Batch Bioprocessing Centrifuge Rotors

Abstract

A rotor (10, 150) for use in a centrifuge and an adapter (18, 154) for connecting one or more processing vessels (142, 156) to the rotor (10, 150). The rotor (10, 150) includes a rotor body (22, 152) having a plurality of receptacles (140, 194), each configured to receive an adapter (18, 154). Each adapter (18, 154) includes an outer surface configured to interface with one of the receptacles (140, 194) and one or more cavities (92, 200), each configured to receive a processing vessel (142, 156). The rotor (10, 150) may also include a rotor liner (20) positioned between the adapter (18, 154) and the rotor body (22, 152). The rotor liner (20) provides a plurality of receptacles (100) that engage with the receptacles (140, 194) of the rotor body and receive the adapters (18, 154), thereby providing an interface connection between the adapters (18, 154) and the receptacles (140, 194) of the rotor body (22, 152).

Description

[Technical Field]

[0001] The present invention relates generally to centrifuge rotors, and more particularly to rotors configured for batch processing of biological suspensions in a centrifuge. [Background technology]

[0002] Bioreactors and fermenters are used to cultivate biological suspensions containing cells or microorganisms suspended in a liquid medium. Once the biological suspension has been sufficiently cultivated, it is typically separated into liquid and solid components. The separated components are then recovered 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 the biological suspension.

[0003] Centrifugation typically involves dispensing a volume of the suspension from a bioreactor or fermenter into a processing vessel, such as a bottle or bag. The vessel is then closed and spun in a centrifuge. The centrifugal force created by the spinning rotor in the centrifuge causes solids in the suspension to settle, forming a generally solid pellet toward the bottom of the vessel. A supernatant, containing liquid less dense than the pellet, collects in the vessel above the pellet. Once the supernatant and pellet have formed, the supernatant is decanted by pouring or pumping it out of the vessel. The pellets can then be individually removed from the vessel.

[0004] Conventional centrifugation processes have many drawbacks. For example, to increase throughput, it is typically desirable for the container to hold as much suspension as possible. However, as the size of the container increases, it becomes more difficult for the operator to place the container in the centrifuge and remove the container from there. Increasing the number of containers loaded into the centrifuge can also increase throughput. However, having a large number of containers also increases the time it takes the operator to load and unload each batch of containers from the centrifuge.

[0005] Another challenge of centrifugation is how to separate the supernatant from the pellet without disturbing the concentration of particles in the previously suspended pellet. This challenge can be exacerbated when the container is large or otherwise difficult to remove from the centrifuge due to increased container collisions, which can cause portions of the pellet to be resuspended in the supernatant.

[0006] Therefore, there is a need for improved methods and systems for centrifugation of biological suspensions. Summary of the Invention

[0007] The present invention overcomes the aforementioned and other drawbacks and disadvantages of previously known centrifuge rotors used for centrifugation of biological suspensions. Although the present invention will be discussed in connection with specific embodiments, it will be understood that the invention is not limited to the specific embodiments described herein.

[0008] In one embodiment of the present invention, a rotor for a centrifuge is provided. The rotor includes a rotor body having a plurality of receptacles circumferentially spaced about a rotational axis of the rotor body, and a plurality of adapters. Each of the receptacles in the rotor body can 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. Each adapter can be removably supported within a respective one of the receptacles in the rotor body, and each adapter can be configured to receive a respective process vessel therein.

[0009] In one aspect of the invention, each of the adapters and each of the receptacles on the rotor body may be configured such that the adapters are axially insertable into and removable from their respective receptacles on the rotor body.

[0010] In another aspect of the invention, the rotor may further include a rotor liner having a plurality of circumferentially spaced receptacles, each receptacle of the rotor liner configured to be positioned within a respective one of the plurality of receptacles of the rotor body.

[0011] In another aspect of the invention, each of the adapters and each of the receptacles of the rotor liner may be configured such that the adapters are axially insertable into and removable from their respective receptacles on the rotor liner.

[0012] In another aspect of the invention, the rotor liner may further include a plurality of circumferentially spaced pockets, each located between adjacent pairs of the plurality of receptacles of the rotor liner.

[0013] In another aspect of the invention, each of the plurality of torque transmission members may be located within a respective one of the plurality of pockets of the rotor liner.

[0014] In another aspect of the invention, at least one of the plurality of torque transmitting members may be located within at least one of the plurality of pockets of the rotor liner.

[0015] In another aspect of the invention, each of the plurality of receptacles in the rotor liner may be wedge-shaped.

[0016] In another aspect of the invention, the rotor may further include carbon fiber reinforcement provided about the circumferential sidewall of the rotor body.

[0017] In another aspect of the invention, each of the plurality of torque transmitting members may include radially aligned ribs and axially aligned ribs.

[0018] In another aspect of the invention, each of the plurality of axially aligned ribs can include a first arcuate taper having a wide end and a narrow end, and each axially aligned rib can be joined to the radially inward surface of the circumferential sidewall by the wide end of the first arcuate taper.

[0019] In another aspect of the invention, each of the plurality of radially aligned ribs may extend from a radially outward surface of the torque transfer ring to a respective one of the plurality of axially aligned ribs.

[0020] In another aspect of the 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.

[0021] In another aspect of the 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.

[0022] In another aspect of the invention, each of the plurality of adapters may include an outer wall defining an open-faced cavity configured to receive a respective processing vessel within the adapter, an inner opening, a pair of opposing side walls, a top wall, and a bottom wall.

