Patent Description:
Bioreactors and fermenters are used to grow biological suspensions that include cells or microorganisms suspended in a liquid medium. Once a biological suspension has been sufficiently grown, it is typically separated into liquid and solid components. The separated components are then harvested for subsequent analysis or use. Centrifugation is a common technique for separating biological components, such as cells, organelles, and biopolymers, including proteins, nucleic acids, lipids, and carbohydrates dispersed in biological suspension.

Centrifugation typically involves dispensing quantities of a suspension from a bioreactor or fermenter into a processing container, such as a bottle or a bag. The container is then closed and spun in a centrifuge. The centrifugal force created by spinning a rotor in the centrifuge causes the solids in the suspension to settle out and form a generally solid pellet toward the bottom of the container. A supernatant comprising liquid that is less dense than the pellet collects in the container above the pellet. Once the supernatant and pellet have formed, the supernatant is decanted by pouring or pumping the supernatant out of the container. The pellet can then be separately removed from the container.

Conventional centrifugation processes have a number of shortcomings. For example, in order to increase throughput, it is typically desirable for the containers to hold as much suspension as possible. However, as the size of the container is increased, it becomes more difficult for an operator to place containers in and remove containers from the centrifuge. Increasing the number of containers which are loaded into the centrifuge can also increase throughput. However, having a large number of containers also increases the amount of time it takes the operator to load and unload each batch of containers from the centrifuge.

Another problem with centrifugation is how to separate the supernatant from the pellet without disturbing the concentration of previously suspended particles in the pellet. This problem can be exacerbated if the containers are large or otherwise difficult to remove from the centrifuge due to increased jostling of the container, which can cause portions of the pellet to become resuspended in the supernatant. Centrifugation systems of the background art are described in <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, and <CIT>.

Thus, there is a need for improved methods and systems for centrifugation of biological suspensions.

The present invention overcomes the foregoing and other shortcomings and drawbacks of centrifuge rotors heretofore known for use for centrifugation of biological suspensions.

In an embodiment of the present invention, a rotor for a centrifuge is provided according to claim <NUM>. The rotor includes a rotor body having a plurality of receptacles spaced circumferentially about an axis of rotation of the rotor body, and a plurality of adapters. Each of the receptacles of the rotor body may be defined by a circumferential sidewall of the rotor body, a centrally located torque transfer ring, and a respective pair of circumferentially spaced torque transfer members extending between the torque transfer ring and the circumferential sidewall of the rotor body. Each adapter may be removably supported within a respective one of the plurality of receptacles of the rotor body and each adapter may be configured to receive a respective processing container within the adapter.

In an embodiment of the present invention, each of the adapters and each of the receptacles of the rotor body is configured so that the adapter is insertable into and removable from a respective receptacle of the rotor body in an axial direction.

In another embodiment of the present invention, the rotor includes a rotor liner having a plurality of circumferentially spaced receptacles, and each receptacle of the rotor liner is configured to be located within a respective one of the plurality of receptacles of the rotor body.

In another aspect of the present invention, each of the adapters and each of the receptacles of the rotor liner may be configured so that the adapter is insertable into and removable from a respective receptacle of the rotor liner in an axial direction.

In another aspect of the present invention, the rotor liner may further include a plurality of circumferentially spaced pockets each located between an adjacent pair of the plurality of receptacles of the rotor liner.

In another aspect of the present invention, each of the plurality of torque transfer members may be located within a respective one of the plurality of pockets of the rotor liner.

In another aspect of the present invention, at least one of the plurality of torque transfer members may be located within at least one of the plurality of pockets of the rotor liner.

In another aspect of the present invention, each of the plurality of receptacles of the rotor liner may be wedge shaped.

In another aspect of the present invention, the rotor may further include a carbon fiber reinforcement provided about the circumferential sidewall of the rotor body.

In another aspect of the present invention, each of the plurality of torque transfer members may include a radially-aligned rib and an axially-aligned rib.

In another aspect of the present invention, each of the plurality of axially-aligned ribs may include a first arcuate taper having a wide end and a narrow end, and each axially-aligned rib may be joined to a radially inwardly-facing surface of the circumferential sidewall by the wide end of the first arcuate taper.

In another aspect of the present invention, each of the plurality of radially-aligned ribs may extend from a radially outwardly-facing surface of the torque transfer ring to a respective one of the plurality of axially-aligned ribs.

In another aspect of the present invention, the rotor body may include a base having an upper surface, and each of the plurality of radially-aligned ribs may extend upwardly from the upper surface of the base.

In another aspect of the present invention, each of the plurality of radially-aligned ribs may include a second arcuate taper having a wide end and a narrow end, and each radially-aligned rib may be joined to the upper surface of the base by the wide end of the second arcuate taper.

In another aspect of the present invention, each of the plurality of adapters may include an outer wall, an inner opening, a pair of opposite sidewalls, a top wall, and a bottom wall that define an open-faced cavity configured to receive the respective processing container within the adapter.

In another aspect of the present invention, a circumferential length of the outer wall may be greater than the circumferential length of the inner opening.

In another aspect of the present invention, each of the adapters may be wedged shaped.

In another aspect of the present invention, the rotor may further include at least one processing container received within a respective adapter.

In another aspect of the present invention, the processing container may include one of a biobag or a processing bottle.

In another aspect of the present invention, each of the plurality of adapters may be generally rectangular shaped and include two oppositely and circumferentially extending lobes.

In another aspect of the present invention, each adapter may further include at least one horizontally oriented cavity configured to receive a processing container within the cavity.

