Centrifuge and skid for separating biological components and method of use

Abstract

To provide a single-use continuous flow centrifugal separator and a modular skid in which the separator can be incorporated, in relation to a centrifugal separator in a bio-production industry.SOLUTION: A system for separating biological components, the system comprising a skids 700 and a centrifuge 12C removably disposed within a compartment 708 of the skids 700, the centrifuge inner wall comprising: And a centrifuge 12C supported on the mounting plate of the load assembly 800, the skids 700 including a housing 701 partially bounding the compartment 708A B with a mounting platform 709, and the load assembly 800 secured to the housing 701 so as to communicate with the compartment, the mount being movable between a raised position in which the mounting plate is aligned with the alignment plate and a second lowered position in which the mounting plate is disposed lower than the alignment plate.SELECTED DRAWING: Figure 48

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Application No. 63 / 115,938, filed November 19, 2020, and U.S. Provisional Application No. 63 / 219,339, filed July 7, 2021, which are hereby incorporated by specific reference.

[0002] FIELD OF THE INVENTION The present disclosure relates to centrifuges used in the bioproduction industry, and more particularly to single-use continuous flow centrifuges for separating biological fluids, solids, mixtures, solutions, and suspensions, as well as modular skids into which the separators can be incorporated. [Background technology]

[0003] Bioreactors and fermenters are used to culture a variety of different types of biological suspensions. Such suspensions are broadly defined as including cells or microorganisms and the liquid medium in which they are suspended. Once the suspension has been sufficiently cultured, it is common to separate the biological suspension into components and then harvest the separated components for subsequent analysis or use. Centrifugation is a technique often used during the isolation or analysis of various cells, organelles, and biopolymers, including proteins, nucleic acids, lipids, and carbohydrates, dissolved or dispersed in the biological suspension.

[0004] In one approach to centrifugation, a volume of suspension is dispensed from a bioreactor or fermenter into an open-top bottle. The bottle is then closed by manually capping it and then spun using a centrifugal rotor. The centrifugal force created by the rotor's rotation causes solids in the suspension, such as cells or microorganisms, to settle toward the bottom of the bottle, while lighter components collect toward the top of the bottle. Once the bottle is removed from the centrifugal rotor, the lighter components are poured out of the bottle for collection, and then the solids are removed from the bottle for collection.

[0005] While the above process is effective, it has many drawbacks. For example, in the above process, the bottles are reused, which requires each bottle to be cleaned and sterilized after each use. This process is time-consuming, labor-intensive, and requires specialized sterilization equipment, such as an autoclave. Furthermore, although the bottles are cleaned and sterilized between uses, they are used as open-top containers. As a result, when the suspension is initially dispensed into the bottle, both the suspension and the interior of the bottle are exposed to the ambient environment. Then, when the separated components are removed from the bottle, they are again exposed to the ambient environment. This exposure to the environment increases the likelihood of contamination of the suspension and / or the separated components. As a result, a subsequent purification step may be required to remove any contaminants from one or both of the separated components. In addition to the above, conventional systems can have difficulty effectively separating the lighter components from the heavier components from the bottle without causing some mixing between the two.

[0006] Furthermore, because the process operates by continuously separating discrete portions of the suspension volume, the process cannot be used where it is desired to have a continuous flow perfusion system. Similarly, where it is desired to harvest the cells / microorganisms for reuse, such as in inoculum, the prolonged removal of the cells / microorganisms from the reactor for separation can stress the cells / microorganisms and reduce their viability.

[0007] In one alternative embodiment of the above, a centrifugal rotor is provided having a cavity with an inlet and an outlet. As the centrifugal rotor rotates, a suspension is delivered into the cavity through the inlet. Heavier components of the suspension collect within the cavity against the outer wall of the rotor, while lighter components exit the cavity through the outlet. Once a predetermined amount of the heavier components has collected within the cavity, the flow of suspension is stopped and a portion of the heavier components is removed from the cavity. The flow is then resumed, and the process is repeated until the entire batch of suspension has been sufficiently separated. The cavity of the centrifugal rotor is then cleaned and sterilized for use with the next batch of suspension.

[0008] While this latter process is more efficient than the first, it still has some drawbacks. For example, it cannot function in a continuous-flow perfusion system because it still collects heavier components in a batch-type mode. Additionally, because the cells / microorganisms are collected within the rotor, they are again maintained outside the reactor for extended periods, which can reduce their viability. Centrifugal rotors are also typically very sturdy mechanical components, primarily made of metal and with many different parts assembled together. Once the rotor is finished using, it must be cleaned and sterilized for future use. As such, centrifuge rotors are expensive to manufacture and labor-intensive to maintain.

[0009] Therefore, there is a need in the art for improved separators, systems, and methods that address all or some of the above and other existing shortcomings. Summary of the Invention

[0010] A first independent aspect of the present disclosure includes a skid for use in separating biological components, the skid comprising: an enclosure bounding a compartment, the compartment being bounded in part by a mounting platform; a loading assembly secured to the housing in communication with the compartment, the loading assembly comprising: an alignment plate having a top surface with a cavity recessed therein, the cavity communicating with the compartment; a drive rotor rotatably disposed below the alignment plate and at least partially surrounding the cavity, the drive rotor including one or more magnets; a motor coupled to the drive rotor for selectively rotating the drive rotor about the cavity; and a loading assembly comprising a mounting portion at least partially surrounding the drive rotor and in communication with the compartment, the mounting portion including a mounting plate upstanding from one or more mounting elements, the mounting portion being movable between a raised position in which the mounting plate is aligned with the alignment plate and a second lowered position in which the mounting plate is disposed at a height lower than the alignment plate.

[0011] An alternative embodiment is a doorway formed in the housing and communicating with the compartment; The housing further includes a door attached thereto, the door being movable between an open position in which the door opening is exposed and a closed position in which the door covers the door opening.

[0012] In another embodiment, a notch is recessed into the exterior surface of the housing and extends between the side of the housing and the door opening, the notch bounding a channel that communicates with the compartment whether the door is in the open or closed position.

[0013] Another embodiment is a mounting platform having an opening extending therethrough; a loading assembly secured to the housing such that the alignment plate is aligned with the opening extending through the mounting platform.

[0014] In another embodiment, at least a portion of the top surface of the mounting platform, the top surface of the alignment plate, and the top surface of the mounting plate are horizontally aligned when the mounting is in the raised position.

[0015] In another embodiment, the loading assembly comprises: an annular inner sleeve surrounding the opening, the annular inner sleeve having an upper end with an alignment plate attached thereto; a receiver extending from a bottom surface of the alignment plate and projecting into the opening in the annular inner sleeve, the receiver bounding the cavity; a drive rotor at least partially disposed within the opening in the inner sleeve.

[0016] Another embodiment includes a loading assembly further comprising an annular outer sleeve surrounding the inner sleeve, the outer sleeve having an upper end with a mounting plate mounted thereon, the outer sleeve and mounting plate being movable relative to the inner sleeve.

[0017] Another embodiment is a support on which the inner sleeve stands; a pivotal mounting block secured to the support at a location spaced from the inner sleeve; a pair of pivot arms each having a first end pivotally mounted to a pivot mounting block such that the pair of pivot arms extend along opposite sides of the outer sleeve; and a pair of support pins projecting outwardly from opposite sides of the outer sleeve and connecting with corresponding ones of the pair of pivot arms.

[0018] Another embodiment further includes a linear actuator positioned to selectively raise and lower the outer sleeve relative to the inner sleeve.

[0019] In another embodiment, the one or more mounting elements comprise one or more L-shaped clips upstanding from the mounting plate and facing toward the cavity.

[0020] Another embodiment further includes one or more peristaltic pumps mounted on the exterior surface of the housing.

[0021] Another embodiment further includes one or more pinch valves mounted on the exterior surface of the housing.

[0022] Another embodiment further includes one or more of a pressure sensor, a conductivity sensor, a flow meter sensor, a pH sensor, a temperature sensor, or a turbidity sensor mounted on the exterior surface of the housing.

[0023] Another independent aspect of the present disclosure includes a system for separating a biological component, the system comprising: A skid as described above, with or without any of the alternative features described above or otherwise within the scope of this application; a centrifuge removably disposed within a compartment of the skid, the centrifuge being supported on a mounting plate of the loading assembly.

[0024] Another embodiment further includes a first fluid line fluidly coupled to the centrifuge within the compartment of the skid, the first fluid line exiting the compartment and removably secured to an exterior surface of the housing.

[0025] In another embodiment, the first fluid line is removably coupled to a peristaltic pump and / or pinch valve secured to the exterior surface of the housing.

[0026] Another embodiment further includes a sensor mounted in the first fluid line, the sensor being removably plugged into an electrical outlet formed in an exterior surface of the housing.

[0027] In another embodiment, the centrifuge is at least partially secured to the mounting plate by magnetic forces generated by one or more magnets in the drive rotor.

[0028] Another embodiment is 1. A centrifuge comprising: a separate stator bounding a chamber, the separate stator having a floor from which a receptacle projects outwardly, the receptacle bounding a recess in communication with the chamber of the separate stator; a split rotor rotatably disposed within the split stator chamber; a drive coupling portion coupled to the separation rotor and extending from the separation rotor so as to protrude into the recess of the receiving portion; a driver sleeve projecting outwardly from the floor of the split stator and at least partially surrounding the receiver of the split stator; The centrifuge further includes a separator rotor positioned such that the receiver is aligned with the cavity in the alignment plate and the one or more mounting elements engage the driver sleeve.

[0029] In another embodiment, the receivers of the isolated stators are received within the cavities of the alignment plate when the mounting plate is moved to the lowered position, and the receivers of the isolated stators are removed from within the cavities of the alignment plate when the mounting plate is moved to the raised position.

[0030] In another embodiment, the driver sleeve has one or more holes or recesses into which portions of one or more mounting elements are received.

[0031] In another embodiment, the centrifuge is rigidly secured to the skid housing by moving the mounting plate to a lowered position with one or more mounting elements engaged with the driver sleeve.

[0032] Another independent aspect of the present disclosure includes a method for separating a biological component, the method comprising: Positioning the centrifuge on the top surface of a mounting platform of a skid as described above, with or without any of the alternative features described above or otherwise within this application; moving the centrifuge laterally within the compartment of the housing so that the centrifuge is supported on the mounting plate of the mounting portion and the mounting element engages the centrifuge; moving the mounting plate to a lowered position so that the centrifuge is lowered relative to the alignment plate, wherein a drive coupling of the centrifuge is received within a cavity in the alignment plate when the mounting plate is moved to the lowered position; and operating the motor to rotate a drive rotor that magnetically rotates a separation rotor of the centrifuge.

[0033] In another embodiment, moving the centrifuge laterally includes sliding the centrifuge laterally on the mounting platform into proximity with a magnetic field generated by one or more magnets in the drive rotor, the magnetic field assisting in positioning the centrifuge.

[0034] In another embodiment, the centrifuge is rigidly secured to the skid housing by moving the mounting plate to a lowered position.

[0035] In another embodiment, the step of positioning the centrifuge on the top surface of the mounting platform comprises: Passing the centrifuge into the compartment through a doorway formed on the housing; and closing the door covering the door opening after the centrifuge is inside the compartment.

[0036] In another embodiment, the centrifuge is positioned on the top surface of the mounting platform such that a first fluid line coupled to the centrifuge exits a compartment of the housing, and the method further includes removably securing the first fluid line to a pinch valve and / or a peristaltic pump mounted on an exterior surface of the housing.

[0037] Another independent aspect of the present disclosure includes a centrifuge, the centrifuge comprising: a separate stator bounding the chamber, the separate stator having an inlet opening, a first outlet opening, and a second outlet opening; a separation rotor bounding a compartment, the separation rotor being at least partially disposed within the chamber of the separation stator and rotatable within the chamber about an axis of rotation, the separation rotor having a floor with an inner surface and an opposite bottom surface, the bowl being formed on the bottom surface of the floor and projecting outwardly from the bottom surface, the bowl bounding a recess formed on the inner surface of the floor and communicating with the compartment of the separation rotor; an annular bearing assembly extending between the separated stator and the separated rotor to enable the separated rotor to rotate relative to the separated stator, the annular bearing assembly surrounding and disposed directly adjacent to an outer surface of the bowl so as to surround at least a portion of the recess.

[0038] In another embodiment, during operation, fluid flowing between the inlet opening and the first and second outlet openings passes through a recess in the bowl to form a heat sink for the bearing.

[0039] Another embodiment further includes a plurality of fins projecting downwardly from the bottom surface of the floor and projecting radially outwardly away from the bowl.

[0040] Another independent aspect of the present disclosure includes a centrifuge, the centrifuge comprising: a separate stator bounding the chamber, the separate stator having an inlet opening, a first outlet opening, and a second outlet opening; a separation rotor bounding the compartment, the separation rotor being at least partially disposed within the chamber of the separation stator and rotatable about an axis of rotation within the chamber, the heavy component collection recess and the light component collection recess being disposed between the separation stator and the separation rotor at spaced apart positions, the heavy component collection recess communicating with the first outlet opening and the light component collection recess communicating with the second outlet opening, the separation rotor comprising: Floor and a sidewall assembly upstanding from the floor and surrounding the compartment, the sidewall assembly including a plurality of separated heavy component fluid paths, each of the plurality of separated heavy component fluid paths communicating upstream with the inlet opening and downstream with a heavy component collection recess; a separation rotor comprising: a plurality of upper partitions projecting radially inward from the sidewall assembly into the compartment to at least partially divide the compartment into a plurality of separated light component fluid paths, each of the plurality of separated light component fluid paths communicating upstream with the inlet opening and downstream with a light component collection recess; Each light component fluid pathway communicates with at least two of the separated heavy component fluid pathways but is isolated from at least some of the plurality of separated heavy component fluid pathways.

[0041] In another embodiment, each of the plurality of separated light component fluid paths extends along a length and is isolated from one another along their lengths.

[0042] In another embodiment, at least some of the plurality of separated heavy component fluid paths are isolated from others of the plurality of separated heavy component fluid paths upstream of the heavy component collection recess.

[0043] In another embodiment, each light component fluid pathway communicates with two or three of the separated heavy component fluid pathways but is isolated from the remainder of the plurality of separated heavy component fluid pathways.

[0044] In another embodiment, the sidewall assembly includes an annular outer sidewall and an annular inner sidewall surrounded by the outer sidewall, and the plurality of separated heavy component fluid paths are bounded between the inner sidewall and the outer sidewall.

[0045] Another embodiment further includes a plurality of dividers extending between the inner and outer sidewalls and separating the heavy component fluid paths from each other.

[0046] In another embodiment, the outer sidewall extends to the floor and the inner sidewall is spaced from the floor.

[0047] In another embodiment, at least a portion of the outer sidewall has a frustoconical configuration.

[0048] In another embodiment, at least a portion of the inner sidewall has a frustoconical configuration.

[0049] In another embodiment, a plurality of top compartments project radially inward from the outer and inner sidewalls.

[0050] Another embodiment further includes a tubular conduit disposed within the compartment of the separated stator along the rotational axis, the tubular conduit having a first end coupled to the inlet opening of the separated stator and an opposite second end.

[0051] Another embodiment further includes a dispersion member disposed within the compartment of the separation rotor, the dispersion member having a body positioned above the floor such that a space is formed between the floor and the body of the dispersion member.

[0052] In another embodiment, the dispersion member has an opening through its center, the second end of the conduit is coupled to or passes through the opening in the dispersion member, and the conduit is configured such that fluid passing through the conduit from the inlet opening exits the conduit within a space formed between the floor and the body of the dispersion member.

[0053] In another embodiment, a plurality of upper partitions extend radially from the conduit and along the top surface of the body of the dispersion member.

[0054] In another embodiment, the body of the dispersion member has a flat plate configuration or a frusto-conical configuration.

[0055] Another embodiment further includes a plurality of lower partitions extending between the body and the floor of the dispersion member, the plurality of lower partitions extending radially outward from the opening in the dispersion member.

[0056] In another embodiment, the lower bulkheads extend to the sidewall assembly and are aligned with corresponding ones of the plurality of upper bulkheads.

[0057] In another embodiment, the second end of the conduit is disposed outside the isolated rotor and rotatably secured to the isolated stator by a bearing assembly.

[0058] Another embodiment is a drive coupling secured to the floor of the separation rotor so as to project outward; and a drive rotor surrounding the drive coupling, the drive rotor producing a magnetic field on the drive coupling such that rotation of the drive rotor facilitates rotation of the drive coupling.

[0059] In another embodiment, the drive coupling is disposed within the isolated stator and the drive rotor is disposed outside the isolated stator.

[0060] In another embodiment, the isolated rotor further comprises a stem assembly coupled to the first end of the sidewall assembly, the stem assembly comprising a stem, the stem comprising: a tubular spout having an interior surface and an opposite exterior surface, the interior surface bounding a light component collection channel providing fluid communication between each of the light component fluid paths and the light component collection recess; and a plurality of partitions projecting radially outward from the outer surface of the tubular spout and at least partially bounding a plurality of heavy collecting channels, the heavy collecting channels being in fluid communication with the heavy component fluid path.

[0061] In another embodiment, the stem assembly further comprises a tubular sleeve surrounding the stem, the tubular sleeve having an inner surface and an opposite outer surface, with a plurality of radially spaced openings extending through the tubular sleeve between the inner and outer surfaces, each of the plurality of openings providing fluid communication between the heavy collection channel and the heavy component collection recess.

[0062] In another embodiment, the sleeve and stem are made of different materials.

[0063] In another embodiment, the material of the sleeve is more thermally conductive than the material of the stem.

[0064] In another embodiment, the sleeve is made of a metal and the stem is made of a polymer.

[0065] Another embodiment further includes one or more seals disposed between the split stator and the sleeve.

[0066] Another embodiment further includes a tubular spout first end that flares radially outward away from the axis of rotation and terminates in an annular end surface, with the sleeve disposed against the annular end surface of the spout.

[0067] Another embodiment further includes one or more bearing assemblies disposed between the isolated stator and the isolated rotor.

[0068] In another embodiment, the chamber of the separated stator extends between a first end and an opposite second end, and the inlet opening, the first outlet opening, and the second outlet opening are each disposed at or toward the first end.

[0069] In another independent aspect of the present disclosure, the centrifuge comprises: a separate stator bounding the chamber, the separate stator having an inlet opening, a first outlet opening, and a second outlet opening; a separate rotor bounding the compartment, the separate rotor being at least partially disposed within the chamber of the separate stator and rotatable within the chamber about an axis of rotation, the separate rotor comprising: A floor portion and a sidewall assembly upstanding from the floor and surrounding the compartment, the sidewall assembly including a plurality of separated heavy component fluid paths, each of the plurality of separated heavy component fluid paths communicating upstream with the inlet opening and downstream with the first outlet opening; a plurality of upper partitions projecting radially inwardly from the sidewall assembly into the compartment so as to at least partially divide the compartment into a plurality of separated light component fluid paths, each of the plurality of separated light component fluid paths communicating upstream with the inlet opening and downstream with the second outlet opening; a stem assembly coupled to the first end of the sidewall assembly, the stem assembly comprising: a stem made from a material, the stem including a tubular spout having an interior surface and an opposite exterior surface, the interior surface bounding at least one light component collection channel providing fluid communication between the light component fluid path and the second outlet opening; a stem assembly comprising: a tubular sleeve surrounding the stem and having an inner surface and an opposite outer surface, at least one heavy component collection channel disposed between the stem and the sleeve and providing fluid communication between the plurality of heavy component fluid paths and the first outlet.

[0070] In another embodiment, the tubular sleeve comprises a first heat dissipation portion having an interior surface and an opposite exterior surface, the interior surface of the first heat dissipation portion directly bounding a portion of the at least one heavy collection channel.

[0071] Another embodiment further includes a seal disposed between the split stator and the tubular sleeve, the seal bearing directly against an inner surface of the first heat dissipation portion of the sleeve.

[0072] In another embodiment, the tubular sleeve comprises a second heat dissipating portion having an inner surface and an opposite outer surface, the inner surface of the second heat dissipating portion directly bounding a portion of the at least one light collection channel.

[0073] Another embodiment further includes a seal disposed between the split stator and the tubular sleeve, the seal bearing directly against an inner surface of the second heat dissipation portion of the sleeve.

[0074] In another embodiment, the tubular sleeve is made from a material that is more thermally conductive than the material of the stem.

[0075] In another embodiment, the tubular sleeve has a thickness extending between its inner and outer surfaces of less than 2.5 mm.

[0076] Another embodiment is the stem further comprises a plurality of partitions projecting radially outward from the exterior surface of the tubular spout; The at least one heavy collecting channel comprises a plurality of heavy collecting channels separated by a plurality of partitions.

[0077] Another embodiment further includes a tubular sleeve having a first end and an opposite second end and having a plurality of radially spaced openings extending through the tubular sleeve between the inner surface and the outer surface so as to be disposed between the first end and the second end, each of the plurality of openings being aligned with a corresponding one of the plurality of heavy collection channels to provide fluid communication between the heavy collection channel and the first outlet.

[0078] Another embodiment is a first seal disposed between the split stator and the tubular sleeve, the first seal disposed at a first end of the tubular sleeve directly against an outer surface of the tubular sleeve to provide a fluid-tight seal between the split stator and the tubular sleeve; and a second seal disposed between the split stator and the tubular sleeve, the second seal disposed at a second end of the tubular sleeve directly against an outer surface of the tubular sleeve to provide a fluid-tight seal between the split stator and the tubular sleeve.

[0079] Another embodiment further includes a heavy component collection recess disposed between the separated stator and the separated rotor, the heavy component collection recess being in fluid communication upstream with each of the plurality of separated heavy component fluid paths and in fluid communication downstream with the first fluid outlet.

[0080] Another embodiment further includes a light component collection recess disposed between the separated stator and the separated rotor, the light component collection recess being in fluid communication upstream with each of the plurality of separated light component fluid paths and in fluid communication downstream with the second fluid outlet.

[0081] In another embodiment, the plurality of light component fluid paths are separated from the plurality of heavy component fluid paths and disposed radially inward of the plurality of heavy component fluid paths.

[0082] In another independent aspect of the present disclosure, the centrifuge comprises: a separate stator bounding the chamber, the separate stator having an inlet opening, a first outlet opening, and a second outlet opening; a separation rotor bounding the compartment, the separation rotor being at least partially disposed within the chamber of the separation stator and rotatable within the chamber about an axis of rotation, the separation rotor comprising: A floor portion and a sidewall assembly upstanding from the floor and surrounding the compartment, the sidewall assembly including an annular outer sidewall and an annular inner sidewall surrounded by the outer sidewall, a plurality of separated heavy component fluid paths being bounded between the inner sidewall and the outer sidewall, the outer sidewall including an upper sidewall portion having an inner surface with a frustoconical configuration, the inner surface of the upper sidewall portion being inclined at an angle in the range of 40° to 50° relative to the axis of rotation, each of the plurality of separated heavy component fluid paths communicating upstream with the inlet opening and downstream with the first outlet; and a separation rotor comprising a plurality of upper partitions protruding radially inward from the sidewall assembly into the compartment to at least partially divide the compartment into a plurality of separated light component fluid paths, each of the plurality of separated light component fluid paths communicating upstream with the inlet opening and downstream with the second outlet.

[0083] In another embodiment, the outer sidewall extends to the floor and the inner sidewall is spaced from the floor.

[0084] In another embodiment, at least a portion of the inner sidewall has a frustoconical configuration.

[0085] Another embodiment further includes a tubular conduit disposed within the compartment of the separated stator along the rotational axis, the tubular conduit having a first end coupled to the inlet opening of the separated stator and an opposite second end.

[0086] Another embodiment further includes a dispersion member disposed within the compartment of the separation rotor at a location above the floor such that a space is formed between the floor and the dispersion member.

[0087] In another embodiment, the dispersion member has an opening through its center, the second end of the conduit is coupled to or passes through the opening in the dispersion member, and the conduit is configured such that fluid passing through the conduit from the inlet opening exits the conduit within a space formed between the floor and the dispersion member.

[0088] In another independent aspect of the present disclosure, the centrifuge comprises: a separate stator bounding the chamber, the separate stator having an inlet opening, a first outlet opening, and a second outlet opening; a separation rotor bounding the compartment, the separation rotor being at least partially disposed within the chamber of the separation stator and rotatable within the chamber about an axis of rotation, the separation rotor comprising: A floor portion and a sidewall assembly upstanding from the floor and surrounding the compartment, the sidewall assembly including an annular outer sidewall and an annular inner sidewall surrounded by the outer sidewall, the outer sidewall extending to the floor and the inner sidewall spaced apart from the floor, a plurality of separated heavy component fluid paths bounded between the inner sidewall and the outer sidewall, each of the plurality of separated heavy component fluid paths communicating upstream with the inlet opening and downstream with the first outlet; a dispersion member disposed within the compartment of the separation rotor at a location above the floor such that a space containing a portion of the compartment is formed between the floor and the dispersion member, the dispersion member having a top surface and an opposite bottom surface, an opening extending through the center of the dispersion member between the top and bottom surfaces; a tubular conduit disposed at least partially within the compartment of the separated stator along the axis of rotation, the tubular conduit having a first end coupled to an inlet opening of the separated stator and an opposite second end coupled to or passing through an opening in the distribution member, wherein fluid passing through the conduit from the inlet opening exits the conduit within a space formed between the floor and the distribution member; a plurality of upper partitions extending between the inner sidewall and an upper surface of the dispersion member and projecting radially outward from the tubular conduit, the plurality of upper partitions dividing at least a portion of the compartment into a plurality of separated light component fluid paths, each of the plurality of separated light component fluid paths communicating upstream with the inlet opening and downstream with the second outlet; and a separated rotor comprising a plurality of lower partition walls extending between the floor and the lower surface of the dispersion member and projecting radially inward from the outer sidewall in alignment with the rotation axis, the plurality of lower partition walls at least partially dividing the space into a plurality of separated inlet fluid paths, each of the plurality of separated inlet fluid paths communicating upstream with the inlet opening and communicating downstream with both the plurality of separated light component fluid paths and the plurality of separated heavy component fluid paths.

[0089] In another embodiment, each of the plurality of separated inlet fluid paths communicates with at least two of the plurality of separated heavy component fluid paths but is isolated from at least some of the plurality of separated heavy component fluid paths.

[0090] In another embodiment, at least a portion of the outer sidewall has a frustoconical configuration and at least a portion of the inner sidewall has a frustoconical configuration.

[0091] In another embodiment, at least some of the upper partitions extend to the outer sidewall and intersect with a corresponding one of the lower partitions.

[0092] In another embodiment, a tubular conduit extends through the floor of the isolation rotor, and a plurality of lower bulkheads project radially outward from the conduit.

[0093] In another independent aspect of the present disclosure, a method for separating a biological suspension comprises: Culturing biological cells or microorganisms in a suspension in a reactor vessel, the suspension further comprising a culture medium; Passing an inlet stream of suspension from the reactor vessel through an inlet opening of a centrifuge as defined in claim 1, 30, 43, or 49, wherein the centrifuge separates the inlet stream into a first outlet stream that exits the centrifuge through a first outlet opening and a second outlet stream that exits the centrifuge through a second outlet opening, the first outlet stream having a higher density or percent of solids than the second outlet stream.

[0094] Another embodiment further comprises returning the first outlet stream to the reactor vessel.

[0095] Another embodiment further comprises passing the first outlet stream to a collection vessel separate from the reactor.

[0096] Another embodiment further includes continuously operating the centrifuge for a period of at least 20 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 24 hours, or 48 hours to separate the suspension into the first outlet stream and the second outlet stream.

[0097] Another embodiment is using a first pump to control a flow rate of the first outlet stream out of the first outlet opening; and using a second pump to control the flow rate of the second outlet stream out of the second outlet opening.

[0098] Another embodiment is using a first control valve to control a flow rate of the first outlet stream out of the first outlet opening; and using a second control valve to control the flow rate of the second outlet stream out of the second outlet opening.

[0099] Another embodiment further comprises mixing the suspension in the reactor vessel while the centrifuge is operating.

[0100] In another embodiment, the first outlet stream and the second outlet stream exit the centrifuge simultaneously as the inlet stream enters the centrifuge.

[0101] Another embodiment further includes passing the second outlet stream through a second centrifuge.

[0102] In another independent aspect of the present disclosure, a method for separating a biological suspension comprises: Culturing biological cells or microorganisms in a suspension in a reactor vessel, the suspension further comprising a culture medium; passing an inlet stream of the suspension from the reactor vessel through an inlet opening of a centrifuge, the centrifuge separating the inlet stream into a first outlet stream that exits the centrifuge through a first outlet opening and a second outlet stream that exits the centrifuge through a second outlet opening, the first outlet stream having a higher density or percent of solids than the second outlet stream.

[0103] In another independent aspect of the present disclosure, a modular system for separating a biological component comprises: a skid having a base, sidewalls, and a top forming an enclosure having an enclosure compartment; a motor positioned at least partially within the housing compartment; a magnetic drive comprising a drive rotor mechanically coupled to a motor, the drive rotor having an interior surface bounding a cavity and at least one magnet mounted on the interior surface, the magnet generating a magnetic field; 1. A centrifuge assembly comprising: a stator having a base, sidewalls, and a top that form a stator chamber, the stator having a fluid inlet port and at least two fluid outlet ports; a separation rotor rotatably coupled to the stator chamber and in fluid communication with the inlet port and at least two outlet ports of the stator, the separation rotor forming a separation vessel; a drive coupling having a first end mechanically coupled to and extending from the separation rotor and a second magnetic end magnetically coupled to the drive rotor, the second magnetic end positioned proximate to a magnetic field to generate an alignment force that aligns a central axis of the separation rotor with a central axis of the drive rotor; The stator chamber includes a centrifuge assembly that forms a sterile and hermetic seal around the isolated rotor and drive coupling.

[0104] In another embodiment, at least a portion of the magnetic driver and the drive coupling are arranged within the housing compartment.

[0105] In another embodiment, the stator further comprises a recess forming a housing shroud extending from the bottom surface of the stator for receiving and housing the drive coupling.

[0106] In another embodiment, the stator includes a mounting surface and the housing includes mounting clips extending from a surface of the housing and engaging the mounting surface for mechanically coupling the stator to the housing.

[0107] In another embodiment, the mounting clip is positioned to apply a downward force to the mounting surface and the stator.

[0108] In another embodiment, the mounting surface is a flange, a slot, a cavity, or an elbow.