[0023] In another aspect of the invention, the outer wall may have a circumferential length greater than the circumferential length of the inner opening.

[0024] In another aspect of the invention, each of the adapters may be wedge-shaped.

[0025] In another aspect of the invention, the rotor may further include at least one process vessel received within a respective adapter.

[0026] In another aspect of the invention, the processing vessel may include one of a biobag or a processing bottle.

[0027] In another aspect of the invention, each of the plurality of adapters may be generally rectangularly shaped and may include two lobes extending in opposite circumferential directions.

[0028] In another aspect of the invention, each adapter may further include at least one horizontally oriented cavity configured to receive a process vessel therein.

[0029] In another aspect of the invention, each adapter may include a handle configured to provide a grip that facilitates placement of the adapter into one of the multiple receptacles of the rotor body.

[0030] In another aspect of the invention, the handle may project upwardly from the adapter.

[0031] In another aspect of the invention, the rotor may further include a lid having a bottom surface with a plurality of cavities, each configured to receive one of the adapter handles.

[0032] In another embodiment of the present invention, another rotor for a centrifuge is provided that includes a rotor body defining a plurality of first receptacles circumferentially spaced about an axis of rotation of the rotor body.

[0033] In one aspect of the invention, the rotor may further include a plurality of adapters, each configured to receive a processing vessel and to engage a respective first receptacle such that each adapter is held in place within the rotor by the respective first receptacle.

[0034] In another aspect of the invention, the adapter and receptacle may each be configured such that the adapter is axially inserted into and removed from the respective receptacle.

[0035] In another aspect of the invention, the rotor may further include a rotor liner including a plurality of second receptacles arranged circumferentially around the rotational axis of the rotor body, and each second receptacle may be configured to be received by a respective one of the first receptacles.

[0036] In another aspect of the invention, each adapter may be configured to engage a respective second receptacle such that each adapter is held in place within the rotor by the respective second receptacle.

[0037] In another aspect of the invention, the rotor body may include a base having an upper surface and a plurality of radially aligned ribs extending upwardly from the upper surface of the base.

[0038] In another aspect of the invention, the radially aligned ribs may at least partially define the receptacle.

[0039] In another aspect of the 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.

[0040] In another aspect of the invention, the rotor body may include a circumferential sidewall having a radially inwardly facing surface and a plurality of axially aligned ribs extending inwardly from the radially inwardly facing surface of the circumferential sidewall, wherein each pair of circumferentially adjacent axially aligned ribs may at least partially define one of the receptacles.

[0041] In another aspect of the invention, the axially aligned rib may include a first arcuate taper having a wide end and a narrow end, the wide end of the first arcuate taper being joined to the radially inward surface of the circumferential sidewall.

[0042] In another aspect of the invention, the rotor body may include a torque transmission 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 transmission ring to the radially inwardly facing surface of the circumferential side wall.

[0043] In another aspect of the invention, the rotor body may include a base having an upper surface, and the radially aligned ribs may extend upwardly from the upper surface of the base.

[0044] In another aspect of the 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.

[0045] In another embodiment of the present invention, an adapter for operably coupling a processing vessel to a centrifuge rotor having a plurality of receptacles is provided, the adapter including 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 vessel.

[0046] In one aspect of the invention, the body of the adapter may include an outer wall, a first side wall, a second side wall opposite the first side wall, a top wall, and a bottom wall opposite the top wall.

[0047] In another aspect of the invention, the outer wall, the first side wall, the second side wall, the top wall, and the bottom wall can be operably coupled to one another to define opposing interior openings in the outer wall that provide access to the cavity.

[0048] In another aspect of the invention, the first and second side walls can have radial lengths such that when the adapter is positioned in the receptacle, the inner opening is radially offset from the inner wall toward the outer wall of the receptacle.

[0049] In another aspect of the invention, the first and second side walls of the adapter may be oriented at an angle that, when multiplied by the number of receptacles in the centrifuge rotor, equals 360 degrees.

[0050] In another aspect of the invention, the angle between the first and second side walls of the adapter may provide the adapter with a wedge shape.

[0051] In another aspect of the invention, the top and bottom walls of the adapter may be parallel to one another.

[0052] In another aspect of the invention, the outer wall of the adapter may include a radially inward facing surface having an axially aligned curved taper.

[0053] In another aspect of the invention, the axially aligned curved taper may be provided by a gradual increase in thickness of the outer wall as it extends from the bottom wall to the top wall.

[0054] In another aspect of the invention, the receptacle may be provided by a rotor liner of a centrifuge rotor.

[0055] In another aspect of the invention, the processing vessel may be a biobag.

[0056] In another aspect of the invention, the adapter may include a handle configured to provide a grip to facilitate placement of the adapter into one of the receptacles of the rotor body.

[0057] In another aspect of the invention, the handle may project upwardly from the adapter.

[0058] In another aspect of the invention, the cavity of the adapter can be one of a plurality of cavities each configured to receive one of a plurality of process vessels.

[0059] In another aspect of the invention, the cavity of the adapter may face radially inward.

[0060] In another aspect of the invention, the cavity of the adapter may be oriented horizontally.

[0061] In another aspect of the invention, each receptacle of the rotor may be defined at least in part by a plurality of axially aligned ribs, and the body of the adapter may include a plurality of oppositely and circumferentially extending lobes that engage the axially aligned ribs.

[0062] In another aspect of the 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 rib.

[0063] In another embodiment of the present invention, another adapter for operably connecting a processing vessel to a centrifuge rotor is presented. The adapter includes a plurality of walls defining an open-faced cavity configured to receive the processing vessel. The plurality of walls includes an outer wall opposite an inner opening of the adapter, the outer wall including a radially inward surface having an axially aligned curved taper.