In another aspect of the present invention, each adapter may include a handle configured to provide a grip that facilitates placing the adapter into one of the plurality of receptacles of the rotor body.

In another aspect of the present invention, the handle may project upwardly from the adapter.

In another aspect of the present invention, the rotor may further include a lid having a bottom surface with a plurality of cavities each configured to accommodate one of the adapter handles.

In the present invention, the rotor for a centrifuge is provided that includes a rotor body defining a plurality of first receptacles spaced circumferentially about an axis of rotation of the rotor body.

In the present invention, the rotor includes a plurality of adapters each configured to receive a processing container and to engage a respective first receptacle so that each adapter is held in place within the rotor by the respective first receptacle.

In another aspect of the present invention, each of the adapters and the receptacles may be configured so that the adapter is inserted into and removed from a respective receptacle in an axial direction.

In the present invention, the rotor includes a rotor liner including a plurality of second receptacles placed circumferentially about the axis of rotation of the rotor body, and each second receptacle is configured to be received by a respective one of the first receptacles.

In another aspect of the present invention, each adapter may be configured to engage a respective second receptacle so that each adapter is held in place within the rotor by the respective second receptacle.

In another aspect of the present invention, the rotor body may include a base having an upper surface and a plurality of radially-aligned ribs extending upward from the upper surface of the base.

In another aspect of the present invention, the radially-aligned ribs may at least partially define the receptacles.

In another aspect of the present invention, the rotor may further include a rotor liner having a plurality of pockets each configured to engage a respective radially-aligned rib of the rotor body.

In another aspect of the present invention, the rotor body may include a circumferential sidewall having an radially inwardly-facing surface and a plurality of axially-aligned ribs extending inwardly from the radially inwardly-facing surface of the circumferential sidewall, and each pair of circumferentially adjacent axially-aligned ribs may at least partially define one of the receptacles.

In another aspect of the present invention, the axially-aligned ribs may include a first arcuate taper having a wide end and a narrow end, and are joined to the radially inwardly-facing surface of the circumferential sidewall by the wide end of the first arcuate taper.

In another aspect of the present invention, the rotor body may include a torque transfer ring symmetrically disposed about the axis of rotation and having a radially outwardly-facing surface, and a plurality of radially-aligned ribs extending from the radially outwardly-facing surface of the torque transfer ring to the radially inwardly-facing surface of the circumferential sidewall.

In another aspect of the invention, the rotor body may include a base having an upper surface and the radially-aligned ribs may extend upward from the upper surface of the base.

In another aspect of the present invention, the radially-aligned ribs may have a second arcuate taper, and are joined to the upper surface of the base by a wide end of the second arcuate taper.

In the present invention, an adapter for operatively coupling a processing container to a centrifuge rotor having a plurality of receptacles is provided. The adapter includes a body configured to be received by a respective one of the plurality of receptacles of the centrifuge rotor, and a cavity configured to receive the processing container.

In an aspect of the present invention, the body of the adapter may include an outer wall, a first sidewall, a second sidewall opposite the first sidewall, a top wall, and a bottom wall opposite the top wall.

In another aspect of the present invention, the outer wall, the first sidewall, the second sidewall, the top wall, and the bottom wall may be operatively coupled together to define an inner opening opposite the outer wall that provides access to the cavity.

In another aspect of the present invention, the first sidewall and the second sidewall may have a radial length such that, when the adapter is placed in the receptacle, the inner opening is offset radially toward the outer wall from an inner wall of the receptacle.

In another aspect of the present invention, the first sidewall and the second sidewall of the adapter may be oriented at an angle that, when multiplied by the number of receptacles in the centrifuge rotor, equals <NUM> degrees.

In another aspect of the present invention, the angle between the first sidewall and the second sidewall of the adapter may provide the adapter with a wedge shape.

In another aspect of the present invention, the top wall and the bottom wall of the adapter may be parallel to each other.

In another aspect of the present invention, the outer wall of the adapter may include a radially inwardly-facing surface having an axially-aligned curved taper.

In another aspect of the present invention, the axially-aligned curved taper may be provided by a progressively increasing thickness of the outer wall as the outer wall extends from the bottom wall to the top wall.

In another aspect of the present invention, the receptacle may be provided by a rotor liner of the centrifuge rotor.

In another aspect of the present invention, the processing container may be a biobag.

In another aspect of the present invention, the adapter may include a handle configured to provide a grip that facilitates placing the adapter into one of the plurality of receptacles of the rotor body.

In another aspect of the invention, the handle may project upwardly from the adapter.

In another aspect of the present invention, the cavity of the adapter may be one of a plurality cavities each configured to receive one of a plurality of processing containers.

In another aspect of the present invention, the cavity of the adapter may face radially inward.

In another aspect of the present invention, the cavity of the adapter may be oriented in a horizontal direction.

In another aspect of the present invention, each receptacle of the rotor may be at least partially defined by a plurality of axially-aligned ribs, and the body of the adapter may include a plurality of opposing and circumferentially extending lobes that engage the axially-aligned ribs.

In another aspect of the present invention, each of the axially-aligned ribs may have an arcuate taper, and each lobe may have a radius of curvature that matches the radius of curvature of the arcuate taper of the axially-aligned ribs.

In the present invention, an adapter for operatively coupling a processing container to a centrifuge rotor is presented according to claim <NUM>. The adapter includes a plurality of walls that define an open-faced cavity configured to receive the processing container. The plurality of walls includes an outer wall opposite an inner opening of the adapter, and the outer wall includes a radially inwardly-facing surface having an axially-aligned curved taper.