[0109] Another embodiment is a loading assembly comprising: a mounting platform coupled to the housing compartment and extending laterally across the housing compartment, the mounting platform including a recess and a movable mounting plate coupled to the mounting platform and positioned at least partially within the recess; a mounting clip protruding from a surface of the mounting plate; and a linear actuator having an arm having a first end coupled to the movable mounting plate, the linear actuator configured to move the arm and the movable mounting plate to move the mounting clip to a secured position and an unlocked position.

[0110] Another embodiment further includes an inlet pump coupled to the housing compartment and in fluid communication with the fluid inlet port of the stator.

[0111] In another embodiment, the inlet pump is a centrifugal pump.

[0112] Another embodiment further includes at least one outlet pump coupled to the housing compartment and in fluid communication with the at least two fluid outlet ports.

[0113] In another embodiment, the outlet pump is a peristaltic pump.

[0114] In another embodiment, the centrifuge assembly is removably attached to the housing by a magnetic field.

[0115] Another embodiment further includes a programmable power supply in wired or wireless communication with a controller comprising a memory, a processor, and a non-transitory computer-readable medium, the non-transitory computer-readable medium including instructions that are executed by the processor to control the programmable power supply to provide power to the motor.

[0116] Another embodiment further includes a programmable power supply in wired or wireless communication with a controller comprising a memory, a processor, and a non-transitory computer-readable medium, the non-transitory computer-readable medium including instructions that are executed by the processor to control the programmable power supply to provide power to the inlet pump and the outlet pump.

[0117] In another independent aspect of the present disclosure, a method for separating a biological component comprises: pumping a culture comprising medium and cells or microorganisms from the bioprocess container to a centrifuge with an inlet pump through an inlet line; The centrifuge includes a stator having an inlet port, a light outlet port, a heavy outlet port, and a separation rotor rotatably coupled to the stator and in fluid communication with the inlet port, the light outlet port, and the heavy outlet port; an inlet pump located downstream of the bioprocess container and upstream of the centrifuge and in fluid communication with the bioprocess container and the centrifuge; venting gas from the inlet line, inlet pump and centrifuge along with the culture; measuring turbidity downstream of the centrifuge using a turbidity sensor; and rotating the separation rotor to apply a rotational force to the culture based on the turbidity downstream of the centrifuge.

[0118] Another embodiment further includes measuring a pressure downstream of the centrifuge with a pressure sensor and providing a first power input to the inlet pump based on the pressure downstream of the centrifuge.

[0119] Another embodiment is providing a first electrical power input to a lights outlet pump in fluid communication with the lights outlet port based on turbidity downstream of the centrifuge; Further comprising providing a second electrical power input to a heavy outlet pump in fluid communication with the heavy outlet port based on the turbidity downstream of the centrifuge.

[0120] Another embodiment is providing a second electrical power input to a lights outlet pump in fluid communication with the lights outlet port based on the turbidity and pressure downstream from the centrifuge; and providing a third power input to a heavy outlet pump in fluid communication with the heavy outlet port based on the turbidity and pressure downstream of the centrifuge.

[0121] Another embodiment further includes removably mounting the centrifuge on a skid that houses the inlet pump.

[0122] In another embodiment, removably loading the centrifuge includes moving the centrifuge into proximity with a magnetic field at a surface of the skid that provides a magnetic force coupling the centrifuge to the skid.

[0123] Another embodiment further includes measuring an inlet pressure at the inlet of the centrifuge with an inlet pressure sensor and ceasing operation of the centrifuge when the inlet pressure reaches a predetermined stop inlet pressure.

[0124] In another embodiment, the inlet pump is a centrifugal pump.

[0125] In another independent aspect of the disclosure, a controller comprises a memory, a processor, and a non-transitory computer-readable medium containing instructions for execution by the processor, the instructions comprising: pumping a culture comprising medium and cells or microorganisms from the bioprocess container to a centrifuge with an inlet pump through an inlet line; The centrifuge includes a stator having an inlet port, a light outlet port, a heavy outlet port, and a separation rotor rotatably coupled to the stator and in fluid communication with the inlet port, the light outlet port, and the heavy outlet port; an inlet pump located downstream of the bioprocess container and upstream of the centrifuge and in fluid communication with the bioprocess container and the centrifuge; venting gas from the inlet line, inlet pump and centrifuge along with the culture; measuring turbidity downstream of the centrifuge using a turbidity sensor; Rotating the separation rotor and applying a rotational force to the culture based on the turbidity downstream of the centrifuge.

[0126] It should be understood that each of the independent aspects described herein may include any of the features, options, and possibilities described in relation to the other independent aspects described herein or described elsewhere within this specification. [Brief explanation of the drawings]

[0127] Various embodiments of the present disclosure will now be described with reference to the accompanying drawings, It should be understood that these drawings illustrate only typical embodiments of the disclosure and therefore should not be considered limiting of the scope of the disclosure. [Figure 1] FIG. 1 is a schematic diagram of a system incorporating a reactor and a continuous flow centrifuge. [Figure 2] FIG. 2 is a front elevation view of a manifold assembly that can be used in the system of FIG. 1. [Figure 3] FIG. 2 is a schematic diagram of the system shown in FIG. 1 with modified flow control components. [Figure 4] FIG. 2 is a cross-sectional view of one embodiment of the centrifuge shown in FIG. 1. [Figure 5] FIG. 2 is a schematic diagram of a modified version of the system shown in FIG. 1. [Figure 6] FIG. 6 is a top perspective view of a centrifuge that can be used in the systems of FIGS. 1, 3 and 5. [Figure 7] FIG. 7 is a bottom perspective view of the centrifuge shown in FIG. 6. [Figure 8] FIG. 7 is a partial exploded view of the centrifuge shown in FIG. 6. [Figure 9] FIG. 7 is a front cross-sectional view of the centrifuge shown in FIG. 6. [Figure 10]FIG. 10 is a front view of the separation stator of the centrifuge shown in FIG. 9, exploded from the rotor assembly. [Figure 11] FIG. 11 is an exploded perspective view of the separation rotor shown in FIG. [Figure 12] FIG. 12 is a bottom perspective view of the cap portion of the separated rotor shown in FIG. [Figure 13] FIG. 10 is an enlarged cross-sectional view of a first end of the centrifuge shown in FIG. 9. [Figure 14] FIG. 14 is a partial exploded view of a first end of the centrifuge shown in FIG. 13. [Figure 15] FIG. 15 is an exploded view of the stem assembly shown in FIG. 14. [Figure 16] FIG. 15 is a perspective view of the assembled components shown in FIG. 14. [Figure 17] FIG. 12 is a bottom perspective view of the insert shown in FIG. [Figure 18] FIG. 7 is a front elevational cross-sectional view of the centrifuge shown in FIG. 6. [Figure 19] 19 is a cross-sectional view of the isolated rotor shown in FIG. 18 taken along line 19-19. [Figure 20] FIG. 10 is a front elevation cross-sectional view of another embodiment of a centrifuge. [Figure 21] FIG. 21 is a top perspective view of the dispersion member shown in FIG. 20. [Figure 22] FIG. 10 is a top perspective view of an alternative embodiment of a centrifuge. [Figure 23] FIG. 23 is a bottom perspective view of the centrifuge shown in FIG. 22. [Figure 24] FIG. 23 is a cross-sectional view of the centrifuge shown in FIG. 22. [Figure 25] FIG. 23 is a partial exploded view of the centrifuge shown in FIG. 22. [Figure 26] FIG. 26 is an exploded view of the separation rotor shown in FIG. 25. [Figure 27] FIG. 27 is a perspective view of the inside of the base of the separated rotor shown in FIG. 26. [Figure 28] FIG. 28 is a perspective view of a bottom view of the base shown in FIG. 27. [Figure 29] FIG. 27 is a top perspective view of the dispersion member shown in FIG. 26. [Figure 30]FIG. 30 is a bottom perspective view of the dispersion member shown in FIG. 29. [Figure 31] FIG. 27 is a top perspective view of the disk shown in FIG. 26. [Figure 32] FIG. 32 is a bottom perspective view of the disk shown in FIG. 31. [Figure 33] FIG. 27 is a bottom perspective view of the cap portion shown in FIG. 26. [Figure 34] 23 is an enlarged side cross-sectional view of the peripheral portion of the separated rotor shown in FIG. 22. [Figure 35] FIG. 27 is a top perspective view of the insert shown in FIG. 26. [Figure 36] FIG. 36 is a bottom perspective view of the insert shown in FIG. 35. [Figure 37] FIG. 23 is an enlarged cross-sectional view of the upper end of the centrifuge shown in FIG. 22. [Figure 38] FIG. 23 is a further cross-sectional view of the centrifuge shown in FIG. 22. [Figure 39] FIG. 23 is a cross-sectional view of the centrifuge shown in FIG. 22. [Figure 40] FIG. 10 is an enlarged side cross-sectional view of the periphery of an alternative split rotor. [Figure 41] FIG. 10 is an enlarged cross-sectional side view of the periphery of another alternative split rotor. [Figure 42] FIG. 23 is a front perspective view of a skid for use with the centrifuge of FIG. [Figure 43] FIG. 43 is a rear perspective view of the skid shown in FIG. 42. [Figure 44] FIG. 43 is an elevated side view of the skid shown in FIG. 42. [Figure 45] FIG. 43 is an elevated rear view of the skid shown in FIG. 42. [Figure 46] FIG. 43 is a front perspective view of the skid shown in FIG. 42 with the door removed. [Figure 47] FIG. 47 is a front perspective view of the skid shown in FIG. 46 with the centrifuge removed. [Figure 48] FIG. 46 is a cross-sectional view of the skid shown in FIG. 45. [Figure 49] FIG. 43 is a front perspective view of the loading assembly of the skid shown in FIG. 42 in a lowered position. [Figure 50]FIG. 50 is a front perspective view of the loading assembly shown in FIG. 49 in a raised position. [Figure 51] FIG. 50 is a rear perspective view of the loading assembly shown in FIG. 49. [Figure 52] FIG. 50 is a cross-sectional view of the loading assembly shown in FIG. 49. [Figure 53] FIG. 50 is an enlarged cross-sectional view of the loading assembly of FIG. 49 coupled with a centrifuge. [Figure 54] FIG. 1 is a schematic diagram of an exemplary centrifuge skid incorporated into an exemplary bioproduction process. [Figure 55A] FIG. 1 illustrates a process flow diagram of an exemplary process for operating an exemplary centrifuge skid. [Figure 55B] FIG. 1 illustrates a process flow diagram of an exemplary process for operating an exemplary centrifuge skid. [Figure 55C] FIG. 1 illustrates a process flow diagram of an exemplary process for operating an exemplary centrifuge skid. [Figure 56] FIG. 1 illustrates a process flow diagram of an exemplary process for operating an exemplary centrifuge skid. [Figure 57] 1 illustrates bar graphs of process performance parameters generated from an exemplary separation process carried out with an exemplary skid-mounted centrifuge. [Figure 58] 1 illustrates an exemplary pressure-volume depth filtration curve. DETAILED DESCRIPTION OF THE INVENTION

[0128] Before describing the present disclosure in detail, it is to be understood that this disclosure is not limited to particularly exemplified apparatus, systems, methods, or process parameters, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments of the present disclosure only, and is not intended to limit the scope of the present disclosure in any way.

[0129] All publications, patents, and patent applications cited in this specification, whether supra or infra, are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

[0130] The term "comprising," which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps.

[0131] It should be noted that as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly indicates otherwise. So, for example, reference to a "septum" includes one, two, or more septums.

[0132] As used in this specification and the appended claims, directional terms such as "top," "bottom," "left," "right," "upper," "lower," "superior," "lower," "proximal," "distal," and the like, are used herein merely to indicate relative directions and are not intended to limit the scope of the disclosure or the claims.

[0133] Where possible, similar element numbering is used in the various figures. Furthermore, multiple instances of an element and / or sub-elements of a parent element may each include a separate letter appended to the element number. For example, two instances of a particular element "10" or two alternative embodiments of a particular element may be labeled "10A" and "10B." In that case, the element label may be used without an appended letter (e.g., "10") to generally refer to all instances of the element or any one of the elements. An element label including an appended letter (e.g., "10A") may be used to refer to a particular instance of the element or to distinguish or draw attention to multiple uses of the element. Furthermore, an element label with an appended letter may be used to designate alternative designs, structures, functions, implementations, and / or embodiments of an element or feature without the appended letter. Similarly, an element label with an appended letter may be used to indicate sub-elements of a parent element. For example, element "12" may comprise sub-elements "12A" and "12B."

[0134] Various aspects of the present devices and systems may be illustrated by describing components that are coupled, attached, and / or joined together. As used herein, the terms “coupled,” “attached,” and / or “joined” are used to indicate either a direct connection between two components or, where appropriate, an indirect connection to one another through intervening or intermediate components. In contrast, when a component is referred to as being “directly coupled,” “directly attached,” and / or “directly joined” to another component, no intervening components are present. Furthermore, as used herein, terms such as “connection,” “connected,” and the like do not necessarily imply direct contact between two or more elements.

[0135] Various aspects of the present devices, systems, and methods may be illustrated with reference to one or more exemplary embodiments. As used herein, the term "embodiment" means "serving as an example, instance, or illustration," and should not necessarily be construed as preferred or advantageous over other embodiments disclosed herein.

[0136] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although many methods and materials similar or equivalent to those described herein can be used in the practice of this disclosure, the preferred materials and methods are described herein.

[0137] Generally, the present disclosure relates to centrifuge systems used in the bioproduction industry to separate biological components. More specifically, the present disclosure is directed to centrifuges for separating biological components, such as biological fluids, solids, mixtures, solutions, and suspensions, including media, cells, blood, plasma, organelles, proteins, nucleic acids, lipids, plasmids, viral vectors, nucleic acids, and / or carbohydrates dissolved or dispersed in biological mixtures, solutions, and suspensions. The centrifuges can be manually portable, single-use, continuous-flow, and / or closed-system centrifuges used in separating biological components. The present disclosure also relates to methods, systems, and modular skids that can incorporate such centrifuges.

[0138] Although the devices and methods disclosed herein are primarily designed for use in biological processes, the devices and methods of the present disclosure can also be used in non-biological processes where it is desirable to separate solids from liquids using a centrifuge. Such applications can be found in the manufacture of chemicals, pharmaceuticals, food, and other products. Therefore, the descriptions and examples provided herein for separating biological components and collecting the separated components are also applicable to, and should be considered as, a disclosure for separating non-biological components and collecting the separated components.

[0139] An exemplary centrifuge system / skid can provide a sealed, sterile environment for continuous flow separation of biological components in liquid, solid, gas, and mixed phase separations. Embodiments disclosed herein can be modular, sterile, portable, and continuous flow centrifuge systems, including centrifuge skids, that improve process efficiency, product purification, and yield.

[0140] The exemplary centrifuge system / skid is also portable and easily transported to a bioproduction facility and integrated into a bioproduction process, typically downstream, to purify biological products. To account for a diverse set of bioproduction processes, equipment, and control requirements, the exemplary centrifuge system / skid can incorporate mounting arrangements and single-use, disposable, and modular separators and other components that are easily installed and removed to increase the versatility, efficiency, and yield of continuous-flow centrifugation. For example, in one embodiment, the exemplary mounting arrangement can include controller mountings, pump mountings, sensor ports, valve ports, terminals and manifolds, bulkhead connectors, motor mountings, tubing holders, and a cable management system. These mountings can facilitate portability, universal compatibility, and ease of installation across a wide range of bioproduction process equipment, tubing, cables, controllers, motors, pumps, sensors, and valves.

[0141] Additionally, an exemplary centrifuge system / skid may be equipped with a loading assembly that may magnetically, mechanically, and / or releasably load, mount, center, and lock the centrifuge to the skid. Preferably, the centrifuge is a single-use, disposable assembly that can be easily and quickly removed, disposed of, and replaced with a sterile separator to increase efficiency in continuous flow processes.

[0142] Illustrated in FIG. 1 is an exemplary embodiment of a system incorporating features of the present disclosure and used to separate a biological suspension or other mixture and harvest one or more of its components. More specifically, FIG. 1 illustrates a biological production vessel 10 fluidly coupled to a continuous-flow centrifuge 12. The biological production vessel 10 is configured to culture a biological suspension and may comprise one or more bioreactors, fermentors, storage vessels, fluid management systems, cell culture equipment, or any other device designed to culture or produce cells and / or other biological products. An example of such other devices may include the Cell Factory multi-plate culture chamber produced by Thermo Fisher Scientific. It should also be understood that the biological production vessel 10 may comprise any conventional bioreactor, fermentor, or cell culture device, such as a stirred-tank reactor, rocker reactor, or paddle mixer reactor.

[0143] In the illustrated exemplary embodiment, the biological production vessel 10 includes a vessel 14 that bounds a chamber 16. The vessel 14 is supported by a rigid support housing 15. A liquid suspension 18 is disposed within the chamber 16. The suspension 18 typically includes a biological suspension containing cells or microorganisms and a culture medium in which the cells or microorganisms are suspended and cultured. By way of example and not limitation, the suspension 18 may include one or more biological components, including bacteria, fungi, algae, plant cells, animal cells, protozoa, nematodes, plasmids, viral vectors, and the like. Examples of some common biological agents cultured include E. coli, yeast, Bacillus, and CHO cells. The suspension 18 may also include cell therapy cultures and may include aerobic or anaerobic, adherent or non-adherent cells and microorganisms. Different media compositions known in the art may be used to accommodate the particular cells or microorganisms to be cultured and the desired end product. In some applications, the biological production vessel 10 is primarily used solely for culturing and harvesting cells for subsequent use (e.g., preparing vaccine material from the cells themselves). However, in many applications, the ultimate purpose of culturing cells in the biological production vessel 10 is to produce and subsequently harvest a biological product (e.g., a recombinant protein) that is exported from the cells into a culture medium. It is also common for the biological production vessel 10 to be used to culture cells in a masterbatch and prepare an aliquot of cells for subsequent use as an inoculum for multiple subsequent batches of cells cultured to harvest the biological product.

[0144] In one exemplary embodiment, the container 14 comprises a flexible, foldable bag. For example, the container 14 may be constructed from one or more sheets of a flexible, water-impermeable polymer film, such as low-density polyethylene. The polymer film may have a thickness of at least 0.02 mm, 0.05 mm, 0.1 mm, 0.2 mm, 0.5 mm, 1 mm, 2 mm, 3 mm, or less, or a range between any two of the foregoing. Other thicknesses may also be used. The film is sufficiently flexible to be wrapped around a tube without plastic deformation and to be folded through an angle of at least 90°, 180°, 270°, or 360° without plastic deformation.

[0145] The film may be constructed from a single ply of material or may include two or more layers that are either sealed together or separated to form a double-walled container. When the layers are sealed together, the material may include a laminated or extruded material. A laminated material includes two or more separately formed layers that are then secured together with an adhesive. One example of an extruded material that may be used in the present disclosure is Thermo Scientific CX3-9 film, available from Thermo Fisher Scientific. Thermo Scientific CX3-9 film is a three-layer, 9-mil cast film manufactured in a cGMP facility. The outer layer is a polyester elastomer coextruded with an ultra-low density polyethylene product contact layer. Another example of an extruded material that may be used in the present disclosure is Thermo Scientific CX5-14 cast film, also available from Thermo Fisher Scientific. Thermo Scientific's CX5-14 cast film includes a polyester elastomer outer layer, an ultra-low density polyethylene contact layer, and an EVOH barrier layer disposed therebetween.

[0146] The materials may be approved for direct contact with living cells and may be capable of maintaining the solution sterile. In such embodiments, the materials may also be sterilizable, such as by ionizing radiation. Examples of materials that may be used in different situations are disclosed in U.S. Pat. No. 6,083,587, issued July 4, 2000, and U.S. Patent Application Publication No. 2003-0077466A1, published April 24, 2003, which are incorporated herein by specific reference.

[0147] In one embodiment, container 14 comprises a two-dimensional pillow-shaped bag in which two sheets of material are placed in overlapping relationship and bonded together around their periphery to form chamber 16. Alternatively, a single sheet of material may be folded and seamed along its periphery to form the interior compartment. In another embodiment, container 14 may be formed from a continuous tubular extrusion of polymeric material that is cut to length and seamed closed at the ends. In yet other embodiments, container 14 may comprise a three-dimensional bag having not only an annular sidewall, but also two-dimensional top and bottom end walls.

[0148] It should be understood that the container 14 can be manufactured to have virtually any desired size, shape, and configuration. For example, the container 14 can be formed with a chamber 16 sized to 0.5 liters, 1 liter, 5 liters, 10 liters, 30 liters, 50 liters, 100 liters, 250 liters, 500 liters, 750 liters, 1,000 liters, 1,500 liters, 3,000 liters, 5,000 liters, 10,000 liters, or other desired volumes. The size of the chamber 16 can also range between any two of the above volumes. In other embodiments, the chamber 16 can have a larger or smaller volume. While in the above-described embodiment, the container 14 is described as a flexible, collapsible bag, it should be understood that in alternative embodiments, the container 14 includes any form of collapsible or semi-rigid container. In some embodiments, the container 14 can include a rigid container, such as one made of metal, molded plastic, or composite material. In this embodiment, the support housing 15 may be omitted as the vessel 14 is self-supporting.

[0149] Optionally, sensors 20 and probes 22 may be coupled to the vessel 14 to detect properties of the suspension 18. By way of example and not limitation, the sensors 20 and probes 22 may include temperature probes, pH probes, CO2 sensors, oxygen sensors, pressure sensors, etc. Optionally, a sparger 24 may be coupled to the vessel 14 to supply gas to the suspension 18 within the chamber 16.

[0150] In one exemplary embodiment of the present disclosure, a means is provided for mixing the suspension 18 within the vessel 14. In the illustrated embodiment, a movable mixing element 26 is disposed within the chamber 16 and is used to mix the suspension 18. In one exemplary embodiment, the mixing element 26 may include an impeller coupled to a drive shaft 28. The drive shaft 28 is coupled to the vessel 14 via a dynamic seal 30. A motor may be coupled to the drive shaft 28 to rotate the mixing element 26 and facilitate mixing of the suspension 18.

[0151] In another embodiment, the drive shaft 28 may extend into the vessel 14 through a flexible tube having one end rotatably connected to the vessel 14 and a second, opposite end connected to the mixing element 26. The drive shaft 28 passes through the flexible tube and removably couples with the mixing element 26, such that the drive shaft 28 may rotate the mixing element 26 without directly contacting the suspension 18. Examples of this mixing system are disclosed in U.S. Pat. No. 7,384,783, issued June 10, 2008, and U.S. Pat. No. 7,682,067, issued March 23, 2010, both of which are incorporated herein by specific reference. In another alternative embodiment, the drive shaft 28 may be configured to repeatedly raise and lower the mixing element 26 located within the vessel 14 to mix the suspension 18. Alternatively, mixing element 26 may comprise a magnetic stir bar or impeller disposed within chamber 16 of vessel 14 and rotated by a magnetic mixer disposed outside vessel 14. In yet other embodiments, mixing element 26 may comprise a stir bar, paddle, or the like that protrudes into chamber 16 of vessel 14 and can be pivoted, swung, rocked, or otherwise moved to mix suspension 18. Additionally, mixing may be achieved by circulating fluid through chamber 16, such as by using a peristaltic pump to move fluid in and out of chamber 16 through a tube having both ends sealed to vessel 14. Air bubbles may also be passed through suspension 18 to achieve the desired mixing. Finally, support housing 15 and vessel 14 may be swirled, rocked, rotated, or moved to mix suspension 18 within vessel 14. Other conventional mixing techniques may also be used. Specific examples of methods for incorporating mixers into flexible bags such as container 14 are disclosed in U.S. Pat. No. 7,384,783, issued June 10, 2008, U.S. Pat. No. 7,682,067, issued March 23, 2010, and U.S. Patent Application Publication No. 2006 / 0196501, issued September 7, 2006, which are incorporated herein by specific reference.

[0152] A plurality of ports 34 are coupled to the vessel 14 for supplying materials into or removing materials from the chamber 16. A port 35 is disposed at the lower end of the vessel 14 and is fluidly coupled to the centrifuge 12. Note that the reactor 10 is not necessarily drawn to scale with respect to the centrifuge 12. The chamber 16 of the reactor 10 will typically have a fluid capacity that is at least 3, 5, 10, 20, 50, 100, 200, or more times the fluid capacity of the centrifuge 12.

[0153] In the system shown in FIG. 1 , the container 14 is fluidly coupled to the centrifuge 12 by a fluid line 36 extending from port 35 to an inlet port 38 of the centrifuge 12. The fluid line 36 and other fluid lines described herein typically comprise flexible polymeric tubing that can be coiled without plastic deformation. However, in other embodiments, the fluid line may comprise other flexible or rigid conduits. The centrifuge 12 also has a first outlet port 40 and a second outlet port 42. The fluid line 44 has a first end 46 coupled to the first outlet port 40 of the centrifuge 12 and an opposite second end 48 fluidly coupled to the chamber 16 of the container 14, such as via a port 50 attached to the container 14. Similarly, the fluid line 52 has a first end 54 coupled to the second outlet port 42 of the centrifuge 12 and an opposite second end 56 fluidly coupled to a collection container 58. The collection container 58 typically comprises a collapsible bag made from one or more sheets of polymer film. The collection container 58 may be made using the same materials, methods, and properties as the container 14 described above. For example, the collection container 58 may comprise a two-dimensional pillow-shaped bag or a larger, three-dimensional bag. The collection container 58 may have a volume that is the same as, smaller than, or larger than the volume of the container 14. For example, the collection container 58 may have a volume that is less than 0.7, 0.5, or 0.2 times the volume of the container 14, or more than 1.2, 1.5, 2, or 3 times the volume of the container 14. If the collection container 58 is a flexible bag, the collection container 58 may be supported within a rigid support housing. In other embodiments, the collection container 58 may comprise a rigid or semi-rigid container.

[0154] In an alternative embodiment, the single collection vessel 58 may be replaced with a manifold system 62, as shown in Figure 2. Generally, the manifold system 62 comprises a manifold 64 fluidly coupled to multiple collection vessels 58A, 58B, 58C, and 58D. In one embodiment, the manifold 64 comprises multiple separate sections of a fluid line 66, such as flexible tubing, joined together by fittings 68, such as a Y-connector, so that fluid flowing from the fluid line 52 can be delivered along a sterile pathway to each of the collection vessels 58A-58D.

[0155] Each collection container 58A-58D may include a flexible, collapsible bag 70 that bounds a compartment 72. Each collection container 58A-58D further includes a first port 74A and a second port 74B coupled to the bag 70 and in communication with the compartment 72. While two ports 74A and 74B are shown, other numbers of ports, such as one, three, four, or more ports, may be used. The bag 70 is generally sized so that the compartment 72, when fully inflated, has a volume of at least 0.5 liters, 1 liter, 1.5 liters, 2 liters, 2.5 liters, 3 liters, 5 liters, 10 liters, or a range between any two of the foregoing. Other volumes may also be used.

[0156] Fluid line 66 includes inlet lines 80A-80D that are fluidly coupled to port 74A disposed on bag 70. Clamps 82A-82D are attached to inlet lines 80A-80D, respectively. Clamps 82A-82D may be manually adjusted to regulate the flow of fluid streams through inlet lines 80A-80D and may seal to prevent fluid flow through inlet lines 80A-80D. In addition, outlet lines 84A-84D are coupled to port 74B disposed on bag 70. Each outlet line 84 has a terminal end that may be sealed closed, such as by welding or crimping, or by attaching a fitting thereto, such as a sterile connector that may be selectively coupled to another fluid line.

[0157] During use, once the bags 70 are filled with a desired amount of fluid, a portion of the inlet line 80 upstream of the clamp 82 is sealed closed and then severed, thereby isolating each bag 70 from the manifold 64. The collection vessels 58A-58D are coupled to the manifold 64 in parallel rather than in series. By selectively opening and closing the clamps 82, the transfer of fluid from the container 14 to selected collection vessels 58A-58D can be controlled. For example, all of the clamps 82 can be opened simultaneously to simultaneously fill all of the collection vessels 58A-58D. Alternatively, by closing all of the clamps 82 and then sequentially opening the clamps 82, the collection vessels 58A-58D can be filled in sequential order. It should be understood that clamps 82, valves, or other flow control devices can also be positioned elsewhere on the manifold 64 to control the flow of fluid therethrough.

[0158] In the illustrated embodiment, the manifold 64 is fluidly coupled to four collection vessels 58A-58D. In alternative embodiments, the manifold 64 may be fluidly coupled to or with at least 2, 3, 5, 6, 8, 12, 16, or any other number of collection vessels 58. In yet another alternative embodiment, the collection vessels 58A-58D may be fluidly coupled to the manifold 64 in series rather than in parallel.

[0159] In yet another alternative to the embodiment shown in FIG. 1, collection vessel 58 may be omitted and fluid line 52 may be directly coupled to downstream processing equipment, such as a filtration system, for example, a depth filter or a sterilizing filter.

[0160] 1 , a first pump 100A is coupled to fluid line 44, and a second pump 100B is coupled to fluid line 52. As described in more detail below, pump 100 is used to control the flow rate of suspension 18 through centrifuge 12. In one embodiment, pump 100 may comprise a peristaltic pump that pumps fluid through fluid lines 44 and 52 but does not directly contact the fluid. In this manner, pump 100 may be reused without cleaning. However, other types of pumps, such as positive displacement pumps, may also be used.

[0161] In one exemplary embodiment, a controller 98 may be used to automatically and separately control the operation of pumps 100A and 100B to selectively and separately control and regulate the flow rates of fluid in fluid lines 44 and 52. Controller 98 may include a programmable processor and non-transitory memory. In an alternative embodiment shown in FIG. 3 , the flow rate of fluid through centrifuge 12 may be controlled by having a single pump 100C coupled to fluid line 36 and having a control valve 96A coupled to fluid line 44 and / or a control valve 96B coupled to fluid line 52. Pump 100C and control valves 96A and 96B may also be controlled by controller 98. In another alternative, vessel 14 may be pressurized or elevated to effect flow of suspension 18 into centrifuge 12, while control valves 96 on one or both of fluid lines 44 and 52 may be used to control the flow rates through fluid lines 44 and 52. In yet another alternative, pumps 100A and 100B can be retained as in FIG. 1, while pump 100C is added to fluid line 36. Fluid flow would then be controlled by three pumps regulated by controller 98.