[0064] In one aspect of the invention, the plurality of walls may further include a top wall and a bottom wall, and the axially aligned curved taper may be provided by a gradual increase in thickness of the outer wall as it extends from the bottom wall to the top wall.

[0065] In another aspect of the invention, the axially aligned curved taper may be coupled with centrifugal forces generated by rotating the centrifuge rotor to cause suspended solids to collect in a portion of the treatment vessel adjacent the bottom wall.

[0066] In another aspect of the invention, the adapter may further include a handle operably coupled to the top wall of the adapter.

[0067] In another aspect of the invention, the handle may project upwardly from the top wall of the adapter. [Brief explanation of the drawings]

[0068] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate specific embodiments of the present invention and, together with the general description of the invention given above and the detailed description given below, serve to explain the invention.

[0069] [Figure 1] FIG. 1 is a perspective view of a centrifuge rotor according to one embodiment of the present invention. [Figure 2] FIG. 2 is a partially exploded perspective view of the centrifuge rotor of FIG. 1. [Figure 3] FIG. 3 is a perspective view of the body of the centrifuge rotor of FIGS. 1 and 2. [Figure 4] FIG. 4 is a cross-sectional view of the centrifuge rotor of FIG. 1 taken along line 4-4 in accordance with one embodiment of the present invention. [Figure 4A] 4 is a cross-sectional view of the centrifuge rotor of FIG. 1 taken along line 4-4 according to another embodiment of the present invention. [Figure 5] FIG. 10 is a perspective view of a centrifuge rotor according to yet another embodiment of the present invention. [Figure 6] FIG. 6 is a partially exploded perspective view of the centrifuge rotor of FIG. 5. [Figure 7] FIG. 7 is a perspective view of the body of the centrifuge rotor of FIGS. 5 and 6. DETAILED DESCRIPTION OF THE INVENTION

[0070] SUMMARY OF THE INVENTION An embodiment of the present invention is directed to a rotor for batch processing of biological suspensions using processing vessels in the form of biobags and processing bottles.

[0071] 1-4A, a rotor 10 according to an exemplary embodiment of the present invention includes a lid handle 12, a lid 14, a drive hub 16, a plurality of adapters 18, a rotor liner 20, a rotor body 22, a stiffener 24, and a retaining nut 26, each of which is concentrically positioned about a rotation axis 28. The components of the rotor 10 may be symmetrically disposed about the rotation axis 28 such that rotation of the rotor 10 does not generate a significant amount of centrifugal force or couple, i.e., such that the rotor 10 is dynamically balanced about the rotation axis 28.

[0072] The lid handle 12 includes a handle flange 30 that projects radially outward from a lower portion of the lid handle 12. The lid handle 12 may provide a grip that facilitates lifting the rotor 10 in a substantially axial (e.g., vertical) direction, such as when inserting or removing the rotor 10 into or from a centrifuge. As best shown in Figures 4 and 4A, the lid handle 12 includes a handle bore 32 that is centered about the axis of rotation 28 and configured to receive a clamp screw 34. The handle bore 32 includes top and bottom openings and a bore shoulder 36 that narrows the diameter of the handle bore 32 at a point located between the top and bottom openings.

[0073] The clamp screw 34 includes a head 38 configured to engage a bore shoulder 36 when inserted into the top opening of the handle bore 32. The bore shoulder 36 may be positioned along the length of the handle bore 32 such that a threaded portion 40 of the clamp screw 34 extends from the bottom opening of the handle bore 32 when the head 38 of the clamp screw 34 engages the bore shoulder 36. A plug 42 may be inserted into the top opening of the handle bore 32. The plug 42 may be configured to prevent the clamp screw 34 from rotating relative to the lid handle 12 such that the clamp screw 34 rotates with the lid handle 12 when the lid handle 12 is twisted. The plug 42 may also prevent the clamp screw 34 from falling out of the handle bore 32 when the lid handle 12 is removed from the lid 14.

[0074] The lid 14 includes a lid flange 44 along its periphery and a central bore 46 centered about the axis of rotation 28. A bottom surface 48 of the lid flange 44 is connected to a bottom surface 50 of the lid 14 by a bevel 52. The bottom surface 50 of the lid 14 may include a plurality of cavities 53, each configured to accommodate an adapter handle 55. The central bore 46 may be configured to receive a clamp screw retainer 54. The clamp screw retainer 54 includes a cylindrical body 56 axially centered about the axis of rotation 28, a threaded bore 58 centered on and axially aligned with the cylindrical body 56, a clamp screw retainer flange 60 projecting radially outward from the cylindrical body 56, and a threaded rod 62 projecting downward from the cylindrical body 56. The cylindrical body 56 may further include one or more pin holes 57, each configured to receive a pin 59. The pin 59 may engage a corresponding pin hole 33 in the lid handle 12 , thereby preventing the lid handle 12 from rotating relative to the retainer 54 when the lid handle 12 is secured to the retainer 54 by the clamp screw 34 .

[0075] The cylindrical body 56 of the clamp screw retainer 54 may have a diameter that is the same as or slightly smaller than the diameter of the central bore 46 of the lid 14, thereby enabling the clamp screw retainer 54 to position the lid 14 about the axis of rotation 28. The threaded bore 58 of the clamp screw retainer 54 is configured to threadingly engage the threaded portion 40 of the clamp screw 34. In response to rotation of the lid handle 12 relative to the clamp screw retainer 54, the threaded portion 40 of the clamp screw 34 is drawn into and expelled from the threaded bore 58 of the clamp screw retainer 54, depending on the direction of rotation. When the clamp screw 34 is tightened, it presses its head 38 against the bore shoulder 36 to provide a compressive force that secures the lid 14 between the handle flange 30 and the clamp screw retainer flange 60.

