slot, extends through door <NUM>. Opening <NUM> is configured to align with ports <NUM> (<FIG>) of container assembly <NUM> when container assembly <NUM> is received within chamber <NUM> so that ports <NUM> project into or can otherwise be accessed through opening <NUM>. In some embodiments, a line for carrying fluid or gas will be couple with port <NUM> and can extend out of chamber <NUM> through opening <NUM>. As previously mentioned, any number of ports <NUM> can be formed on container <NUM> and thus any number of separated lines may pass out through opening <NUM> or through other openings formed on support housing <NUM>. Alternatively, different types of probes, inserts, connectors, or the like may be coupled with ports <NUM> which can be accessed through opening <NUM> or other openings.

In one embodiment of the present invention means are provided for regulating the temperature of the fluid that is contained within container <NUM> when container <NUM> is disposed within support housing <NUM>. By way of example and not by limitation, sidewall <NUM> can be jacketed so as to bound one or more fluid channels that encircle sidewall <NUM> and that communicate with an inlet port <NUM> and an outlet port <NUM>. A fluid, such as water or propylene glycol, can be pumped into the fluid channel through inlet port <NUM>. The fluid then flows in a pattern around sidewall <NUM> and then exits out through outlet port <NUM>.

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

As will be discussed below in greater detail, a yoke <NUM> is centrally mounted on the interior surface of floor <NUM> of support housing <NUM>. Yoke <NUM> has a U-shaped slot <NUM> that is bounded by an inwardly projecting U-shaped catch lip <NUM>. Yoke <NUM> is configured so that when container assembly <NUM> is received within chamber <NUM> of support housing <NUM>, second rotational assembly 42B can be manually slid into slot <NUM> (<FIG>) so that mounting flange <NUM> of second rotational assembly 42B is captured within slot <NUM> below catch lip <NUM>, thereby securing second rotational assembly 42B to yoke <NUM> and preventing rotational assembly 42B from being raised vertically relative to yoke <NUM>. It is appreciated that the function of yoke <NUM> is to releasably engage second rotational assembly 42B and as such, yoke <NUM> can be in the form of a variety of different slots, clamps, ties, fasteners or the like. It is likewise appreciated that second rotational assembly 42B can be attached to yoke <NUM> by reaching in through access <NUM> on sidewall <NUM> of support housing <NUM>.

As depicted in <FIG>, docking station <NUM> comprises a stand <NUM>, an adjustable arm assembly <NUM> coupled to stand <NUM> and a drive motor assembly <NUM> mounted on arm assembly <NUM>. Drive motor assembly <NUM> is used in conjunction with drive shaft <NUM> (<FIG>) and can be used for mixing and/or suspending a culture, solution, suspension, or other liquid within container <NUM> (<FIG>). Turning to <FIG>, drive motor assembly <NUM> comprises a housing <NUM> having a front face <NUM> that extends from a top surface <NUM> to an opposing bottom surface <NUM>. An opening <NUM> extends through housing <NUM> from top surface <NUM> to bottom surface <NUM>. A tubular motor mount <NUM> is rotatably secured within opening <NUM> of housing <NUM>. Upstanding from motor mount <NUM> is a locking pin <NUM>. A drive motor <NUM> is mounted to housing <NUM> and engages with motor mount <NUM> so as to facilitate select rotation of motor mount <NUM> relative to housing <NUM>. Drive shaft <NUM> is configured to pass through motor mount <NUM> so that engaging portion <NUM> of drive shaft <NUM> is retained within motor mount <NUM> and locking pin <NUM> of motor mount <NUM> is received within notch <NUM> of drive shaft <NUM>. As a result, rotation of motor mount <NUM> by drive motor <NUM> facilitates rotation of drive shaft <NUM>. Further discussion of drive motor assembly <NUM> and how it engages with drive shaft <NUM> and alternative designs of drive motor assembly <NUM> are discussed in <CIT>.

Arm assembly <NUM> is used to adjust the position of drive motor assembly <NUM> and thereby also adjust the position of drive shaft <NUM>. As depicted in <FIG>, arm assembly <NUM> comprises a first arm <NUM> mounted to stand <NUM> that vertically raises and lowers, a second arm <NUM> mounted to the first arm <NUM> that slides horizontally back and forth, and a third arm <NUM> mounted to second arm <NUM> that rotates about a horizontal axis <NUM>. Drive motor assembly <NUM> is mounted to third arm <NUM>. Accordingly, by movements of arms <NUM>, <NUM>, and/or <NUM>, drive motor assembly <NUM> can be positioned in any desired location or orientation relative to support housing <NUM> and container assembly <NUM>. For example, drive motor assembly <NUM> can be positioned so that drive shaft <NUM> is centered and vertically oriented when connected with container assembly <NUM>. In other embodiments, drive shaft <NUM> can be oriented at an angle, such as in a range between <NUM>° to <NUM>° from vertical when connected with container assembly <NUM>. Further discussion and alternative embodiments with regard to docking station <NUM>, arm assembly <NUM>, and container station <NUM> is provided in <CIT>.

During use, container station <NUM> and docking station <NUM> are removably coupled together as shown in <FIG>. One example of how docking station <NUM> and container assembly <NUM> can be coupled together is disclosed in <CIT>.

Other methods can also be used. Either before or after coupling together container station <NUM> and docking station <NUM>, container assembly <NUM> is positioned within chamber <NUM> of support housing <NUM> and second rotational assembly 42B is secured to yoke <NUM> as discussed above.