[0162] 1 and 3, the controller 98 may control the operation of the pump 100 and / or the valve 98 based on input from sensors 94 attached to the fluid lines 44 and / or 52, or may otherwise sense characteristics of the outlet stream flowing through the fluid lines 44 and / or 52. Depending on the intended method of operation, the sensors 94 may include pressure sensors, flow sensors, turbidity sensors, capacitance sensors, conductivity sensors, in-line spectroscopic sensors, etc.

[0163] In one method of operation, the function of centrifuge 12 is to continuously separate suspension 18 received from container 14 into a first outlet stream and a second outlet stream, the first outlet stream having a higher concentration of cells or microorganisms, and therefore a higher density or percentage of solids, than the second outlet stream. More specifically, during a single use as shown in FIG. 1 , pump 100 can be operated to cause an inlet stream of suspension 18, indicated by arrow 102, to flow from container 14 through fluid line 36 and into centrifuge 12 through an inlet at inlet port 38. Centrifuge 12 then separates inlet stream 102 into a first outlet stream, indicated by arrow 104, which exits centrifuge 12 through an outlet at outlet port 40. Centrifuge 12 also separates inlet stream 102 into a second outlet stream, indicated by arrow 106, which exits centrifuge 12 through an outlet at outlet port 42 and into fluid line 52. As noted above, the first outlet stream 104 has a higher concentration or volume of cells or microorganisms than the second outlet stream 106, i.e., a higher percentage of solids per unit volume than the second outlet stream 106.

[0164] FIG. 4 illustrates a simplified embodiment of a centrifuge 12 incorporating features of the present disclosure. Generally, the centrifuge 12 includes a separation stator 114 that defines a chamber 116. A separation rotor 118 is rotatably disposed within the chamber 116 of the separation stator 114. A means, such as a magnetic drive, is provided for rotating the separation rotor 118 within the separation stator 114. Ports 38, 40, and 42 are attached to the separation stator 114 and communicate with the chamber 116. As the inlet stream 102 enters the chamber 116 through the inlet port 38, the rotation of the separation rotor 118 causes the suspension 18 to rotate within the chamber 116, such that the suspension 18 is subjected to centrifugal force. Due to the centrifugal force, heavier components of the suspension 18 collect toward the interior surface of the separation stator 114 and exit through the outlet port 40 as the first outlet stream 104. The lighter components of the suspension 18 collect towards the outer surface of the separator rotor 114 and exit through the outlet port 42 as the second outlet stream 106 .

[0165] It should be understood that in some embodiments, the second outlet stream 106 may not contain the cells or microorganisms that were separated into the first outlet stream 104. However, typically, when the suspension 18 passes through a single centrifuge, some cells or microorganisms remain in the second outlet stream 106. The remaining cells or microorganisms may then be removed from the second outlet stream 106 by passing the second outlet stream 106 through one or more additional centrifuges and / or by passing the second outlet stream 106 through other conventional filtration systems, as described in more detail below.

[0166] In the embodiment shown in Figure 1, first outlet stream 104 is pumped back to vessel 14 through fluid line 44 to help retain the cells or microorganisms within vessel 14, while second outlet stream 106 is collected through collection vessel 58 for subsequent use. Thus, the system of Figure 1 is a perfusion system in which cells or microorganisms are maintained within vessel 14 for continuous cultivation while medium and by-products from the cells or microorganisms are continuously collected. To compensate for medium loss due to collection, new medium is added to vessel 14 through port 34 continuously or as needed.

[0167] Referring to FIG. 5 , as opposed to returning the first outlet stream 104 to the container 14, the first outlet stream 104 can be harvested by being collected in a collection container 110. The collection container 110 typically comprises a collapsible bag made from one or more sheets of polymeric film. The collection container 110 can be made from the same materials and using the same methods as the collection container 58 described above, and can have the same properties, sizes, and alternative configurations. For example, the collection container 110 can comprise a two-dimensional pillow-shaped bag or a larger, three-dimensional bag. If the collection container 110 is a flexible bag, the collection container 110 can be supported within a rigid support housing. In other embodiments, the collection container 110 can comprise a rigid or semi-rigid container.

[0168] In an alternative embodiment, a single collection vessel 110 may be substituted for the manifold system 62, as described above with respect to Figure 2. Thus, the first outlet stream 104 may be collected in separate collection vessels 58A-58D. All of the above-described uses and alternatives for the manifold system 62 described above with respect to the collection of the second outlet stream 106 are also applicable to the collection of the first outlet stream 104. Furthermore, the system of Figure 5 operates in the same manner as described above with respect to the system of Figure 1, except that the first outlet stream 104 is collected rather than returned to vessel 14.

[0169] 5, the container 14 need not form part of a reactor for culturing the biologic. Rather, the container 14 may simply comprise a rigid or flexible container that simply holds the just-prepared suspension 18.

[0170] 6 and 7 show a detailed exemplary embodiment of a continuous-flow centrifuge 12A that may be used as the centrifuge 12 in the systems and alternatives described above with respect to FIGS. 1-5. Generally, the centrifuge 12A comprises a body assembly 130 and a driver sleeve 132 that is integrally formed with, releasably attached to, or otherwise interacts with the body assembly 130. During operation, a magnetic driver 148 (FIG. 8) is received within and rotated by the driver sleeve 132 to facilitate operation of the centrifuge 12A during use. As described in more detail below, the body assembly 130 / centrifuge 12A includes an inlet port 38, a first outlet port 40, and a second outlet port 42.

[0171] 8 , driver sleeve 132 includes an exterior surface 134 and an interior surface 136 surrounding an opening 138. Driver sleeve 132 has a first end 140 through which opening 138 extends and, in one embodiment, may be releasably coupled to body assembly 130. For example, first end 140 may be releasably coupled to body assembly 130 by a fastener, such as a screw or bolt, a clamp, a threaded connection, or a twist connection, such as a bayonet connection. In other exemplary embodiments, driver sleeve 132 may be integrally formed with body assembly 130 and may be positioned only against or adjacent to body assembly 130. For example, one purpose of driver sleeve 132 is to serve as a protective cover for magnetic driver 148. As such, driver sleeve 132 may be formed as part of separator 12A that interacts with magnetic driver 148, or may be formed as part of magnetic driver 148 that interacts with separator 12A. In other embodiments, driver sleeve 132 may be omitted.

[0172] In one embodiment, the driver sleeve 132 may comprise a tubular sleeve body 142 having a flange 144 projecting outwardly from a first end 140 thereof. The flange 140 may be used to couple with the body assembly 130. In one exemplary embodiment, the sleeve body 142 may have a second end 141 opposite the first end 140, with a flange 145 projecting outwardly from the second end 141. The flange 145 may be used to secure the separator 12A to a separate structure, such as a skid or other framework that supports the magnetic driver 148. In other embodiments, the driver sleeve 132 need not be in the form of a tubular sleeve.

[0173] The magnetic driver 148 includes a drive rotor 150 that aligns with the body assembly 130 and is rotatably disposed within the opening 138 of the driver sleeve 132, as described below. The drive rotor 150 includes a sleeve 152 having an inner surface 154 and an opposing outer surface 156 extending between a first end 158 and an opposite second end 160. The inner surface 154 bounds a cavity 162. For example, in one embodiment, the sleeve 152 is annular and surrounds the cavity 162. In other embodiments, the sleeve 152 need not completely surround the cavity 162. The first end 158 of the sleeve 152 terminates in an end face 164 that bounds an opening 166 to the cavity 162. A magnet 168 is secured to the inner surface 154 of the sleeve 152. In the illustrated embodiment, the magnet 168 includes a plurality of spaced magnet portions 170 secured to the interior surface 154 of the sleeve 152 to surround the cavity 162. In one embodiment, the magnet 168 may include at least 2, 4, 6, 12, 18, 24, or 30 separate magnet portions 170, or may range between any two of the foregoing numbers. The magnet portions 170 may be oriented perpendicular to the axis of rotation such that the poles of the magnetic portions are axially oriented. In such an embodiment, the magnetic poles of each magnet portion 170 are preferentially axially alternating.

[0174] In other embodiments, the magnet 168 may include a magnetic ring secured to the interior surface 154 to surround the cavity 162. In such embodiments, the magnetic ring may be a dipole, quadrupole, hexapole, or octapole. In such a magnetic ring, the magnetic poles are preferentially arranged radially. The magnetic coupling may consist of any magnetic pair that provides sufficient torque to meet the torque requirements to overcome power losses and rotor and fluid accelerations. For example, the torque requirement in one exemplary embodiment is 10 to 70 in-lb. f The magnets may be made of a material capable of carrying a permanent magnetic field on the rotor side and either a permanent magnet or an electromagnet on the motor side of the coupling. In one embodiment, the magnets may be made of neodymium.

[0175] 9, the magnetic driver 148 further comprises a motor 169 coupled to and selectively rotating the drive rotor 150 / sleeve 153. For example, in one embodiment, the drive rotor 150 further comprises a stem 172 protruding from the second end 160 of the sleeve 152 and coupled to the motor 169 for rotation of the drive rotor 150. The motor 169 may be housed or at least partially housed within the housing 134. As previously mentioned, the driver sleeve 132 is optional and may function in part as a protective cover for the drive rotor 150 and / or the motor 169.

[0176] 9, the separator 12A / body assembly 130 generally includes a split stator 180 and a rotor assembly 182 rotatably disposed within the split stator 180. The rotor assembly 182 includes a split rotor 184 rotatably disposed within the split stator 180 and a drive coupling 186 coupled to the split rotor 184, which may also be rotatably disposed within the split stator 180. A central axis 230 passes through the centers of the split stator 180 and the rotor assembly 182 and coincides with the axis of rotation, also identified by reference numeral 230, about which the rotor assembly 182 rotates. Thus, the terms "central axis 230" and "axis of rotation 230" are used interchangeably herein.

[0177] 9 and 10 , in one embodiment, the separated stator 180 includes a base portion 190 and a head portion 192 that are coupled together prior to use. The separated stator 180 has an inner surface 202 and an opposing outer surface 203. The inner surface 202 defines a chamber 194 in which the rotor assembly 182 is at least partially received. The assembled separated stator 180 has a first end 196 at which the head portion 192 is disposed and an opposing second end 198 at which the base portion 190 is disposed. A central axis 230 extends between the first end 196 and the second end 198. The separated stator 180 includes an inlet port 38, a first outlet port 40, and a second outlet port 42, each located at the first end 196 of the head portion 192.

[0178] Continuing to refer to FIG. 9 , base 190 (i.e., second end 198 of isolated stator 180) includes a floor 200 extending radially outward to an annular sidewall 204. Sidewall 204 upstands from floor 200 and projects toward first end 196. An annular mounting flange 205 projects outward from sidewall 204. In one embodiment, inner surface 202 of sidewall 204 is cylindrical. In other embodiments, inner surface 202 of sidewall 204 may be outwardly sloped. Disposed centrally in floor 200 and projecting outward from outer surface 203 of floor 200 is receiver 206. Receiver 206 bounds recess 212 that forms a portion of chamber 194. In one embodiment, receiver 206 includes a sidewall 208 that projects from floor 200 and terminates in end wall 210. In one embodiment, the sidewall 208 and the recess 212 each have a cylindrical configuration. The receiver 206 is configured to be receivable within the opening 166 of the drive rotor 150, as shown in FIG. 9 and described below.

[0179] 10, base 190 (i.e., first end 198 of isolation stator 180) also includes a plurality of fins 226 that project outwardly from the exterior surface of floor 200 aligned parallel to central axis 230 and are evenly spaced about receiver 206. Fins 226 extend longitudinally from mounting flange 205 to or toward receiver 206. In one embodiment, centrifuge 12A is designed to be disposable after a single use. To that end, the isolated stator 180, and more specifically, the base 190 and head 192, are typically made from a polymeric material such as polyvinylidene fluoride (PVDF), high-density polyethylene (HDPE), polyetherimide (PEI), or polyether ether ketone (PEEK), and are generally molded by injection molding, rotational molding, or the like. These materials and manufacturing methods allow the isolated stator 180 to be manufactured more cheaply than if it were made from metal. In part, the fins 226 function to add strength and stability to the isolated stator 180 when made from a lower-strength polymeric material. However, in alternative embodiments, the isolated stator 180 may be made from a higher-strength metal such as aluminum or stainless steel, or alternatively, a higher-strength polymer such as liquid crystal polymer or polycarbonate. In such cases, the fins 226 may be omitted.

[0180] Returning to FIG. 9 , the head portion 192 of the split stator 180 includes a nose portion 214 disposed at the first end 196. The nose portion 214 has a sidewall 216 that terminates in an end wall 218. The nose portion 214 bounds a recess 213. In one embodiment, the inner surface 202 of the sidewall 216 that bounds the recess 213 may have a cylindrical configuration. An inlet port 38 projects centrally outwardly from the end wall 218. A first outlet port 40 and a second outlet port 42 project outwardly from the sidewall of the nose portion 214. The head portion 192 also includes an annular mounting flange 228 and an annular transition wall 220 extending between the mounting flange 228 and the sidewall 216 of the nose portion 214. In one embodiment, at least a portion of the transition wall 220 has a frustoconical configuration, with the interior surface 202 thereof typically disposed at an angle relative to the central axis 230 that is at least 30°, 40°, 50°, or 60° or less, or a range between any two of the foregoing. In the illustrated embodiment, the portion of the transition wall 220 extending from the mounting flange 228 may be cylindrical or have a different configuration than the remainder of the transition wall 220. Like the base 190, the head portion 192 is also shown formed with fins 229 ( FIG. 10 ) that project outwardly from the transition wall 220 to extend between the mounting flange 228 and the nose portion 214. The fins 229 also extend in alignment parallel to the central axis 230 and are equally spaced about the transition wall 220. As mentioned above, when the isolated stator 180 is fabricated from a plastic material, the fins 229 add structural strength and stability while adding minimal material and cost. If the isolated stator 180 is made from a higher strength material, the fins 229 may be omitted.

[0181] During assembly, the mounting flanges 205 and 228 are coupled together such that the rotor assembly 182 / isolated rotor 184 is captured within the isolated stator 180. The mounting flanges 205 and 228 may be coupled together by welding, clamps, fasteners such as screws or bolts, or by using other fastening techniques.

[0182] The rotor assembly 182 is rotatably positioned within the chamber 194 of the separation stator 180 and is used to separate the inlet stream 102 (FIGS. 1-5) of biological suspension into the first outlet stream 104 and the second outlet stream 106. Referring to FIG. 10 , as previously described, the rotor assembly 182 includes a separation rotor 184 and a drive coupling 186 extending from the separation rotor 184. More specifically, the separation rotor 184 has a first end 240 and an opposite second end 242 with a central axis / rotation axis 230 extending centrally therebetween. The drive coupling 186 is centrally mounted to and projects outwardly from the second end 212 of the separation rotor 184 such that the central axis 230 passes through the center of the second end 242. The drive coupling 186 typically has an encircling side surface 244 terminating in an end face 246. In one embodiment, the drive coupling 186 has a cylindrical configuration and is configured to be rotatably received within the recess 212 of the receiver 206, as shown in Figure 9. A gap 248 is formed between the side surface 244 of the drive coupling 186 and the side wall 208 of the receiver 206 such that the drive coupling 186 can freely rotate within the receiver 206.

[0183] In one embodiment, gap 248 is less than 10 mm, 8 mm, 6 mm, 4 mm, 2 mm, or within a range between any two of the foregoing. Typically, it is desirable to minimize the size of gap 248 to help facilitate magnetic rotation of drive coupling 186. Drive coupling 186 is made of and configured from a material that can be controlled by the magnetic field generated by magnet 168. For example, drive coupling 186 may include another magnet or a material that is attracted to a magnet, such as iron or an iron composite. During operation, drive coupling 186 is positioned within receiver 206, which in turn is received within cavity 162 of drive rotor 150. Rotation of drive rotor 150 by motor 169 promotes simultaneous rotation of drive coupling 186 as a result of the magnetic force generated on drive coupling 186 by magnet 168. Rotation of drive coupling 186, in turn, promotes simultaneous rotation of isolation rotor 184 to which it is attached. It should be appreciated that in an alternative embodiment, receiver 206, which generally functions as a protective cover, may be omitted, with drive coupling 186 being received directly within cavity 162 of drive rotor 150.

[0184] 11, the split rotor 184 comprises a base portion 250 to which the drive coupling portion 186 is attached, a dispersion member 252 seated on the base portion 250, a cap portion 254 coupled to the base portion 250, an insert 256 captured between the cap portion 254 and the base portion 250, and a stem assembly 258 disposed on the cap portion 254. The various elements of the split rotor 184 will now be described in further detail.

[0185] As better seen in FIG. 9 , the base 250 has an interior surface 260 that partially bounds the compartment 261 and has an opposing exterior surface 262. The base 250 includes a floor 264 and an annular sidewall 266 that projects upward from the outer periphery of the floor 264 toward the cap portion 254. The sidewall 266 is hereinafter referred to as the lower sidewall 266. A mounting portion 268 projects outward from the exterior surface 262 of the floor 264 in alignment with the central axis 230. The drive coupling 186 is secured to the mounting portion 268 by adhesive, a press fit, fasteners, a threaded connection, or the like. An annular bearing assembly 270, such as a race bearing, extends between the mounting portion 268 and the base 190 of the isolated stator 180. The bearing assembly 270 serves to center and stabilize the isolated rotor 184 relative to the isolated stator 180 , allowing the isolated rotor 184 to easily rotate relative to the isolated stator 180 .

[0186] 11, a plurality of partitions 272A-272F project upward from the interior surface 260 of the floor 264. The partitions 272 are evenly spaced apart and project radially outward in alignment with the central axis 230. The partitions 272A, 272C, and 272E also have elongated slots 273 formed along their lengths. As explained in more detail below, the partitions 272 function to space the dispersion member 252 from the interior surface 260 of the floor 264 and to secure the dispersion member 252 to the base 250 so that the base 250 and dispersion member 252 rotate simultaneously. The interior surface 260 of the lower sidewall 266 has an annular frustoconical configuration that tapers outward from the outer periphery of the floor 264 to an annular lip 274. In one embodiment, lower sidewall 266 slopes at an outward angle relative to central axis 230 that is at least 10°, 15°, 20°, 25°, 30°, 35°, or less, or within a range between any two of the foregoing angles. An annular slot 276 is recessed in lip 275 and is used to couple cap portion 254 to base portion 250, as described in more detail below.

[0187] As described herein, the dispersion member 252 can have a variety of different configurations. In the currently illustrated embodiment, the dispersion member 252 comprises a body 280 in the form of a circular plate having a top surface 282 and an opposing bottom surface 284, each of which extends to an outer peripheral edge 286. An opening 290 extends centrally through the body 280, aligned with the central axis 230, so as to pass between the opposing surfaces 282 and 284. Typically, equally spaced lower partitions 288A, 288B, and 288C project from the bottom surface 284 of the body 280. The lower partitions 288 are linear and project radially outward from the openings 290. The lower partitions 288 are configured to be received in slots 273 in the partitions 272A, 272C, and 272E and terminate in terminal ends 291 that project beyond the outer peripheral edge 286. During assembly, the distribution member 252 is positioned on the septum 272 of the base 250 so that the lower septa 288A, 288B, 288C are received in the slots 273 and so that the terminal end 291 abuts or is disposed directly adjacent to the interior surface 260 of the lower sidewall 266 of the base 250. This assembly centers the distribution member 252 on the floor 264 to ensure that the peripheral edge 286 is evenly spaced from the lower sidewall 266, and also interlocks the distribution member 252 with the base 250 so that rotation of the base 250 promotes simultaneous orbital rotation of the distribution member 252. Additionally, as described in more detail below, the lower septum 288 and the septum 272 function to form an inlet fluid channel that flows radially outward from between the distribution member 252 and the floor 264 to help facilitate separation of the biological suspension. It should be understood that various other structural designs may be used to securely center the distribution member 252 on the floor 264 while forming the inlet fluid channel, however, the presently illustrated embodiment is uniquely configured to allow for quick and easy positioning of the distribution member 252 without requiring the use of separate fasteners.

[0188] 11, dispersion member 252 further includes retaining rails 292A-292C equally spaced on top surface 282 of body 280 and projecting radially outward from opening 290 to outer peripheral edge 286. Each retaining rail 292 has a slot 294 extending along its length.

[0189] 9, 11, and 12, cap portion 254 has an inner surface 300 and an opposing outer surface 302 extending between a first end 307 and an opposing second end 308. Cap portion 254 includes an annular sidewall 304 extending from an annular lip 306 formed at second end 308 to an annular lip 310 disposed at first end 307. Sidewall 304 is hereinafter referred to as "upper sidewall 304." Upper sidewall 304 and its inner surface 300 have a frustoconical configuration that tapers inward from annular lip 306 to annular lip 310. In one embodiment, sidewall 304 is configured such that its inner surface 300 is inclined at an angle between 35° and 55°, more typically between 40° and 50° or between 42° and 48°, relative to central axis 230. A plurality of spaced apart guides 309 project radially inward from the interior surface 300 at the second end 308. Each guide 309 bounds a slot 311 configured to engage an insert 256, as described below.

[0190] As best seen in FIG. 9 , the lip 306 may have a cylindrical configuration configured to fit within and have a complementary configuration to the slot 276 formed on the base 250. This configuration helps facilitate a fluid-tight seal between the base 250 and the cap portion 254. A fastener 312 ( FIG. 11 ), such as a screw or bolt, extends from the exterior surface 262 into the sidewall of the base 250 and passes through the lip 306 to facilitate secure engagement. As best shown in FIG. 13 , the annular lip 310 at the first end 196 of the cap portion 254 has an annular first shoulder 314 recessed in the exterior surface 302 and an annular second shoulder 315 recessed in the exterior surface 302, the shoulder 315 being spaced apart from the shoulder 314.

[0191] 14 and 15, stem assembly 258 is coupled to lip 310 at first end 307 of cap portion 254. Stem assembly 258 includes a stem 358 and a sleeve 390 mounted thereon. Specifically, in the illustrated embodiment, stem 358 has a substantially cylindrical configuration with central axis 230 passing through the center and projects outward from annular lip 310. In the illustrated embodiment, stem 358 is integrally formed with cap portion 254 as a single, unitary member. However, in other embodiments, stem 358 may be separately mounted and secured to cap portion 254. Referring to FIGS. 13 and 15, stem 358 includes a tubular spout 360 having an inner surface 362 and an opposite outer surface 364 extending between a first end 366 and an opposite second end 368. The interior surface 362 bounds a light collection channel 379 that passes through the center of the spout 360. A second end 368 of the spout 360 is connected to the insert 256, as described below. A first end 366 of the spout 360 flares radially outward and terminates in an annular end face 370. The end face 370 surrounds the central axis 230 and is typically disposed parallel thereto. Bulkhead segments 372A-372F project outward from the exterior surface 364 of the spout 360 and are equally spaced about the spout 360. The bulkhead segments 372 are typically disposed parallel to the central axis 230 and extend longitudinally between the annular end face 370 and the annular lip 310 of the cap portion 254.

[0192] Heavy collection channels 382A-382F, separated by septum segment 372, extend between spout 360 and annular lip 310 of cap portion 254. For example, heavy collection channel 382A passes between annular lip 310 of cap portion 254 and exterior surface 364 of spout 360 at first end 366 and is further bounded between septum segments 372A and 372B. As heavy collection channel 382A extends upward toward first end 366, heavy collection channel 382A communicates with opening 384A formed on the exterior of stem 358. Opening 384A is bounded between septum segments 372A and 372B and between annular lip 310 and end portion 370. Heavy collection channels 382B-382F are similarly configured and communicate with corresponding openings 384B-384F, respectively. It should be understood that in alternative embodiments, other numbers of septum segments 372 and heavy collection channels 382 may be formed. For example, in one embodiment, septum segment 372A may be omitted such that only a single heavy collection channel 382 partially bounded between the exterior surface 364 of spout 360 and sleeve 390 is formed.

[0193] In one embodiment, a plurality of braces 376A-376F project inward from the interior surface 362 of the spout 360 and extend between a first end 366 and a second end 368. The braces 376A-376F are equally spaced around the spout 360, are typically straight, and extend in parallel alignment with the central axis 230. Each brace 376 terminates at an interior surface 378 spaced apart from the central axis 230. In one embodiment, the braces 376 may divide the light collection channel 379 into multiple separate light collection channels 379. In other embodiments, the braces 376 may be omitted such that only a single, integral light collection channel 379 is formed.

[0194] Although the stem 358 is shown as having six bulkhead segments 372, six openings 384, six heavy collection channels 382, ​​and six braces 376, in alternative embodiments as described in more detail below, other numbers may be used, such as at least 2, 3, 4, 5, 6, 7, 8, 9, or 10, or a range between any two of the foregoing.

[0195] Sleeve 390 has an exterior surface 394 extending between a first end 391 and an opposite second end 392, and an opposite interior surface 395. Interior surface 395 defines a passageway 396 extending therethrough, the passageway 396 being configured to receive stem 358. Specifically, sleeve 390 is configured to receive stem 358 such that second end 392 of sleeve 390 seats on shoulder 315 and is flush against and spans annular lip 310 and annular end face 370. Sleeve 390 spans opening 384 of stem 358, which is disposed between annular lip 310 and annular end face 370. A plurality of equally spaced partial openings 398A-398F extend through the sleeve 390 along its circumference, with each opening 398A-398F aligned with a corresponding opening 384A-384F / heavy collection channel 382A-382F. However, the openings 398 in the sleeve 390 are smaller than the opening 384 in the stem 358. Thus, a portion of the sleeve 390 directly borders a portion of the heavy collection channel 382. Specifically, the sleeve 390 includes an annular heat radiator 388 that surrounds the spout 360 and extends between the annular lip 310 and the opening 398 in the sleeve 390. An inner surface 395 of the heat radiator 388 directly borders a portion of the heavy collection channel 382. The sleeve 390 also includes an annular heat radiator 389 disposed on the annular end portion 370 of the spout 360 opposite the opening 398. That is, annular heat dissipation portion 389 protrudes beyond spout 360 and surrounds central axis 230. Heat dissipation portion 389 extends between annular end portion 370 and the terminal end of sleeve 390, with an interior surface 395 of heat dissipation portion 389 immediately surrounding and bounding a portion of light collection channel 379. The function of heat dissipation portions 388, 389 will be described below. Segments 400 of sleeve 390 are disposed between each adjacent pair of openings 398 and align with corresponding bulkhead segments 372, as shown in FIG. 14 .

[0196] Each of the stem 358, base 250, dispersion member 252, insert 256, and cap portion 254 is typically made from a polymeric material, such as liquid crystal polymer, polycarbonate, PVDF, HDPE, PEI, or PEEK. The different portions can be made from the same or different materials. As previously mentioned, making the components from a polymeric material minimizes the cost of the centrifuge, allowing it to be economically discarded after a single use, thereby avoiding the need for subsequent sterilization or other cleaning. However, in alternative embodiments, one or more of the components can be made from a metal, such as aluminum or stainless steel. For reasons described in more detail below, in one embodiment, the sleeve 390 is made from a material that has a higher thermal conductivity than the material used to form the stem 358. For example, in one embodiment, the stem 358 is made from a polymeric material, while the sleeve 390 is made from a metal, such as aluminum, copper, brass, stainless steel, or an alloy thereof, that has a higher thermal conductivity than the polymer used to form the stem 358. In other embodiments, the sleeve 390 may be formed from a non-metallic material such as a composite, polymer, or other material that is more thermally conductive than the material used to form the stem 358 .

[0197] The stem assembly 258 rotates simultaneously with the cap portion 254 and, therefore, forms part of the separated rotor 184. The centrifuge 12A also includes elements disposed between the separated rotor 184 and the separated stator 180. For example, as shown in FIGS. 13, 14, and 16, such elements include an annular bearing assembly 404, such as a race bearing or other bearing assembly, that surrounds the annular lip 310 and seats on the shoulder 314. Annular seals 406A and 406B, such as lip seals or other types of annular seals, surround the stem 358 above the bearing assembly 404. The seals 406 typically seal directly against the outer surface 394 of the sleeve 390 at the second end 392 below the opening 398. More specifically, one or both of the seals 406 are typically disposed directly against the outer surface 394 of the heat sink 388.

[0198] An annular seal 408, such as a lip seal or other type of annular seal, surrounds stem 358 and seals flush against outer surface 394 of sleeve 390 at a first end 391 above opening 398. More specifically, seal 408 is typically disposed flush against outer surface 394 of heat sink 389. A cylindrical ring 410 has an inner surface 412 and an opposite outer surface 414 and surrounds sleeve 390 in alignment with opening 398. Ring 410 is disposed between seal 408 and seal 406A and has a passageway 416 extending laterally therethrough between inner surface 412 and opposite outer surface 414.

[0199] As described further below, the centrifuge 12A also includes a tubular conduit 420 having an interior surface 412 and an opposite exterior surface 414 extending between a first end 426 and an opposite second end 428. The interior surface 422 bounds a passageway 430 extending therethrough. A dynamic seal 432 surrounds the first end 426 of the conduit 420. The dynamic seal 432 provides a fluid-tight seal with the conduit 420 while allowing the conduit 420 to rotate relative to the seal 432.

[0200] 11 and 17 , insert 256 includes an annular, frustoconical sidewall 320, referred to herein as inner sidewall 320. Inner sidewall 320 has an inner surface 322 that converging inwardly from second end 326 to opposite first end 238 and an opposite outer surface 324. Second end 326 of inner sidewall 320 terminates in a periphery 330, and first end 328 terminates in an annular lip 332. Lip 332 surrounds an opening 334 that passes through the center of insert 256 along central axis 230. In one embodiment, inner surface 322 of inner sidewall 320 may be disposed at the same angle as inner surface 300 of sidewall 304. For example, the interior surface 322 of the inner sidewall 320 may be inclined at an angle ranging from 35° to 55°, more typically from 40° to 50°, or from 42° to 48°, relative to the central axis 230. Other angles may also be used.

[0201] The insert 256 also includes three radially spaced upper partitions 336A-336C, which are equally spaced apart. The upper partitions 336A-336C project away from the interior surface 322 and are aligned with the central axis 230, extending radially outward to and beyond the periphery 330. More specifically, each partition 336 has a top edge extending along the interior surface 322 from the periphery 330 to the opening 334, an inner edge 340 extending along the opening 334 and parallel to the central axis 230, a bottom edge 342 projecting below the inner sidewall 320 and configured to be received in a slot 294 ( FIG. 11 ) of the dispersion member 252, and an outer edge 344 angled to abut the interior surface 260 of the sidewall 266 of the base 250. Upper bulkheads 336B and 336C have the same configuration and elements as upper bulkhead 336A, and therefore like elements between each of the upper bulkheads 336B and 336C are identified by like reference numerals.