In the present invention, the plurality of walls includes a top wall and a bottom wall, and the axially-aligned curved taper may be provided by a progressively increasing thickness of the outer wall as the outer wall extends from the bottom wall to the top wall.

In another aspect of the present invention, the axially-aligned curved taper may work in conjunction with centrifugal force generated by rotating the centrifuge rotor to cause suspended solids to collect in a portion of the processing container proximate the bottom wall.

In another aspect of the present invention, the adapter may further include a handle operatively coupled to the top wall of the adapter.

In another aspect of the present invention the handle may project upwardly from the top wall of the adapter.

The accompanying drawings, which constitute a part of this specification, illustrate certain embodiments of the present invention and, together with a general description of the invention given above, and the detailed description given below, serve to explain the invention.

Embodiments of the present invention are directed to rotors for batch processing of biological suspensions using processing containers in the form of biobags and processing bottles.

Referring to <FIG>, a rotor <NUM> according to an exemplary embodiment of the present invention includes a lid handle <NUM>, a lid <NUM>, a drive hub <NUM>, a plurality of adapters <NUM>, a rotor liner <NUM>, a rotor body <NUM>, a reinforcement <NUM>, and a retaining nut <NUM>, each concentrically located about an axis of rotation <NUM>. Each component of the rotor <NUM> may be arranged symmetrically about the axis of rotation <NUM> so that rotation of the rotor <NUM> does not produce a significant amount of centrifugal force or couple, i.e., so that the rotor <NUM> is dynamically balanced about the axis of rotation <NUM>.

The lid handle <NUM> includes a handle flange <NUM> that projects radially outward from a lower portion of the lid handle <NUM>. The lid handle <NUM> may provide a grip that facilitates lifting the rotor <NUM> in a substantially axial (e.g., vertical) direction, such as when inserting the rotor <NUM> into, or removing the rotor <NUM> from, a centrifuge. As best shown by <FIG> and <FIG>, the lid handle <NUM> includes a handle bore <NUM> centered on the axis of rotation <NUM> and configured to receive a clamp screw <NUM>. The handle bore <NUM> includes top and bottom openings and a bore shoulder <NUM> that narrows the diameter of the handle bore <NUM> at a point located between the top and bottom openings.

The clamp screw <NUM> includes a head <NUM> configured to engage the bore shoulder <NUM> when inserted into the top opening of handle bore <NUM>. The bore shoulder <NUM> may be positioned along the length of the handle bore <NUM> such that, when the head <NUM> of clamp screw <NUM> engages the bore shoulder <NUM>, a threaded portion <NUM> of clamp screw <NUM> extends from the bottom opening of handle bore <NUM>. A plug <NUM> may be inserted into a top opening of the handle bore <NUM>. The plug <NUM> may be configured to prevent the clamp screw <NUM> from rotating relative to the lid handle <NUM> so that twisting the lid handle <NUM> causes the clamp screw <NUM> to rotate with the lid handle <NUM>. The plug <NUM> may also prevent the clamp screw <NUM> from falling out of the handle bore <NUM> when the lid handle <NUM> is removed from the lid <NUM>.

The lid <NUM> includes a lid flange <NUM> along the perimeter thereof, and a center hole <NUM> centered on the axis of rotation <NUM>. A bottom surface <NUM> of lid flange <NUM> is connected to a bottom surface <NUM> of lid <NUM> by a bevel <NUM>. The bottom surface <NUM> of lid <NUM> may include a plurality of cavities <NUM> each configured to accommodate an adapter handle <NUM>. The center hole <NUM> may be configured to receive a clamp screw retainer <NUM>. The clamp screw retainer <NUM> includes a cylindrical body <NUM> axially centered on the axis of rotation <NUM>, a threaded bore <NUM> axially-aligned and centered in the cylindrical body <NUM>, a clamp screw retainer flange <NUM> that projects radially outward from the cylindrical body <NUM>, and a threaded rod <NUM> that projects downward from the cylindrical body <NUM>. The cylindrical body <NUM> may further include one or more pin holes <NUM> each configured to accept a pin <NUM>. The pins <NUM> may engage corresponding pin holes <NUM> in the lid handle <NUM>, thereby preventing the lid handle <NUM> from rotating relative to the retainer <NUM> when the lid handle <NUM> is fastened to the retainer <NUM> by clamp screw <NUM>.

The cylindrical body <NUM> of clamp screw retainer <NUM> may have a diameter the same as or slightly less than the diameter of the center hole <NUM> of lid <NUM>. The clamp screw retainer <NUM> may thereby position the lid <NUM> about the axis of rotation <NUM>. The threaded bore <NUM> of clamp screw retainer <NUM> is configured to threadedly engage the threaded portion <NUM> of clamp screw <NUM>. In response to the lid handle <NUM> being rotated relative to the clamp screw retainer <NUM>, the threaded portion <NUM> of clamp screw <NUM> may be drawn into, or urged out of, the threaded bore <NUM> of clamp screw retainer <NUM>, depending on the direction of rotation. When the clamp screw <NUM> is tightened, the head <NUM> thereof presses against the bore shoulder <NUM> to provide an axial compressive force that secures the lid <NUM> between the handle flange <NUM> and the clamp screw retainer flange <NUM>.