[0076] Drive hub 16 includes a cylindrical body 64 centered on and aligned with rotational axis 28, a threaded bore 66 centered on and axially aligned with cylindrical body 64, a drive hub flange 68 projecting radially outward from cylindrical body 64, and a tapered bore 70 configured to receive a centrifuge spindle. Drive hub flange 68 may generally divide cylindrical body 64 of drive hub 16 into an upper portion 72 and a lower portion 74. Threaded bore 66 and tapered bore 70 may be connected by a passage 76. Lower portion 74 of cylindrical body 64 includes threads 78 on a portion of its outer surface configured to threadably engage retaining nut 26.

[0077] Each adapter 18 is configured to receive a process vessel 142, e.g., a biobag. Each adapter 18 may be made of a variety of materials, such as chopped carbon fiber in an epoxy matrix or a 20% glass fiber filler in a polypropylene matrix. Each adapter 18 may include an adapter body 79 having an outer wall 80, an inner opening 82, side walls 84, 86, a top wall 88, and a bottom wall 90. Each side wall 84, 86 may join a respective axially aligned edge of the outer wall 80 to a respective axially aligned edge of the inner opening 82. The side walls 84, 86 of the adapter 18 may be oriented at an angle θ in the radial dimension. In one embodiment of the present invention, the angle θ is

number

[0078] The angle θ at which the side walls 84, 86 of the adapter 18 are oriented may impart a wedge shape to the adapter 18. This wedge shape may result in the outer wall 80 having a circumferential length greater than the circumferential length of the inner opening 82, with the difference in circumferential length being inversely related to the radial distance between the outer wall 80 and the inner opening 82. The top wall 88 and bottom wall 90 may be generally parallel to one another, may have a wedge shape, and may join the respective edges of the outer wall 80, the inner opening 82, and the side walls 84, 86 to define an open-faced cavity 92 configured to receive a process vessel.

[0079] The radial extent of the side walls 84, 86 may be such that the inner opening 82 is radially offset from the inner wall 104 of the rotor liner 20 toward the outer wall 80. This offset may provide space for fluid lines, clamps, manifolds, or other attachments to the process vessel between the adapter 18 and the rotor liner 20. Fluid lines and other components may be used to add suspension to the process vessel before centrifugation and to remove process vessel supernatant or pellet material after centrifugation.

[0080] Advantageously, allowing the supernatant or pellet material to be removed without removing the processing vessel from the adapter 18 may reduce the amount of pellet that resuspends in the supernatant due to movement of the processing vessel. The processing vessel may be inserted into and removed from the cavity 92 of the adapter 18 through the interior opening 82. Insertion of the processing vessel into the adapter 18 may occur before or after the suspension is added to the processing vessel, and removal of the processing vessel from the adapter 18 may occur before or after removal of one or both of the processed components of the suspension.

[0081] As best shown by FIG. 2 , the outer wall 80 may have a curved shape when viewed from above that generally corresponds to the wall's radial distance from the axis of rotation 28 when the adapter 18 is seated within the rotor liner 20. As best shown in FIG. 4 , the radially inwardly facing surface of the outer wall 80 may be generally straight in the axial direction. In an alternative embodiment of the invention shown in FIG. 4A , the radially inwardly facing surface of the outer wall 80 may include an axially aligned curved taper 80a. The curved taper 80a may be provided by a gradual increase in the thickness of the outer wall 80 as it extends from the bottom wall 90 toward the top wall 88. Advantageously, the curved taper 80a may funnel suspended solids toward the bottom wall 90 during centrifugation, as indicated by arrow 99. This may facilitate both decanting the supernatant as well as recovering the pellet without resuspending a portion of the pellet.

[0082] The side walls 84, 86, the top wall 88, and the bottom wall 90 may be generally flat. The adapter handle 55 may project upwardly from the adapter body 79. In particular, the adapter handle 55 may be located on the top wall 88. The adapter handle 55 may thereby provide a grip that facilitates placing the adapter 18 in and removing the adapter 18 from the rotor liner 20. As shown in Figures 4 and 4A, the bottom surface 50 of the lid 14 includes circumferentially spaced cavities 53 to accommodate the handles 55 of the adapter 18. The processing vessel may be a disposable vessel that is sealed before being placed in the rotor liner 20, thereby eliminating the need to wash the rotor 10 after centrifugation.

[0083] The rotor liner 20 may include a plurality (e.g., eight) of receptacles 100, each configured to hold an adapter 18. Each receptacle 100 may be spaced from its adjacent receptacle 100 by a distance sufficient to provide a pocket 102 between each pair of adjacent receptacles 100. Each receptacle 100 may be configured to receive and secure an adapter 18 disposed within the rotor 10 using axial movement. Allowing an adapter 18 to be inserted into and removed from the rotor liner 20 without tilting the adapter 18 relative to the rotation axis 28 may reduce the amount of pellet resuspension due to collision of processing vessels after centrifugation. The use of receptacles 100 to secure each adapter 18 may also allow the rotor 10 to be operated with fewer processing vessels than fully loaded, as long as the mass of the adapters 18 and their contents is evenly distributed relative to the rotation axis 28. For example, two of eight, four of eight, or six of eight receptacles 100 may be occupied by adapters 18, with each adapter 18 positioned opposite a corresponding adapter 18 and the remaining receptacles 100 empty. Each receptacle 100 may include an inner wall 104, an outer wall 106, and two side walls 108, 110 and may have a wedge shape. The side walls 108, 110 of each receptacle 100 may extend radially. The inner and outer walls 104, 106 may be curved such that each of their surfaces is a fixed distance from the axis of rotation 28.