[0202] A plurality of radially spaced apart component dividers 350A-350F project outwardly from the exterior surface 324 of the inner sidewall 320. The dividers 350 are in the form of equally spaced apart linear rails that extend radially outward from the annular lip 332 to the peripheral edge 330.

[0203] 9 and 11, during assembly, the dispersion member 252 is disposed on and interlocked with the diaphragm 272 of the base 250 by the lower diaphragm 288 received in the slot 276. In this configuration, the dispersion member 252 is fixed to the base 250 such that rotation of the base 250 about the central axis 230 facilitates rotation of the dispersion member 252. However, the body 280 of the dispersion member 252 is spaced from the floor 264 of the base 250, thereby forming a space 448 therebetween.

[0204] The insert 256 rests on and interlocks with the dispersion member 252 with the bottom edge 342 of the upper bulkhead 336 ( FIG. 17 ) received in the slot 294 of the retaining rail 292. As a result, rotation of the base 250 also facilitates subsequent rotation of the insert 256. As described above, the cap portion 254, on which the stem assembly 258 is disposed, is secured to the base 250 by securing the lip 306 of the cap portion 254 within the slot 276 of the base 250. The slot 311 of the guide 309 ( FIG. 12 ) receives the corresponding divider 350 of the insert 256 to help ensure proper centering, alignment, and engagement between the cap portion 254 and the insert 256. As a result of assembly, the insert 256 and dispersion member 252 are enclosed between the base 250 and the cap portion 254. When the base 250 is secured to the cap 254, the lip 332 at the first end 328 of the insert 256 is secured to the second end 368 of the spout 360 ( FIG. 13 ). For example, in the illustrated embodiment, an annular slot 436 is formed in the second end 368 of the spout 360, within which the lip 332 can be securely received. In other embodiments, the second end 368 of the spout 360 can be secured to the lip 332 of the insert 256 by adhesive, threaded engagement, a press-fit connection, a snap-fit ​​connection, through the use of fasteners, or other conventional mechanisms.

[0205] During further assembly, as shown in FIGS. 14 and 16 , the bearing assembly 404, seals 406 and 408, and ring 410 are disposed on the stem assembly 258 as previously described. The conduit 420 is also positioned. Specifically, referring to FIG. 9 , the second end 428 of the conduit 420 is secured within the opening 290 that extends centrally through the dispersion member 252. This connection may be by a press-fit connection, a threaded connection, an adhesive, or other connection configuration. The remainder of the conduit 420 protrudes centrally along the central axis 230 through the opening 334 in the insert 256 and centrally upwardly through the light collection channel 379 in the spout 360. In this position, the conduit 420 is laterally supported by the inner surface 378 of the brace 376 ( FIG. 16 ). During operation, the conduit 420 rotates simultaneously with the remainder of the split rotor 184 relative to the split stator 180.

[0206] The assembled split rotor 184 is enclosed within the split stator 180. Specifically, with reference to FIG. 13 , the inlet port 38 projects outward from the end wall 218 of the nose portion 214 and defines a passageway 45 aligned with the central axis 230. The passageway 45 passes through the end wall 218 to the interior surface 202. An annular groove 438 is recessed in the interior surface 202 of the end wall 218 to surround the passageway 45. A dynamic seal 432 is received within and secured to the groove 438. The stem assembly 258, having the bearing assembly 404, the seals 406 and 408, and the ring 410 disposed thereon, is received within the recess 213 of the nose portion 214, thereby rotatably and fluidly coupling the first end 426 of the conduit 420 to the passageway 45 of the inlet port 38 via the dynamic seal 432.

[0207] 13 , an annular upper shoulder 440 projects inwardly from the inner surface 202 of the sidewall 216 of the nose portion 214 toward the end wall 218. A light components collection recess 444 is formed between the upper shoulder 440 and the end wall 218. The second outlet port 42 ( FIG. 6 ) bounds a passageway 47 that communicates with the light components collection recess 444. The seal 408 abuts the upper shoulder 440, and the seal 408, ring 410, and each of the seals 406A and 406B abut against the inner surface 202 of the sidewall 216 of the nose portion 214. Thus, the seal 408, ring 410, and each of the seals 406A and 406B are captured between the sidewall 216 of the nose portion 214 and the sleeve 390. More specifically, seals 406 and 408 directly contact sleeve 390 to form a dynamic fluid-tight seal, thereby allowing sleeve 390 and the remainder of isolated rotor 184 to rotate relative to isolated stator 180 and relative to seals 406 and 408 while maintaining a fluid-tight seal therebetween.

[0208] An annular heavy component collection recess 446 surrounds the sleeve 390 and is coupled between the sleeve 390 and the ring 410 and between the seals 408 and 406A. The first outlet port 42 (FIG. 6) defines a passage 49 that aligns with the passage 416 in the ring 410 to communicate with the heavy component collection recess 446. In an alternative embodiment, the ring 410 may be omitted such that the heavy component collection recess 446 is directly coupled between the nose 214 of the isolation stator 180 and the sleeve 390. The heavy component collection recess 446 aligns with, and is in communication with, the opening 398 in the sleeve 390 and the heavy component collection channel 382.

[0209] An annular lower shoulder 442 projects inwardly from the inner surface 202 of the sidewall 216 of the nose portion 214. The bearing assembly 404 seats against the shoulders 442 and 314 and is captured between the lip 310 of the cap portion 254 and the head portion 192 of the split stator 180. Similar to the bearing assembly 270 (FIG. 9), the bearing assembly 404 functions to center and stabilize the split rotor 184 within the split stator 180 so that the split rotor 184 may rotate freely within the split stator 180.

[0210] 18 , during operation, motor 169 is activated to rotate drive rotor 150 relative to isolated stator 180 about central axis 230. The magnetic force generated by magnet 168 then acts on drive coupling 186, as previously described, causing drive coupling 186 and isolated rotor 184 to simultaneously rotate about central axis 230 relative to isolated stator 180. During operation, isolated rotor 184 typically rotates at a speed of at least 1,000, 2,000, 2,500, 3,000, or 3,500 revolutions per minute (RPM), or within a range between any two of the foregoing values. Other speeds may be used, depending on the application.

[0211] When the separation rotor 184 is activated to rotate, the inlet stream 102 ( FIGS. 1 , 3 , and 5 ) of suspension 18 is forced through the inlet port 38, travels along the central axis 230 through the conduit 420, and passes through the opening 290 in the dispersion member 252 and into the space 448 between the dispersion member 252 and the floor 264 of the separation rotor 184. The inlet stream 102 flows radially outward in all directions within the space 448 toward the periphery 286 of the dispersion member 252. In part, the dispersion member 252 functions to force the inlet stream 102 to flow radially outward from the central axis 230 to maximize the velocity and force with which the inlet stream 102 begins to separate into heavy and light components. Specifically, as the inlet stream 102 travels radially outward away from the central axis 230, the inlet stream 102 is subjected to increasing centrifugal forces caused by the rotation of the separation rotor 184. Thus, as the inlet stream 102 passes around the periphery 286 of the dispersion member 252, centrifugal force causes the inlet stream 102 to separate into heavier components moving radially outward and lighter components moving radially inward.

[0212] Additionally, radially extending partitions 272 and lower partitions 288 ( FIG. 11 ) extend between the dispersion member 252 and the floor 264 to divide the space 448 into a plurality of inlet fluid paths 460 that extend from the conduit 420 to the periphery 286 of the dispersion member 252. Each inlet fluid path 460 is bounded between adjacent pairs of partitions 272 / lower partitions 288 to force the inlet stream 102 to flow radially outward along a generally linear path, as opposed to spiraling in a circle within the space 448 about the central axis 230. This linear radial flow of the inlet stream 102 again helps to move the inlet stream 102 rapidly away from the central axis 230 to increase the rate of separation of the inlet stream 102 into heavier and lighter components. Additionally, the linear radial flow helps maintain laminar, as opposed to turbulent, flow in the inlet stream, which further aids in separating the inlet stream 102 into heavier and lighter components. In the illustrated embodiment, six inlet fluid paths 460 (FIG. 11) are formed. In alternative embodiments, other numbers of inlet fluid paths 460 may be formed, such as at least 3, 4, 5, 6, 7, 8, 9, or 10, or a range between any two of the foregoing numbers.

[0213] The lower sidewall 266 of the base portion 250 and the upper sidewall 304 of the cap portion 254 combine to form the outer sidewall 450 of the separation rotor 184, while the inner sidewall 320 of the insert 256 forms the inner sidewall 320 of the separation rotor 184. The outer sidewall 450 and the inner sidewall 320 combine to form a sidewall assembly 452 of the separation rotor 184, which encloses a compartment 454 of which the space 448 forms a part.

[0214] 19, the lower partition 288 projects radially outward within the space 448 from or toward the opening 290 in the distribution member 252 to the sidewall assembly 452, and more specifically to the outer sidewall 450 / lower sidewall 216. As a result, the lower partition 288 also extends between the body 280 and the floor 264 of the distribution member 252, and the lower partition 288 creates three isolated inlet fluid paths 460 that do not have open communication downstream of the opening 290.

[0215] Similarly, the upper partition 336 projects radially outward from the conduit 420 along the top surface 282 of the distribution member 252 to the sidewall assembly 452, more specifically to the inner sidewall 320, and along its length to the outer sidewall 450 below the inner sidewall 320 (lower sidewall 266). As a result, the upper partition 336 in combination with the rail 292 divides the compartment 454 above the distribution member 252 into a plurality of light component fluid paths 456A-456C. In one embodiment, the light component fluid paths 456A-456C are substantially isolated from one another such that fluid cannot flow freely between the light component fluid paths 456A-456C.

[0216] Furthermore, each upper partition 336 also extends radially along the top surface 282 of the dispersion member 252 from the conduit 420 to the periphery 286 as the upper partition 336 extends from the periphery 286 to the sidewall assembly 452, and then aligns with and intersects with a corresponding one of the lower partitions 288. As a result, each inlet fluid path 460 bounded between adjacent lower partitions 288 aligns with a corresponding light component fluid path 456, and the fluids do not mix as they pass therebetween. That is, fluid traveling along an inlet fluid path 460 to a corresponding light component fluid path 456 does not mix with separated fluids traveling along separate inlet fluid paths 460 to the separate corresponding light component fluid paths 456. Again, this configuration helps the fluid to flow continuously along a generally linear path as opposed to swirling in circles around the conduit 420 / central axis 230, and helps maintain a more laminar flow as opposed to a turbulent flow, both of which help separate the fluid into heavy and light components. In the illustrated embodiment, three upper partitions 336 and three lower partitions 288 are shown. In alternative embodiments, the separation rotor 184 may be formed with at least 3, 4, 5, 6, 7, 8, 9, 12, 15, 18, 21, or more upper partitions 336 and lower partitions 288, or a range between any two of the foregoing.

[0217] Again, as previously described, as a result of centrifugal force created by the rotation of the separation rotor 184, the lighter components of the inlet stream 102 passing around the periphery 286 of the dispersion member 252 flow radially inward into a corresponding one of the light component fluid paths 456 at the second end 242 of the separation rotor 184. As shown in FIGS. 13 and 18 , the separated light components flow toward the first end 240 of the separation rotor 184 through the light component fluid path 456, through the light component collection channel 379 bounded between the spout 360 and the conduit 420, and into the light component collection recess 444. The light components from each light component fluid path 456 are combined in the light component collection recess 444. Finally, the light components exit the light components collection recess 444 through the second outlet port 42 as the second outlet stream 106 (FIGS. 1, 3, and 5) and may be further processed or transported as previously described.

[0218] Continuing to refer to FIG. 13 , during operation, the seal 408 is stationary and rests against the sleeve 390, which rotates with the rest of the isolation rotor 184. Frictional engagement between the seal 408 and the sleeve 390 can heat the seal 408 and shorten its useful life. To minimize heating of the seal 408 and thereby help extend its useful life, the seal 408 presses directly against the heat dissipation portion 389 of the sleeve 390. As previously mentioned, the inner surface 395 of the heat dissipation portion 389 bounds a portion of the light collection channel 379. Thus, as the light components of the fluid flow through the light collection channel 379 and into the light component collection recess 444, the fluid flows over the inner surface 395 of the heat dissipation portion 389 to cool the heat dissipation portion 389 / sleeve 390, thereby cooling the seal 408. Additionally, as previously mentioned, by making the sleeve 390 from a material with relatively high thermal conductivity, heat from the sleeve 390 dissipates more quickly, thereby further improving cooling of the sleeve 390 and the seal 408.

[0219] In contrast to the light components, which flow radially inward into the light component fluid pathway 456, the heavier components, which typically include cells, microorganisms, particles thereof, and other solids, flow radially outward toward the sidewall assembly 452 / outer sidewall 450. As a result of the divider 350 projecting outward from the outer surface 324 of the insert 256, an annular frustoconical gap 462 is formed between the insert 256 and the cap portion 254. The outer edge of the divider 350 seats against the inner surface 300 of the cap portion 254 such that the divider 350 separates the annular frustoconical gap 462 into a plurality of separate heavy component fluid pathways 464A-464F. That is, the sidewall assembly 452 bounds a plurality of separate heavy component fluid pathways 464. Each heavy component fluid pathway 464 has an opening 466 disposed in the periphery 330 of the insert 256 / inner sidewall 320.

[0220] During operation, as the inlet stream 102 exits through the inlet fluid pathways 460 between the floor 264 and the dispersion member 252, the heavy components of the fluid flow radially outward toward the sidewall assembly 452 / outer sidewall 450 and through openings 466 into the corresponding heavy component fluid pathways 464. The heavy components then flow within the heavy component fluid pathways 464 toward the first end 196 of the separation rotor 184. Referring to FIGS. 13 and 18 , when the heavy components reach the stem assembly 258, they enter the corresponding heavy collection channels 382, ​​exit through openings 398 on the sleeve 390, and enter the heavy component collection recesses 446. The heavy components from each of the different heavy component fluid pathways 464 are combined together in the heavy component collection recesses 446. Finally, the heavy components pass through passage 416 on ring 410 and then exit through first outlet port 40 as first outlet stream 104 (FIGS. 1, 3, and 5), where they may be further processed or transported as previously described.

[0221] Continuing to refer to FIG. 13 , during operation, the seal 406 is stationary and rests against the sleeve 390, which rotates with the rest of the isolation rotor 184. Frictional engagement between the seal 406 and the sleeve 390 can heat the seal 406 and shorten its useful life. To minimize heating of the seal 406 and thereby help extend its useful life, the seal 406 presses directly against the portion 388 of the sleeve 390. As previously mentioned, the inner surface 395 of the heat dissipation portion 388 bounds a portion of the heavy collection channel 382. Thus, as the heavy components of the fluid flow through the heavy collection channel 382 and into the heavy component collection recess 446, the fluid flows over the inner surface 395 of the heat dissipation portion 388 to cool the heat dissipation portion 388 / sleeve 390, thereby also cooling the seal 406. Additionally, as previously mentioned, by making the sleeve 390 from a material with relatively high thermal conductivity, heat from the sleeve 390 dissipates more quickly, thereby further improving cooling of the sleeve 390 and the seal 406.

[0222] Again, using dividers 350 to form and separate the heavy component fluid paths 464 helps the heavy components entering and flowing along the heavy component fluid paths 464 to flow continuously along a generally linear path, as opposed to swirling in a circle around the central axis 230, and also helps maintain the heavy components in a more laminar flow, as opposed to a turbulent flow, both of which aid in fluid separation and limit the application of excessive forces that may be damaging or harmful to the separated cells or microorganisms. In the illustrated embodiment, six dividers 350 are used to form six heavy component fluid paths 464. In alternative embodiments, the separation rotor 184 may be formed with at least 3, 4, 5, 6, 7, 8, 9, 12, 15, 18, 21, 26, 32, 38, or more dividers 350 and / or heavy component fluid paths 464, or may range between any two of the foregoing.

[0223] As shown in FIG. 19 , the aligned upper and lower partitions 336 and 288 are also radially aligned with the corresponding dividers 350. As a result, fluid flowing from an inlet fluid path 460 to a corresponding aligned light component fluid path 456 can only communicate with the corresponding aligned heavy component fluid path 464. For example, as shown in FIG. 19 , inlet fluid path 460A, light component fluid path 456A, and heavy component fluid paths 464A and 464B are aligned and communicate with each other. However, they are restricted by the upper partition 336, the lower partition 288, and the divider 350 from freely communicating with the other inlet fluid paths 460B and C, the other light component fluid paths 456B and C, and the other heavy component fluid paths 464C-464F. This configuration and isolation of the fluid paths helps to separate the heavy and light components.

[0224] The development of the present disclosure has also uncovered surprising and unexpected results. For example, it has been discovered that when using upper partition 336, lower partition 288, and divider 350 to isolate fluid communication between selected inlet fluid paths 460, light component fluid paths 456, and heavy component fluid paths 464 as described herein, solids separation efficiency increases by fluidly connecting each light component fluid path 456 with an increasing number of heavy component fluid paths 464. For example, listed below is a table listing parameters and results of three tests operating three different separation rotor designs.

[0225] [Table 1]

[0226] In each of the three tests, the rotation of the separation rotor was set to 2,500 revolutions per minute, the feed rate delivering the inlet stream to the centrifuge was set to 3 liters per minute, and the percent solids in the inlet stream was maintained at 10%. Furthermore, in each of the three tests, the separation rotor was designed similarly to the separation rotor 184 previously disclosed herein, having three separate light component fluid paths 456A-456C separated by three spaced-apart upper partitions 336A-336C. ​​However, the number of heavy component fluid paths 464 communicating with each light component fluid path 456 varied from test to test.

[0227] In Test 1, the separation rotor 184 was designed to include only three dividers 350, each with a sidewall assembly 452 aligned with a corresponding upper partition 336. Thus, each light component fluid path 456 communicated with only a single heavy component fluid path 464. In this test, 78.2% of the solids collected in the first outlet stream 104 collecting the heavier components, and 21.8% of the solids collected in the second outlet stream 106 collecting the lighter components.

[0228] In Test 2, with all other variables held constant, the separation rotor 184 was designed as in the present disclosure, and the sidewall assembly 452 included six dividers 350, with every other divider aligned with a corresponding upper bulkhead 336. Thus, each light component fluid path 456 communicated with two heavy component fluid paths 464. In this test, 88.9% of the solids collected in the first outlet stream 104 collecting the heavier components, and 11.1% of the solids collected in the second outlet stream 106 collecting the lighter components.

[0229] Finally, in Test 3, with all other variables held constant, the separation rotor 184 was designed similarly to the present disclosure, except that the sidewall assembly 452 included 12 dividers 350, with every fourth divider aligned with a corresponding upper bulkhead 336. Thus, each light component fluid path 456 communicated with four heavy component fluid paths 464. In this test, 96.6% of the solids collected in the first outlet stream 104 collecting the heavier components, and 3.4% of the solids collected in the second outlet stream 106 collecting the lighter components.

[0230] Test results confirm that increasing the number of heavy component fluid paths 464 relative to the aligned light component fluid paths 456 increases solids separation efficiency. Thus, in one embodiment of the present disclosure, the separation rotor 184 may be formed such that the ratio of heavy component fluid paths 464 to light component fluid paths 456 is 1:1, while in other embodiments, to help improve solids separation efficiency, the separation rotor 184 may be designed such that the ratio is at least 2:1, 3:1, 4:1, 5:1, 6:1, 8:1, 10:1, 20:1, 40:1, or within a range between any two of the foregoing ratios.

[0231] Additionally, some common centrifuges use angled sidewalls to aid in separation. Generally, the angling of the sidewalls serves two purposes: 1) to encourage the heavy components to flow into a colocalized volume for collection and potential discharge, and 2) to reduce the separation time of the heavy components by reducing the radial distance the separated material must travel for separation. However, the present disclosure also employs angled upper and / or lower sidewalls for the additional purpose of mitigating inertial fluid flow effects that may impede separation.

[0232] Fluids flowing radially through a rotating chamber are subject to the Coriolis effect (i.e., inertial effect). The Coriolis effect affects fluids flowing primarily perpendicular to the axis of rotation. For example, when a fluid flows radially inward, its radial velocity accelerates relative to the radial velocity of the rotating chamber due to the fluid's inertia imparted by the chamber at a larger radius. This velocity difference allows the fluid to overtake the chamber at a radius smaller than the outermost radius and then drives the fluid back toward the outermost radius. Overall, the Coriolis (inertial) effect creates flow dynamics that result in vortex formation in a plane perpendicular to the axis of rotation. Such vortices can generate flows that disrupt centrifugation. In a chamber with upper and lower sidewalls that remain axially equidistant, as in one embodiment of the present disclosure, the radial cross-sectional area varies linearly with radius. This causes fluids flowing radially within such a chamber to accelerate in a manner that maintains a flow rate through the chamber's given radial cross-sectional area. In such a chamber, the radial acceleration of the fluid exacerbates the Coriolis effect and increases the fluid flow velocity, which generates vortices.

[0233] To help mitigate these above-described effects, embodiments of the present disclosure may employ upper or lower sidewalls, or both, that increase the axial distance between them as the radius decreases. In one embodiment, the upper sidewall, e.g., the inner surface 322 of the inner sidewall 320 (FIGS. 17 and 18), may be angled between 40° and 50°, more typically between 42° and 48°, or between 43° and 47°, relative to the central axis 230, i.e., the axis of rotation. The resulting frustoconical shape may help mitigate the above-described flow effects. That is, the expanding chamber height counteracts the change in radial cross-sectional area through which the fluid flows radially, thereby reducing, eliminating, or reversing the acceleration of the fluid as it flows radially. The additional axial dimension of the chamber may thereby act to disrupt vortex formation due to the Coriolis effect by encouraging the fluid to exit a plane perpendicular to the axis of rotation. This combined mitigation prevents compound acceleration of the fluid, which can lead to strong vortex formation that can disrupt separation within the chamber.

[0234] Figure 20 illustrates another alternative embodiment of a centrifuge 12B that may be used as the centrifuge 12 in the systems and alternatives described above with respect to Figures 1-5. Centrifuge 12B is substantially similar to centrifuge 12A, and like elements are identified by like reference numerals. Furthermore, unless otherwise described and / or illustrated, it should be understood that like elements among centrifuge 12B function in the same manner as, and may have the same alternative configuration as, corresponding elements in centrifuge 12A.

[0235] As shown in FIG. 20, the centrifuge 12B includes a separation rotor 184 that rotates within the separation stator 180 and functions to separate the inlet stream 102 into heavy and light components. The separation rotor 184 includes a base 250, a dispersion member 252A, an insert 256, a cap portion 254, and a stem assembly 258. In contrast to the dispersion member 252, which has a body 470 in the form of a flat plate, the dispersion member 252A includes a body 280 having a frustoconical configuration and an opening 290 extending centrally therethrough, as shown in FIGS. 20 and 21. The body 470 has a top surface 282 and an opposite bottom surface 284 that slope outward from the opening 290 to an outer peripheral edge 286. Three upper partitions 474A-474C project outward from the top surface 282. The upper partitions 474A-474C extend radially from the opening 290 and terminate at free ends 484 that extend beyond the peripheral edge 286. The free ends 484 are designed to abut the outer sidewall 450. Each upper partition 474 has an outer edge 476 configured to seat against the interior surface of the insert 256, thereby forming light component fluid paths 456A-456C between adjacent pairs of the upper partitions 474 through which the light components pass to the stem assembly 258. In the illustrated embodiment, a plurality of elongated dividers 486 also project outward from the top surface 282 of the dispersion member 252A between adjacent pairs of the upper partitions 474. The dividers extend radially from the opening 290 to the outer peripheral edge 286. However, the dividers 486 do not extend all the way to the outer sidewall 450. The dividers 486 partially subdivide each of the light component fluid paths 456A-456C, although some fluid communication is permitted between the sub-portions of each of the light component fluid paths 456A-456C. In contrast, fluid communication is limited between the different light component fluid paths 456A-456C. In the illustrated embodiment, three dividers 486 are formed between each pair of upper partitions 474. Other numbers of dividers 486, such as at least 1, 2, 4, 5, 6, 8, or 10, may also be used.

[0236] Centrifuge 12B also includes a conduit 420A. A first end 426 of conduit 420A is rotatably sealed to end wall 218 of nose section 214 by a pair of dynamic seals 432A and 432B. In contrast to centrifuge 12A, a second end 428 of conduit 420A passes through the center of floor 264 and drive coupling 186 and is rotatably secured to end wall 210 of receiver 206 by an annular bearing assembly 478, such as a race bearing. A seal 482 is formed between conduit 420A and floor 264 to prevent liquid from leaking therebetween. Bearing assembly 270 is omitted; therefore, bearing assemblies 404 and 478 are used to support and stabilize split rotor 184 within split stator 180. A plurality of openings 480 extend radially through the conduit 420A between the floor 264 and the dispersion member 252A to communicate with the passages 430. Three equally spaced lower partitions 490 extend between the floor 264 and the dispersion member 252A and project radially outward from the conduit 420A to the outer sidewall 450. The lower partitions 490 align with and intersect the corresponding upper partitions 474. The lower partitions 490 divide the space into separate, isolated inlet fluid paths 460A-460C that communicate with corresponding light component fluid paths 456A-456C.

[0237] Note that the outer peripheral edge 330 of the insert 256 is disposed radially outward from the outer peripheral edge of the dispersion member 252A. During operation, the separation rotor 184 rotates with the separation stator 180 through the use of the drive coupling 186, as previously described. The inlet stream 102 is delivered to the inlet port 38, where it travels downward through the conduit 420A and exits through the opening 480 into the inlet fluid path 460. The fluid stream flows radially outward toward the outer sidewall 450. The lighter components enter the light component fluid path 456, pass through the spout 360 of the stem assembly 258, into the light component collection recess 444, and exit through the second outlet port 42, as previously described with respect to the centrifuge 12A. Similarly, the heavier components flow radially outward, entering the heavy component fluid path 464, through the heavy collection channel 382, ​​into the heavy component collection recess 446, and exiting through the first outlet port 40, as previously described with respect to the centrifuge 12A.

[0238] 22 and 23 illustrate an exemplary embodiment of another alternative continuous-flow centrifuge 12C that may be used as the centrifuge 12 in the systems and alternatives described above with respect to FIGS. 1-5. Separator 12C has similar components and operates similarly to separator 12A. As such, similar elements between separators 12A and 12C are identified by similar reference numerals. Furthermore, unless explicitly or inherently understood otherwise, the alternatives, modifications, operations, features, and functions described above with respect to the conventional separators are also applicable to separator 12C.

[0239] Generally, the centrifuge 12C includes a body assembly 130C and a driver sleeve 132C projecting outwardly therefrom. In the exemplary illustrated embodiment, the driver sleeve 132C is integrally formed as a single, unitary member with a portion of the body assembly 130C. However, in other embodiments, the driver sleeve 132C may be secured to the body assembly 130C in the same manner as described above with respect to the driver sleeve 132 (FIG. 8). Again, as described in more detail below, during operation of the centrifuge 12A, a magnetic driver 148 (FIG. 8) may be positioned and rotated within the driver sleeve 132. As described in more detail below, the body assembly 130C / centrifuge 12C includes an inlet port 38, a first outlet port 40, and a second outlet port 42.

[0240] 23 , the driver sleeve 132C includes an outer surface 134C and an inner surface 136C that surround an opening 138C. The driver sleeve 132C has a first end 140C extending from the body assembly 130C and an opposite second end 141C. In the exemplary embodiment, the driver sleeve 132C includes a cylindrical sleeve body 142C and a plurality of spaced apart reinforcing fins 143C that project radially inward from the inner surface 136C and outward along the floor of the body assembly 130C. The fins 143C add reinforcement and structural stability to both the driver sleeve 132C and the body assembly 130C.

[0241] Spaced apart holes 146A-146C extend through the driver sleeve 132C between the exterior surface 134C and the interior surface 136C and may be used to releasably secure the separator 12C to a skid or other structure, as described in more detail below. In this embodiment, all three holes 146A-146C are formed in one half of the driver sleeve 132C. In other embodiments, holes 146A-146C may be replaced with two holes or four or more holes. In still other embodiments, holes 146A-146C may be replaced with one or more recesses extending into the exterior surface 134C or one or more flanges projecting outward from the exterior surface 134C, such as flange 145 (FIG. 8).

[0242] 24, the separator 12C / body assembly 130C generally includes a splitter stator 180C and a rotor assembly 182C rotatably disposed within the splitter stator 180C. The rotor assembly 182C includes a splitter rotor 184C rotatably disposed within the splitter stator 180C and a drive coupling 186C coupled to the splitter rotor 184C and which may be rotatably disposed within the splitter stator 180C. A central axis 230C passes through the centers of the splitter stator 180C and the rotor assembly 182C and coincides with the axis of rotation, also identified by reference numeral 230C, about which the rotor assembly 182C rotates. Thus, the terms "central axis 230C" and "axis of rotation 230C" are used interchangeably herein.

[0243] As shown in Figures 24 and 25, in one exemplary embodiment, the split stator 180C includes a base portion 190C and a head portion 192C that are coupled together prior to use. In one exemplary embodiment, the head portion 192C includes a tapered neck portion 174C to which a nose portion 214C is coupled. The split stator 180C has an inner surface 202C and an opposing outer surface 203C. The inner surface 202C bounds a chamber 194C in which the rotor assembly 182C is at least partially received. The assembled split stator 180C has a first end 196C at which the head portion 192C / nose portion 214C are disposed and an opposite second end 198C at which the base portion 190C is disposed. A central axis 230C extends between the first end 196C and the second end 198C. The split stator 180C includes an inlet port 38, a first outlet port 40, and a second outlet port 42, each located on the head portion 192 / nose portion 214C at a first end 196C.