In this position, arm assembly <NUM> is used to properly position drive motor assembly <NUM> so that first rotational assembly 42A can be coupled with drive motor assembly <NUM>. Specifically, as depicted in <FIG>, housing <NUM> of drive motor assembly <NUM> has a U-shaped receiving slot <NUM> that is recessed on a front face <NUM> and bottom surface <NUM> so as to communicate with opening <NUM> extending through housing <NUM>. Receiving slot <NUM> is bounded by an inside face <NUM> on which a U-shaped catch slot <NUM> is recessed. As shown in <FIG>, a door <NUM> is hingedly mounted to housing <NUM> and selectively closes the opening to receiving slot <NUM> from front face <NUM>. As depicted in <FIG>, to facilitate attachment of rotational assembly 42A to housing <NUM>, with door <NUM> rotated to an open position, rotational assembly 42A is horizontally slid into receiving slot <NUM> from front face <NUM> of housing <NUM> so that mounting flange <NUM> that is radially outwardly extending from the upper end of rotational assembly 42A is received and secured within catch slot <NUM>. First rotational assembly 42A is advanced into receiving slot <NUM> so that opening <NUM> of rotational assembly 42A aligns with the passage extending through motor mount <NUM>. Door <NUM> (<FIG>) is then moved to the closed position and secured in place by a latch or other locking mechanism so that first rotational assembly 42A is locked to drive motor assembly <NUM>.

Rotational assemblies 42A and 42B are now secured to drive motor assembly <NUM> and yoke <NUM>, respectively, as shown in <FIG>. Arm assembly <NUM> (<FIG>) can now be used to remove any slack from or to tension flexible drive line <NUM> by raising drive motor assembly <NUM> to which rotational assembly 42A is coupled. Likewise, arm assembly <NUM> can be used to adjust the orientation of drive line <NUM>. For example, by adjusting the position of drive motor assembly <NUM>, drive line <NUM> can be adjusted so as to be centered within support housing <NUM> and vertically oriented or drive line <NUM> can be oriented at an angle, such as in a range between <NUM>° to <NUM>° from vertical. Other positions and orientations can also be used.

Once first rotational assembly 42A is secured to drive motor assembly <NUM>, drive shaft <NUM> can be advanced down through motor mount <NUM> of drive motor assembly <NUM> and into opening <NUM> of rotational assembly 42A so that drive shaft <NUM> engages with hub <NUM>. Fluid and other components can be delivered into container <NUM>. Drive motor <NUM> can be activated so as to rotate drive shaft <NUM> which in turn begins to rotate hub <NUM>, drive line <NUM> and impeller <NUM>. Where container <NUM> is functioning as a bioreactor or fermentor, cells or microorganisms along with nutrients and other standard components can be added to container <NUM>. Rotation of impeller <NUM> facilitates mixing and/or suspension of the fluid and components contained within container <NUM>. Where drive line <NUM> is made of a material that flexes under torsion, such as a flexible cable, cord, solid core line or the like, drive line <NUM> will typically be able to axially twist along the length thereof. That is, first end <NUM> will begin to rotate concurrently with the rotation of hub <NUM> of first rotational assembly 42A but second end <NUM> and hub <NUM> of second rotational assembly 42A will not begin to rotate until drive line <NUM> has sufficiently twisted along its length so that second end <NUM> produces a torsion force on hub <NUM> of second rotational assembly 42A sufficient to overcome the frictional resistance on hub <NUM>. Impeller <NUM> also produces resistance against the fluid within container <NUM> which results in twisting of drive line <NUM> during rotation. In other embodiments, such as where drive line <NUM> is a type of linkage, axle twisting of drive line <NUM> may be negligible.

In one embodiment, at least a portion of drive line <NUM> is sufficiently flexible so that the flexible portion of drive line <NUM> can be twisted under torsion about longitudinal axis <NUM> of drive line <NUM> over an angle of at least <NUM>°, <NUM>°, <NUM>°, <NUM>°, <NUM>°, <NUM>°, <NUM>° or more without elastic deformation of drive line <NUM>. In other embodiments, at least a portion of drive line <NUM> is sufficiently flexible so that the flexible portion of drive line <NUM> can be bent or folded relative to a linear longitudinal axis <NUM> (<FIG>) of drive line <NUM> over an angle α (<FIG>) of at least <NUM>°, <NUM>°, <NUM>°, <NUM>°, <NUM>°, <NUM>° or more without elastic deformation of drive line <NUM>. Expressed in other terms, drive line <NUM> or the flexible portion of drive line <NUM> can have a bend radius wrapped <NUM>° without elastic deformation in a range between about <NUM> to about <NUM> with about <NUM> to about <NUM>, about <NUM> to about <NUM>, or about <NUM> to about <NUM> being more common. Other flexibilities can also be used. It is appreciated that the entire length of drive line <NUM> need not be flexible. For example, a percentage of the entire length of drive shaft <NUM>, such as at least or not to exceed <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>% or more of drive shaft <NUM>, 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 hub <NUM> of second rotational assembly 42B though a hole formed in floor <NUM> of support housing <NUM>. In this embodiment, both ends <NUM> and <NUM> of drive line <NUM> could be concurrently rotated although there may still be some twisting of drive line <NUM> along a central length or adjacent to impeller <NUM>.

In mixing system <NUM>, docking station <NUM> is used which includes arm assembly <NUM>. In this design, docking station <NUM> can be coupled with any number of different container stations <NUM> having a container assembly <NUM> therein. In an alternative embodiment, however, docking station <NUM> can be eliminated and arm assembly <NUM> can be mounted directly onto support housing <NUM>. Alternative examples of arm assembles and how they can be mounted onto support housing <NUM> is disclosed in <CIT>.

In the above discussed embodiment depicted in <FIG>, yoke <NUM> is mounted on the interior surface of floor <NUM> of support housing <NUM> for engaging with second rotational assembly 42B (<FIG>). In an alternative embodiment as depicted in <FIG>. A yoke 140A can be mounted on the exterior surface of floor <NUM> of support housing <NUM>. A hole <NUM> centrally extends through floor <NUM> so as to communicate with chamber <NUM>. In this embodiment, yoke 140A has an opening <NUM> that is bounded between a body <NUM> and a locking arm <NUM> hingedly mounted thereto. During use, with locking arm <NUM> in an open position, the free end of second rotational assembly 42B (<FIG>) is passed down through hole <NUM> so as to be received within opening <NUM>. Locking arm <NUM> is then moved to the closed position, as shown in <FIG>, and secured in place by a latch <NUM>. In this configuration, the end of second rotational assembly 42B is secured to yoke 140A. It is appreciated that yokes <NUM> and 140A 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 housing <NUM> but can be located on a separate structure at a position below support housing <NUM>. Second rotational assembly 42B can be configured to pass down through hole <NUM> and engage with the yoke.