[0084] The rotor body 22 includes a generally circular base 112 and a circumferential sidewall 114 that define a chamber 116 with an upwardly facing opening 118. The sidewall 114 includes a radially outwardly facing surface 120 and a rim 122. The rim 122 may define the perimeter of the opening 118 and may include a radially inwardly facing surface 124 configured to engage the bevel 52 of the lid 14. The bevel 52 of the lid 14 and the radially inwardly facing surface 124 of the rim 122 may thereby cooperate to seal the chamber 116 when the lid 14 is coupled to the rotor 10. The seal between the lid 14 and the rotor body 22 may prevent any leakage from processing vessels within the rotor body 22, thereby reducing both the potential for sample contamination and the introduction of biological material into the workspace of a centrifuge operator.

[0085] The rim 122 may project outwardly from the sidewall 114 to form an upper shoulder 126 on the radially outward surface 120 of the sidewall 114. A ridge 128 projecting outwardly from the radially outward surface 120 of the sidewall 114 may provide a lower shoulder 130 positioned proximate the bottom edge of the sidewall 114. The upper and lower shoulders 126, 130 may prevent axial movement of the stiffener 24.

[0086] The rotor body 22 includes a central bore 132 in its base 112 and a plurality of torque transmission members 134. The central bore 132 of the rotor body 22 may be configured to receive the lower portion of the drive hub 16. A torque transmission ring 136 having the same inner diameter as the central bore 132 projects upwardly from the base 112 of the rotor body 22. The torque transmission ring 136 includes a top surface 138 configured to engage the bottom surface of the drive hub flange 68 such that the rotor body 22 is securely fastened to the drive hub 16 when the retaining nut 26 threadably engages the threads 78 of the lower portion 74 of the drive hub 16.

[0087] The torque transmission members 134 may operate to transmit torque, transmitted through the torque transmission ring 136, from the centrifuge spindle to the rotor liner 20. The torque transmission members 134 may be integral with the rotor body 22, such that the base 112, sidewall 114, torque transmission members 134, and torque transmission ring 136 are formed from a single piece of material using, for example, a molding process. Each torque transmission member 134 of the rotor body 22 may extend radially from the radially outward surface of the torque transmission ring 136 to the radially inward surface of the sidewall 114. While the exemplary embodiment of the rotor 10 depicts eight torque transmission members 134, the present invention is not limited to a particular number of torque transmission members 134. For example, the rotor 10 may have between two and twelve torque transmission members 134. However, it should be understood that there is no fixed upper limit to the number of torque transmission members 134 that may be included in the rotor 10.

[0088] Torque transmitting member 134 each includes radially aligned ribs 137 projecting upward from base 112 and axially aligned ribs 139 projecting radially inward from the radially inward surface of sidewall 114 toward rotational axis 28 to reinforce rotor body 22. Radially aligned ribs 137 and axially aligned ribs 139 may each include a taper that reduces their circumferential width along the axial dimension toward opening 118. This taper may provide a tight fit between rotor liner 20 and receptacle 100, thereby reducing or eliminating lateral movement of rotor liner 20 within rotor body 22. The taper may also facilitate removal of rotor body 22 from a mold for embodiments in which rotor body 22 is injection molded, and may have an angle of 10 degrees or greater.

[0089] The radially aligned ribs 137 may include an arcuate taper having a wide end and a narrow end, and may be joined by the wide end of the taper to the upper surface of the base 112. The axially aligned ribs 139 may also include an arcuate taper having a wide end and a narrow end, and may be joined by the wide end of the taper to the radially inward surface of the sidewall 114. The arcuate tapers of the radially and axially aligned ribs 137, 139 may provide a smooth transition between the torque transfer member 134 and the adjacent surface of the rotor body 22. Torque transfer members and rings are described in detail in U.S. Patent No. 10,086,383, issued October 2, 2018, the entire disclosure of which is incorporated herein by reference.

[0090] The torque transmission member 134 defines a plurality of circumferentially spaced receptacles 140, each configured to receive a corresponding receptacle 100 on the rotor liner 20. In this way, the torque transmission member 134 may engage the rotor liner 20 in a manner that prevents the rotor liner 20 from rotating relative to the rotor body 22. This may allow rotational force imparted to the rotor 10 through the drive hub 16 and the torque transmission ring 136 to be transmitted to the rotor liner 20 without significant movement of the rotor liner 20 relative to the rotor body 22.

[0091] To this end, the torque transmission members 134 may be configured to fit or engage with the pockets 102 between the receptacles 100 of the rotor liner 20 when the rotor liner 20 is disposed within the rotor body 22. In one embodiment of the present invention, the number of torque transmission members 134 may match the number of receptacles 100, such that one torque transmission member 134 extends between each receptacle 100 of the rotor liner 20 when the rotor liner 20 is disposed within the rotor body 22. In another embodiment of the present invention, there may be fewer torque transmission members 134 than receptacles 100. In this case, the torque transmission members 134 may extend into only some of the pockets 102 of the rotor liner 20 when the rotor liner 20 is disposed within the rotor body 22, such as every other pocket 102, every third pocket 102 (e.g., for a rotor having six receptacles), or every fourth pocket 102.