[0244] Continuing to refer to FIG. 24, the base 190C (i.e., the second end 198C of the separator stator 180C) includes a floor 200C that extends radially outward to an annular sidewall 204C. The sidewall 204C stands upright from the floor 200C and projects toward the first end 196C. An annular mounting flange 205C projects outward from the sidewall 204C. A pair of handles 199A and 199B project radially outward from opposite sides of the flange 205C. The handles 199A and 199B are used to manually lift and transport the separator 12C. In one embodiment, the inner surface 202C of the sidewall 204C is cylindrical. In other embodiments, the inner surface 202C of the sidewall 204C may be outwardly sloped. The driver sleeve 132C is typically centered on the floor 200C and projects outward therefrom. The receiver 206C is centrally disposed on the floor 200C and projects outward from its outer surface 203C. The receiver 206C is disposed within an opening 138C of the driver sleeve 132C so as to be surrounded by the driver sleeve 132C. In an exemplary embodiment, the receiver 206C is concentrically disposed within the driver sleeve 132C. The receiver 206C bounds a recess 212C that forms a portion of the chamber 194C. In one embodiment, the receiver 206C includes a sidewall 208C that projects from the floor 200C and terminates in an end wall 210C. In one embodiment, the sidewall 208C and the recess 212C each have a cylindrical configuration. An annular notch 211C may be recessed in the sidewall 208C at its intersection with the floor 200C to receive a bearing assembly 270C, as described in further detail below. The receiving portion 206C is configured to be received within the opening 166 of the magnetic driver 148 / drive rotor 150 (FIG. 8), which in turn is received within the opening 138C of the driver sleeve 132C.

[0245] 23, the base 190C (i.e., the first end 198C of the isolated stator 180C) also includes fins 143C projecting outwardly from the exterior surface of the floor 200C, as previously described. The fins 143C may be aligned parallel to the central axis 230C (FIG. 24) and may be equally spaced about the receiver 206C.

[0246] In one embodiment, the centrifuge 12C is designed to be disposable after a single use. To that end, the separation stator 180C, and more specifically, the base 190C, head 192C, and driver sleeve 132C, are typically made from a polymeric material such as polyvinylidene fluoride or polyvinylidene difluoride (PVDF), high-density polyethylene (HDPE), polyetherimide (PEI), or polyetheretherketone (PEEK), and are generally molded by injection molding, rotational molding, or the like. These materials and manufacturing methods allow the separation stator 180C to be manufactured more cheaply than if it were made from metal. In part, the fins 143C function to add strength and stability to the separation stator 180C and driver sleeve 132C when made from a lower-strength polymeric material. However, in other embodiments, the isolated stator 180C may be made from a stronger metal such as aluminum or stainless steel, or alternatively, a high strength polymer such as liquid crystal polymer or polycarbonate, in which case the fins 143C may be omitted.

[0247] 24 and 25, the nose portion 214C of the head portion 192C has a sidewall 216C terminating at an upper end in an end wall 218C and an annular, outwardly projecting flange 219C at an opposite, lower end. The nose portion 214C bounds a recess 213C. In one embodiment, the inner surface 202C of the sidewall 216C bounding the recess 213C may have a substantially cylindrical configuration. An inlet port 38 protrudes centrally and outwardly from the end wall 218C. A first outlet port 40 and a second outlet port 42 protrude outwardly from the sidewalls of the nose portion 214C. The inlet port 38 bounds a passageway 45, and the outlet ports 40 and 42 bound passageways 47 and 49, respectively. An annular light components collection recess 444C is recessed in the end wall 218C to surround the passageway 45 and communicate with the recess 213C. The light component collection recess 444C is in direct communication with the passage 47 of the second outlet port 42.

[0248] The neck portion 174C of the head portion 192C includes an annular transition wall 220C extending between an annular mounting flange 227C at its upper end and an annular mounting flange 228C at its opposite lower end. The flanges 219C and 227C are coupled to one another by fasteners 221C, such as screws, bolts, or clamps, to form a gas-tight seal between the nose portion 214C and the neck portion 174C, with an O-ring 223C disposed therebetween. In one embodiment, at least a portion of the transition wall 220C has a frustoconical configuration, with the inner surface 202C thereof typically disposed at an angle relative to the central axis 230C of at least 30°, 40°, 50°, or 60° or less, or a range between any two of the foregoing. In the illustrated embodiment, the portions of the transition wall 220C extending from the mounting flanges 227C and / or 228C may be cylindrical or have a different configuration than the remainder of the transition wall 220C. Forming the nose portion 214C and the neck portion 174C as two separate members secured by fasteners may simplify the manufacture of the head portion 192C and assembly with the separator 12C, although in other embodiments the nose portion 214C and the neck portion 174C may be integrally formed as one unitary member, thereby eliminating the need for fasteners.

[0249] During assembly, mounting flanges 205C and 228C are coupled together such that rotor assembly 182C / isolated rotor 184C is captured within isolated stator 180C. Mounting flanges 205C and 228C may be coupled together by fasteners 233C, such as screws, bolts, clamps, or other fasteners or techniques. O-ring 235C is disposed between flanges 205C and 228C to form an airtight seal therebetween.

[0250] The rotor assembly 182C is rotatably positioned within the chamber 194C of the separation stator 180C and is used to separate the inlet stream 102 (FIGS. 1-5) of biological suspension or other mixture into the first outlet stream 104 and the second outlet stream 106. Referring to FIG. 25, as previously described, the rotor assembly 182C includes a separation rotor 184C and a drive coupling 186C extending from the rotor assembly 182C. More specifically, the separation rotor 184C has a first end 240C and an opposite second end 242C with a central axis / rotation axis 230 extending centrally therebetween. The drive coupling 186C is centrally mounted to and projects outwardly from the second end 242C of the separation rotor 184C, such that the central axis 230 passes through the center. Referring to FIG. 24 , the drive coupling 186C typically has an enclosing side surface 244C terminating in an end surface 246C. A fastener 247C, such as a screw or bolt, may extend through an opening formed on the drive coupling 186C and engage with the separated rotor 184C, such as by a threaded connection or other technique, to secure the drive coupling 186C to the separated rotor 184C. In an exemplary embodiment, a shear pin 249C protrudes from the separated rotor 184C into an opening 251C formed on the drive coupling 186C. The engagement between the shear pin 249C and the drive coupling 186C helps ensure that the separated rotor 184C and the drive coupling 186C rotate simultaneously. In an alternative embodiment, the shear pin 249C may protrude outward from the drive coupling 186C and into an opening 251C formed on the separated rotor 184C.

[0251] The drive coupling 186C typically has a cylindrical configuration and is configured to be rotatably received within a recess 212C of the receiver 206C, as shown in Figure 24. A gap 248C is formed between a side surface 244C of the drive coupling 186C and a side wall 208C of the receiver 206C so that the drive coupling 186C can freely rotate within the receiver 206C.

[0252] In an exemplary embodiment, gap 248C is less than 10 mm, 8 mm, 6 mm, 4 mm, 2 mm, or within a range between any two of the foregoing. Typically, it is desirable to minimize the size of gap 248C to help facilitate magnetic rotation of drive coupling 186C. Drive coupling 186C is made of and configured from a material that can be controlled by the magnetic field generated by magnet 168 of magnetic driver 148 ( FIG. 8 ). For example, drive coupling 186C may include another magnet or a material that is attracted to a magnet, such as iron or an iron composite. During operation, drive coupling 186C is positioned within receiver 206C, which in turn is received within cavity 162 of drive rotor 150 ( FIG. 8 ). Rotation of drive rotor 150 by motor 169 facilitates simultaneous rotation of drive coupling 186C as a result of the magnetic force generated on drive coupling 186C by magnet 168. Rotation of the drive coupling 186C, in turn, promotes simultaneous rotation of the isolation rotor 184C to which it is attached. It should be understood that in alternative embodiments, the receiver 206C, which generally functions as a protective cover, may be omitted. In this case, the drive coupling 186C is received directly within the cavity 162 of the drive rotor 150.

[0253] 26, the split rotor 184C generally comprises a base 250C to which the drive coupling 186C is attached, a dispersion member 252C seated on the base 250C, a disk stack 253C disposed on the dispersion member 252C, a cap 254C coupled to the base 250C, and an insert 256C captured between the cap 254C and the disk stack 253C. The various elements of the split rotor 184C will now be described in further detail.

[0254] As shown in FIGS. 27 and 28 , the base 250C has an interior surface 260C that partially bounds the compartment 261C and an opposing exterior surface 262C. The base 250C includes a floor 264C and an annular sidewall 266C that projects upward from the outer periphery of the floor 264C toward the cap portion 254C. The sidewall 266C is hereinafter referred to as the lower sidewall 266. A mounting flange 265C surrounds the upper end sidewall 266C and projects radially outward therefrom. A recess 267C is centrally formed in the interior surface 260C of the floor 264C and communicates with the compartment 261C. More specifically, in one exemplary embodiment, a bowl 269C is centrally formed on the exterior surface 262C of the floor 264C and projects outward from the exterior surface 262C. Recess 167C is formed in bowl 269C. In one embodiment, both bowl 269C and recess 267C may be circular. Mounting portion 268C projects outward from exterior surface 262C of bowl 269C in alignment with central axis 230A. Bowl 269C and recess 167C are optional and may be omitted. If not used, mounting portion 268C may project outward directly from exterior surface 262C of floor 264C in alignment with central axis 230C. Drive coupling 186C is secured to mounting portion 268C, such as by fastener 247C, as described above, or by other fastening techniques, such as adhesive, press fit, or threaded coupling.

[0255] A plurality of optional cooling fins 271C are formed on and project outwardly from floor 264C. In one exemplary embodiment, fins 271C are spaced apart and project radially outward away from bowl 269C. Fins 271C may be straight or curved. If bowl 269C is not used, fins 271C may project radially outward away from central axis 230C. Base 250C may be formed with at least 1, 3, 5, 6, 8, or more fins 271C, or a range between any two of the foregoing.

[0256] Returning to FIG. 24 , an annular bearing assembly 270C, such as a race bearing, is received within the annular notch 211C and extends between the base 250C of the separated rotor 184C and the base 190C of the separated stator 180C. The bearing assembly 270C functions to support, center, and stabilize the separated rotor 184C relative to the separated stator 180C, facilitating rotation of the separated rotor 184C relative to the separated stator 180C. In an exemplary embodiment, the bearing assembly 270C is fixed relative to the exterior of the bowl 269C or directly adjacent thereto. As will be explained in more detail below, one function of the bowl 269C / recess 267C is that during operation, when the separated rotor 184C is rotating relative to the separated stator 180C through the use of the bearing assembly 270C, the biological suspension or other mixture being processed can flow through the recess 267C, thereby helping to cool the adjacent bearing assembly 270C. That is, bowl 269C / recess 267C functions as a heat sink. In one embodiment, bearing assembly 270C is horizontally aligned with and / or surrounds a portion of recess 276C and / or bowl 269C.

[0257] The cooling fins 271C (FIG. 28) may also serve to assist in cooling the bearing assembly 270C. That is, when the isolated rotor 184C rotates relative to the isolated stator 180C through the use of the bearing assembly 270C, the fins 271C rotate within the gap between the isolated rotor 184C and the isolated stator 180C. The fins 271C move air within the gap above the bearing assembly 270C, thereby helping to cool the bearing assembly 270C.

[0258] Returning to FIG. 27, a plurality of partitions 272A-272F project upward from the inner surface 260C of the floor 264C. The partitions 272 are evenly spaced and project radially outward in alignment with the central axis 230 and / or the recess 267C. The partitions 272A, 272C, and 272E also have elongated slots 273 formed along their lengths. As described in more detail below, the partitions 272 function to space the dispersion member 252C from the inner surface 260C of the floor 264C and to secure the dispersion member 252C to the base 250C so that the base 250C and dispersion member 252C rotate simultaneously. The inner surface 260C of the lower sidewall 266C may have an annular frustoconical configuration that tapers outward from the outer periphery of the floor 264C to an annular flange 265C. In one embodiment, the interior surface of the lower sidewall 266C is inclined at an outward angle relative to the central axis 230 that is at least 10°, 15°, 20°, 25°, 30°, 35° or less, or within a range between any two of the aforementioned angles.

[0259] 29 and 30 , as described herein, the dispersion member 252C can have a variety of different configurations. In the currently illustrated embodiment, the dispersion member 252C comprises a body 280C in the form of a circular plate having a top surface 282C and an opposite bottom surface 284C, each of which extends to an outer circumferential edge 286C. An opening 290C extends centrally through the body 280C, aligned with the central axis 230C, so as to pass between the opposing surfaces 282C and 284C. Lower partitions 288A, 288B, and 288C project from the bottom surface 284C of the body 280C and are typically equally spaced apart. The lower partitions 288A, 288B, and 288C are linear and project radially outward from the openings 290C. Lower septum 288 is configured to be received within slot 273C of septum plates 272A, 272C, and 272E and terminates in a terminal end 291C that projects beyond peripheral edge 286C.

[0260] During assembly, the dispersion member 252C is disposed on and interlocked with the base 250C (FIG. 26) by the lower partitions 288A-288C of the dispersion member 252C (FIG. 30) being received in the slots 273C of the partitions 272A, 272C, and 272E (FIG. 27). The terminal end 291C abuts or is disposed directly adjacent to the inner surface 260C of the lower sidewall 266C of the base 250C. This assembly centers the dispersion member 252C on the floor 264C to ensure that the peripheral edge 286C is evenly spaced from the lower sidewall 266C, and also interlocks the dispersion member 252C with the base 250C such that rotation of the base 250C about the central axis 230C promotes simultaneous orbital rotation of the dispersion member 252C. Additionally, the body 280C of the distribution member 252C is spaced apart from the floor 264C of the base 250C, thereby forming a space 448C therebetween. As described in further detail below, the lower septum 288 and the septum 272 function to form an inlet fluid channel that flows radially outward through the space 448C between the distribution member 252C and the floor 264C to help facilitate separation of the biological suspension. It should be understood that various other structural designs may be used to securely center the distribution member 252C on the floor 264C while forming the inlet fluid channel. However, the currently illustrated embodiment is uniquely configured to allow for quick and easy positioning of the distribution member 252C without requiring the use of separate fasteners.

[0261] 29, dispersion member 252C further includes a tubular stem portion 289C that projects outward from top surface 282C of body 280C in alignment with opening 290C. Specifically, stem portion 289C defines a passageway 293C that communicates with opening 290C. Retaining rails 296A-296C extend upward from top surface 282C and project radially outward from stem portion 289C in alignment with lower partitions 288A-288C, respectively. Each retaining rail 296A-296C may intersect a corresponding lower partition 288A-288C outside of periphery 286C and extend to a terminal end 291C. Each retaining rail 296 includes a support portion 297C having a triangular shape with an upper edge 298C sloping upwardly toward the stem portion 289C and an extension portion 299C projecting outwardly from the support portion 297C beyond the peripheral edge 286C.

[0262] The disk stack 253C (FIG. 26) includes multiple disks 500C nested within one another. As shown in FIGS. 31 and 32, each disk 500C includes a disk body 502C having a top surface 504C and an opposing bottom surface 506C, each of which has a complementary frustoconical configuration. The disk body 502C extends between a central inner edge 508C and an outer peripheral edge 510C. The inner edge 508C is circular and surrounds an opening 512C through which the axis 230C passes. The peripheral edge 510C is also typically circular. A plurality of spaced apart partitions 514C project outward from the top surface 504C. Diaphragms 514C function to keep discs 500C spaced apart when nested together in disc stack 253C, especially when disc stack 253C is being rotated at high speeds.

[0263] Three radially spaced guides 516A-516C are formed on the disk body 502C. Each guide 516A-516C is radially aligned with the axis 230C and disposed between the inner edge 508C and the peripheral edge 510C. More specifically, each guide 516A-516C is elongated and has a first end 518C disposed toward the inner edge 508C and an opposite second end 520C disposed toward the peripheral edge 510C. An upper notch 522C passes through the disk body 502C and extends from the first end 518C to the inner edge 508C, while a lower notch 524C extends from the second end 520C to the peripheral edge 510C. Each guide 516A-516C has an inner surface 526 formed on the bottom surface 506C of the disk body 502C and an outer surface 528C formed on the top surface 504C of the disk body 502C. A guide slot 530C is recessed in the inner surface 526 and extends between opposite ends 518C and 520C. A guide rail 532C projects outward from the outer surface 528C and extends between opposite ends 518C and 520C. When the disks 500C are nested together, the guide rail 532C of one disk 500C is received within the guide slot 530C of an adjacent disk 500C. The coupling between the guide rail 532C and the guide slot 530C functions, in part, to help interlock the disks 500C for simultaneous rotation. Additionally, the guide rails 532C and guide slots 530C are sized to help achieve and maintain proper spacing between the disks 500C so that fluid can flow between them. While the spacing between the disks 500C can vary based on the intended use and operation, in one embodiment, the spacing between each adjacent pair of nested disks 500C is typically less than 1.5 cm, 1 cm, 0.8 cm, 0.6 cm, or 0.4 cm, or within a range between any two of the aforementioned values. The number of disks 500C can also vary depending on the intended use. In one embodiment, the number of disks 500C used in the separator can be at least 1, 3, 5, 7, 10, 12, 15, or 20, or no more than 1, 3, 5, 7, 10, 12, 15, or 20, or within a range between any two of the aforementioned numbers.Finally, the interlocking between guides 516, i.e., the interlocking between guide rails 532C and guide slots 530C, forms a continuous wall portion along nested disks 500C that prevents fluid from flowing radially around disks 500C. For example, Figure 24 shows stacked guides 516A and 516B forming wall portions 534A and 534B, respectively.

[0264] As shown in FIG. 31 , each disk 500C also includes an elongated flow rail 536A-536C. Each flow rail 536A-536C is positioned between an adjacent pair of guides 516A-516C and radially aligned with the opening 512C / axis 230C. The flow rails 536A-536C extend partially between the inner edge 508C and the outer periphery 510C, but do not extend completely therebetween. In one exemplary embodiment, the radial linear distance from the inner edge 508C to the outer periphery 510C is “D.” Each flow rail 536A-536C extends between 20% and 90% of the radial distance D, more typically between 30% and 80% or 40% and 70% of the radial distance D. Other dimensions may also be used. The flow rails 536A-536C are typically spaced apart from the periphery 510C and extend to the inner edge 508C. However, in other embodiments, the flow rails 536 may be spaced apart from the inner edge 508C. As described in more detail below, during operation, liquid flows radially in opposite directions between the periphery 510C and the inner edge 508C along separate channels bounded by the guides 516. The formation of the flow rails 536 is optional, but serves to limit or eliminate swirling of fluid within the separate channels. Swirling of fluid within vortices can increase turbulence, which reduces settling and separation of the fluid. In other words, the flow rails 536 serve to maintain a radial and laminar flow that aids separation. Spaced aft from the periphery 510C, the flow rails 536A-536C allow fluid to freely enter each of the separate channels.

[0265] During assembly, the disks 500C are stacked on top of and interlocked with the dispersion member 252C. The disks 500C can be stacked incrementally or in groups, i.e., as a disk stack 253C. Referring to FIGS. 29 and 32, the disks 500C are stacked so that the top edges 298C of the support portions 297C of the retaining rails 296 are received in corresponding guide slots 530 on the bottom disks 500C, and the extension portions 299C of the retaining rails 296 are received in lower notches 524C of the bottom disks 500C. This positioning interlocks the disks 550C with the dispersion member 252C, causing them to rotate simultaneously, and also results in the retaining rails 296 extending vertically up the wall formed by the stacked guides 516C to the main body 280C of the dispersion member 252C.

[0266] 26, 35, and 36, insert 256C includes an annular sidewall 320C, herein referred to as inner sidewall 320C. Inner sidewall 320C has an inner surface 322C and an opposite outer surface 324C extending between first end 238C and opposite second end 326C. Inner sidewall 320C includes an annular first portion 560C at first end 238C, which has a substantially cylindrical configuration configured to be received within cap portion 254C. Inner sidewall 320C also includes an annular second portion 562C at second end 326C, which has a substantially frustoconical configuration tapering inwardly toward first portion 560C. In one embodiment, the inner surface 322C of the second portion 562C of the inner sidewall 320C may be inclined at an angle ranging from 35° to 55°, more typically 40° to 50° or 42° to 48°, relative to the central axis 230. Other angles may also be used. The second end 326C of the inner sidewall 320C terminates in a peripheral edge 330C, and the first end 328 terminates in an annular lip 332C. The lip 332C surrounds an opening 334C that passes through the center of the insert 256C along the central axis 230C. An annular flange 563C surrounds the sidewall 320C at the first end 238C and projects radially outward. An annular groove 564C surrounds the flange 563C immediately below the lip 332C and is recessed therein. The annular groove 564C is configured to receive an O-ring 566C.

[0267] The insert 256C further includes a tubular conduit portion 570C disposed within the opening 334C of the insert 256C so as to extend along the first portion 560C of the inner sidewall 320C and along at least a portion of the second portion 562C of the inner sidewall 320C. A free end 571C of the conduit portion 570C projects from the opening 334C at the first end 238C. The conduit portion 570C bounds a passage portion 572C through which the shaft 230C extends. Three upper partitions 574A-574C project radially outward along the length of the conduit portion 570C to the interior surface 322C of the inner sidewall 320C. The upper partitions 574A-574C function, in part, to secure the conduit portion 570C to the inner sidewall 320C and separate the opening 334 through the first portion 560C into three separate channels. Braces 576C also extend radially between the conduit portion 570C and the sidewall 320C between each adjacent pair of the upper partitions 574A-574C. The braces 576C serve to further support the conduit portion 570C at the first end 238C, but typically do not extend the entire length of the conduit portion 570C and are typically not as long as the upper partitions 574A-574C. As shown in FIG. 36 , the outer partitions 578A-578C are radially aligned with but spaced apart from the upper partitions 574A-574C. The outer partitions 578A-578C project outward from the interior surface 322C at the second end 326C of the inner sidewall 320C so as to project beyond the peripheral edge 330C. The outer partitions 578A-578C are radially aligned with the upper partitions 574A-574C, respectively.

[0268] A plurality of radially spaced-apart component dividers 350A-350F project outward from the exterior surface 324C of the inner sidewall 320D. The dividers 350 extend radially outward from the exterior of the inner sidewall 320C aligned with the axis 230C and are in the form of linear rails extending longitudinally from a flange 563C at the first end 238C to the periphery 330C at the second end 326C. The dividers 350A, 350C, and 350E are aligned with and intersect the upper and outer partition walls 574A-574C and the outer partition walls 578A-578C, respectively.

[0269] During assembly, insert 256C rests on and interlocks with both disk 500 and dispersion member 252. Specifically, referring to FIGS. 29, 31, and 36, insert 256C nests atop disk stack 253C such that upper bulkheads 574A-574C pass through corresponding upper notches 522 in disk 500C and engage the upper ends of retaining rails 296A-296C, respectively, of dispersion member 252C. Concurrently, the lower end of conduit portion 570C passes through opening 512 in disk 500C and mates with the upper end of stem portion 289C of dispersion member 252C. Conduit portion 570C and stem portion 289C combine to form conduit 568C, which bounds passageway 569C (FIG. 24). Outer bulkheads 578A-578C of insert 256C pass through lower notch 524C of disk 500C and engage extensions 299C of retaining rails 296A-296C, respectively. In this nested configuration, rotation of base 250C also facilitates the ongoing rotation of each of dispersion member 252C, disk 500C, and insert 256C.

[0270] 26 and 33, the cap portion 254C has an inner surface 300C and an opposing outer surface 302C extending between a first end 307C and an opposing second end 308C. The cap portion 254C includes a tubular stem 358C disposed at the first end 307C and an annular sidewall 304C disposed at the second end 308C. The sidewall 304C is hereinafter referred to as the "upper sidewall 304C." The upper sidewall 304C and its inner surface 300C have a frustoconical configuration that tapers inward from the annular flange 305C at the lower end to the stem 358C. In one embodiment, the sidewall 304C is configured such that its inner surface 300C is inclined at an angle between 35° and 55°, more typically between 40° and 50° or between 42° and 48°, relative to the central axis 230C. Other angles may also be used.

[0271] As best seen in FIG. 34 , during assembly, cap portion 254C is coupled to base portion 250C by covering flanges 256C and 305C. To help ensure proper alignment and centering, an annular ridge 540C upstanding from flange 305C may be received in an annular slot 542C formed on flange 265C. In another embodiment, ridge 540C and slot 542C may be reversed. With flanges 256C and 305C overlapping, an annular mounting ring 544C having threaded holes 546C ( FIG. 26 ) extending therethrough may be positioned against the bottom surface of flange 265C. Fasteners 548, such as screws or bolts, may then be advanced downwardly through the aligned openings in flanges 305C and 265C and threaded into holes 546 in mounting ring 544C. Mounting ring 544C is typically made of a metal such as aluminum or stainless steel and provides reinforced, uniform compression between flanges 256C and 305C while adding increased structural stability. A tapered annular slot 550C, such as a triangular or wedge-shaped slot, is formed between flanges 256C and 305C. An O-ring 552C is received in slot 550C and compressed to form an airtight seal between cap portion 254C and base portion 250C. As a result of the tapered shape of slot 550C, as fluid pressure increases within isolation rotor 184C, O-ring 552C is pressed further into contraction slot 550C, which further improves the sealing effectiveness of O-ring 552C.

[0272] Returning to FIG. 26 , the stem 358C has a substantially cylindrical configuration and projects outward from the upper sidewall 304C such that the central axis 230 passes through the center of the stem 358C. In the illustrated embodiment, the stem 358C is integrally formed with the cap portion 254C as a single, unitary member. However, in other embodiments, the stem 358C may be separately attached and secured to the cap portion 254C. As described in further detail below, the stem 358C terminates in an end face portion 544C having an end opening 556C extending therethrough in alignment with the axis 230C. A plurality of radially spaced side openings 558C extend laterally through the stem 358C between the inner surface 300C and the outer surface 302C. In one embodiment, six side openings 558C are formed, all of which are disposed in a common plane perpendicular to the axis 230C. Other numbers of side openings 558C may also be formed.

[0273] 21 , when the cap portion 254C is placed over the insert 256C and secured to the base 250C, the first portion 560C of the insert 256C is received within the stem 358C of the cap portion 254C, as previously described. The free end 571C of the conduit 568C protrudes through the end opening 556C of the stem 358C, and the O-ring 566C forms a seal between the first portion 560C of the insert 256C and the interior surface of the stem 348C above the side opening 556C. In the assembled state, the base 250C, dispersion member 252C, insert 256C, disk 500C, and cap portion 254C are secured to one another and rotate simultaneously with the rotation of the base 250C.

[0274] The assembled split rotor 184C is enclosed within the split stator 180C. Specifically, as previously described, the base 250C of the split rotor 184C is seated within the base 190C of the split stator 180C so that it is supported on the bearing assembly 270C. In this position, the drive coupling 186C is freely disposed within the receiver 206C. The neck 174C of the head 192C is secured to the base 190C using fasteners 233C and O-ring 235C, as previously described. Simultaneously with or subsequent to the installation of the neck 174C, the nose 214C of the head 192C is secured to the neck 174C using fasteners 221C and O-ring 223C, as previously described.

[0275] Each of the base portion 250C, dispersion member 252C, disk body 500C, insert 256C, and cap portion 254C is typically made from a polymeric material, such as liquid crystal polymer, polycarbonate, PVDF, HDPE, PEI, or PEEK. The different portions may be made from the same or different materials. As previously mentioned, making the parts from a polymeric material minimizes the cost of the centrifuge, so that the centrifuge can be economically discarded after a single use, thereby avoiding the need for subsequent sterilization or other cleaning. However, in alternative embodiments, one or more of the parts may be made from a metal, such as aluminum or stainless steel.

[0276] Referring to FIG. 37 , during assembly, the bearing assembly and various seals are positioned between the nose portion 214C / head portion 192C and the upper end of the rotor assembly 182C. Specifically, the free end 571C of the conduit 568C / conduit portion 570C is received within the passage 45 of the inlet port 38 during assembly. A dynamic seal 580C is used to form a seal between the conduit 568C and the head portion 192C / nose portion 214C, allowing the conduit 568C to rotate relative to the head portion 192C / nose portion 214C. In one exemplary embodiment, the dynamic seal 580C may be spring-loaded. For example, in the illustrated embodiment, the dynamic seal 580C includes a spring-loaded rotating face seal. Other types of dynamic seals may also be used.

[0277] Dynamic seal 580A includes an annular mounting portion 582A that is received and secured within an annular notch 584A that surrounds passageway 45 of inlet port 38. An annular static sealing element 586A is secured to mounting portion 582A to surround the free end of conduit 568C. In one embodiment, static sealing element 586A includes a ceramic ring. An annular mounting portion 588A is secured around the outside of conduit 570C. An annular dynamic sealing element 590A is secured to mounting portion 588A to seat against static sealing element 586A. Dynamic sealing element 590A is made from a material that forms an abradable seal with static sealing element 586A when dynamic sealing element 590A is rotated thereon. The materials of static sealing element 586A and dynamic sealing element 590A can be the same as those used in conventional rotary pump seals. Mounting portion 582A and / or mounting portion 588A are typically made from a flexible elastomeric material and are generally more flexible than static sealing element 586A and dynamic sealing element 590A. One end of spring 592A is disposed in a recess 594C formed in the end of insert 256C to seat against brace 576C and / or upper bulkhead 574 ( FIG. 35 ). The opposite end of spring 594A resiliently biases dynamic sealing element 590A to load or press dynamic sealing element 590A against static sealing element 586A. The flexibility of mounting portion 588A allows dynamic sealing element 590A to float or move along shaft 230A while being biased by spring 592A to accommodate expansion and / or contraction of rotor assembly 182C during use, and to account for wear of dynamic sealing element 590A and / or static sealing element 586A while still achieving a fluid-tight seal therebetween. With dynamic sealing portion 580C in mind, fluid entering inlet port 38 and traveling along passage 45 is forced to enter and travel downwardly into passage 569C of conduit 568C.

[0278] A bearing assembly 596C, such as a race bearing, extends between the cap portion 254C and the head portion 192C / nose portion 214C of the isolated rotor 184C. The bearing assemblies 596C and 270C (FIG. 24) support and stabilize the rotor assembly 182C / isolated rotor 184C within the isolated stator 180C while allowing the rotor assembly 182C / isolated rotor 184C to rotate within the isolated stator 180A. A dynamic seal 580B extends below the side opening 558C between the head portion 192C / nose portion 214C and the isolated rotor 184C, and a dynamic seal 580C extends above the side opening 558C between the head portion 192C / nose portion 214C and the isolated rotor 184C. In one embodiment, dynamic seals 580B and 580C are again spring-loaded and may include spring-loaded rotating face seals. Other types of dynamic seals may also be used. Dynamic seals 580B and 580C are illustrated as having substantially the same elements as dynamic seal 580A. Thus, similar elements are identified by similar reference characters but have corresponding seal letters. For example, dynamic seal 580B includes an annular mounting portion 582B secured to head portion 192C / nose portion 214C and an annular static sealing element 586B secured to mounting portion 582B. Annular diaphragm 582B may extend between bearing assembly 596C and mounting portion 586C. An annular mounting portion 588B is then secured to isolation rotor 184C, and an annular dynamic sealing element 590B is secured to mounting portion 588B. Dynamic sealing element 590B is disposed relative to static sealing element 586B, forming a seal therebetween. Again, mounting portions 582B and / or 588B may be made from a flexible elastomeric material that is more flexible than dynamic sealing element 590B or static sealing element 586B, thereby allowing dynamic seal 580B to float or move. Dynamic seal 580C is similarly constructed on the opposite side of side opening 558C. A single spring 592B has one end biased against mounting portion 588B and a second, opposite end mounted to mounting portion 588C to load or press against dynamic seals 580B and 580C. As a result, a single spring 592B can operate with two separate dynamic seals.Spring 592B surrounds cap portion 254C and is positioned within annular heavy components collection recess 446C that extends between dynamic seals 580B and 580C. First outlet port 40 is aligned with and communicates with heavy components collection recess 446C, which in turn is aligned with and communicates with side opening 558C. Thus, fluid exiting through side opening 558C is forced to exit through passage 49 of first outlet port 40.