In one embodiment of the present invention, means are provided for holding the lower end <NUM> of container <NUM> stationary while flexible drive line <NUM> is rotated within compartment <NUM> of container <NUM>. Examples of this means includes yoke <NUM> mounted on the interior surface of floor <NUM>, yoke 140A mounted on the exterior surface of floor <NUM> and yoke 140A mounted on a separate structure located below floor <NUM>.

Depicted in <FIG> is an alternative embodiment of an impeller assembly 40A. Like elements between impeller assemblies <NUM> and 40A are identified by like reference characters. Impeller assembly 40A comprises a first rotational assembly 160A and a second rotational assembly 160B with drive line <NUM> extending therebetween. First rotational assembly 160A has substantially the same configuration as first rotational assembly 42A and includes outer casing <NUM> having sealing flange <NUM> for securing to container <NUM> and mounting flange <NUM>. First rotational assembly 160A has a hub <NUM> that rotates relative to casing <NUM>. However, in contrast to having an opening <NUM> (<FIG>) located at the end thereof, hub <NUM> includes an outwardly projecting stem <NUM>. Stem <NUM> has a non-circular transverse cross section, such as polygonal, so that a drive shaft 17A having a complementary socket <NUM>, that replaces driver portion <NUM> (<FIG>), can securely engage with and rotate hub <NUM>.

As depicted in <FIG>, second rotational assembly 160B comprises an outer casing <NUM> that includes a cylindrical base <NUM> having one or more mounting flanges <NUM> radially outwardly projecting from a lower end thereof and an enlarged annular sealing flange <NUM> radially outwardly projecting from the upper end thereof. Base <NUM> and mounting flanges <NUM> are configured to be engaged by yoke 140A (<FIG>). Sealing flange <NUM> is configured to secure to container <NUM>, such as by welding, in the same manner as sealing flange <NUM> (<FIG>). Outer casing <NUM> has a top surface <NUM> on which a cylindrical blind pocket <NUM> is formed.

Second rotational assembly 160B also includes a hub <NUM> having a base <NUM> to which second end <NUM> of drive line <NUM> is secured. Hub <NUM> also includes an annular flange <NUM> encircling and radially outwardly projecting from a lower end of base <NUM>. Flange <NUM> is configured so that it can be rotatably received within blind pocket <NUM>. Annular bearings 184A and 184B, such as roller thrust bearings, are also received within pocket <NUM> on opposing sides of flange <NUM> so that hub <NUM> can freely rotate relative to outer casing <NUM>. A cover plate <NUM> encircles hub <NUM> and/or drive line <NUM> and is positioned over bearing 184A. Cover plate <NUM> is secured in place by engaging with locking fingers <NUM> that project from top surface <NUM> at spaced apart locations around pocket <NUM>. In this configuration, cover plate <NUM> retains hub <NUM> within outer casing <NUM>. It is appreciated that because pocket <NUM> is blind, it is not necessary to position a seal between hub <NUM> and outer casing <NUM>, although a seal can be used if desired. It is also appreciated that the rotational assemblies can have a variety of other configurations.

Returning to <FIG>, disposed at an upper end of drive line <NUM> is a foam breaker <NUM>. Foam breaker <NUM> includes a hub <NUM> secured to drive line <NUM> and a bar <NUM> that outwardly projects from opposing sides of hub <NUM>. Foam breaker <NUM> rotates concurrently with drive line <NUM> to break up foam that is formed at the upper end of container <NUM>. It is appreciated that foam breaker <NUM> can come in a variety of different configurations.

Also disposed along drive line <NUM> are a plurality of spaced apart impellers 190A-D. As depicted in <FIG>, each impeller <NUM> comprises a tubular hub <NUM> which can be advanced over drive line <NUM> and secured in place such as by crimping, clamp, fastener, welding, set screw or the like. As depicted in <FIG>, a flange <NUM> encircles and radially outwardly projects from hub <NUM>. Flange <NUM> has a first side face <NUM> and an opposing second side face <NUM> with a plurality of openings 200A extending therethrough adjacent to a perimeter edge of flange <NUM>. Outwardly projecting from first side face <NUM> are a plurality of spaced apart stops <NUM> with each stop <NUM> being disposed adjacent to a corresponding opening 200A. Outwardly projecting from the end of each stop <NUM> is a key <NUM>.

Impeller <NUM> also includes a plurality of blades <NUM>. Each blade <NUM> comprises of an elongated arm <NUM> having an enlarged blade head <NUM> located at one end and an axle <NUM> disposed at the opposing end. Axle <NUM> has a first end <NUM> and an opposing second end <NUM> that project from opposing sides of arm <NUM>. First end <NUM> of axle <NUM> is configured to be received within a corresponding opening 200A so that axle <NUM> can rotate within opening 200A. An annular retainer <NUM> has a central passage <NUM> through which hub <NUM> can be advanced. A plurality of spaced apart openings 200B that are sized to receive second end <NUM> of axle <NUM> extend between opposing sides of retainer <NUM>. A plurality of spaced apart keyways <NUM> are recessed on an outer edge of retainer <NUM>. Retainer <NUM> is configured to be advanced over hub <NUM> so that each key <NUM> is received within a corresponding keyway <NUM>, and second end <NUM> of each axle <NUM> is received within a corresponding opening 200B. Retainer <NUM> can be secured to keys <NUM> such as by press fit connection, adhesive, welding, fasteners, or the like. Hub <NUM>, flange <NUM> and retainer <NUM> combine to form an impeller body to which blades <NUM> are attached.