The drive hub <NUM> includes a cylindrical body <NUM> centered on and aligned with the axis of rotation <NUM>, a threaded bore <NUM> axially-aligned and centered in the cylindrical body <NUM>, a drive hub flange <NUM> that projects radially outward from the cylindrical body <NUM>, and a tapered bore <NUM> configured to receive a spindle of the centrifuge. The drive hub flange <NUM> may generally divide the cylindrical body <NUM> of drive hub <NUM> into an upper portion <NUM> and a lower portion <NUM>. The threaded bore <NUM> and tapered bore <NUM> may be connected by a passage <NUM>. The lower portion <NUM> of cylindrical body <NUM> includes threads <NUM> on a portion of its outer surface configured to threadedly engage the retaining nut <NUM>.

Each adapter <NUM> is configured to receive a processing container <NUM>, e.g., a biobag. Each adapter <NUM> may be made of various materials such as cut carbon fibers in an epoxy matrix, or <NUM>% glass fiber fill in a polypropylene matrix. Each adapter <NUM> may include an adapter body <NUM> comprising an outer wall <NUM>, an inner opening <NUM>, sidewalls <NUM>, <NUM>, a top wall <NUM>, and a bottom wall <NUM>. Each sidewall <NUM>, <NUM> may join a respective axially-aligned edge of the outer wall <NUM> to a respective axially-aligned edge of the inner opening <NUM>. The sidewalls <NUM>, <NUM> of adapter <NUM> may oriented at an angle θ in the radial dimension. In an embodiment of the present invention, the angle θ ≈ <NUM>/N, where N is the number of adapters <NUM> that can be held by the rotor liner <NUM>.

The angle θ at which the sidewalls <NUM>, <NUM> of adapter <NUM> are oriented may give the adapter <NUM> a wedge shape. This wedge shape may result in the circumferential length of the outer wall <NUM> being larger than the circumferential length of the inner opening <NUM>, with the difference in circumferential length having an inverse relationship to the radial distance between the outer wall <NUM> and the inner opening <NUM>. The top wall <NUM> and bottom wall <NUM> may be generally parallel to each other, have a wedge shape, and join respective edges of the outer wall <NUM>, inner opening <NUM>, and sidewalls <NUM>, <NUM> to define an open-faced cavity <NUM> configured to receive a processing container.

The radial length of the sidewalls <NUM>, <NUM> may be such that the inner opening <NUM> is offset radially toward the outer wall <NUM> from an inner wall <NUM> of the rotor liner <NUM>. This offset may provide space for fluid lines, clamps, manifolds, or other attachments to the processing containers between the adapter <NUM> and the rotor liner <NUM>. The fluid lines and other components may be used to add a suspension to the processing container before centrifuging, and remove supernatant or pellet material from the processing container after centrifuging.

Advantageously, enabling supernatant or pellet material to be removed without removing the processing container from the adapter <NUM> may reduce the amount of pellet that becomes resuspended in the supernatant due to movement of the processing container. Processing containers may be inserted into and removed from the cavity <NUM> of adapter <NUM> through the inner opening <NUM>. Insertion of the processing container into the adapter <NUM> may occur before or after the suspension has been added to the processing container, and removal of the processing container from the adapter <NUM> may occur before or after removal of one or both of the processed components of the suspension.

As best shown by <FIG>, the outer wall <NUM> may have a curved shape as viewed from the top that generally corresponds to the radial distance of the wall from the axis of rotation <NUM> when the adapter <NUM> is seated in the rotor liner <NUM>. As best shown by <FIG>, the radially inwardly-facing surface of outer wall <NUM> may be generally straight in the axial direction. In an alternative embodiment of the present invention shown by <FIG>, the radially inwardly-facing surface of outer wall <NUM> may include an axially-aligned curved taper 80a. The curved taper 80a may be provided by a progressively increasing thickness of the outer wall <NUM> as the outer wall extends from the bottom wall <NUM> toward the top wall <NUM>. Advantageously, the curved taper 80a may cause suspended solids to collect toward the bottom wall <NUM> during centrifugation, as indicated by arrow <NUM>. This may facilitate both decanting of the supernatant without resuspending a portion of the pellet, as well as harvesting of the pellet.

Sidewalls <NUM>, <NUM>, top wall <NUM>, and bottom wall <NUM> may be generally flat. The adapter handle <NUM> may project upwardly from the adapter body <NUM>. In particular, the adapter handle <NUM> may be located on the top wall <NUM>. The adapter handle <NUM> may thereby provide a grip that facilitates placing adapters <NUM> into and removing adapters <NUM> from the rotor liner <NUM>. As shown in <FIG> and <FIG>, the bottom surface <NUM> of lid <NUM> includes the circumferentially spaced cavities <NUM> to accommodate the handles <NUM> of adapter <NUM>. Processing containers may be one-time use containers that are sealed before being placed in the rotor liner <NUM>, thereby eliminating the need to clean the rotor <NUM> after centrifugation.

The rotor liner <NUM> may include a plurality of (e.g., eight) receptacles <NUM> each configured to hold an adapter <NUM>. Each receptacle <NUM> may be spaced from its neighboring receptacles <NUM> by a distance sufficient to provide a pocket <NUM> between each pair of adjoining receptacles <NUM>. Each receptacle <NUM> may be configured to receive and secure an adapter <NUM> placed in the rotor <NUM> using an axial motion. Enabling the adapter <NUM> to be inserted and removed from the rotor liner <NUM> without having to tilt the adapter <NUM> relative to the axis of rotation <NUM> may reduce the amount of resuspension of the pellet due to jostling of the processing container after centrifuging. The use of receptacles <NUM> to secure each adapter <NUM> may also allow the rotor <NUM> to be operated with less than a full load of processing containers so long as the mass of the adapters <NUM> and their contents is evenly distributed relative to the axis of rotation <NUM>. For example, two of eight, four of eight, or six of eight receptacles <NUM> may be occupied by adapters <NUM>, with each adapter <NUM> positioned opposite of a corresponding adapter <NUM>, and the remaining receptacles <NUM> being empty. Each receptacle <NUM> may include the inner wall <NUM>, an outer wall <NUM>, and two sidewalls <NUM>, <NUM>, and have a wedge shape. The sidewalls <NUM>, <NUM> of each receptacle <NUM> may extend in a radial direction. The inner and outer walls <NUM>, <NUM> may be curved so that each of their surfaces are a respective fixed distance from the axis of rotation <NUM>.