[0279] 38, during operation, motor 169 is actuated to rotate drive rotor 150 relative to isolated stator 180C about central axis 230C. Magnetic forces generated by magnets 168 then act on drive coupling 186C, as previously described, causing drive coupling 186C and isolated rotor 184C to simultaneously rotate relative to isolated stator 180C about central axis 230C. During operation, isolated rotor 184C typically rotates at a speed of at least 1,000, 2,000, 2,500, 3,000, or 3,500 revolutions per minute (RPM), or within a range between any two of the foregoing values. Depending on the application, other speeds may also be used.

[0280] When rotation of the separation rotor 184C is activated, the inlet stream 102 (FIGS. 1, 3, and 5) of suspension 18 is passed through the inlet port 38, travels along the central axis 230C through the conduit 568C, through the opening 290C in the dispersion member 252C, and enters the space 448C between the dispersion member 252C and the floor 264C of the separation rotor 184C. The inlet stream 102 flows radially outward in all directions within the space 448C toward the periphery 286C of the dispersion member 252C. The dispersion member 252D functions, in part, to force the inlet stream 102 to flow radially outward from the central axis 230C in a manner that maximizes the speed and force with which the inlet stream 102C begins to separate into heavy and light components. Specifically, as the inlet stream 102 moves radially outward, away from the central axis 230C, the inlet stream 102 is subjected to increasing centrifugal forces caused by the rotation of the separation rotor 184C. Thus, as the inlet stream 102 passes around the peripheral edge 286C of the dispersion member 252C, the centrifugal forces cause the inlet stream 102 to separate into heavier components moving radially outward and lighter components moving radially inward.

[0281] Additionally, radially extending partitions 272 and lower partitions 288 extend between the dispersion member 252C and the floor 264C to divide the space 448 into multiple inlet fluid paths 460C that extend from the conduit 420C to the periphery 286C of the dispersion member 252C. Each inlet fluid path 460C is bounded between adjacent pairs of partitions 272C / lower partitions 288C to force the inlet stream 102 to flow radially outward along a generally linear path, as opposed to swirling in a circle within the space 448C around the central axis 230. This linear radial flow of the inlet stream 102 again helps to rapidly move the inlet stream 102 away from the central axis 230C to increase the rate at which the inlet stream 102 separates into heavier and lighter components. Additionally, the linear radial flow helps maintain laminar flow of the inlet stream 102, as opposed to turbulent flow, which further aids in separating the inlet stream 102 into heavier and lighter components. In the illustrated embodiment, six inlet fluid paths 460C ( FIG. 27 ) are formed. In alternative embodiments, other numbers of inlet fluid paths 460C may be formed, such as at least 3, 4, 5, 6, 7, 8, 9, or 10, or a range between any two of the foregoing numbers. Furthermore, as the inlet stream 102 flows radially outward along the inlet fluid paths 460C, the fluid also flows through recesses 267C formed in the floor 264C. As previously described, the fluid flowing through recesses 267C helps to cool the adjacent bearing assembly 270C.

[0282] The lower sidewall 266C of the base portion 250C and the upper sidewall 304C of the cap portion 254C combine to form the outer sidewall 450C of the isolation rotor 184C, while the inner sidewall 320C of the insert 256C forms the inner sidewall 320C of the isolation rotor 184C. The outer sidewall 450C and the inner sidewall 320C combine to form a sidewall assembly 452C of the isolation rotor 184C, which encloses a compartment 454C of which the space 448C forms a part.

[0283] 39, the lower partition 288C projects radially outward within the space 448C from or toward the opening 290C in the distribution member 252C to the sidewall assembly 452C, more specifically, to the outer sidewall 450C / lower sidewall 216C. As a result, the lower partition 288C forms three isolated inlet fluid paths 460 below the distribution member 252C.

[0284] Similarly, as shown in FIGS. 24 and 29, three walls 600A-600C are formed within compartment 454C, extending radially outward from conduit 568C to both inner sidewall 320C and lower sidewall 266C, and longitudinally from top surface 282C of base 280C to first end 238C of insert 256C, typically above side opening 558C. Walls 600A-600C extend longitudinally along separation rotor 184C and bound a plurality of light component fluid paths 456A-456C through which portions of the fluid pass. Walls 600A-600C prevent or limit fluid traveling within fluid paths 456A-456C from radially surrounding conduit 568C. A side view of wall 600A is shown in FIG. 24. As shown therein, wall 600A is formed from the combination of retaining rail 296A, outer separator 578A, upper separator 574A, and stacked guide 516A. Other walls 600B and C are similarly formed from corresponding retaining rails 296A, outer separators 578A, upper separators 574A, and stacked guides 516B and C, respectively.

[0285] Walls 600A-600C also align with and intersect lower partitions 288A-288C, respectively. As a result, each inlet fluid path 460 bounded between adjacent lower partitions 288 aligns with a corresponding light component fluid path 456, and fluids do not mix as they pass between them. That is, fluid traveling along an inlet fluid path 460 to a corresponding light component fluid path 456 does not mix with separated fluid traveling along a separate inlet fluid path 460 to a separate corresponding light component fluid path 456. Again, this configuration helps the fluid to flow continuously along a generally linear path, as opposed to swirling in a circle around conduit 568C / central axis 230C, and helps maintain a more laminar, as opposed to turbulent, flow of the fluid, both of which help separate the fluid into heavy and light components. In the illustrated embodiment, three walls 600 and three lower partitions 288 are shown. In alternative embodiments, the isolation rotor 184 may be formed of at least 3, 4, 5, 6, 7, 8, 9, 12, 15, 18, 21 or more walls 600 and lower bulkheads 288, or a range between any two of the foregoing.

[0286] 33, 35, 38, and 39, a plurality of heavy component fluid paths are formed between the insert 256C and the cap portion 254C. Specifically, as a result of the dividers 350A-350F projecting outward from the outer surface 324C of the insert 256C, an annular frustoconical gap 462C is formed between the inner sidewall 320C of the insert 256C and the inner surface 300C of the cap portion 254C. The outer edges of the dividers 350A-350F seat against the inner surface 300C of the cap portion 254C such that the dividers 350A-350F divide the annular frustoconical gap 462C into a plurality of separate heavy component fluid paths 464A-464F. That is, the sidewall assembly 452C bounds the plurality of separate heavy component fluid paths 464A-464F. Each heavy component fluid pathway 464 has an opening 466C disposed in a periphery 330C of insert 256C / inner sidewall 320C. For example, FIG. 38 shows heavy component fluid pathway 464A. Walls 600A-600C typically align with dividers 350A, 350C, and 350E, respectively.

[0287] The use of dividers 350C to form and isolate heavy component fluid paths 464A-464F helps the heavy components entering and flowing along heavy component fluid path 464 to flow continuously along a generally linear path, as opposed to swirling in a circle around central axis 230C, and also helps maintain a more laminar flow of the heavy components, as opposed to a turbulent flow, both of which aid in fluid separation and limit the application of excessive forces to separated cells or microorganisms that may be damaging or harmful. In the illustrated embodiment, six dividers 350A-350F are used to form six heavy component fluid paths 464A-464F. In alternative embodiments, separation rotor 184C may be formed with at least 3, 4, 5, 6, 7, 8, 9, 12, 15, 18, 21, 26, 32, 38, or more dividers 350 and / or heavy component fluid paths 464, or may be within a range between any two of the foregoing.

[0288] 38, as a result of the centrifugal force created by the rotation of the separation rotor 184C, the lighter components of the inlet stream 102 first flow radially outward away from the openings 290C, pass around the periphery 286C of the dispersion member 252C, and then flow radially inward at the second end 242C of the separation rotor 184C into a corresponding one of the lighter component fluid paths 456. As the lighter components enter the fluid path 456, the fluid travels between the disks 500C where the fluid can be further separated. That is, as the fluid moves between the disks 500C, the heavier portions of the light components separate toward the bottom surfaces 506C of the disks 500C and flow downward and radially outward toward one of the heavy component fluid paths 464, while the lighter portions separate toward the top surfaces 504C of the disks 500C and flow radially inward toward the conduits 568C. As the lighter components exit between the disks 500C, they flow along the channel between the conduits 568C and the insert 256C toward the first end 196C, out the end of the insert 256C, through the light component collection recess 444C, and out the second outlet port 42 as the second outlet stream 106 ( FIGS. 1 , 3 , and 5 ). The second outlet stream 106 can then be further processed or transported as described above.

[0289] In contrast to the light components, which flow radially inward into the light component fluid pathway 456, the heavy components, which typically include cells, microorganisms, particles thereof, and other solids, flow radially outward toward the sidewall assembly 452C / outer sidewall 450C. More specifically, the heavy components of the fluid flow through openings 466C into the corresponding heavy component fluid pathway 464. The heavy components then flow within the heavy component fluid pathway 464 toward the first end 196C of the separation rotor 184C. Once the heavy components reach the first end 196C, they pass through the side openings 558C, through the heavy component collection recess 446C, and then through the first outlet port 40 to exit as the first outlet stream 104 ( FIGS. 1 , 3 , and 5 ). The first outlet stream 104 may then be further processed or transported, as previously described.

[0290] Returning to FIG. 34 , as previously described, the heavy component passes through opening 466C and enters heavy component fluid pathway 464. Opening 466C and heavy component fluid pathway 464 are bounded between outer sidewall 450C and inner sidewall 320C. During operation, heavy component particles may collect at narrowed opening 466C and form pellets. These pellets may block or restrict the flow of heavy component through opening 466C and into heavy component fluid pathway 464. Separator 12C and other separators disclosed herein may be operated in different manners and / or modified with different designs to minimize pellet formation and / or aid in removing pellets after formation. For example, pump 100A, as shown in FIG. 5 , may be applied to first outlet stream 104 to draw heavy component fluid through heavy component fluid pathway 464. Increasing the flow rate of pump 100A can minimize pellet formation and / or draw formed pellets through opening 466 and out of first outlet port 40. For example, pump 100A can be operated at a first flow rate and then periodically operated at a second flow rate higher than the first flow rate. Periodic operation at the higher flow rate can minimize pellet formation and / or draw formed pellets through opening 466 and out of first outlet port 40. Operation of pump 100A at the higher flow rate can be based on set time intervals or on sensed operating parameters, such as flow rate and / or pressure readings. Operation at the higher flow rate can be for only short time intervals so as not to significantly disrupt the natural separation process. For example, pump 100A can be operated at the high flow rate for a time interval of less than 30 seconds, 20 seconds, 10 seconds, 5 seconds, or any range between any two of the foregoing.

[0291] The shape of the inner sidewall 320C can also be modified to help control pellet formation and / or removal. For example, in the embodiment shown in FIG. 34 , the second end of the inner sidewall 320C has an annular tip 612A that terminates in a circular end surface 614C. In the illustrated embodiment, the sides 322C / 324C on either side of the tip 612A are parallel to and remain aligned with the sides 322C / 324C on either side of the central portion of the inner sidewall 320C. In an alternative embodiment shown in FIG. 40 , the inner sidewall 320C can be formed with an annular tip 612B that curves or bends radially inward toward the axis 230C. For example, an inner corner or curve can be formed on the interior surface 322C of the inner sidewall 320C at the tip 612B. This configuration results in the tip 612B having an orientation similar to that of the adjacent outer sidewall 450C, which may aid in feeding larger particles and / or pellets through the opening 466C.

[0292] In another alternative embodiment, shown in FIG. 41 , the inner sidewall 320C may be formed with an annular tip 612C at a second end that curves or bends radially outward, away from the axis 230C. For example, an inner corner or curve may be formed on the outer surface 324C of the inner sidewall 320C at the tip 612C. This configuration narrows the width of the opening 466C. The narrowing of the opening 466C increases the flow rate directly at the opening 466C, which may help to draw larger solid particles and / or pellets through the opening 466C and then move the larger solid particles and / or pellets downstream.

[0293] In addition to the aforementioned advantages, centrifuges 12A, 12B, and / or 12C have several unique advantages. For example, many prior art centrifuges used to separate cells from culture media can only operate in batch mode, as opposed to continuous flow. That is, the centrifuge is loaded with a defined batch of suspension, operated to facilitate separation of the defined batch, and then stopped and reloaded with a new batch of suspension for separation. In other prior art centrifuges, the centrifuge must be temporarily stopped after a period of operation to backflush the system or remove components collected therein. In contrast, centrifuges 12A-12C of the present invention can be operated continuously without the need to stop to reload with new suspension, remove collected components, or clean the system. Therefore, as used herein and in the appended claims, a "continuous flow" centrifuge is a centrifuge that can continuously separate a fluid stream without the need to stop the centrifuge to remove components collected therein or to flush the separator. For example, centrifuges 12A-12C can be operated to continuously separate inlet stream 102 of suspension 18 into both outlet streams 104 and 106 for extended periods of time, such as at least 30 minutes, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours, 48 ​​hours, or more, without having to be stopped to remove collected components or to clean the system. Thus, one of the advantages of the present disclosure is that outlet streams 104 and 106 can simultaneously exit centrifuges 12A-12C while inlet stream 102 enters centrifuges 12A-12C.

[0294] Furthermore, because centrifuges 12A-12C operate in a continuous flow process, processing of suspension 18 is faster with less downtime. Thus, the cells and microorganisms are subjected to less stress. For example, in the perfusion system of FIG. 1 , centrifuges 12A-12C can rapidly and continuously separate inlet stream 102 into outlet streams 104 and 106 and return outlet stream 104 to vessel 14, such that the amount of time the cells and microorganisms are separated from the sparged gas and nutrients in vessel 14 is minimized, thereby minimizing stress on the cells and microorganisms. Furthermore, due to the configuration of centrifuges 12A-12C, mechanical stress is minimized on the cells and microorganisms as they pass through the separator.

[0295] A further advantage of the centrifuge embodiments is that they have few parts and are simple and inexpensive to manufacture, making them disposable after a single use. For example, the separation stator 180 and separation rotor 184 can be easily molded from polymers, so the material costs for manufacturing the body assembly 130 are relatively low. As a result, once the suspension liquid 18 has been completely processed from the container 14, the body assembly 130 can be simply disposed of, such as by recycling, thereby avoiding any need for cleaning or sterilization. A new body assembly 130 can then be used with the magnetic driver 132 to process a new container 14 holding a new amount of suspension liquid 18. Because the magnetic driver 132 does not directly contact the suspension liquid 18, the magnetic driver 132 can be reused repeatedly without the need for sterilization or cleaning.

[0296] Another advantage of centrifuges 12A-12C is that body assembly 130 can be easily sterilized prior to shipping and use. For example, once body assembly 130 is assembled, it can be sealed and then sterilized by irradiation, such as gamma irradiation, as described above. Depending on the materials used, some embodiments can also be sterilized by autoclaving. As used herein and in the appended claims, the terms "aseptic" and "sterilized" mean free from bacteria or other living microorganisms. Because body assembly 130 contains minimal metal parts, interference with the irradiation process is minimal.

[0297] Finally, the unique configuration of centrifuges 12A-12C allows for highly efficient separation of solids.Other advantages exist as well.

[0298] The centrifuges and assemblies disclosed herein can be incorporated into portable and modular skids, as described in detail. Figures 42 and 43 illustrate front and rear perspective views, respectively, of an exemplary centrifuge skid 700. Skid 700 can include a platform or base 702 having wheel assemblies 703, which provide portability, ease of movement, and positioning of skid 700 to and within a bioproduction facility and / or during processing. Wheel assemblies 703 can be caster-mounted red urethane wheels with bearings and mounting plates for mounting wheel assemblies 703 to base 702. In other embodiments, wheel assemblies 703 can be omitted.

[0299] Skid 700 further comprises a housing 701 supported on a base 702. Housing 701 may include opposing side panels 704A and 704B extending between a front panel 705 and an opposing rear panel 706. Panels 704, 705, and 706 extend between base 702 at a lower end and a top panel 707 at an upper end to form an enclosed and contained unit having one or more compartments 708 within skid 700 / housing 701. Panels 704, 705, 706, and 707 may be made from one unitary piece or several pieces of metal, plastic, or other rigid material that form walls of one or more compartments 708 of skid 700.

[0300] Bumpers and / or handles 710 may be attached to one or both of the side panels 704A and 704B on either side of the enclosure 701, or to other panels, so that an operator or automated system can grasp the handles 710 and move the skid 700 to an optimal position for integration into a bioproduction process.

[0301] As shown in FIG. 46 , a mounting platform 709 may be disposed within the enclosure 701 and may extend laterally between panels 704, 705, and 706 of the skid 700 / enclosure 701 for mounting the centrifuge 12 thereon. While any of the centrifuges disclosed herein may be used on the skid 700, the separator 12C is illustrated and described with the skid 700. The mounting platform 709 divides the compartment 708 into a top compartment 708A and a bottom compartment 708B ( FIG. 43 ). The top compartment 708A and / or the bottom compartment 708B may be sealed from the environment, but need not be. In one exemplary embodiment, the top compartment 708A and the bottom compartment 708B are hermetically sealed from each other and from the environment.

[0302] Also shown in FIG. 46, a door opening 710 is formed on the enclosure 701 to provide communication and access to the top compartment 708A. The door opening 710 is sized and configured to allow the separator 12C to be manually inserted into and removed from the top compartment 708A. The door opening 710 is shown extending through the front panel 705 and a portion of the top panel 707. In other embodiments, the door opening 710 may extend through only the front panel 705 or the top panel 707, or may extend through other panels. Referring to FIG. 42, a door assembly 711 may be disposed on the enclosure 701 to selectively open and close the door opening 710. More specifically, in one exemplary embodiment, the door assembly 711 includes a door 716 that may be movably mounted to the enclosure 701, such as hingedly mounted thereto, so that the door 716 may be moved between an open position ( FIG. 46 ) in which the door opening 710 is open and a closed position ( FIG. 42 ) in which the door opening 710 is closed. When in the open position, the mounting platform 709 is exposed so that the separator 12C may be mounted on or removed from the platform 709 in the top compartment 708A or otherwise accessed within the top compartment 708A. In the closed position, the door opening 710 is covered by the door 716 to act as a seal or cover in the event of a failure of the separator 12C during operation. In one embodiment, the door assembly 711 / door 716 may be automatically locked during operation of the centrifuge 12C, for example, the door assembly 711 may be auto-locking or may be programmed to automatically lock.

[0303] 45 , door assembly 711 may include a switch block 715, a latch 713, a locking guard switch 719, and an actuation locking key 720, which interact with door 716. Switch block 712 and locking guard switch 719 communicate via wires or wirelessly with a controller 798, which includes a programmable processor and non-transitory memory programmed to actuate switch block 715 and locking guard switch 719 and move latch 713 from a locked position to an unlocked position. In the exemplary embodiment, switch block 712 and locking guard switch 719 form a key- or tongue-operated solenoid interlock switch with a key entry slot. An actuation locking key 720 may be inserted into one or more key entry slots to unlock door 716, or door 716 may be automatically unlocked using controller 798. The door assembly 711 may further include hinges, bearings, bushings, and / or radial dampers 762 (shown in FIG. 48) that facilitate rotation of the door 716 about its axis of rotation, opening it radially upward and closing it radially downward. The radial dampers 762 also prevent the door 716 from opening or closing with excessive speed or force to prevent damage. The door assembly 711 / door 716 acts as a containment seal capable of withstanding the maximum forces associated with failure of the centrifuge 12C at maximum speed or rpm.

[0304] In the exemplary embodiment, the controller 798 is programmed to automatically lock the door assembly 711 / door 716 when the centrifuge 12C is operating and to automatically unlock the door assembly 711 / door 716 when the centrifuge 12C is not operating. The controller 798 is also programmed to preclude lockdown of the centrifuge 12C (described in detail with respect to the loading assembly 800) and activation of the mounting clip 804 when the door 716 is open.

[0305] The centrifuge skid 700 is a modular and portable unit containing single-use process equipment and components that can be easily attached, mounted, and removed from the skid 700 / enclosure 701 through quick-release and easy-connect ports and mounting assemblies. As a result, the exemplary skid 700 can be fully equipped with a diverse set of process components and equipment necessary for efficient integration of the centrifuge 12C into various bioproduction processes. The exemplary skid 700 can also be provided without process equipment, but with ports and mounting assemblies, so that an operator or end user can select a custom set of process components and equipment for loading through the skid 700's quick-release and easy-connect ports and mounting assemblies.

[0306] Exemplary quick-release and easy-connect ports and mounting assemblies include tubing and tubing holders, cable management systems, mounts, connectors and ports for centrifuges, controllers, sensors, valves, power supplies, and pumps. Exemplary process equipment and components include tubing, tubing, cabling and electronics, controllers, pumps, power supplies, sensors, probes, valves, and centrifuges. In a preferred embodiment, one or more exemplary process components are single-use and / or disposable components. Exemplary quick-release and easy-connect ports and mounting assemblies, process equipment, and components may be mounted and attached to any surface of the skid 700 / chassis 701, including the side panels 704, front panel 705, back panel 706, and top panel 707 of the skid 700 / chassis 701, within compartments 708 of the skid 700 / chassis 701, or on the mounting platform 709 of the skid 700.

[0307] In an exemplary embodiment, a power supply 733 (FIG. 45) is provided on the rear panel 706 of the skid 700 / enclosure 701. The power supply 733 can provide power to all process equipment mounted on the skid 700, including centrifuges, centrifuge motors, controllers, door assemblies, fieldbuses, fieldbus nodes and switches, linear actuators, linear actuator motors, pumps, pump motors, sensors, switches, valves, and valve control systems. The power supply 733 can be a single power supply, multiple power supply units, a programmable power supply, a DC power supply, a variable AC power supply, a switch mode power supply (SMPS), or an uninterruptible power source (UPS). In an exemplary embodiment, the power supply 733 is a variable AC 240 voltage power supply.

[0308] 22A, one or more, typically a plurality of, capillary holders 722 are mounted to the enclosure 701, and in one exemplary embodiment, are mounted to a side panel 704A of the skid 700. The capillary holders 722 may be shaped as clips configured to hold the capillaries and / or piping used to flow biological fluids and solids to and from the process equipment mounted on the skid 700.

[0309] As shown in FIG. 46, the separator 12C is removably secured within the top compartment 708A. As previously described with respect to FIGS. 1-5, fluid lines 36, 44, and 52 are attached to the separator 12C and extend outwardly therefrom. Fluid line 36 is used to deliver an inlet stream, such as from a bioreactor production vessel 10, to the separator 12C. Fluid line 44 is connected to the first outlet port 40 and is used to transport the heavy component outlet stream downstream. Finally, fluid line 52 is connected to the second outlet port 42 and is used to transport the light component outlet stream downstream. Each of the fluid lines 36, 44, and 52 passes through a notch 764 extending through the side panel 704A and / or the top panel 707 to communicate with the top compartment 708A. Within the notch 764, a guide rail 766, which separates channels 768, extends upright. Typically, three separate channels 768 are formed. Each channel 768 is sized to receive a corresponding one of the fluid lines 36, 44, and 52. The notches 764 are configured so that when the door 716 is moved to the open position, the separator 12 with pre-connected fluid lines can be positioned in the top compartment 708A, with the fluid lines 36, 44, and 52 positioned in the corresponding channels 768. The door 716 can then be moved to the closed position, and the separator 12C can be operated while the fluid lines 36, 44, and 52 exit the top compartment 708A through the notches 764. In part, the guide rails 766 are shaped to minimize any open space between the fluid lines 36, 44, and 52 passing through the notches 764, thereby minimizing the risk of any material being ejected from the top compartment 708A in the event of a separator 12 malfunction.

[0310] As shown in FIG. 44 , fluid lines 36, 44, and 52, which may also be referred to as a line set, may be removably mounted along the height of side panel 704A by capillary tube holders 722. As previously mentioned, fluid lines 36, 44, and 52 are typically formed from flexible capillary tubes, but may also include rigid capillary tubes. Fluid line 36, carrying inlet fluid, is removably coupled to a pinch valve 726 mounted to side panel 704A. Pinch valve 726 may selectively pinch closed fluid line 36 to prevent fluid from flowing therethrough, or release fluid line 36 to allow fluid to flow therethrough. An inlet pump 721 and one or more sensors 730 are coupled to fluid line 36.

[0311] The inlet pump 721 may be removably mounted to the enclosure 501 / sidewall panel 504A of the skid 700 to pump biological fluids, solids, mixtures, solutions, and suspensions through the inlet line 36 to the centrifuge 12. The inlet pump 721 may include a pump assembly box having a quick-release connector connecting the inlet port 721A and the outlet port 721B of the pump 721, and a motor for driving the pump 721. The pump assembly box may surround the pump 721 and provide a hermetic seal therearound. The inlet port 721A may be fluidly connected to the biological production vessel 10. The biological production vessel 10 may be any biological production vessel, including, but not limited to, mixers, cell factories, bioreactors, fermenters, laboratory and bench-scale vessels, and other vessels capable of supplying fluids, solids, or mixed-phase biological components to the skid 700 for separation.

[0312] The inlet pump 721 may be a positive displacement pump, such as a centrifugal pump or a peristaltic pump. Preferably, the inlet pump 721 is a single-use, disposable centrifugal pump without bearings or seals. The inlet pump 721 may be enclosed in a sterile, sealed casing, such as a pump assembly box, and equipped with a suspended impeller driven by the magnetic field of an inlet pump motor. The inlet pump 721 is typically a centrifugal pump to provide a high flow rate of fluid to and through the separator 12C for efficient processing. However, other types of pumps may be used in other applications. The pump 721 is removably coupled to the housing 701. This allows the separator 12C, fluid lines 36, 44, and 52, and pump 721 to be pre-assembled, sterilized, such as by irradiation, and then mounted on the skid 700 as a unitary assembly.

[0313] The one or more sensors 730 may comprise one or more of a pressure sensor, a conductivity sensor, a flow meter sensor, a pH sensor, a temperature sensor, or a turbidity sensor, which may be spaced along the fluid line 36. The one or more sensors 730 may be removably plugged into corresponding electrical outlets 723 by electrical cables 765. In various embodiments, the sensors 730 may be equipped with quick-release bulkhead connectors for easy connection and release for single use. The electrical outlets 723 may provide power to the one or more sensors 730 and may couple the one or more sensors 730 to a controller 798 for operating and monitoring the one or more sensors 730. The controller 798 may convert the electrical signals from the sensors into measurable process parameters. In other embodiments, the one or more sensors 730 may be wireless.

[0314] Fluid line 44 carrying the heavy component outlet stream is removably coupled to pump 749, typically a peristaltic pump, mounted to housing 701 / side panel 704A. One or more sensors 758 are coupled to fluid line 44. The one or more sensors 758 may comprise one or more of a pressure sensor, a conductivity sensor, a flow meter sensor, a pH sensor, a temperature sensor, or a turbidity sensor, which may be spaced along fluid line 44. The one or more sensors 758 may be removably plugged into an electrical outlet 759 by an electrical cable 767. In various embodiments, the sensor 758 may be equipped with a quick-release bulkhead connector for easy connection and release for single use. The electrical outlet 759 may provide power to the one or more sensors 758 and may couple the one or more sensors 758 to a controller 798 for operating and monitoring the one or more sensors 758. The controller 798 may convert the electrical signals from the sensors into measurable process parameters. In other embodiments, one or more sensors 758 may be wireless. The lower end of fluid line 44 branches at a tee 761, from which fluid lines 44A and 44B extend. Each of fluid lines 44A and 44B is removably coupled to a pinch valve 728A and 728B, respectively, mounted on housing 701. Thus, by controlling the operation of pinch valves 728A and 728B, the heavy component outlet stream can be returned to bioproduction vessel 10 or delivered to a different location, such as a collection vessel, a waste vessel, or other downstream processing equipment. In other embodiments, tee 761 may be omitted, and fluid line 44 may be coupled to a single pinch valve 728.

[0315] Fluid line 52 carrying the light components outlet stream is removably coupled to pump 748, typically a peristaltic pump, mounted to housing 701 / side panel 704A. A flow meter sensor 763, a pressure sensor 731, a turbidity sensor 729, and a sensor 735 are connected to fluid line 52. Sensor 735 may comprise one or more of a pressure sensor, a conductivity sensor, a flow meter sensor, a pH sensor, a temperature sensor, or a turbidity sensor. Each of sensors 763, 731, 729, and 735 may be removably plugged by an electrical cable into an electrical outlet disposed on housing 701. The electrical outlet may provide power to sensors 763, 731, 729, and 735 and may couple sensors 763, 731, 729, and 735 to controller 798 for operating and monitoring the sensors. In other embodiments, sensors 763, 731, 729, and 735 may be wireless. The lower end of fluid line 52 branches at T-fitting 761, with fluid lines 52A and 52B extending from T-fitting 761. Each of fluid lines 52A and 52B is removably coupled to pinch valves 727A and 727B, respectively, mounted on housing 701. Thus, by controlling the operation of pinch valves 727A and 727B, the heavy component outlet stream can be returned to bioproduction vessel 10 or delivered to a different location, such as a collection vessel, a waste vessel, or other downstream processing equipment. In other embodiments, T-fitting 737 may be omitted, and fluid line 52 may be coupled to a single pinch valve 727.

[0316] The various sensors described above with respect to fluid lines 36, 44, and 52 may measure and provide signals indicative of pressure, flow rate, turbidity, density, motor power, rotor rpm, temperature, pH, O2 concentration, CO2 concentration, and other process parameters at various locations throughout the process flow lines, within the centrifuge and other tubing and equipment upstream and downstream of centrifuge 12.