In the assembled configuration, axle <NUM> is free to rotate within openings 200A and 200B so that blades <NUM> are movable between a collapsed position, such as where a blade 206A is folded toward flange <NUM> in <FIG>, and an extended position, such as where blade 206A is folded away from flange <NUM> in <FIG>. In the extended position, arm <NUM> hits against stop <NUM> to prevent further rotation away from the collapsed position. Blades <NUM> typically radially outwardly project from hub <NUM> when in the extended position but can project at angles relative to hub <NUM>. In most embodiments, however, an outer tip <NUM> of blades <NUM> is spaced farther from hub <NUM> when 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 blades <NUM> can be rotatable connected to hub <NUM>. For example, axles <NUM> could be rigidly fixed to flange <NUM> and/or retainer <NUM>. Arms <NUM> could then pivot about axles <NUM>. In another embodiment, axles <NUM> could be hingedly secured to flange <NUM> so as to eliminate the need for retainer <NUM>. In addition, both flange <NUM> and retainer <NUM> could be integrally formed as a unitary member with hub <NUM> and blades <NUM> could 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 container <NUM> into a more compact structure so that it is easier to handle and occupies less space. By making drive line <NUM> out of a flexible material, this enables drive line <NUM> to be concurrently folded up or rolled up with container <NUM>. 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 blades <NUM> movable 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 container <NUM>. Collapsing of the blades enables container <NUM> to be folded smaller, helps prevents blades <NUM> from puncturing container <NUM> and can result in less stress being placed on blade <NUM>. However, as will be discuss below in greater detail, as each impeller <NUM> is rotated within the fluid contained within container <NUM>, each of blades <NUM> catch the fluid and automatically move to the expanded position which is a more optimal position for mixing the fluid.

Another benefit of the impeller <NUM> is that it is a modular system that can be used within a variety of different blade configurations. For example, in the embodiment depicted in <FIG>, each blade <NUM> has a blade head <NUM> having a generally flat rectangular configuration. This configuration of blade is commonly referred to as a Rushton blade. Depicted in <FIG> is an impeller <NUM> with like elements between impeller <NUM> and impeller <NUM> being identified by like reference characters. The only difference between impellers <NUM> and <NUM> is that in impeller <NUM>, blades <NUM> have been replaced with blades <NUM>. Blades <NUM> include arm <NUM> and axle <NUM> but in contrast to having a flat rectangular blade head <NUM>, they have a blade head <NUM> having a curved surface. More specifically, blade head <NUM> has a length with an arched or substantially semi-circular transverse cross section along the length. Again, each of blades <NUM> can be moved from a collapsed position to an extended position. Depicted in <FIG> is still another embodiment of an impeller <NUM> having foldable blades <NUM> with a blade head <NUM> that slopes relative to the longitudinal axis of hub <NUM>.

In each of impellers <NUM>, <NUM>, and <NUM>, 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 in <FIG> is an alternative embodiment of an impeller <NUM> that is hingedly mounted to drive line <NUM>. Like elements between impellers <NUM> and <NUM> are identified by like reference characters. Impeller <NUM> is substantially identical to impeller <NUM> except that in contrast to hub <NUM> (<FIG>) which is tubular and received over drive line <NUM>, impeller <NUM> includes an elongated hub <NUM> having a first end <NUM> with a U-shaped connecter 244A formed thereat and an opposing second end <NUM> with a U-shape connector 244B formed thereat. Each of connectors 244A and B bound a slot <NUM> and have an opening <NUM> transversely extending therethrough. Flexible line <NUM> is comprised of line portion 252A having connector 254A mounted on the end thereof and line portion 252B having a connector 254B mounted on the end thereof. Each of connecters 254A and B also have an opening <NUM> transversely extending therethrough. During assembly, connectors 254A and B are received within slots <NUM> of U-shaped connectors 244A and B, respectively, so that openings <NUM> and <NUM> are aligned. Hinge pins <NUM> are then received within aligned openings <NUM> and <NUM> and secured in place so that connectors 254A and B can freely pivot relative to impeller <NUM>. Hinge pins <NUM> can be attached to connectors 244A 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 portions 252A and B to opposing ends of hub <NUM>.

<FIG> again depicts impeller <NUM>. However in contrast to being hingedly coupled to flexible drive line <NUM>, impeller <NUM> in <FIG> is hingedly coupled to line portions 262A and B of a rigid drive line <NUM>. That is, line portions 262A and B can have openings <NUM> extending 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 portions 262A and B can have a bend radius wrapped <NUM>° that must be greater than <NUM> meters, <NUM> meters or <NUM> meters to prevent elastic deformation.

Depicted in <FIG> is a perspective view of an alternative embodiment of a container assembly 16B that includes an alternative embodiment of a flexible drive line. Container assembly 16B can be operated within support housing <NUM> (<FIG>) in substantially the same manner as the other container assemblies discussed herein. Specifically, container assembly 16B comprises container <NUM> having an impeller assembly 40B coupled thereto. Impeller assembly 40B comprises a first rotational assembly <NUM> mounted to upper end wall <NUM> of container <NUM> and a second rotational assembly <NUM> mounted to lower end wall <NUM> of container <NUM>. As depicted in <FIG> and <FIG>, upper rotational assembly <NUM> comprises outer casing <NUM> and hub <NUM> as previously discussed. Various bearing assemblies <NUM> can be positioned between outer casing <NUM> and hub <NUM> to facilitate ease of rotation of hub <NUM>. One or more seals <NUM> can also be positioned between outer casing <NUM> and hub <NUM> to form a liquid-tight seal therebetween. An adapter <NUM> is coupled with hub <NUM> and has a stem <NUM> that projects away from hub <NUM>. In an alternative embodiment, stem <NUM> can be integrally formed as a unitary structure with hub <NUM>.

Second rotational assembly <NUM> includes outer casing <NUM>, bearings 184A and B and cover plate <NUM> as previously discussed. Second rotational assembly <NUM> also includes a hub <NUM> having an upwardly extending stem <NUM> that passes through cover plate <NUM> and an outwardly projecting flange <NUM> that is positioned between bearings 184A and B. Located between rotational assemblies <NUM> and <NUM> is an impeller <NUM>. Impeller <NUM> comprises a tubular hub <NUM> having a first end <NUM> and an opposing second end <NUM>. Flange <NUM> encircles and radially outwardly projects from hub <NUM>. Blades <NUM> hingedly mounted between flange <NUM> and retainer <NUM> as previously discussed. In an alternative embodiment, fixed blades can be secured to hub <NUM> or flange <NUM>.