[0092] In embodiments having fewer torque transfer members 134 than pockets 102, the rotor body 22 may include radially and axially aligned "passive" ribs located between the torque transfer members 134. These passive ribs may be configured to engage empty pockets 102 and help secure the rotor liner 20 within the rotor body 22, but may lack the structural rigidity of the torque transfer members 134 necessary to transfer torque from the torque transfer ring 136 to the remainder of the rotor body 22. The use of passive ribs may reduce the overall mass of the rotor 10.

[0093] By way of example, in one embodiment, half (e.g., four ribs) of the circumferentially spaced ribs 137, 139 may comprise torque transmission members 134 circumferentially spaced 90 degrees from one another, with the remaining ribs 137, 139 only providing a support function intermediate each pair of adjacent torque transmission members 134. In another embodiment, all of the circumferentially spaced ribs 137, 139 may serve only to support the rotor liner 20. In this embodiment, the torque transmission members that transmit torque from the drive hub 16 to the circumferential sidewall 114 may be located below the base 112 of the rotor body 22.

[0094] The rotor body 22 may be constructed of a carbon fiber reinforced composite material including one or more layers of carbon fiber laminates in a binder material. One or more layers of carbon fiber laminates (e.g., the layer comprising the base 112 of the rotor body 22) may be rotated relative to the layer immediately below so that the carbon fibers run at an angle, e.g., a 45-degree angle, compared to the carbon fibers of the adjacent layer. One or more carbon fiber layers (e.g., the layer comprising the torque transfer member 134) may be configured so that at least some of the fibers are oriented longitudinally, radially from the torque transfer ring 136 to the sidewall 114 of the rotor body 22. These radially aligned fibers may increase the rotor body 22's ability to withstand centrifugal forces. The binder material may be a polymer, such as a thermosetting resin (e.g., epoxy), polyester, vinyl ester, nylon, or any other suitable binder material. The rotor body 22 may also be compression molded from layers of resin-coated carbon fiber material.

[0095] The rotor liner 20 may be bonded to the rotor body 22 of the rotor 10 or may be removably attached to the rotor body 22. A removably attached rotor liner 20 may have a friction fit with the rotor body 22, allowing the rotor liner 20 to be removed, for example, for cleaning. The rotor liner 20 may be formed from a rigid material, such as a composite material including carbon fiber. The rotor liner 20 may be manufactured using injection molding, additive manufacturing (e.g., 3D printing), or any other suitable process.

[0096] The radially inward surfaces of the sidewall 114 and the torque transmission members 134 of the rotor body 22 can resist loads caused by acceleration of the receptacles 100 during centrifugation. This allows each receptacle 100 to be independently supported within the rotor 10 by the base 112, the sidewall 114, and a pair of circumferentially adjacent torque transmission members 134 of the rotor body 22. In one embodiment of the present invention, the rotor 10 can be rotated at a maximum speed of 5,000 to 6,000 revolutions per minute (RPM), generating a centripetal acceleration within the process vessel of approximately 10,000 times the Earth's gravity.

[0097] The stiffener 24 may include one or more helical windings extending around the sidewall 114 of the rotor body 22 and may be formed by a filament winding process followed by a compression molding process using a suitable material, such as epoxy-coated carbon fiber. For example, the stiffener 24 may be compression molded onto the rotor body 22 after placing a layer of resin-coated carbon fiber laminate material on the radially outward surface of the sidewall 114 or after wrapping one or more strands of carbon fiber. The stiffener 24 may be configured to withstand a majority of the centrifugal forces imposed on the rotor 10. Methods of forming centrifuge rotor stiffeners using a filament winding process are described in detail in U.S. Patent No. 8,323,169, issued December 4, 2012, the entire disclosure of which is incorporated herein by reference.

[0098] The retaining nut 26 threadingly engages threads 78 on the lower portion 74 of the drive hub 16 to provide an axial compressive force that presses the lid 14 against one or more of the adapter 18, rotor liner 20, rotor body 22, and stiffener 24. The lid handle 12, drive hub 16, retaining nut 26, clamp screw 34, plug 42, clamp screw retainer 54, and pin 59 may be made from metal (e.g., 316 stainless steel) or other suitable material.

[0099] The processing vessel 142 in the form of a biobag may include a flexible, collapsible bag 144 defining a compartment for receiving the suspension and one or more (e.g., two) fluid lines 146 operably connected to the compartment by a like number of ports 147. A clamp 148 may be configured to selectively clamp each fluid line 146 to prevent escape of liquid within the compartment during centrifugation. The bag 144 may be constructed from two overlapping sheets bonded together to form a seam that encircles the compartment. The seam may be formed using any suitable technique, such as heat welding. One or more ports 147 may be bonded between the sheets to form a sealed connection.

[0100] Each sheet forming the bag 144 may be composed of a flexible, water-impermeable polymer film, such as low-density polyethylene. The film may include one or more layers that are sealed together or separated to form the double-walled biobag. In embodiments where the layers are sealed together, the biobag material may include a laminated or extruded material. A laminated material may be formed by bonding two or more separately formed layers together using heat, adhesives, or any other suitable process for adhering the layers.

[0101] An example of an extruded material that can be used to manufacture biobags is Thermo Scientific CX3-9 film, available from Thermo Fisher Scientific of Logan, Utah. The biobag material can be a material that is acceptable for direct contact with living cells and capable of maintaining the sterility of the sterile solution. Biobags are also described in detail in International Publication No. WO 2019 / 166998, incorporated by reference above.