[0317] One or more cable management modules 753 may also be mounted in various desired locations on the enclosure 701 / side panel 704A of the skid 700. The one or more cable management modules 753 may be a low-profile, breakthrough, multi-cord cable management system that provides a spool or other surface for wrapping and retaining electrical cables. One or more liquid-tight sealing grommets may also be used in conjunction with the cable management modules 753 and the capillary tubing holders 722, or independently. The grommets form a liquid-tight seal around the capillary tubing, wiring, cables, and cords routed to and from the process equipment mounted on the skid 700. One or more ports may be provided to allow the capillary tubing holders 722 and cable management modules 753 to protrude from the ports during loading, retraction (e.g., flush with the side panel 704A / enclosure 701 of the skid 700), or storage. The example capillary tube holder 722 and cable management module 753 provide the operator of the skid 700 with improved equipment access, operational efficiency, and safety.

[0318] Skid 700 may also be equipped with a valve control system 760, which includes flow control valve 726A and tubing 725 (also shown in FIG. 48 ), a series of operating valves 726, 727, 728, 744, valve terminals 739, and a fieldbus node 747. Valve control system 760 may be an electric or pneumatic control system, and valves 726, 727, 728, 744 may be electrically or pneumatically actuated. In an exemplary embodiment, valves 726, 727, 728, 744 are pneumatic pinch valves or pinch clamps. Valves 726, 727, 728, 744 may be gate valves, globe valves, check valves, plug valves, ball valves, butterfly valves, needle valves, pinch valves, or solenoid valves equipped with solenoid elements for opening and closing the valves. Valves 726, 727, 728, 744 may also include optical digital position feedback sensors to detect whether the valves are open or closed. An exemplary pneumatic valve control system may include a capillary tube 725 and a flow control valve 726A through which air or other gas or hydraulic fluid is distributed through a manifold to each of the valves 726, 727, 728, 744 to facilitate valve actuation. Valves 726, 727, 728, 744 may be in wired or wireless communication with controller 98. The valves may also be self-actuating or manually operated.

[0319] Valves 726, 727, 728, 744 may be arranged and mounted on any surface of skid 700, including side panel 704A of skid 700, to control the flow of biological fluids, solids, mixtures, solutions, and suspensions through flow lines, to and from centrifuge assembly 12C, and through other process equipment. Valves 726, 727, 728, 744 may also include snap-in tube slots for rapid loading and unloading of tubing into and out of the valves. In the exemplary embodiment, valves 726, 727, 728, 744 are single-use valves made from disposable materials to allow for inexpensive and easy replacement after use.

[0320] Valve terminal 739 may be mounted to base 702, panels 704, 705, 706, 707, or mounting platform 709 of skid 700. In an exemplary embodiment, valve terminal 739 is mounted within bottom compartment 708B of skid 700. Valve terminal 739 may include a communications port, a communications link, a circuit board, and a manifold having multiple pneumatic ports pneumatically coupled to the inlet and outlet ports of valves 726, 727, 728, 744. In one embodiment, gas or hydraulic fluid may be routed through capillary 725 and flow control valve 726A and the manifold to distribute and actuate each of valves 726, 727, 728, 744.

[0321] In an exemplary embodiment, the communication ports and links may be I / O ports and links coupled to a fieldbus node 747. The valve terminals 739 and fieldbus node 747 may be in wired or wireless communication with a controller 798, which controls the operation of the valves 726, 727, 728, and 744 by electrical signals or pneumatic or hydraulic pressure applied through the valve terminals 739 and manifolds. The valve control system 760 may use a particular communication protocol to facilitate data and electrical signal transmission between the valve terminals 739, fieldbus node 747, valves 726, 727, 728, and 744, and the controller 798. Exemplary industrial fieldbus and Ethernet protocols include, but are not limited to, Profibus, Modbus, DeviceNET, Profinet, Ethernet / IP, Ethernet CAT, and Modbus TCP. In an exemplary embodiment, the communication protocol used by the control system 760 is Profinet.

[0322] One or more process flow lines, including inlet line 36 and outlet lines 44, 52 and valves 726, 727, 728, 744, may be configured and operated to route biological components to centrifuge assembly 12C for separation. In an exemplary embodiment, inlet line 36 and inlet valve 726 located upstream of inlet pump 721 may be configured and operated by controller 798 to bypass centrifuge 12C during start-up and route air, other gases, liquids, solids, or biological components downstream of inlet pump assembly 721 and centrifuge assembly 12C. This operation may be used to flush the system of air and gases before or after use. Inlet line 36 and inlet valve 726 located upstream of inlet pump 721 may also be configured and operated by controller 798 to route biological components from the biological production vessel to centrifuge 12C for separation.

[0323] The lights outlet line 52 and one lights outlet valve 727 may be configured to flow and route the light biological components separated from the centrifuge assembly 12C downstream for processing and may be controlled via the controller 798, while the other lights outlet valve 727 may be configured to recirculate and route the light biological components separated from the centrifuge assembly 12C back to the bio-production vessel that fed the system.

[0324] Similarly, the heavy outlet line 44 and one heavy outlet valve 728 may be configured to flow and route the heavy biological components separated from the centrifuge assembly 12C downstream for processing and may be controlled via the controller 798, while the other heavy outlet valve 728 may be configured to recirculate and route the heavy biological components separated from the centrifuge assembly 12C back to the bioproduction vessel that fed the system.

[0325] Recirculated biological components exiting the bioprocess container can be flowed and routed to the centrifuge 12C through the inlet pump 721 or can bypass the centrifuge 12C via a split in the inlet line set.

[0326] Skid 700 may be equipped with an emergency shut-off valve 744 (FIG. 45) that closes one or more outlet lines 44, 52 exiting centrifuge assembly 12C during an emergency, leak, or otherwise. Each of valves 726, 727, 728, 744 may function as an emergency shut-off valve.

[0327] 42, skid 700 may include a user input and digital display 756, a switch block 717, a switch reset button 74, and an emergency stop button 714 that may be used to start, stop, and otherwise control operation of centrifuge 12C and / or components of skid 700. In one embodiment, if the emergency stop button 714 is activated to stop centrifuge 12C, a user may be required to activate the switch reset button 774 to reset switch block 717 for operation. The user input and digital display 756 allows an operator to provide process parameter inputs and read process parameter outputs that control and direct process parameters, such as pressure, flow rate, turbidity, density, temperature, pH, motor power, rotor rpm, and other process parameters, through the flow lines and process equipment on skid 700.

[0328] In an exemplary embodiment, process equipment and components, including tubing, pipes, cables, and electronics, controllers, motors, pumps, power supplies, sensors, probes, valves, and centrifuges, may be mounted in various locations on skid 700 depending on the particular requirements and configuration of the bioprocess into which skid 700 is incorporated. For example, process equipment and components may be mounted and attached on any surface of skid 700, including side panels 704, front panel 705, back panel 706, and top panel 707 of skid 700, within compartments 708 of skid 700, or on mounting platform 709 of skid 700.

[0329] 48 and 49 illustrate cross-sectional front and side views, respectively, of an exemplary centrifuge skid 700. Additional components and features of skid 700 are illustrated by the cross-section.

[0330] The mounting platform 709 may be used to mount the centrifuge 12C to the skid 700. The mounting platform 709 may be a flat table having a recess 812 that receives and interfaces with the loading assembly 800. The loading assembly 800 may releasably load, mount, center, and lock the centrifuge assembly 12C to the skid 700. The skid 500 houses the centrifuge assembly 12C in the top compartment 708A. The housed centrifuge may be any of the centrifuges disclosed and described herein or in related U.S. Provisional Patent Application No. 63 / 115,938, which is incorporated herein by reference in its entirety for all purposes.

[0331] As previously described, the centrifuge assembly 12C may include a separation stator 180C forming a stator chamber 188C and a separation rotor 184C rotatably mounted and / or coupled to the stator chamber 188C. The separation rotor 184C forms a separation container 190C in which biological components are separated during rotation of the separation rotor 184C. A mounting surface 804 may be fixed to or integral with the separation stator 180C and used to mount and / or lock the separation stator 180C and the centrifuge 12C to the skid 700. The mounting surface 804 may be a flange, cavity, elbow, recess, or slot on the separation stator 180C. A drive coupling 186C having two ends, preferably with a magnet on one end, is coupled to the separation rotor 184C at one end and magnetically coupled to the magnetic driver 148 at the other end. The magnetic driver 148 can include an outer housing 134 and a drive rotor 150 coupled at one end to the motor 169. The drive rotor 150 includes magnets that create a magnetic field that can interact with the drive rotor and magnetically couple the drive rotor to the drive coupling 186C and / or the magnets on the drive coupling 186C. When the motor 169 rotates the drive rotor 150, the rotation of the drive rotor 150 and the magnetic field rotate the drive coupling 186C and the isolated rotor 184C. The stator chamber 188C can form a sterile and hermetic seal around the isolated rotor 184C and the drive coupling 186C to provide a sterile chamber sealed from the environment.

[0332] The centrifuge 12C is preferably housed within the top compartment 708A of the skid 700, where the door assembly 711 is located. A hermetic seal may be formed around all components of the centrifuge assembly 12C in the top compartment 708A of the skid 700. The isolated stator 180C functions as a containment seal and can withstand the maximum force associated with breaking the isolated rotor 180C at maximum speed or rpm. The top compartment 708A and the door assembly 711 act as a second containment seal and can withstand the maximum force associated with breaking the isolated rotor 180C at maximum speed or rpm. Thus, the skid 700 and centrifuge 12C together provide dual containment with two containment seals for increased safety. Dual containment is particularly appropriate when working with potentially hazardous materials such as viruses, vaccines, and clinical-stage products and compositions.

[0333] The drive coupling 186C has one end coupled to the separated rotor 184C and another end magnetically centered and coupled to the magnetic drive body 148. The drive coupling 186C may be mechanically attached to the separated rotor 184C at one end. The drive coupling 186C may be made from metal, a magnetic material, or magnets similar to those attached to the magnetic drive body 148 so that the magnetic field generated by the magnets on the magnetic drive body 148 can interact with, magnetically couple to, and rotate the drive coupling 186C, which in turn rotates the separated rotor 184C.

[0334] The drive coupling 186C may be disposed within the separated stator 180C or external to the separated stator 180C. The drive coupling 186C may also be disposed within a drive coupling sleeve 187C attached to the separated stator 180C. The drive coupling sleeve 187C and / or the separated stator 184C may partially or completely form a sterile and airtight seal around the drive coupling 186C, the separated rotor 184C, and the separation container 190C, such that no seals are required to create an airtight and watertight seal around the separated rotor 184C and the drive coupling 186C. The separated rotor 184C may then be magnetically driven by the drive coupling 186C and the magnetic driver 148 without requiring a seal between the drive coupling 186C and the magnetic driver 148 or between the top and bottom compartments 708A and 708B of the skid 700. This configuration prevents contamination of the contents of the separation vessel 190C and the components of the centrifuge assembly 12C, and allows an operator to easily dispose of all or part of the centrifuge assembly 12C after use.

[0335] One or more magnets (not shown) may be attached to and mounted on the drive coupling 186C. In an exemplary embodiment, the drive coupling 186C is annular and partially or completely surrounds the annular cavity. The one or more magnets are fixed to the interior surface of the cavity. The magnets may be multiple magnet sections fixed to the interior surface at spaced intervals to surround the cavity. In an exemplary embodiment, the magnets may include at least 2, 4, 6, 12, 18, 24, or 30 separate magnet sections. The magnetic sections may be oriented perpendicular to the axis of rotation such that the magnetic poles of the magnetic sections are axially oriented. The magnetic poles of each magnetic section are preferentially arranged axially alternating. The magnet may also be a magnetic ring fixed to and surrounding the cavity. The magnetic ring may be a dipole, quadrupole, hexapole, or octapole, and the magnetic poles may preferentially be arranged radially. The one or more magnets may be made of one or more magnetic materials, including neodymium.

[0336] Other details of the exemplary centrifuge assembly 12, including the drive coupling 186C, are described in related U.S. Provisional Patent Application No. 63 / 115,938, which is incorporated herein by reference in its entirety for all purposes.

[0337] The skid 700 is equipped with a loading assembly 800 for releasably loading, mounting, and locking the centrifuge assembly 12C to the skid 700. Referring to FIGS. 49-52, the loading assembly 800 includes a housing 802 having a support 804 projecting outward from its upper end. In one embodiment, the support 804 is annular and may project radially outward from the housing 802. A tubular inner sleeve 806 is aligned with the housing 802 and upstanding from the support 804. An alignment plate 808 is secured to the upper end of the inner sleeve 806 and surrounds a central opening 810. As best shown in FIG. 52, a receiver 812 is secured to an inner surface of the alignment plate 808 aligned with the opening 810 and projects downwardly therefrom. The receiver 812 defines a cavity 814 that communicates with the opening 810. In one embodiment, alignment plate 808 and central opening 810 are circular, and cavity 814 has a cylindrical configuration.

[0338] A mounting portion 816 at least partially surrounds the inner sleeve 806. In one embodiment, the mounting portion 816 includes an outer sleeve 818 having an annular mounting plate 820 disposed at its upper end. Both the outer sleeve 818 and the mounting plate 820 may completely or at least partially surround the inner sleeve 806 and may be circular. The mounting plate 820 may surround the outer sleeve 818 and project radially outward a distance therefrom. One or more mounting elements 822 are disposed on the top surface of the mounting plate 820 and project upward therefrom. In the illustrated embodiment, the one or more mounting elements 822 comprise three radially spaced clips 822A-C, each having a substantially L-shaped configuration. As described in more detail below, in alternative embodiments, the one or more mounting elements 822 may have a variety of different configurations. The mounting portion 816 is slidable relative to the inner sleeve 806. Additionally, the mounting portion 816 / outer sleeve 118 has a shorter height than the inner sleeve 806. Thus, the mounting portion 816 / outer sleeve 118 can be moved between a lowered position, as shown in FIG. 49, in which the mounting plate 820 is disposed at a lower height, and a raised position, as shown in FIG. 50, in which the top surfaces of the mounting plate 820 and the alignment plate 808 can be disposed in substantially the same plane.

[0339] The lift assembly 824 is used to selectively move the mounting portion 816 between a lowered position and a raised position. The lift assembly 824 includes a pivot mounting block 826 fixed to and upright on the support 804. A pair of pivot arms 828A and 828B each have a first end hingedly attached to opposite ends of the mounting block 826. The pivot arms 828A and 828B project from the mounting block 826 to extend beyond opposite sides of the mounting portion 816 / outer sleeve 118 to the second ends of the pivot arms 828A and 828B. A brace 830 extends between the second ends of the pivot arms 828A and 828B. In this configuration, pivot arms 828A and 828B are disposed on opposite sides of the mounting portion 816 / outer sleeve 118, and pivot mounting block 826 and brace 830 are disposed on opposite sides of the mounting portion 816 / outer sleeve 118. Openings 834A and 834B are formed in the centers of or extend through pivot arms 828A and 828B. Support pins 832A and 832B project outward from opposite sides of mounting portion 816 / outer sleeve 118 and are received in openings 834A and 834B, respectively. Openings 834A and 834B are sized / configured such that pivot arms 828A and 828B can both be supported by support pins 832A and 832B but can also pivot thereabout. In one embodiment, openings 834A and 834B are elongated to allow support pins 832A and 832B to slide laterally a distance within openings 834A and 834B.

[0340] A mounting bracket 836 projects downwardly from support 804 in alignment with brace 803. A linear actuator 838 extends between a lower end of mounting bracket 836 and brace 803. Linear actuator 838 generally includes a housing 840, a linear actuator rod 842 that can extend from and retract into housing 840, and an electric motor that controls movement of linear actuator rod 842 relative to housing 840. Housing 840 is fixed to mounting bracket 836, and linear actuator rod 842 is fixed to brace 836. Linear actuator 838 is electrically coupled to controller 798, which can control the operation of linear actuator 838 automatically or via manual or sensed prompts.

[0341] In operation, linear actuator 838 may be actuated to raise linear actuator rod 842, thereby raising brace 830 and the second ends of pivot arms 828A and 828B. Pivot arms 828A and 828B pivot on pivot mounting block 826, simultaneously raising mount 816 via engagement with support pin 832. Mount 816 is raised to a raised or unlocked position, where mounting plate 820 is flush with alignment plate 808. Optionally, linear actuator 838 may be actuated to lower linear actuator rod 842, which lowers mount 816 to a lowered or locked position, where mounting plate 820 is disposed at a height below alignment plate 808.

[0342] A proximity sensor 846 mounted via a proximity sensor mounting portion 848 may be positioned proximate to the pivot arm 828 and / or brace 830 to sense whether the linear actuator 838 is actuated up or down and whether the loading assembly 800 is in a locked or unlocked position.

[0343] 51 , the pivot mounting block 826 can be spring-loaded to allow resilient movement. Specifically, in one embodiment, the pivot mounting block 826 can be slidably secured to a pair of guide pins 850 that are fixed to the support 804 and pass through the pivot mounting block 826. A retaining pin 852 is also fixed to the support 804 and passes freely through a portion of the pivot mounting block 826. An enlarged head 854 is formed on the upper end of the retaining pin 852, and a spring 856 surrounds the retaining pin 852 and extends between the enlarged head 854 and the pivot mounting block 826. As such, the pivot mounting block 826 can resiliently slide upward along the pins 850 and 852 as needed during movement of the lift assembly 824, such as to prevent binding and overloading, and then resiliently return to its original position under the force of the spring 856. As such, the pivoting mounting block 826 moves according to the spring constant, tension, and force, thereby providing clearance between the mounting plate 820 and other components of the loading assembly 800 during centrifuge lockdown.

[0344] 47 and 48 , an opening 858 extends through the mounting platform 709 in the top compartment 708A to communicate with the bottom compartment 708B. The loading assembly 800 is secured within the bottom compartment 708B, such as by one or more brackets 860 extending between the supports 804 and the platform 709 or some other portion of the enclosure 701. The loading assembly 800 is positioned in alignment with the opening 858, such that the top surface of the alignment plate 808 is substantially flush with the top surface of the platform 709 in the top compartment 708A. In this mounted position, the linear actuator 838 can again be actuated to move the loading assembly 800 between the raised or unlocked position shown in FIG. 47 and the lowered and locked position shown in FIG. 49 .

[0345] Returning to FIG. 52 , the previously described magnetic driver 148 is housed within the loading assembly 800. More specifically, the magnetic driver 148 includes a drive rotor 150 rotatably housed within an opening 864 surrounded by an inner sleeve 806. The drive rotor 150 may include a sleeve 152 having one or more magnets 168 secured thereto, as previously described. A stem 172 protrudes from the sleeve 152 and couples to a motor 169 disposed within the housing 802. In the exemplary embodiment, the motor 169 is a 2 HP, 3-phase, 230 / 460 VAC, 3600 RPM induction motor. The motor 169 may be housed, or at least partially housed, within the bottom compartment 708B of the skid 700. The bottom compartment 708B may form an airtight and sterile seal around the motor 169, the magnetic driver 148, or both. The motor 169 may be electrically coupled to and operated by the controller 798 or may be otherwise manually controlled such that operation of the magnetic drive 150 facilitates rotation of the drive rotor 150 / one or more magnets 168 about the receiver 812.

[0346] The one or more magnets 168 may be mounted and attached to the drive rotor 150 or the sleeve 152 of the drive rotor 150. As described in further detail, the one or more magnets 168 are configured to create a magnetic field around components of the skid 700 that interact with the isolation rotor 184C and the drive coupling 186C to magnetically couple, center, and rotate the rotor 184C during loading and operation. Exemplary embodiments of the magnetic driver 148 are disclosed and described in U.S. Provisional Patent Application No. 63 / 115,938 (e.g., FIG. 8), which is incorporated herein by reference in its entirety for all purposes.

[0347] In an exemplary embodiment, the drive rotor 150 and / or sleeve 152 are annular and partially or completely surround an annular cavity or cup 162. The cavity of the cup 162 may form part or all of a hermetic seal that prevents water from entering the components of the magnetic drive body 148. One or more magnets are fixed to the interior surface of the cavity 162. The one or more magnets 168 may be multiple magnet sections fixed at spaced intervals to the interior surface of the drive rotor 150 and / or sleeve 152. In an exemplary embodiment, the one or more magnets 168 may comprise at least 2, 4, 6, 12, 18, 24, or 30 separate magnet sections. The magnetic sections may be oriented perpendicular to the axis of rotation such that the magnetic poles of the magnetic sections are axially oriented. The magnetic poles of each magnetic section are preferentially axially alternating. The one or more magnets 168 may also be magnetic rings fixed to and surrounding the cavity 162 of the drive rotor 150 and / or sleeve 152. The magnetic ring may be a dipole, quadrupole, hexapole, or octapole, and the magnetic poles may preferentially be arranged radially. The one or more magnets 168 may be made from one or more magnetic materials, including neodymium.

[0348] In the exemplary embodiment, several magnets are mounted circumferentially spaced apart within the annular cavity 162 of the drive rotor 150. In this and all other exemplary configurations, the magnet arrangement generates a magnetic field around the magnetic driver 148, the mounting portion 816, the mounting plate 820, the cavity 814, and / or a portion of the mounting platform 709. When the drive coupling 186 is positioned within the vicinity of the magnetic field, magnetic attraction and / or normal load assist forces load the centrifuge assembly 12C, including the separation rotor 184C and the drive coupling 186C, onto the skid 700, centering the separation rotor 184C relative to the drive rotor 150.

[0349] One or more magnets 168 mounted and attached to the drive rotor 150 or the sleeve 152 of the drive rotor 150 provide optimal centering of the separation rotor 184C during loading and torque during operation. The magnetic coupling between the drive rotor 150 and the drive coupling 186C can be any magnetic pairing that provides sufficient torque to meet the process torque requirements. For example, in one exemplary embodiment, the torque requirements are between 10 and 70 in-lb. f The magnets may be made of a material capable of carrying a permanent magnetic field on the rotor side and either a permanent magnet or an electromagnet on the motor side of the coupling. In an exemplary embodiment, the magnets may be made of neodymium.

[0350] The magnetic drive 148 is coupled to the motor 844 and may be mounted to the skid 700 via the motor 169 / housing 802, the supports 804, or via another surface of the loading assembly 800. The magnetic drive 148, motor 169, and / or loading assembly 800 may be mounted to any surface of the skid 700, including the base 7022, the panels (704, 705, 706, 707), or the mounting platform 709. In a preferred embodiment, the coupled magnetic drive 148 and motor 169 are mounted to the bottom of the mounting platform 709 or to supports 804 mounted to the mounting platform 709. The motor 169 may be disposed partially or completely within the bottom compartment 708B of the skid 700. The mounting plate 820 and / or a portion of the drive rotor 150 may be mounted to extend through an opening 858 in the mounting platform 709. A portion of the mounting plate 820 and / or the drive rotor 150 may be mounted flush with an opening in the mounting platform 709 .

[0351] One or more magnets 168 attached to the drive rotor 150 and / or the sleeve 152 of the drive rotor 150 create a magnetic field near and / or around the drive rotor 150, the opening 810, the mounting plate 820, the receiver 812, the cavity 814, and / or the mounting platform 709. The strength and location of the magnetic field near and / or around the opening 810, the mounting plate 820, the receiver 812, the cavity 814, and / or the mounting platform 709 of the drive rotor 150 can be varied to create a load-assisting effect that pulls the centrifuge assembly 12C, and specifically the drive coupling 186C, toward the cavity 814 and the mounting plate 820.

[0352] In an exemplary method for loading the centrifuge assembly 12C onto the skid 800, the loading assembly 800 is moved to a raised, unlocked position, as shown in FIG. 47 , where the mounting plate 820 is flush with the mounting platform 709, with the mounting elements 822 upstanding therefrom. An operator or automated control system can open the door assembly 711 and place the centrifuge 12C on the mounting platform 709 adjacent to the mounting plate 820 (accessible through an opening 885 in the mounting platform 709). Specifically, the lower end of the driver sleeve 132C is positioned on the mounting platform 709, as shown in FIG. 23 , and is used to support the separator assembly 12C. The mounting platform 709 provides a horizontal surface that allows the centrifuge assembly 12C / driver sleeve 132C to translate / slide horizontally across the platform 709 toward the cavity 814 and mounting plate 820. When the centrifuge assembly 12C is moved horizontally across the mounting platform 709 and / or positioned sufficiently close to the drive rotor 150, opening 858, or mounting plate 820 to encounter the drive rotor 150 magnetic field, a horizontal and / or downward vertical load assist force draws the drive coupling 186C ( FIG. 24 ) and centrifuge 12C toward the cavity 814, mounting plate 820, and drive rotor 150. As the separator assembly 12C is moved toward the mounting plate 820, the separator assembly 12C can be oriented so that the holes 146 ( FIG. 23 ) on the driver sleeve 132C are oriented toward the mounting elements 822 upstanding from the mounting plate 820.

[0353] The magnetic field applies a downward vertical force to the drive coupling 186 and centrifuge 12C, which helps self-position and magnetically position the centrifuge assembly 12C for lockdown. Specifically, the centrifuge 12C is operated and moved laterally on the mounting platform 709 until the mounting elements 822 are received within corresponding holes 146 on the driver sleeve 132C. The magnetic field assists horizontal movement and centering. The magnetic field and load-assist force also automatically and magnetically align the central axis of rotation of the separation rotor 184C with the central axis of rotation of the drive rotor 150. The driver sleeve 132C supports and cushions the downward vertical force on the drive coupling 186 caused by the magnetic field during loading and as the centrifuge 12C is moved horizontally across the mounting platform 709.

[0354] 53, the centrifuge 12C can be locked after the mounting elements 822 are received within the corresponding holes 146 on the driver sleeve 132C and the separation rotor 184C self-aligns with the drive rotor 150 via the magnets and magnetic field. Specifically, the linear actuator 838 is actuated to move the loading assembly 800 / mounting portion 816 to the lowered, locked position, as previously described. At that time, the mounting plate 820, with the mounting elements 822 and centrifuge 12C disposed thereon, is lowered below the mounting platform 709, such that the drive coupling 186 is directly received within the cavity 814 of the receiver 812. The drive coupling 186 is then surrounded by or laterally aligned with one or more magnets 168 attached to the drive rotor 150. This positioning optimizes the magnetic force of the one or more magnets 168 on the drive coupling 186 to optimize rotation of the separation rotor 184C. Furthermore, as the loading assembly 800 / mounting portion 816 moves to the lowered, locked position, the base 190C of the separated stator 180C abuts a portion of the mounting platform 709, effectively locking the centrifuge 12C to the skid 700; i.e., the mounting element 822 received in the hole 146 is pulled down on the driver sleeve 132C, while the mounting platform 709 pushes the base 190C of the separated stator 180C upward. The linear actuator 838 holds the loading assembly 800 in this lowered, locked position during operation of the centrifuge 12C. Again, it should be understood that the spring load of the pivotal mounting block 826 prevents overloading of the centrifuge 12C during the locking process and operation of the centrifuge 12C, as previously described.

[0355] It should be understood that various alternative structures can be used to facilitate engagement between the mounting element 822 and the driver sleeve 132C. For example, the mounting element 822 can be replaced with a single semicircular, L-shaped member that is received within a corresponding notch on the driver sleeve 132C. In other embodiments, one or more extensions can extend outward from the driver sleeve 132C and be received within a notch or opening formed on one or more of the mounting elements 822. In other embodiments, different types of fasteners or clamps can be used to secure the mounting element 822 to the driver sleeve 132C. As such, the driver sleeve 132C can be formed with one or more flanges, elbows, cavities, slots, or recesses for engaging the mounting element 822. However, the present design has a unique advantage in facilitating a lateral sliding connection.

[0356] Once operation of the centrifuge 12C is complete, the linear actuator 838 can be used to move the loading assembly 800 back to the raised, unlocked position, allowing removal of the centrifuge 12C from the skid 700 in the reverse process of how it was attached. It should be appreciated that due to the strong magnetic forces, it is difficult to manually separate the centrifuge 12C from the drive rotor 150 when the drive coupling 186 is received within the receiver 812 and engaged with one or more magnets 168. Thus, the skid 700 and loading assembly 800 have the unique advantage of using mechanical force to at least partially separate the centrifuge 12C from the drive rotor 150 before the centrifuge 12C needs to be manually operated.

[0357] 54 is a schematic diagram of an exemplary centrifuge skid 900 incorporated into an exemplary biological production process including a biological production vessel 901. The biological production vessel 901 can be any biological production vessel, including, but not limited to, mixers, cell factories, bioreactors, fermentors, laboratory and bench-scale vessels, and other vessels that can supply fluid, solid, or mixed-phase biological components to the skid 900 for separation. The skid 900 can include an inlet pump 902, a centrifuge assembly 904, an inlet line set 912, a lights outlet line set 914, a heavies outlet line set 916, a lights outlet pump 918, a heavies outlet pump 920, a recirculation line set 922, a series of valves 924, 926, 928, a series of sensors 930-948, 960, a controller 950, a programmable power supply 956, and other process equipment and components described with respect to FIGS. 43-46.

[0358] The centrifuge assembly 904 may be the same centrifuge 12, including all components and equipment described herein, and alternatives described herein, or any one of the centrifuges disclosed and described in related U.S. Provisional Patent Application No. 63 / 115,938, which is incorporated herein by reference in its entirety for all purposes. As previously described, the centrifuge assembly 904 may have an inlet port 906, a light outlet port 908, and a heavy outlet port 910. The ports 906, 908, 910 are fluidly coupled to and communicate with the internal chamber or separation vessel 190C of the separation rotor 184C (shown in FIG. 48) in which the biological components are separated.

[0359] An inlet line or line set 912 connects the bioproduction vessel 901, the inlet line valve 952, the inlet pump 902, and the inlet port 906 of the centrifuge assembly 904. The inlet line valve 952 can be positioned upstream or downstream of the inlet pump 902 and can be actuated to block or allow the biocomponents to flow to the inlet port 910 of the centrifuge assembly 904 for separation. The inlet pump 902 is used to pump and allow liquid, solid, gas, and mixed-phase biocomponents to flow from the bioproduction vessel 901 through the inlet line set 912, the inlet line valve 952, and into the centrifuge assembly 904. The inlet pump 902 can be a positive displacement pump, such as a centrifugal pump or a peristaltic pump. Preferably, the inlet pump 902 is a single-use, disposable centrifugal pump.