Drive line assembly 40B also includes a flexible drive line 44B that includes a drive line portion 294A and a drive line portion 294B. Each of drive line portions <NUM> comprise 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 portions <NUM> can have the same flexibility as drive line <NUM> as previously discussed. Drive line portion 294A has a first end <NUM> that is received over and coupled to stem <NUM> and an opposing second end <NUM> that is received within and secured to first end <NUM> of hub <NUM>. Similarly drive line portion 294B has a first end <NUM> received over and secured to stem <NUM> and an opposing second end <NUM> received within and secured to second end <NUM> of hub <NUM>. In this configuration, rotation of hub <NUM> of first rotational assembly <NUM> facilitates rotation of drive line portions 294A and B, impeller <NUM>, and hub <NUM> of second rotational assembly <NUM>.

Although the above discussed embodiments primarily disclose the use of impellers having pivotable blades with flexible drive lines, it is appreciated that the impellers of the present invention can also be used with rigid drive shafts. For example, depicted in <FIG> is a container assembly 16C that include container <NUM>. A dynamic seal <NUM> is mounted on upper end wall <NUM>. A rigid drive shaft <NUM> passes through dynamic seal <NUM> and has a first end <NUM> disposed outside of container <NUM> and an opposing second end <NUM> disposed within container <NUM>. Dynamic seal <NUM> enables drive shaft <NUM> to freely rotate relative to container <NUM> while forming an aseptic seal between container <NUM> and drive shaft <NUM>. A driver portion <NUM>, which can have a polygonal or other non circular transverse cross section or some other engaging surface, can be formed at first end <NUM> so that a drive motor can engage with and rotate drive shaft <NUM>.

Mounted on second end <NUM> of drive shaft <NUM> is impeller <NUM> as previously discussed herein. Rotation of drive shaft <NUM> causes blades <NUM> to move to the expanded position and mix the fluid within container <NUM>. Impeller <NUM> can 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 blades <NUM>, container <NUM> can be more fully collapsed around impeller <NUM> while minimizing risk of damage to container <NUM> and to blades <NUM>.

Depicted in <FIG> is another alternative embodiment of mixing system that incorporates an impeller with pivotable or foldable blades. The mixing system includes an impeller assembly 40C that comprises an elongated tubular connector <NUM> having a rotational assembly <NUM> mounted at one end and an impeller <NUM> or other mixing element mounted on the opposing end. More specifically, tubular connector <NUM> has a first end <NUM> and an opposing second end <NUM> with a passage <NUM> that extends therebetween. In one embodiment, tubular connector <NUM> comprises a flexible tube, such as a polymeric tube, having the same flexibility as discussed above with regard to drive line <NUM>. As such, tubular connector <NUM> can comprise a flexible drive line as claimed herein. In other embodiments, tubular connector <NUM> can comprise a rigid tube or other tubular structure.

Rotational assembly <NUM> is mounted to first end <NUM> of tubular connector <NUM>. Rotational assembly <NUM> comprises outer casing <NUM> having an outwardly projecting annular sealing flange <NUM> and an outwardly projecting mounting flange <NUM> as previously discussed. A tubular hub <NUM> is rotatably disposed within outer casing <NUM>. One or more bearing assemblies, as previously discussed, can be disposed between outer casing <NUM> and hub <NUM> to permit free and easy rotation of hub <NUM> relative to casing <NUM>. Likewise, one or more seals, as previously discussed, can be formed between outer casing <NUM> and hub <NUM> so that during use an aseptic seal can be maintained between outer casing <NUM> and hub <NUM>.

Hub <NUM> has an interior surface <NUM> that bounds an opening <NUM> extending therethrough. Interior surface <NUM> includes an engaging portion having a polygonal or other non-circular transverse cross section so that driver portion <NUM> of drive shaft <NUM>, as also shown in <FIG>, passing through opening <NUM> can engage the engaging portion and facilitate rotation of hub <NUM> by rotation of drive shaft <NUM>. Hub <NUM> can also comprise a tubular stem <NUM> projecting away from outer casing <NUM>. Hub <NUM> can couple with first end <NUM> of tubular connector <NUM> by stem <NUM> being received within first end <NUM>. A pull tie, clamp, crimp or other fastener can then be used to further secure stem <NUM> to tubular connect <NUM> so that a liquid tight seal is formed therebetween. Other conventional connecting techniques can also be used.

Impeller <NUM> comprises a central hub <NUM> having blades <NUM> pivotably coupled thereto through the use of flange <NUM> and retainer <NUM> as previously discussed with regard to <FIG>. Alternative embodiments as discussed herein with regard to other impellers having pivotable blades can also be incorporated into impeller <NUM>. Hub <NUM> has a first end <NUM> with a blind socket <NUM> formed thereat. Socket <NUM> typically has a noncircular transverse cross section, such as polygonal, so that it can engage a driver portion <NUM> of drive shaft <NUM>. Accordingly, when driver portion <NUM> is received within socket <NUM>, driver portion <NUM> engages with impeller <NUM> such that rotation of drive shaft <NUM> facilities rotation of impeller <NUM>.

Impeller <NUM> can be attached to connector <NUM> by inserting first end <NUM> of hub <NUM> within connector <NUM> at second end <NUM>. A pull tic, clamp, crimp, or other type of fastener can then be cinched around second end <NUM> of connector <NUM> so as to form a liquid tight sealed engagement between impeller <NUM> and connector <NUM>.

Rotational assembly <NUM> is secured to container <NUM> in substantially the same manner that rotational assembly <NUM> was secured to container <NUM>, as previously discussed with regard to <FIG>, so that tubular connector <NUM> and impeller <NUM> extend into or are disposed within compartment <NUM> of container <NUM>.