The rotor body <NUM> includes a generally circular base <NUM> and a circumferential sidewall <NUM> that define a chamber <NUM> having an upward-facing opening <NUM>. The sidewall <NUM> includes a radially outwardly-facing surface <NUM> and a rim <NUM>. The rim <NUM> may define a perimeter of the opening <NUM> and include a radially inwardly-facing surface <NUM> configured to engage the bevel <NUM> of lid <NUM>. The bevel <NUM> of lid <NUM> and radially inwardly-facing surface <NUM> of rim <NUM> may thereby operate cooperatively to seal the chamber <NUM> when the lid <NUM> is coupled to the rotor <NUM>. The seal between the lid <NUM> and rotor body <NUM> may contain any leakage from the processing containers within the rotor body <NUM>, thereby reducing both the potential for contamination of the samples and introduction of biological materials into the workspace of the centrifuge operator.

The rim <NUM> may project outward from the sidewall <NUM> to form an upper shoulder <NUM> on the radially outwardly-facing surface <NUM> of sidewall <NUM>. A ridge <NUM> that projects outward from the radially outwardly-facing surface <NUM> of sidewall <NUM> may provide a lower shoulder <NUM> positioned proximate to a bottom edge of sidewall <NUM>. The upper and lower shoulders <NUM>, <NUM> may prevent axial movement of reinforcement <NUM>.

The rotor body <NUM> includes a center hole <NUM> in the base <NUM> thereof, and a plurality of torque transfer members <NUM>. The center hole <NUM> of rotor body <NUM> may be configured to receive the lower portion of drive hub <NUM>. A torque transfer ring <NUM> having the same inner diameter as the center hole <NUM> projects upward from the base <NUM> of rotor body <NUM>. The torque transfer ring <NUM> includes a top surface <NUM> configured to engage a bottom surface of drive hub flange <NUM> so that the rotor body <NUM> is securely fastened to the drive hub <NUM> when the retaining nut <NUM> is threadedly engaged with the threads <NUM> of the lower portion <NUM> of drive hub <NUM>.

The torque transfer members <NUM> may operate to transfer torque transmitted through the torque transfer ring <NUM> from the spindle of the centrifuge to the rotor liner <NUM>. The torque transfer members <NUM> may be integral with the rotor body <NUM> such that the base <NUM>, sidewall <NUM>, torque transfer members <NUM>, and torque transfer ring <NUM> are formed from a single piece of material, e.g., using a molding process. Each torque transfer member <NUM> of rotor body <NUM> may extend radially from a radially outwardly-facing surface of the torque transfer ring <NUM> to a radially inwardly-facing surface of sidewall <NUM>. Although the exemplary embodiments of the rotor <NUM> depict eight torque transfer members <NUM>, the present invention is not limited to a particular number of torque transfer members <NUM>. For example, rotor <NUM> may have between two and twelve torque transfer members <NUM>. However, it should be understood that there is no fixed upper limit on the number of torque transfer members <NUM> that may be included in the rotor <NUM>.

The torque transfer members <NUM> each include a radially-aligned rib <NUM> that projects upward from the base <NUM>, and an axially-aligned rib <NUM> that projects radially inward toward the axis of rotation <NUM> from the radially inwardly-facing surface of sidewall <NUM> to reinforce the rotor body <NUM>. The radially-aligned ribs <NUM> and axially-aligned ribs <NUM> may each include a taper that reduces their circumferential width along the axial dimension toward the opening <NUM>. This taper may provide a close fit between the rotor liner <NUM> and receptacle <NUM>, thereby reducing or eliminating lateral movement of the rotor liner <NUM> within the rotor body <NUM>. The taper may also facilitate removal of the rotor body <NUM> from a mold for embodiments in which the rotor body <NUM> is injection molded, and may have an angle of <NUM> degrees or more.

The radially-aligned ribs <NUM> may include an arcuate taper having a wide end and a narrow end, and may be joined to an upper surface of the base <NUM> by the wide end of the taper. The axially-aligned ribs <NUM> may also include an arcuate taper having a wide end and a narrow end, and may be joined to the radially inwardly-facing surface of sidewall <NUM> by the wide end of the taper. The arcuate tapers of the radially and axially-aligned ribs <NUM>, <NUM> may provide a smooth transition between the torque transfer members <NUM> and the adjoining surfaces of the rotor body <NUM>. Torque transfer members and rings are described in detail by <CIT>.

The torque transfer members <NUM> define a plurality of circumferentially-spaced receptacles <NUM> each configured to accept a corresponding receptacle <NUM> of rotor liner <NUM>. The torque transfer members <NUM> may thereby engage the rotor liner <NUM> so as to prevent the rotor liner <NUM> from rotating relative to the rotor body <NUM>. This may allow rotational forces applied to the rotor <NUM> through the drive hub <NUM> and torque transfer ring <NUM> to be transferred to the rotor liner <NUM> without significant movement of the rotor liner <NUM> relative to the rotor body <NUM>.