[0102] The fluid line 146 may be part of a manifold system (not shown) used to add or remove liquid from the processing vessel 142. The processing vessel 142 may be filled with a biological suspension before placing the processing vessel 142 in the adapter 18 or after the processing vessel 142 is placed in the adapter 18. Similarly, the supernatant or pellet may be decanted from the processing vessel 142 after centrifugation while the processing vessel 142 is still in the adapter 18, or the processing vessel 142 may be removed from the adapter 18 before decanting the supernatant or pellet. Filling / decanting may also be performed while the adapter 18 is in the rotor body 22.

[0103] When emptied, placing each process vessel 142 into its respective adapter 18 and removing only the pellets from the adapter 18 may facilitate loading and unloading of the adapters 18 and may enable the use of larger process vessels. To facilitate filling / emptying the process vessels while in the adapter 18, one or more adapters 18 may be supported by a rack having a curved surface configured to support the outer wall 80 of each filled / emptied adapter 18. The rack may be configured so that the inner opening 82 of each adapter 18 in the rack faces upward and the outer wall 80 faces downward. The rack may hold multiple adapters 18, each housing an empty process vessel 142, so that the process vessels 142 can be filled simultaneously, for example, through a manifold connected to a bioreactor or other suspension source.

[0104] After centrifugation, a similar or equivalent rack can be used to remove the supernatant from the processing vessels 142 in each vessel adapter 18. To this end, the adapter 18 can be raised upward from the rotor 10 and then tilted (e.g., 90 degrees) until the outer wall 80 is aligned with a receptacle in the rack and the inner opening 82 is in a position (e.g., facing upward) that facilitates supernatant removal. Once aligned with the receptacle, the adapter 18 can be placed in the rack. The supernatant can be pumped from the processing vessels 142 until most of the supernatant is removed, so that the pellets are concentrated along the inner surface of the processing vessels 142 adjacent the outer wall 80 of the adapter 18. Once the pellets are concentrated, most or all of the remaining supernatant can be removed using a clamp and gravity. Alternatively, air (e.g., from a compressor) can be introduced into the processing vessels 142 to evacuate the remaining supernatant from each processing vessel 142. The manifold used to fill the processing vessels 142 can be disconnected from the processing vessels 142 before centrifugation and then reconnected to decant supernatant from one or more processing vessels 142 into a common collection bag after centrifugation. In another embodiment, the manifold used to fill the processing vessels 142 can be left in place during centrifugation and then used to remove the supernatant.

[0105] The manifold may facilitate filling and removing fluid from the processing vessel 142 during batch processing. For example, between periods of centrifugation, the supernatant may be removed and fresh suspension may be added to the processing vessel 142. Advantageously, this feature may allow multiple batches of suspension (e.g., 15 batches for a suspension that produces a small pellet) to be processed in the same processing vessel 142 until the pellets occupy a majority (e.g., 70%) of the processing vessel's 142 volume. The processing vessel 142 and adapter 18 may be configured to accommodate any desired volume of biological suspension, with a typical volume being approximately 6 liters. Filling and decanting bags used in centrifuges is described in detail in International Publication No. WO 2019 / 166998, published September 6, 2019, the entire disclosure of which is incorporated herein by reference.

[0106] In applications where the desired material is found primarily or exclusively in the supernatant, the biobag containing the cellular material may be discarded once the supernatant is removed. In other applications, once the supernatant is removed, an aqueous buffer may be added to the biobag to resuspend the cells. The resuspended cells in the buffer may then be removed from the biobag using, for example, gravity.

[0107] 5-7 depict a rotor 150 according to an alternative embodiment of the present invention. The rotor 150 includes a rotor body 152 configured to receive a plurality of adapters 154, each configured to hold one or more process vessels 156 (e.g., bottles), a drive hub 158, and a retaining nut 160. Process bottles are described in detail in U.S. Patent No. 8,215,508, issued July 10, 2012, the entire disclosure of which is incorporated herein by reference.

[0108] The rotor body 152 includes a generally circular base 162 and a circumferential sidewall 164 that define a chamber 166 with an upwardly facing opening 168. The sidewall 164 may include a stiffener 165 (e.g., carbon fiber windings, etc.), a radially outward surface, and a rim 170 that defines a periphery of the opening 168. The rotor body 152 may further include a central bore (not shown) in the base 162, a plurality of torque transfer members 172, and a torque transfer ring 174 that projects upwardly from the base 162 and is axially aligned with the central bore.

[0109] The drive hub 158 includes a hub shaft 176 extending upwardly from a drive hub flange 178. The hub shaft 176 may be cylindrical and include an upper portion 180, a threaded portion 182, a lower portion 184, and a tapered bore (not shown) configured to receive the spindle of a centrifuge. The lower portion 184 of the hub shaft 176 may be configured to engage the central hole of the base 162 and the inner bore of the torque transfer ring 174 such that the rotor 10 is axially aligned with the spindle of the centrifuge when the drive hub 158 is engaged therewith.

[0110] The torque transfer ring 174 includes a top surface 186 configured to engage the bottom surface of the retaining nut 160 so that the rotor body 152 is securely secured to the drive hub 158 when the retaining nut 160 threadedly engages the threaded portion 182 of the hub shaft 176. When the retaining nut 160 is tightened, it presses its bottom surface against the top surface 186 of the torque transfer ring 174 and the top surface of the drive hub flange 178 against the bottom surface of the base 162 to provide an axial compressive force that secures the rotor body 152 between the retaining nut 160 and the drive hub flange 178.