In general drive shaft <NUM> comprises a head section <NUM> and a shaft section <NUM> that can be coupled together by threaded connection or other techniques. Head section <NUM> has substantially the same configuration as drive shaft <NUM> discussed with regard to <FIG> and thus like features head section <NUM> and drive shaft <NUM> will be identified by like reference characters. Alternatively, drive shaft <NUM> can be formed as a single piece member or from a plurality of attachable sections. Drive shaft <NUM> has a first end <NUM> and an opposing second end <NUM>. Formed at first end <NUM> is a frustoconical engaging portion <NUM> as previously discussed with regard to <FIG>. Formed at second end <NUM> of drive shaft <NUM> is driver portion <NUM>. Driver portion <NUM> has a non-circular transverse cross section so that it can facilitate locking engagement within hub <NUM> of impeller <NUM>. In the embodiment depicted, driver portion <NUM> has a polygonal transverse cross section. However, other non-circular shapes can also be used. Driver portion <NUM> is also formed along drive shaft <NUM> toward first end <NUM>. Driver portion <NUM> also has a non-circular transverse cross section and is positioned so that it can facilitate locking engagement within the engaging portion of rotational assembly <NUM>.

During use, container <NUM> having impeller assembly 40C coupled thereto is received within support housing <NUM> (<FIG>) and rotational assembly is secured to drive motor assembly <NUM> as previously discussed with regard to <FIG>. Drive shaft <NUM> is advanced down through motor mount <NUM>, hub <NUM> of rotational assembly <NUM>, tubular connecter <NUM> and into hub <NUM> of impeller <NUM>. As a result of the interlocking engagement of driver portions <NUM> and <NUM> with hubs <NUM> and <NUM>, respectively, rotation of drive shaft <NUM> by drive motor assembly <NUM> facilitates rotation of hub <NUM>, tubular connecter <NUM> and impeller <NUM> relative to outer casing <NUM> of rotational assembly <NUM> and container <NUM>. The rotation of impeller <NUM> causes blades <NUM> to move to the expanded position and mix the fluid within container <NUM>.

It is appreciated that impeller assembly 40C, drive shaft <NUM> and 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 assembly 40C, drive shaft <NUM>, and the components thereof are disclosed in <CIT> and <CIT>.

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 in <FIG> is an alternative embodiment of a fluid mixing system 10A incorporating features of the present invention. Fluid mixing system 10A comprises a container assembly 16D at least partially disposed within the compartment of a support housing 100A. Like elements between container assembly <NUM> and 16A and between support housing <NUM> and 100A are identified by like reference characters. Furthermore, disclosure and alternative embodiments as previously discussed with regard to container <NUM> and support housing <NUM> are also applicable to corresponding elements of container assembly 16A and support housing 100A.

As depicted in <FIG>, container assembly 16A comprises container <NUM> having flexible drive line <NUM> disposed therein. First end <NUM> of flexible drive line <NUM> is secured to upper end wall <NUM> of container <NUM> by rotational assembly 42A. Mounted on flexible drive line <NUM> as spaced apart locations are mixing elements 400A-C. Each of mixing element 400A-C can comprise a fixed blade impeller, such as previously discussed impeller <NUM>, a foldable impeller, such as previously discussed impellers <NUM>, <NUM>, <NUM>, <NUM>, or other types of mixing elements. In alternative embodiments, container assembly 16A can comprise one one, two, or four or more mixing elements <NUM>. In contrast to container assembly <NUM> where second end <NUM> of drive line <NUM> is secured to lower end wall <NUM>, container assembly 16A has second end <NUM> of drive line <NUM> suspended above lower end wall <NUM>.

To stabilize drive line <NUM> within compartment <NUM> of container <NUM>, container assembly 16A comprises lateral support assemblies 402A-C coupled with flexible drive line <NUM> at space apart locations along the length thereof. Each lateral support assembly 402A-C comprises a retention assembly <NUM> having a first end <NUM> secured to side <NUM> of container <NUM> and an opposing second end <NUM> secured to flexible drive line <NUM>. Lateral support assembly <NUM> also includes a support rod <NUM> that is selectively received and secured within corresponding retention assembly <NUM>. Each retention assembly <NUM> comprises a port fitting <NUM> at first end <NUM> that is coupled with side <NUM> of container <NUM>, a receiver <NUM> at second end <NUM> that is mounted to flexible drive line <NUM>, and a flexible tube <NUM> that extends between port fitting <NUM> and receiver <NUM>.

As depicted in <FIG>, receiver <NUM> comprises an inner housing <NUM> that is securely fixed to flexible drive line <NUM> such as by crimping, adhesive, clamps, fasteners, or the like. Receiver <NUM> also includes an outer housing <NUM> that encircles inner housing <NUM>. A bearing <NUM>, such as a ball thrust bearing, roller thrust bearing, or other type of bearing, is disposed between inner housing <NUM> and outer housing <NUM>. Bearing <NUM> enables inner housing <NUM> and drive line <NUM> to rotate concurrently relative to outer housing <NUM>. Outer housing <NUM> includes a body <NUM> having a tubular stem <NUM> outwardly projecting therefrom. Stem <NUM> can be integrally formed with or secured to body <NUM>. An annular barb <NUM> can encircle and outwardly project on the end of stem <NUM> for engaging with flexible tube <NUM>. Stem <NUM> has an interior surface <NUM> that bounds an opening <NUM> that can extend into body <NUM>. Formed on interior surface <NUM> of stem <NUM> and/or body <NUM> is an engaging thread <NUM>.

As also depicted in <FIG>, port fitting <NUM> comprises a tubular stem <NUM> having a first end <NUM> and an opposing second end <NUM>. An annular barb <NUM> can encircle and outwardly extending from second end <NUM> for engaging with flexible tube <NUM>. Radially outwardly projecting from first end <NUM> is a retention flange <NUM>. As will be discussed below in greater detail, retention flange <NUM> is used to secure port fitting <NUM> to rigid support housing <NUM>. Retention flange <NUM> need not encircle stem <NUM> and can have a variety of different configurations. Encircling and radially outwardly projecting from stem <NUM> at a location between opposing ends <NUM> and <NUM> is a mounting flange <NUM>. Mounting flange <NUM> is welded or otherwise secured to side <NUM> of container <NUM> so as to form a liquid tight seal therewith. As a result, first end <NUM> of port fitting <NUM> disposed outside of container <NUM> while second end <NUM> is disposed within container <NUM>. Stem <NUM> has an interior surface <NUM> that bounds a passageway <NUM> extending therethrough.