To this end, the torque transfer members <NUM> may be configured to fit into or otherwise engage the pockets <NUM> between receptacles <NUM> of rotor liner <NUM> when the rotor liner <NUM> is placed into the rotor body <NUM>. In an embodiment of the present invention, the number of torque transfer members <NUM> may match the number of receptacles <NUM> so that one torque transfer member <NUM> extends between each receptacle <NUM> of rotor liner <NUM> when the rotor liner <NUM> is placed into the rotor body <NUM>. In another embodiment of the present invention, there may be fewer torque transfer members <NUM> than receptacles <NUM>. In this case, torque transfer members <NUM> may only extend into some of the pockets <NUM> of rotor liner <NUM> when the rotor liner <NUM> is placed into the rotor body <NUM>, e.g., every other pocket <NUM>, every third pocket <NUM> (e.g., for a rotor having six receptacles), every fourth pocket <NUM>, etc..

For embodiments having a fewer number of torque transfer members <NUM> than pockets <NUM>, the rotor body <NUM> may include "passive" radially and axially-aligned ribs located between torque transfer members <NUM>. These passive ribs may be configured to engaged empty pockets <NUM> and help secure the rotor liner <NUM> within the rotor body <NUM>, but may lack the structural rigidity of the torque transfer members <NUM> necessary to transfer torque from the torque transfer ring <NUM> to the rest of the rotor body <NUM>. The use of passive ribs may thereby reduce the total mass of the rotor <NUM>.

By way of example, in an embodiment, half of the circumferentially spaced ribs <NUM>, <NUM> (e.g., four ribs) may comprise torque transfer members <NUM> arranged circumferentially spaced <NUM> degrees from each other, with the remaining ribs <NUM>, <NUM> only providing a supporting function located midway between each pair of adjacent torque transfer members <NUM>. In another embodiment, all of the circumferentially spaced ribs <NUM>, <NUM> may only serve to support the rotor liner <NUM>. In this embodiment, torque transfer members that transfer torque from the drive hub <NUM> to the circumferential sidewall <NUM> may be located below the base <NUM> of rotor body <NUM>.

The rotor body <NUM> may comprise a carbon fiber reinforced composite material including one or more layers of a carbon fiber laminate in a binding material. One or more layers of the carbon fiber laminate (e.g., the layers comprising the base <NUM> of rotor body <NUM>) may be rotated relative to the layer immediately below so that the carbon fibers run at an angle compared to those in adjacent layers, e.g., a <NUM> degrees angle. One or more of the carbon fiber layers (e.g., the layers comprising the torque transfer members <NUM>) may be configured so that at least some of the fibers are oriented lengthwise radially from the torque transfer ring <NUM> to the sidewall <NUM> of rotor body <NUM>. These radially-aligned fibers may increase the ability of the rotor body <NUM> to withstand centrifugal forces. The binding material may be a polymer, such as a thermoset resin (e.g., an epoxy), a polyester, a vinyl ester, nylon, or any other suitable binding material. The rotor body <NUM> may also be compression molded from layers of resin-coated carbon fiber material.

The rotor liner <NUM> may be bonded to the rotor body <NUM> of rotor <NUM> or removably attached to the rotor body <NUM>. Removably attached rotor liners <NUM> may have a friction-fit with the rotor body <NUM> that enables the rotor liner <NUM> to be removed, e.g., for cleaning. The rotor liner <NUM> may be formed from a rigid material, such as a composite material including carbon fibers. The rotor liner <NUM> may be manufactured using injection molding, additive manufacturing (e.g., 3D printing), or any other suitable process.

The radially inwardly-facing surface of sidewall <NUM> and the torque transfer members <NUM> of rotor body <NUM> may oppose loads caused by acceleration of the receptacles <NUM> during centrifugation. Each receptacle <NUM> may thereby be independently supported within the rotor <NUM> by the base <NUM>, sidewall <NUM>, and a pair of circumferentially adjacent torque transfer members <NUM> of rotor body <NUM>. In an embodiment of the present invention, the rotor <NUM> may be rotated at a top speed of between <NUM>,<NUM> and <NUM>,<NUM> Rotations Per Minute (RPM), and produce a centripetal acceleration in the processing container of about <NUM>,<NUM> times that of Earth's gravity.

The reinforcement <NUM> may include one or more helical windings that extend around the sidewall <NUM> of rotor body <NUM>, and may be formed by a filament winding process followed a by compression molding process using a suitable material, such as an epoxy-coated carbon fiber. For example, the reinforcement <NUM> may be compression molded onto the rotor body <NUM> after placing layers of resin-coated carbon fiber laminate material, or winding one or more strands of carbon fiber, onto the radially outwardly-facing surface of sidewall <NUM>. The reinforcement <NUM> may be configured to bear the majority of the centrifugal forces placed on the rotor <NUM>. Methods of forming reinforcements for centrifugal rotors using a filament winding process are described in detail by <CIT>.

The retaining nut <NUM> threadedly engages the threads <NUM> of the lower portion <NUM> of drive hub <NUM> to provide an axial compressive force that presses the lid <NUM> against one or more of the adapters <NUM>, the rotor liner <NUM>, rotor body <NUM>, and reinforcement <NUM>. The lid handle <NUM>, drive hub <NUM>, retaining nut <NUM>, clamp screw <NUM>, plug <NUM>, clamp screw retainer <NUM>, pins <NUM> may be made from metal (e.g., <NUM> stainless steel) or other suitable material.