[0111] The torque transfer member 172 may operate to transfer torque from the centrifuge spindle to the rotor body 152 and adapter 154, transmitted through the torque transfer ring 174. In a manner similar to that described above, the torque transfer member 172 may be integral with the rotor body 152, such that the base 162, sidewall 164, torque transfer member 172, and torque transfer ring 174 are formed from a single piece of material, for example, using a molding process.

[0112] Each torque transfer member 172 of the rotor body 152 includes radially aligned ribs 179 extending radially from the torque transfer ring 174 toward the sidewall 164 and axially aligned ribs 188 extending axially upward from the base 162 toward the opening 168. The radially aligned ribs 179 may include an arcuate taper having a wide end and a narrow end, and the wide end of the taper may be joined to the upper surface of the base 162. The axially aligned ribs 188 may also include an arcuate taper having a wide end and a narrow end, and the wide end of the taper may be joined to the radially inward surface of the sidewall 164.

[0113] The torque transfer member 172 may define a plurality of circumferentially spaced receptacles 194 (e.g., eight receptacles) each configured to receive a corresponding adapter 154. The arcuate taper of the radially and axially aligned ribs 179, 188 may provide a smooth transition between adjacent surfaces of the torque transfer member 172 and the rotor body 152 and may also enable the adapters 154 to be placed into and removed from their respective receptacles 194 using axial movement.

[0114] Each adapter 154 includes a generally rectangularly shaped adapter body 196 and an adapter handle 198 that provides a grip. The adapter handle 198 may project upward from the adapter body 196, thereby facilitating placement of the adapter 154 in and removal from the rotor body 152. The adapter body 196 may include one or more (e.g., two) radially inward cavities 200 and two oppositely circumferentially extending lobes 202, each configured to engage an adjacent axially-aligned rib 188. The lobes 202 may have a radius of curvature that matches the radius of curvature of the arcuate taper of the axially-aligned ribs 188. The lobes 202 may be configured to engage the axially-aligned ribs 188 to prevent radial or circumferential movement of the adapter 154 during centrifugation.

[0115] Each of the radially inward cavities 200 may be oriented generally horizontally and configured to receive a process vessel 156. The process vessel 156 may be loaded into the adapter 154 while the adapter 154 is outside of the rotor 150. The ability to load the process vessel 156 into the adapter 154 while the adapter 154 is outside of the rotor 150 may allow for a reduced distance between the axial end of the process vessel 156 and the drive hub 158 compared to rotors in which the process vessel 156 is inserted directly into the rotor.

[0116] While the present invention has been illustrated by the description of specific embodiments thereof, and these embodiments have been described in considerable detail, it is not intended to restrict or in any way limit the scope of the appended claims to such details. Accordingly, the various features discussed herein may be used alone or in any combination. Additional advantages and modifications will be readily apparent to those skilled in the art. Therefore, the invention in its broader aspects is not limited to the specific details, representative apparatus and methods, and illustrative examples shown and described. Accordingly, departures from such details may be made without departing from the scope or spirit of the general inventive concept.

Claims

1. 1. A rotor for a centrifuge, comprising: a rotor body defining a plurality of first receptacles circumferentially spaced about an axis of rotation of the rotor body; a plurality of adapters, each configured to engage a respective first receptacle to receive a process vessel and such that each adapter is held in place within the rotor by the respective first receptacle; a rotor liner including a plurality of second receptacles arranged circumferentially about the rotational axis of the rotor body, each second receptacle configured to be received by a respective one of the first receptacles; A rotor comprising:

2. 2. The rotor of claim 1, wherein each of the adapters and each of the first receptacles are configured such that the adapter is axially inserted into and removed from its respective first receptacle.

3. The rotor of claim 2 , wherein each adapter is configured to engage a respective second receptacle such that each adapter is held in place within the rotor by the respective second receptacle.

4. the rotor body including a base having an upper surface and a plurality of radially aligned ribs extending upwardly from the upper surface of the base; A rotor according to any preceding claim, wherein the radially aligned ribs at least partially define the receptacle.

5. The rotor of claim 4 , further comprising a rotor liner including a plurality of pockets each configured to engage a respective radially aligned rib of the rotor body.

6. the rotor body including a circumferential sidewall having a radially inwardly facing surface, a plurality of axially aligned ribs extending inwardly from the radially inwardly facing surface of the circumferential sidewall, each pair of circumferentially adjacent axially aligned ribs at least partially defining one of the receptacles; 6. The rotor of claim 1, wherein the axially aligned ribs include a first arcuate taper having a wide end and a narrow end, the wide end of the first arcuate taper being joined to a radially inward surface of the circumferential sidewall.

7. The rotor body is a torque transmission ring disposed symmetrically about the axis of rotation and having a radially outward facing surface; a plurality of radially aligned ribs extending from the radially outward surface of the torque transfer ring to the radially inward surface of the circumferential sidewall; the rotor body includes a base having an upper surface, the radially aligned ribs extending upwardly from the upper surface of the base; The rotor of claim 6 , wherein said radially aligned ribs have a second arcuate taper and are joined to said upper surface of said base by a wide end of said second arcuate taper.

8. Each adapter is a handle configured to provide a grip to facilitate placement of the adapter into one of the first receptacle and the second receptacle of the rotor body; A rotor according to any preceding claim, wherein the handle projects upwardly from the adapter.

9. The rotor of claim 8 , further comprising a lid including a bottom surface having a plurality of cavities each configured to receive an adapter handle.

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