Flexible tube <NUM> can comprise any type of flexible tube, tubing, hose, pipe or the like and is typically comprised of an elastomeric polymer. By making tube <NUM> flexible, tube <NUM> can be folded or rolled when collapsing container <NUM> for shipping, storage, disposal or the like. In an alternative embodiment it is appreciated that tube <NUM> need not be flexible but can be rigid or semi-rigid. Tube <NUM> has an interior surface <NUM> that bounds a passageway <NUM> that longitudinally extends through tube <NUM> from a first end <NUM> to an opposing second end <NUM>. First end <NUM> of tube <NUM> is advanced over stem <NUM> of port fitting <NUM> so as to form a liquid tight seal therewith while second end <NUM> of tube <NUM> is received over stem <NUM> of receiver <NUM> so as to form a liquid type seal therewith. A fastener <NUM> such as a pull tie, crimp, clamp, or similar structure can be secured around first end <NUM> and second end <NUM> so as to secure the engagement between tube <NUM> and stems <NUM> and <NUM>.

During use, as depicted in <FIG>, container assembly 16D is received within chamber <NUM> of support housing 100A. Support housing 100A is substantially identical is support housing <NUM> as previously discussed with regard to <FIG> and like elements are identified by like reference characters. Support housing 100A is distinguished from support housing <NUM> in that it does not include yoke <NUM> located on floor <NUM> (<FIG>). Rather, support housing 100A includes a plurality of locking fittings 460A-C mounted at spaced apart locations on sidewall <NUM>. As depicted in <FIG> and <FIG>, each locking fitting <NUM> comprises a base <NUM> having a first end <NUM> and an opposing second end <NUM>. A passageway <NUM> centrally passes through base <NUM> between opposing ends <NUM> and <NUM>. A flange <NUM> can encircle and radially outwardly project from base <NUM> at a location between opposing ends <NUM> and <NUM>. During the manufacture of support housing 100A, vertically spaced apart holes <NUM> (<FIG>) can be formed through sidewall <NUM> so as to extend to chamber <NUM>. Second end <NUM> of each locking fitting <NUM> is received within a corresponding hole <NUM> so that flange <NUM> hits against the exterior surface of sidewall <NUM>. Welding or other fastening techniques can then be used to secure each locking fitting <NUM> to support housing 100A within the corresponding hole <NUM>.

Formed on the end face of base <NUM> at second end <NUM> is a catch <NUM>. Catch <NUM> is disposed adjacent to interior surface <NUM> of support housing 100A and has a U-shaped body <NUM> with a U-shaped opening <NUM> passing therethrough. U-shaped opening <NUM> is aligned with passageway <NUM> passing through base <NUM>. Body <NUM> has an interior surface <NUM> that includes an undercut U-shaped channel <NUM> and a U-shaped catch lip <NUM> that radially inwardly projects adjacent to channel <NUM>. Catch <NUM> is configured so that retention flange <NUM> on port fitting <NUM> can be slidably received and captured within channel <NUM> so that passageway <NUM> of locking fitting <NUM> is aligned with passageway <NUM> of a corresponding port fitting <NUM>. It is appreciated that retention flange <NUM> and/or channel <NUM> can 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 fitting <NUM> to locking fitting <NUM>.

Locking fitting <NUM> also includes a locking slot <NUM> formed on first end <NUM> of base <NUM> and which is located outside of support housing 100A. Locking slot <NUM> includes a first leg <NUM> that passes through base <NUM> to passageway <NUM> and runs parallel to passageway <NUM>. Locking slot <NUM> also includes a second leg <NUM> that extends normal to first leg <NUM> at the end thereof so as to extend around a portion of the perimeter of base <NUM>. Second leg <NUM> also extends to passageway <NUM>.

Returning to <FIG>, each support rod <NUM> comprises a linear shaft <NUM> that extends between a first end <NUM> and an opposing second end <NUM>. A locking thread <NUM> is formed on second end <NUM>. A locking arm <NUM> radially outwardly projects from shaft <NUM> as first end <NUM>. Locking arm <NUM> is sized to be received within locking slot <NUM>. Support rod <NUM> is typically comprised of metal but other rigid or semi-rigid materials can also be used.

During use, as previously discussed and depicted in <FIG>, container assembly 16D is received within chamber <NUM> of support housing 100A. Once inserted, each port fitting <NUM> is secured to a corresponding locking fitting <NUM> as previously discussed and depicted in <FIG>. In this assembled configuration, second end <NUM> of each support rod <NUM> is advanced through passageway <NUM> of locking fitting <NUM> through passageway <NUM> of port fitting <NUM> and into passageway <NUM> of tube <NUM>. Each support rod <NUM> is continued to be advanced until locking thread <NUM> reach engaging thread <NUM> on retention assembly <NUM>. Concurrently, locking arm <NUM> is received within first leg <NUM> (<FIG>) of locking slot <NUM>. In this position, locking arm <NUM> can be rotated downward through second leg <NUM> of locking slot <NUM> so as to lock support rod <NUM> to locking fitting <NUM>. As locking arm <NUM> is rotated, shaft <NUM> with locking threads <NUM> thereon are rotated. As locking threads <NUM> are rotated they threadedly engage with engaging threads <NUM> on receiver <NUM>, thereby securing support rod <NUM> to receiver <NUM>. As a result, opposing ends of support rod <NUM> are secured to locking fitting <NUM> and receiver <NUM> which creates a lateral rigid support for flexible drive line <NUM>. It is appreciated that a variety of other connections can be used for securing one or both of opposing ends of support rod <NUM> such as a bayonet connection, luer-lock connection, clamp, separate fastener, or the like.