Processing containers <NUM> in the form of biobags may include a flexible collapsible bag <NUM> that defines a compartment for receiving a suspension, and one or more (e.g., two) fluid lines <NUM> that are operatively coupled to the compartment by a like number of ports <NUM>. Clamps <NUM> may be configured to selectively pinch each fluid line <NUM> so that liquids in the compartment are unable to escape during centrifugation. The bag <NUM> may comprise two overlying sheets that are bonded together to form a seam line that encircles the compartment. The seam line may be formed using any suitable technique, such as heat welding. The one or more ports <NUM> may be bonded between the sheets so as to form a sealed connection.

Each sheet from which the bag <NUM> is formed may comprise a flexible, water impermeable polymeric film, such as a low-density polyethylene. The film may include one or more layers that are either sealed together or separated to form a double wall biobag. For embodiments in which the layers are sealed together, the biobag material may comprise a laminated or extruded material. Laminated material may be formed by bonding two or more separately formed layers using heat, an adhesive, or any other suitable process for bonding layers.

One example of an extruded material that may be used to manufacture biobags is Thermo Scientific CX3-<NUM> film, which is available from Thermo Fisher Scientific of Logan, Utah. The biobag material may be a material approved for direct contact with living cells and capable of maintaining the sterility of a sterile solution. Biobags are also described in detail by Intl.

The fluid line <NUM> may be part of a manifold system (not shown) that is used to add or remove liquids from the processing container <NUM>. The processing container <NUM> may be filled with a biological suspension prior to placing the processing container <NUM> into the adapter <NUM>, or after the processing container <NUM> has been placed into the adapter <NUM>. Likewise, the supernatant or pellet may be decanted from the processing container <NUM> while the processing container <NUM> is still in the adapter <NUM> after centrifugation, or the processing container <NUM> may be removed from the adapter <NUM> prior to decanting the supernatant or pellet. Filling/decanting may also occur while the adapters <NUM> are in the rotor body <NUM>.

Placing each processing container <NUM> into its respective adapter <NUM> when empty, and removing it from the adapter <NUM> with only the pellet may facilitate loading and unloading the adapters <NUM>, and allow the use of larger processing containers. To facilitate filling/emptying the processing containers while in the adapters <NUM>, one or more adapters <NUM> may be supported by a rack having curved surfaces configured to support the outer wall <NUM> of each adapter <NUM> being filled/emptied. The rack may be configured so that the inner opening <NUM> of each adapter <NUM> in the rack faces upwardly and the outer wall <NUM> faces downwardly. The rack may hold multiple adapters <NUM> each containing an empty processing container <NUM> so that the processing containers <NUM> can be filled concurrently, e.g., through a manifold connected to a bioreactor or other source of suspension.

After centrifugation, the same or a similar rack may be used to withdraw supernatant from the processing container <NUM> within each container adapter <NUM>. To this end, the adapter <NUM> may be pulled upwardly from the rotor <NUM> and then tilted (e.g., <NUM> degrees) until the outer wall <NUM> is aligned with a receptacle in the rack, and the inner opening <NUM> is in a position (e.g., facing upward) that facilitates removal of the supernatant. Once aligned with the receptacle, the adapter <NUM> may be placed into the rack. Supernatant may be pumped out of the processing container <NUM> until most of the supernatant has been removed so that the pellet is concentrated along the interior surface of the processing container <NUM> adjacent to the outer wall <NUM> of adapter <NUM>. Once the pellet has been concentrated, most or all of the remaining supernatant may be removed using a clamp, plus gravity. Alternatively, air may be introduced into the processing container <NUM> (e.g., from a compressor) to expel the remaining supernatant from each processing container <NUM>. The manifold used to fill the processing containers <NUM> may be decoupled from the processing containers <NUM> prior to centrifugation, and then reconnected to decant supernatant from one or more processing containers <NUM> into a common collection bag after centrifugation. In another embodiment, the manifold used to fill the processing containers <NUM> may be left in place during centrifugation, and then later used to remove supernatant.

Leaving the manifold in place may facilitate filling and removing fluids from the processing containers <NUM> during batch processing. For example, supernatant may be removed, and fresh suspension added to the processing containers <NUM> between periods of centrifugation. Advantageously, this feature may allow multiple batches of suspension (e.g., <NUM> batches for suspensions that produce small pellets) to be processed in the same processing containers <NUM> until the pellet occupies a large portion (e.g., <NUM>%) of the capacity of the processing container <NUM>. The processing container <NUM> and adapter <NUM> may be configured to contain any desired volume of biological suspension, with a typical volume being about six liters. The filling and decanting of bags used in centrifuges is described in detail in Intl. No. <CIT>, the disclosure of which is incorporated by reference herein in its entirety.

In applications for which the desired materials are found primarily or exclusively in the supernatant, the biobag with cell material may be discarded once the supernatant has been removed. In other applications, once the supernatant has been withdrawn, an aqueous buffer may be added to the biobag to resuspend the cells. The resuspended cells in the buffer may then be withdrawn from the biobag, e.g., using gravity.

<FIG> depict a rotor <NUM> in accordance with an alternative embodiment of the present invention. The rotor <NUM> includes a rotor body <NUM> configured to receive a plurality of adapters <NUM> each configured to hold one or more processing containers <NUM> (e.g., bottles), a drive hub <NUM>, and a retaining nut <NUM>. Processing bottles are described in detail by <CIT>.