The lateral rigid support of flexible drive line <NUM> achieves a number of benefits. For example, where mixing element <NUM> is an impeller, the rotation of the impeller causes the impeller to tend to migrate laterally. Lateral movement of drive line <NUM> and mixing elements <NUM> can cause damage to container <NUM> and can produce irregular mixing within container <NUM>. Irregular mixing can be especially problematic where the mixing system is being used as a bioreactor or fermetor used for growing cells or microorganism. In those cases, irregular mixing can apply unwanted shear forces on the cells or microorganism or can result in irregular feeding or gas transfer to the cells or microorganism. Use of the lateral support assemblies prevents unwanted lateral movement of drive line <NUM> and mixing elements <NUM> within container <NUM> and helps maintain uniform mixing. Although in the depicted embodiment three separate lateral support assemblies <NUM> are shown, in alternative embodiments, container assembly 16D 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 assembly 16D.

Furthermore, as a result of the lateral support to drive line <NUM>, second end <NUM> of drive line <NUM> need not be connected to lower end wall <NUM> of container <NUM>. In some cases this is beneficial because it permits a more convenient folding of container <NUM>. That is, in some designs for container <NUM>, the most compact folding of container <NUM> requires that the center of opposing end walls <NUM> and <NUM> be pulled away from each other. Where drive line <NUM> is secured to the opposing end walls <NUM> and <NUM>, the end walls cannot be pulled away from each other and thus container <NUM> cannot be folded in the most compact manner.

In addition, where the opposing ends of drive line <NUM> are connected to the top and bottom of container <NUM>, as in <FIG>, drive line <NUM> is tensioned to help prevent lateral walking of the impeller. As previously discussed, to facilitate the tension of drive line <NUM>, the second end of container <NUM> is secured to the floor or relative to the floor of the support housing. In contrast, by using the lateral support assemblies, drive line <NUM> does not need to be tensioned and it is not necessary to secure the second end of container <NUM> to the floor of the support housing.

Depicted in <FIG> is a container assembly 16E disposed within support housing 100A. Container assembly 16E includes lateral support assemblies 402A-C. However, in contrast to being connected to flexible drive line <NUM>, container assembly 16E includes a rigid drive shaft <NUM> such as drive shaft <NUM> as depicted in <FIG>. Lateral support assemblies <NUM> facilitate the lateral support of drive shaft <NUM> along the length thereof. Again, any number of lateral support assemblies <NUM> can be used and any number of mixing elements <NUM> can be mounted thereon. Other alternative embodiments as previously discussed with regard to like elements of container assembly 16D are also applicable container assembly 16D.

In another alternative embodiment, a container assembly can be formed that includes impeller assembly 40C as depicted and previously discussed with regard to <FIG>. One or more lateral support assemblies <NUM> can extend between the side of container <NUM> and tubular connector <NUM>. The container assembly can be housed within support housing 100A.

Depicted in <FIG> is another alternative embodiment of a container assembly 16F disposed within support housing 100A. Container assembly 16F is used where greater stability of drive line <NUM> is required, such as for long containers <NUM>. Container assembly 16F comprises container <NUM> housing drive line <NUM> on which one or more mixing elements <NUM> are disposed. First end <NUM> of drive line <NUM> is secured to upper end wall <NUM> by first rotational assembly 42A and second end <NUM> of drive line <NUM> is secured to lower end wall <NUM> by second rotational assembly 42B in the same manner as previously discussed with regard to container assembly <NUM> depicted in <FIG> and <FIG>. In turn, second rotational assembly 42B can be secured to floor <NUM> of support housing 100A using one of the yokes previously discussed or can be otherwise secured in place. Container assembly 16F also includes one or more lateral support assemblies <NUM> extending between side <NUM> of container <NUM> and flexible drive line <NUM> as previously discussed with regard to container assembly 16D depicted in <FIG>. Thus, in this embodiment flexible drive line <NUM> is 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 assembly 16F.

Finally, depicted in <FIG> is another alternative embodiment of a container assembly <NUM> disposed within support housing 100A. Container assembly <NUM> is substantially the same as container assembly 16D and thus the prior disclosure, alternative embodiments and reference characters for container assembly 16D are also applicable to container assembly 16E. Container <NUM> has a central longitudinal axis <NUM> that extends between upper end wall <NUM> and lower end wall <NUM>. In container assembly 16D, rotational assembly 42A is mounted on upper end wall <NUM> in alignment with central longitudinal axis <NUM> and drive line <NUM> extends along central longitudinal axis <NUM>. In contrast, container assembly <NUM> has rotational assembly 42A disposed on upper end wall <NUM> at a location spaced apart from central longitudinal axis <NUM> and, more specifically, adjacent to sidewall <NUM> of support housing 100A. However, lateral support assemblies <NUM> hold the portion of drive line <NUM> on which mixing elements <NUM> are disposed, along central longitudinal axis <NUM>.

Container assembly <NUM> has the advantage that mixing elements <NUM> are still centrally disposed within container <NUM> so that the fluid within container <NUM> can have uniform mixing but the central area of upper end wall <NUM> is now openly exposed. As such, ports, fitting, probes, sample tubes and the like can now be centrally mounted on upper end wall <NUM>, which is often considered a valuable location. Furthermore, placing rotational assembly 42A closer to sidewall <NUM> of support housing 100A can make it easier to connect rotational assembly 42A to drive motor assembly <NUM> (<FIG>). Thus, because of the flexible nature of drive line <NUM> and the rigid lateral support produced by lateral support assemblies <NUM>, rotational assembly 42A can be located at any position on upper end wall <NUM> and even at the upper end of side <NUM> of container <NUM>.

Claim 1:
A fluid mixing system comprising:
a container (<NUM>) bounding a sterile compartment, the compartment being configured to hold a fluid;
an elongated drive line (<NUM>) or drive shaft (<NUM>) at least partially disposed within the sterile
compartment, the drive line (<NUM>) or drive shaft (<NUM>) being rotatable relative to the container (<NUM>); and
a first impeller (<NUM>) disposed within the sterile compartment, the first impeller (<NUM>) comprising an impeller body coupled to the drive line (<NUM>) or drive shaft (<NUM>) and a plurality of blades pivotably coupled to the impeller body, characterized in that the first impeller (<NUM>) is hingedly coupled to the drive line (<NUM>) or drive shaft (<NUM>).