The rotor body <NUM> includes a generally circular base <NUM> and a circumferential sidewall <NUM> that define a chamber <NUM> having an upward-facing opening <NUM>. The sidewall <NUM> may include a reinforcement <NUM> (e.g., a carbon fiber winding or the like), a radially outwardly-facing surface, and a rim <NUM> that defines the perimeter of the opening <NUM>. The rotor body <NUM> may further include a center hole (not shown) in the base <NUM>, a plurality of torque transfer members <NUM>, and a torque transfer ring <NUM> that projects upward from the base <NUM> and is axially-aligned with the center hole.

The drive hub <NUM> includes a hub shaft <NUM> that extends upward from a drive hub flange <NUM>. The hub shaft <NUM> may be cylindrical, and include a top portion <NUM>, a threaded portion <NUM>, a lower portion <NUM>, and a tapered bore (not shown) configured to receive the spindle of the centrifuge. The lower portion <NUM> of hub shaft <NUM> may be configured to engage the center hole of base <NUM> and an inner bore of torque transfer ring <NUM> such that the rotor <NUM> is axially-aligned with the spindle of the centrifuge when the drive hub <NUM> is engaged therewith.

The torque transfer ring <NUM> includes a top surface <NUM> configured to engage a bottom surface of the retaining nut <NUM> so that the rotor body <NUM> is securely fastened to the drive hub <NUM> when the retaining nut <NUM> is threadedly engaged with the threaded portion <NUM> of hub shaft <NUM>. When the retaining nut <NUM> is tightened, a bottom surface thereof presses against the top surface <NUM> of torque transfer ring <NUM>, and an upper surface of drive hub flange <NUM> presses against a bottom surface of base <NUM> to provide an axial compressive force that secures the rotor body <NUM> between the retaining nut <NUM> and drive hub flange <NUM>.

The torque transfer members <NUM> may operate to transfer torque transmitted through the torque transfer ring <NUM> from the spindle of the centrifuge to the rotor body <NUM> and adapters <NUM>. In a similar manner as described above, the torque transfer members <NUM> may be integral with the rotor body <NUM> such that the base <NUM>, sidewall <NUM>, torque transfer members <NUM>, and torque transfer ring <NUM> are formed from a single piece of material, e.g., using a molding process.

Each torque transfer member <NUM> of rotor body <NUM> includes a radially-aligned rib <NUM> that extends radially from the torque transfer ring <NUM> toward the sidewall <NUM>, and an axially-aligned rib <NUM> that extends axially upward from the base <NUM> toward the opening <NUM>. The radially-aligned ribs <NUM> may include an arcuate taper having a wide end and a narrow end, and may be joined to an upper surface of the base <NUM> by the wide end of the taper. The axially-aligned ribs <NUM> may also include an arcuate taper having a wide end and a narrow end, and may be joined to a radially inwardly-facing surface of the sidewall <NUM> by the wide end of the taper.

The torque transfer members <NUM> may define a plurality of circumferentially-spaced receptacles <NUM> (e.g., eight receptacles) each configured to accept a corresponding adapter <NUM>. The arcuate tapers of the radially and axially-aligned ribs <NUM>, <NUM> may provide a smooth transition between the torque transfer members <NUM> and the adjoining surfaces of the rotor body <NUM>, and may also allow for the adapters <NUM> to be placed in and removed from their respective receptacles <NUM> using an axial motion.

Each adapter <NUM> includes a generally rectangular shaped adapter body <NUM> and an adapter handle <NUM> that provides a grip. The adapter handle <NUM> may project upwardly from the adapter body <NUM>. The adapter handle <NUM> may thereby facilitate placing the adapters <NUM> into and removing the adapters <NUM> from the rotor body <NUM>. The adapter body <NUM> may include one or more (e.g., two) radially inwardly-facing cavities <NUM>, and two opposing and circumferentially extending lobes <NUM> each configured to engage the adjoining axially-aligned rib <NUM>. The lobes <NUM> may have a radius of curvature that matches that of the arcuate taper of the axially-aligned ribs <NUM>. The lobes <NUM> may thereby be configured to engage the axially-aligned ribs <NUM> so as to prevent the adapter <NUM> from shifting radially or circumferentially during centrifugation.

Each of the radially inwardly-facing cavities <NUM> may be oriented in a generally horizontal direction and configured to receive a processing container <NUM>. The processing containers <NUM> may be loaded into the adapter <NUM> while the adapter <NUM> is outside the rotor <NUM>. The ability to load processing containers <NUM> into the adapter <NUM> while the adapter <NUM> is outside the rotor <NUM> may allow the distance between the axis-facing end of the processing container <NUM> and the drive hub <NUM> to be reduced as compared to a rotor in which the processing containers <NUM> are inserted into the rotor directly.

Claim 1:
A rotor (<NUM>, <NUM>) for a centrifuge, comprising:
a rotor body (<NUM>, <NUM>) defining a plurality of first receptacles (<NUM>, <NUM>) spaced circumferentially about an axis of rotation (<NUM>) of the rotor body (<NUM>, <NUM>),
a plurality of adapters (<NUM>, <NUM>) each configured to receive a processing container (<NUM>, <NUM>) and to engage a respective first receptacle (<NUM>, <NUM>) so that each adapter (<NUM>, <NUM>) is held in place within the rotor (<NUM>, <NUM>) by the respective first receptacle (<NUM>, <NUM>), characterized by:
a rotor liner (<NUM>) including a plurality of second receptacles (<NUM>) placed circumferentially about the axis of rotation (<NUM>) of the rotor body (<NUM>, <NUM>), each second receptacle (<NUM>) being configured to be received by a respective one of the first receptacles (<NUM>, <NUM>).