[0360] Lights outlet line set 914 connects the lights outlet port 908 of centrifuge assembly 904, a lights outlet pump 918, a lights recirculation valve 924, and a recirculation line set 922. Lighter components separated in centrifuge assembly 904 naturally flow and are routed through the lights outlet port 908 and the lights outlet line set 914 during operation of centrifuge assembly 904. Lights outlet line set 914 may include a lights recirculation valve 924 positioned at a branch of the lights outlet line set 914. The lights recirculation valve 924 may be operated to flow and route the light biological components separated in centrifuge assembly 904 downstream from skid 900 for further processing, collection, and removal. The lights recirculation valve 924 may also be operated to flow and route the light biological components separated in centrifuge assembly 904 back to the biological production vessel 901 through a recirculation line set 922.

[0361] Lights outlet pump 918 may be driven (by an electric motor or other means) to pump the light biocomponents separated in centrifuge assembly 904 downstream from skid 900 for further processing or through recirculation line set 922 for recirculation to bioproduction vessel 901. Lights outlet pump 918 may also act as a stop valve for lights outlet line set 914 by reversing the action and flow through pump 918, preventing any biocomponents from flowing past pump 918. Lights outlet pump 918 may be a centrifugal pump or a positive displacement pump, such as a peristaltic pump. Preferably, lights outlet pump 918 is a single-use, disposable peristaltic pump.

[0362] Heavy outlet line set 916 connects heavy outlet port 910 of centrifuge assembly 904, heavy outlet pump 920, heavy recirculation valve 928, and recirculation line set 922. Heavier components separated in centrifuge assembly 904 naturally flow and are routed through heavy outlet port 910 and heavy outlet line set 916 during operation of centrifuge assembly 904. Heavy outlet line set 916 may include a heavy recirculation valve 928 positioned at a branch of heavy outlet line set 916. Heavy recirculation valve 928 may be actuated to flow and route the heavy biological components separated in centrifuge assembly 904 downstream from skid 900 for further processing, collection, and removal. Heavy recirculation valve 928 may also be actuated to flow and route the heavy biological components separated in centrifuge assembly 904 back to the biological production vessel 901 through recirculation line set 922.

[0363] Heavy outlet pump 920 may be driven (by an electric motor or other means) to pump the heavy biocomponents separated in centrifuge assembly 904 downstream from skid 900 for further processing or through recirculation line set 922 for recirculation to bioproduction vessel 901. Heavy outlet pump 920 may also act as a stop valve for heavy outlet line set 916 by reversing the action and flow through pump 920, preventing any biocomponents from flowing past pump 920. Heavy outlet pump 920 may be a centrifugal pump or a positive displacement pump, such as a peristaltic pump. Preferably, heavy outlet pump 920 is a single-use, disposable peristaltic pump.

[0364] The exemplary centrifuge skid 900 and line sets 918, 920, 922, 958 may be equipped with and coupled to a series of sensors 930-948, 960 for measuring process parameters at various locations within the skid 900. For example, an inlet pressure sensor 930 may measure the pressure within the inlet line set 912 upstream or downstream of the inlet pump 902 and upstream of the centrifuge assembly 904. An inlet flow sensor 932 may measure the flow rate of the biocomponent upstream or downstream of the inlet pump 902 and upstream of the centrifuge assembly 904.

[0365] Lights outlet lineset 914 is equipped with sensors that measure process parameters and send signals to controller 950 for process control functions. For example, lights lineset pressure sensor 934 may measure the pressure downstream from centrifuge assembly 904 and upstream of lights outlet pump 918. Lights lineset turbidity sensor 936 may measure the turbidity downstream of centrifuge assembly 904 and upstream of lights outlet pump 918. Lights lineset flow sensor 938 may measure the flow rate of biocomponents in lights outlet lineset 914 downstream of centrifuge assembly 904 and upstream of lights outlet pump 918.

[0366] Heavy outlet line set 916 is also equipped with sensors that measure process parameters and send signals to controller 950 for process control functions. For example, heavy line set pressure sensor 940 may measure the pressure downstream from centrifuge assembly 904 and upstream of heavy outlet pump 920. Heavy line set turbidity sensor 942 may measure the turbidity downstream of centrifuge assembly 904 and upstream of heavy outlet pump 920. Heavy line set flow sensor 944 may measure the flow rate of biocomponents in heavy outlet line set 916 downstream of centrifuge assembly 904 and upstream of heavy outlet pump 920.

[0367] The recirculation line set 922 is also equipped with sensors that measure process parameters and send signals to the controller 950 for process control functions. For example, a recirculation line pressure sensor 946 may measure the pressure in the recirculation line set 922. A recirculation line flow sensor 948 may measure the flow rate of a biocomponent in the recirculation line set 922. A recirculation line turbidity sensor 960 may measure the turbidity in the recirculation line set 922. A series of exemplary sensors 930-948, 960 may be positioned at multiple locations along the line sets 918, 920, 922, upstream and downstream from the process equipment of the skid 900, including the pumps 902, 918, 920 and the centrifuge assembly 904. Preferably, the exemplary sensors 930-948, 960 are single-use, disposable sensors that are easily installed, removed, and replaced on the skid 900. In addition to pressure, flow, and turbidity sensors, the skid 900 may be equipped with conductivity sensors, O2 sensors, CO2 sensors, pH sensors, temperature sensors, proximity sensors, rpm sensors, and other sensors selected by the operator and required for the bioproduction process.

[0368] The skid may also be equipped with one or more emergency shut-off valves 926 throughout the skid 900, including upstream of the inlet pump 902 coupled to the lights outlet line set 914 or the heavy outlet line set 916 downstream of the centrifuge assembly 904, downstream of the lights outlet pump and heavy outlet pump (918, 920) coupled to the recirculation line set 922, or elsewhere, to prevent biocomponents from flowing through the lines and process equipment.

[0369] The exemplary skid-mounted valves 924, 926, 928, and 952 may be controlled by a valve control system 760, as described with reference to FIG. 48 . The valve control system 760 may include a flow control valve 726, tubing 725, valve terminals 739, and a fieldbus node 747. The valve control system 760 may be a pneumatic control system, and the valves 924, 926, 928, and 952 may include pneumatic pinch valves or pinch clamps. The valve control system 760 may also be an electrical control system, and the valves 924, 926, 928, and 952 may have solenoid elements for opening and closing various ports on the valves and optical digital position feedback sensors for detecting whether the ports are open or closed. In the exemplary embodiment, the valves 924, 926, 928, and 952 include snap-in tubing slots for quick loading and unloading of tubing into and out of the valves.

[0370] Valve terminal 739 (shown in FIG. 48 ) may include a communication port, communication link, circuit board, and manifold having multiple ports electrically or pneumatically coupled to the inlet and outlet ports of valves 924, 926, 928, and 952. In an exemplary embodiment, the communication port and link may be an I / O port and link coupled to a fieldbus node 747. Valve terminal 739 and fieldbus node 747 may communicate wired or wirelessly with a controller 950 that controls the operation of valves 924, 926, 928, and 952 with electrical signals or pneumatic pressure applied through valve terminal 739 and manifold based on process parameters measured by sensors 930-948 and 960. Valve control system 60 and controller 950 may use a particular communication protocol to facilitate data and electrical signal transmission between valve terminal 739, fieldbus node 747, valves 924, 926, 928, and 952, and controller 950. In an exemplary embodiment, the communication protocol is Profinet.

[0371] A controller 950 mounted on the skid 900 may include a programmable processor and non-transitory memory programmed to operate the valves 924, 926, 928, 952 and provide power to the pumps 902, 918, 920, the centrifuge assembly 904, the valve control system 760, and other process equipment through a programmable power supply 956 based on process parameters measured by the sensors 930-948, 960. The controller 950 may be in wired or wireless communication with the exemplary sensors 930-948, 960, the valve terminals 739 (shown in FIG. 48), the pumps 902, 918, 920 and associated motors, and the motor 169 (shown in FIG. 48) that drives the centrifuge assembly 904. The controller 950 may receive signals from the sensors 930-948, 960 and convert the received signals into readable process parameters. The signals are indicative of process parameters such as pressure, flow rate, turbidity, density, temperature, pH, motor power, rotor rpm, O2 concentration, and / or CO2 concentration throughout the skid 900, line sets 912, 914, 916, 922, and process equipment on the skid 900. The controller 950 may automatically actuate, open, and close exemplary valves 924, 926, 928, 952 equipped on the skid 900 based on the process parameter signals measured and transmitted by the sensors 930-948, 960 and read and converted by the controller 950. The controller 950 may also automatically control a programmable power supply 956 to increase or decrease power to the pumps 902, 918, 920, the centrifuge assembly 904, and / or associated motors based on the process parameter signals measured and transmitted by the sensors 930-948, 960 and read and converted by the controller 950.

[0372] In an exemplary embodiment, the separation rotor 184C (shown in FIG. 48) of the centrifuge assembly 904 is coupled to an rpm sensor (e.g., an accelerometer) proximate the separation rotor 184C to measure the revolutions per minute and / or rotational speed of the separation rotor 184C. The controller 950 can automatically control the programmable power supply 956 to increase or decrease power to the motor 169 (shown in FIG. 48), which in turn increases or decreases the rotational speed of the separation rotor 184C based on the process parameter signals measured and transmitted by the sensors 930-948, 960 and received, interpreted, and converted by the controller 950.

[0373] 55A-55C illustrate process flow diagrams of example operations for loading and locking down the centrifuge skids (700, 900), initializing the valves (924, 926, 928, 952), interlocking the door assembly (711), and performing emergency system shutdown operations. The example operations and processes may be performed by a controller (798, 950) including a programmable processor and non-transitory memory programmed to automatically perform the start-up, separation, discharge, recirculation, and downstream operations of the example process. Aspects of the process may also be operated manually. As described with reference to Figures 45 and 54, the controllers (798, 950) may be in wired or wireless communication with the programmable power supply (733), valves (924, 926, 928, 952), valve control system (760), sensors (930-948, 960), pumps (721, 748, 749, 902, 918, 920), motors (108, 169), and actuators (838) mounted on the exemplary centrifuge skids (700, 900). The controllers (798, 950) are programmed to perform the start-up, separation, discharge, recirculation, and downstream operations of the exemplary process by actuating, opening, closing, moving, and / or providing signals or power to the valves, motors, pumps, centrifuges, linear actuators, and other equipment on the skids (700, 900).

[0374] The controllers (798, 950) are programmed to request data and signals from all sensors in the system, including proximity sensors located on and coupled to the centrifuge skids (700, 900), valves (924, 926, 928, 952), and door assemblies (711), to determine whether the equipment is loaded, locked down, and properly configured for operation.

[0375] Centrifuge Loading and Lockdown Operations Referring to FIG. 55A, the centrifuge skids (700, 900) of FIGS. 42-44 and 54, and the controllers (798, 950) are programmed to perform the centrifuge loading operation by performing the following steps.

[0376] In step 971, the controller (798, 950) is programmed to execute control logic that triggers a proximity sensor to sense whether the linear actuator (838) is actuated in the up and unlocked position or the down and locked position. If the linear actuator (838) is in the down and locked position, the control logic may display an error message, prompt the user, or automatically close and lock the door assembly (711). The control logic may send a signal to the linear actuator (838) to actuate it to the up and unlocked position and trigger an output or notification via the digital display unit (762) indicating that the linear actuator (838) is in the unlocked and up position. At this time, the control logic initiated by the controller (798, 950) may unlock the door assembly (711) for loading the centrifuge assembly (12, 904).

[0377] In step 972, the door assembly 711 may be opened manually or automatically, and the centrifuge assembly 12, 904 may be loaded, which triggers a proximity sensor to sense whether the centrifuge assembly 12, 904 is loaded and properly centered. The centrifuge assembly 12, 904 may be magnetically loaded and centered, as described with respect to FIGS. 49-53. If the centrifuge assembly 12, 904 is not properly loaded, the controller 798, 950 may display an error message on the digital display unit 762 and prompt the user to adjust the centrifuge assembly 12, 904. Notification and indication may be provided once the assembly 12, 904 is properly loaded.

[0378] 55B, in step 973, the operator may be prompted to close the door assembly (711), or the door assembly (711) may close automatically, which triggers a proximity sensor to sense whether the door assembly (711) has achieved proper interlock. If the door assembly (711) has not achieved proper interlock, the digital display unit (762) may provide notification that the door is open or unlocked and prompt the user or automatically to adjust the door assembly (711) for proper interlock. Once proper interlock is achieved, the digital display unit (762) may provide notification that interlock has been achieved.

[0379] In step 974, once the door assembly (711) is locked, control logic is initiated by the controller (798, 950) to move the linear actuator downward to a locked position, locking the centrifuge assembly (12, 904) to the skid (700, 900). This senses whether the linear actuator (838) is in the down, locked position, and if not, triggers the proximity sensor to provide an indication that the linear actuator is up. The controller (798, 950) may then actuate the linear actuator (838) to continue moving the linear actuator (838) downward. Once the centrifuge assembly (12, 904) is locked down to the skid (700, 900), the control logic may provide an indication that the separator is locked down and ready for startup, separation, discharge, recirculation, and downstream operation.

[0380] Referring to FIG. 55C , in step 975, a valve initialization process may be performed by control logic initiated by the controllers (798, 950), which triggers proximity sensors associated with the lights recirculation valve 924 and the heavy recirculation valve 928 to sense whether the valves are activated to recirculate the biological components back to the biological production vessel (901). If the recirculation valves (924, 928) do not recirculate the biological components back to the biological production vessel (901), the digital display unit (762) may provide notification that the valves are not open or are not configured to recirculate. The control logic initiated by the controllers (798, 950) may automatically activate the recirculation valves (924, 928) to recirculate the biological components back to the biological production vessel (901). If the recirculation valves (924, 928) are activated to recirculation mode, the digital display unit (762) may provide notification that the valves are open or in recirculation mode.

[0381] FIG. 56 illustrates a process flow diagram of an exemplary process for operating the exemplary centrifuge skid (700, 900). The exemplary process may be performed by a controller (798, 950) described herein, including a programmable processor and non-transitory memory programmed to automatically execute the start-up, separation, discharge, recirculation, and downstream operations of the exemplary process. As described with reference to FIGS. 45 and 54, the controller (798, 950) may be in wired or wireless communication with the programmable power supplies (733, 956), valves (924, 926, 928, 952), valve control system (760), sensors (930-948, 960), pumps (721, 748, 749, 902, 918, 920), motors (108, 169), and actuators (838) provided on the exemplary centrifuge skid (700, 900). The controllers (798, 950) are programmed to perform the start-up, separation, discharge, recirculation, and downstream operations of the exemplary process by actuating, opening, closing, moving, and / or providing signals or power to the valves, pumps, centrifuges, linear actuators, and other equipment on the skids (700, 900). Referring to the centrifuge skids (700, 900) of Figures 42-54, the controllers (798, 950) are programmed to perform the start-up operations by performing the following steps:

[0382] Centrifuge startup operation In step 601, an operator may provide a run or start input through a user input and digital display unit 762 (shown in FIG. 42) of the skid (700, 900) in wired or wireless communication with the controller (798, 950), or the operator may activate an on switch of the skid (700, 900).

[0383] In step 602, the controller (798, 950) may provide a device ready output or notification via the user input and digital display unit (762) indicating that the inlet pump (721, 902) may be primed.

[0384] In step 603, the control logic begins with the controller (798, 950) starting the inlet pumps (721, 902) by applying power to their motors. If the appropriate ports of the valves (924, 926, 928, 952) are not already open, the controller (798, 950) can be programmed to open and / or activate the valves (924, 926, 928, 952) to create a fluid path from the bioprocess container (901) to the centrifuge assembly (12, 904) through the lights outlet line set and the heavy outlet line set (36, 44, 52, 914, 916, 958) downstream from the centrifuge assembly (12, 904). The controller (798, 950) can be programmed to adjust the valves (924, 926, 928, 952) according to default starting valve positions and modes. In the exemplary embodiment, the default positions of the valves (924, 926, 928, 952) prior to start-up create a fluid path from the bioproduction vessel (901) through the lights outlet line set and the heavy outlet line set (36, 44, 52, 914, 916), through the recirculation line set (922) back to the bioprocess vessel (901), and to the centrifuge assembly (12, 904). Start-up of the inlet pumps (721, 902) causes fluid, which may or may not contain biocomponents and / or solids for separation, to flow from the bioprocess vessel 901 through the inlet pumps (721, 902) to prime the inlet pumps (721, 902). The controller can be programmed to actuate the valves (924, 926, 928, 952) to route the fluid through the centrifuge assembly (12, 904) and through line set 922 (shown in FIG. 54). The flow of fluid through the system primes the pumps and pushes gas out of the system. Fluid, gas, or biological components can be recirculated back into the bioprocess container 901 during priming of the inlet pumps (521, 902).

[0385] In step 604, control logic is initiated by the controller (598, 950) to time delay the start of the light and heavy outlet pumps (36, 44, 52, 918, 920) for a short duration (e.g., 2-10 seconds) or until the inlet pumps (721, 902) are primed. Any of the time delays and / or logic in the following process steps 605 and / or 606 may be used to ensure that the inlet pumps (721, 902) are primed. If pressure measurements are being used to determine whether the inlet pumps (721, 902) are primed, the time delay may be increased. Once the time delay reaches a minimum time limit, the control logic may proceed to the next process step.

[0386] In step 605, the controller (798, 950) initiates control logic that starts the outlet pumps (748, 749, 918, 920) and places the inlet pumps (721, 902) in an automatic mode where constant power is applied to the inlet pumps (721, 902). In the automatic mode, the controller (798, 950) initiates control logic that applies and regulates power from the programmable power supply (733) to the motors of the inlet pumps (721, 902) to maintain a setpoint pressure downstream of the inlet pumps (721, 902) or downstream of the centrifuge (12, 904).

[0387] In step 606, control logic is initiated by the controller (798, 950) to trigger one or more of the light lineset turbidity sensor (936) or the heavy lineset turbidity sensor (942) to measure turbidity in the light and / or heavy outlet linesets (36, 44, 52, 914, 916), respectively, downstream from the centrifuge assembly (12, 904). The light lineset turbidity sensor (936) and / or the heavy lineset turbidity sensor (942) transmits a signal to the controller (98, 950) indicative of the turbidity downstream from the centrifuge assembly (12, 904). The controller (798, 950) receives, converts, interprets, and compares the turbidity measurement to the setpoint turbidity in the light and / or heavy outlet linesets (914, 916) downstream from the centrifuge assembly (12, 904). If the turbidity measurement matches the required setpoint turbidity, priming is complete and the inlet pump (721, 902) continues to operate, pumping the biocomponent from the bioproduction vessel (910), through the system, and back through the recirculation loop. The setpoint turbidity in the lights and heavy outlet line sets (36, 44, 52, 914, 916) downstream from the centrifuge assembly (12, 904) may be set to a minimum turbidity. In an exemplary embodiment, the setpoint turbidity in the lights and heavy outlet line sets (36, 44, 52, 914, 916) downstream from the centrifuge assembly (12, 904) are both greater than 0 FTU. One or more turbidity measurements may be taken over time to verify that the turbidity is not fluctuating over time and to ensure that the inlet pumps (721, 902) are primed and that the outlet pumps (748, 749, 918, 920) and system have reached a steady state. The controllers (798, 950), via user input and digital display unit (762), may provide a "pump priming" or "priming complete" output or notification indicating that the inlet pumps (721, 902) are priming.

[0388] In step 606, instead of or in addition to measuring turbidity in the light outlet line set and / or the heavy outlet line set (36, 44, 52, 914, 916), control logic is initiated by the controller (798, 950) to trigger one or more of the inlet pressure sensor (930) downstream from the inlet pump (721, 902), the light line set pressure sensor (934), or the heavy line set pressure sensor (940) to measure the pressure downstream from the inlet pump (721, 902) or the pressure in the light outlet line set and / or the heavy outlet line set (36, 44, 52, 914, 916) downstream from the centrifuge assembly (12, 904), respectively. The inlet pressure sensor 930, the light set line pressure sensor (934), and / or the heavy set line pressure sensor (940) send signals indicative of the pressure downstream from the inlet pump (721, 902) or the centrifuge assembly (12, 904) to the controller (798, 950). The controller (798, 950) receives, converts, interprets, and compares the pressure measurements to the setpoint pressures in the light and / or heavy outlet line sets (36, 44, 52, 914, 916) downstream from the inlet pump (721, 902) and / or downstream from the centrifuge assembly (12, 904). If the pressure measurements match the required setpoint pressures, priming is complete, the system has reached steady state, and the inlet pump (721, 902) continues to operate, pumping the biocomponent from the bioproduction vessel (910) through the system and back through the recirculation loop. The setpoint pressure may be set to a minimum pressure. One or more pressure measurements may be taken over time to verify that the pressure is not fluctuating over time and to ensure that the inlet pumps (721, 902) are primed and the system has reached a steady state. If pressure measurements are being used to verify priming and steady state, the time delay in step 604 may be increased to ensure that steady state and priming have been achieved. In an exemplary embodiment, the setpoint pressure is equal to or greater than the minimum pressure of 2 psi.The controller (798, 950) may provide a "pump priming" output or notification via user input and digital display unit (62) indicating that the inlet pump (721, 902) is priming.

[0389] In step 607, after the inlet pumps (721, 902) have been primed and both outlet pumps (748, 749, 918, 920) and the system have reached a steady state, the controller (798, 950) initiates control logic that applies power from the programmable power supply (733) to the motor (169) that magnetically drives and rotates the separation rotor (184) of the centrifuge assembly (12, 904). Starting the separation rotor (184) affects process parameters, including pressure, turbidity, and flow rate within the system, which may be perturbed from the steady state achieved prior to starting the centrifuge assembly (12, 904).

[0390] In step 608, control logic is initiated by the controller (798, 950) to trigger one or more of the light lineset turbidity sensor (936), the heavy lineset turbidity sensor (942), the light lineset pressure sensor (934), or the heavy lineset pressure sensor (940), all located upstream from the light and heavy outlet pumps (36, 44, 52, 918, 920), to measure pressure and / or turbidity in the light and heavy outlet linesets (36, 44, 52, 914, 916) downstream from the centrifuge assembly (12, 904). One or more sensors (934, 936, 940, 942) send signals indicative of the pressure or turbidity in the light and heavy outlet line sets (36, 44, 52, 914, 916) downstream from the centrifuge assembly (12, 904) to the controller (98, 950). The controller (798, 950) receives, converts, interprets, and compares the turbidity and / or pressure measurements to outlet pump setpoint turbidity and / or setpoint pressure requirements that must be met at locations downstream from the centrifuge assembly (12, 904). When the turbidity and / or pressure measurements match the required outlet pump setpoint turbidity and / or setpoint pressure, the system has reached a safe steady state. The pressure and turbidity setpoints may be set to minimum or maximum pressure or turbidity. For example, the outlet pump setpoint pressure may be set to the minimum pressure requirement measured at the light lineset pressure sensor (934) or the heavy lineset pressure sensor (940).

[0391] In the exemplary embodiment, the light outlet setpoint turbidity, measured by the light lineset turbidity sensor (936), is set to a predetermined maximum turbidity. The heavy outlet setpoint turbidity, measured by the heavy lineset turbidity sensor (942), is set to a predetermined minimum turbidity. Both the maximum and minimum turbidity setpoints, measured by the light and heavy lineset turbidity sensors (934, 940) at the light and heavy outlet linesets (36, 44, 52, 914, 916), respectively, must be met to achieve a safe steady state and before the control logic can proceed to the next process step.

[0392] One or more pressure and / or turbidity measurements may be taken downstream from the centrifuge assembly (12, 904) over time to verify that the pressure or turbidity is not fluctuating over time and to ensure that the system has reached a safe steady state with all pumps and centrifuges on. The controller (98, 950) may provide a "steady state" output and notification via a user input and digital display unit (762) that the system has reached a safe steady state with all pumps and centrifuges on. Once one or more steady state setpoint requirements governing this step are met, the control logic may proceed to the next process step, which may include a downstream process mode in which the biological components are sent downstream of the centrifuge assembly (12, 904) and skid (700, 900).

[0393] Alternatively, in step 608, the controller (798, 950) initiates control logic to time delay the initiation of a downstream process mode in which the biological components are routed downstream of the centrifuge assembly (12, 904) and skid (700, 900) instead of routing the biological components from the bioprocess container (901) through the recirculation line set (922) and back to the bioprocess container (901). The initiation of the downstream process mode is delayed until a confirmed steady state is reached after start-up of the centrifuge assembly (12, 904) and all pumps. Either the time delay and / or other logic in this process step 613 may be used to ensure that the system has reached a safe steady state after start-up of the centrifuge assembly (12, 904). If pressure measurements are being used to determine whether a steady state has been reached, the time delay may be increased. Once the time delay reaches a minimum time limit, the control logic may proceed to the next process step.

[0394] In step 609, after a steady state is reached with all pumps and centrifuges on, control logic is initiated by the controller (798, 950) to initiate a downstream process mode by actuating one or more valves to route the separated biological components downstream of the centrifuge assembly (12, 904) and skid (700, 900) instead of routing the biological components from the bioprocess container (901) through the recirculation line set (922) and back to the bioprocess container (901). In an exemplary embodiment, the controller (798, 950) is programmed to execute logic to actuate the lights recirculation valve (924) and the heavies recirculation valve (928) (e.g., with the valve control system 760) to route the separated biological components downstream of the centrifuge assembly (12, 904) and skid (700, 900).

[0395] In step 610, another set of pressure and turbidity measurements may be taken as described with respect to the previous step to verify that the system has not been perturbed away from steady state or that the system has again reached steady state after the downstream process mode has been initiated. Once steady state is reached and confirmed after initiating the downstream process mode, the control logic is initiated by the controller (798, 950) to enter cascade mode. Cascade mode may be initiated simultaneously with the downstream process mode. In cascade mode, the controller (798, 950) continuously applies and adjusts power from the programmable power supply (733) to the inlet pumps (721, 902), the lights outlet pumps (748, 918), and the heavy outlet pumps (749, 920) to maintain steady state set points, including operational set points for pressure, turbidity, and flow rate upstream and downstream of the centrifuge assembly (12, 904).

[0396] Referring to FIG. 5C , in step 506, an emergency shutdown event may be initiated by the controller (798, 950) if equipment fails, process parameters are not optimized, or the separation process is not running properly. During an E-STOP event, control logic initiated by the controller (798, 950) may display and / or sound alarms and error messages indicating that an E-STOP is necessary or will occur. The controller (798, 950) may then cut off all electrical power and shut down all pump and centrifuge assemblies (12, 904). The controller (798, 950) may also close all valves (924, 926, 928, 952) to ensure that biological components do not exit the system or skid (700, 900). [Example]

[0397] Example Separation 1 After the loading, lockdown, and start-up operations were performed according to the present disclosure, a CHO cell culture suspension was pumped at 8 liters / min into the inlet of an exemplary centrifuge loaded on a skid. The cell culture suspension was separated by the centrifuge into a light component centrate exiting the centrifuge's light outlet and a heavy component retentate exiting the centrifuge's heavy outlet. Figure 57 shows bar graphs of several process performance parameters, including the percent reduction in turbidity, the percent reduction in packed cell volume (PCV), the concentrated PCV in the retentate stream, and the theoretical yield of soluble product (in this case, secreted protein) measured from the centrifuge's inlet to its outlet. The process performance parameters for Example Separation 1 are shown in the first set of bars in the bar graph of Figure 57.

[0398] The blood packed cell volume is a measure of the volume percentage of cells in a cell culture suspension and was calculated using the following formula:

[0399]

number

[0400] The theoretical yield of soluble product isolated from the cell culture suspension was calculated using the following formula:

[0401]

number

[0402] Example Separation 1 resulted in a turbidity reduction of the cell culture suspension of 87%, a PCV reduction of -95%, a concentrated PCV in the concentrate of 82.5%, and a theoretical yield of soluble product recovery of 99.1%.

[0403] Example Separation 2 After loading, lockdown, and start-up operations, the CHO cell culture suspension was pumped at 5 liters / min into the inlet of an exemplary centrifuge loaded on a skid. The cell culture suspension was separated by the centrifuge into a light component centrate exiting the centrifuge's light outlet and a heavy component retentate exiting the centrifuge's heavy outlet. Figure 57 shows bar graphs of several process performance parameters, including percent turbidity reduction, percent packed cell volume (PCV) reduction, PCV concentrated in the retentate, and theoretical soluble product yield measured from the centrifuge's inlet to outlet. The process performance parameters for Example Separation 2 are shown in the second set of bars in the bar graph of Figure 57.

[0404] The corpuscular volume is a measure of the volume percentage of cells in a cell culture suspension and was calculated using the following formula:

[0405]

number

[0406] The theoretical yield of soluble product isolated from the cell culture suspension was calculated using the following formula:

[0407]

number

[0408] Example Separation 2 resulted in a turbidity reduction of the cell culture suspension of 85%, a PCV reduction of 98%, a concentrated PCV in the concentrate of 87.7%, and a theoretical yield of soluble product of 99.4%.

[0409] Example Separation 3 After loading, lockdown, and start-up operations, the CHO cell culture suspension was pumped at 8 liters / min to the inlet of an exemplary centrifuge loaded on a skid. The cell culture suspension was separated by the centrifuge into a light component centrate exiting the centrifuge's light outlet and a heavy component concentrate exiting the centrifuge's heavy outlet. The centrate exiting the centrifuge's light outlet was subjected to depth filtration using a cellulose-based depth filter with a diatomaceous earth filter aid.

[0410] The same CHO cell culture suspension was also subjected to depth filtration under the same conditions without first passing through a centrifuge. Figure 58 shows the pressure-volume curves corresponding to the depth filtration of the cell culture suspension without separation and the centrate obtained from Example Separation 3. As shown in Figure 58, the pressure over a given volume of depth filtration is much lower for the cell culture suspension that underwent separation using the exemplary centrifuge. These depth filtration results demonstrate high separation performance.

[0411] Various changes and / or modifications of the features of the present invention illustrated herein, and further applications of the principles illustrated herein, which will occur to those skilled in the art and in possession of this disclosure, may be made to the illustrated embodiments without departing from the spirit and scope of the invention as defined by the claims, and should be considered within the scope of this disclosure. Thus, while various aspects and embodiments have been disclosed herein, other aspects and embodiments are contemplated. While many methods and components similar or equivalent to those described herein can be used to practice embodiments of the present disclosure, only certain components and methods are described herein.

[0412] It will also be understood that systems, processes, and / or products according to certain embodiments of the present disclosure may include, incorporate, or otherwise comprise characteristic features (e.g., components, members, elements, parts, and / or portions) described in other embodiments disclosed and / or described herein. Accordingly, various features of a particular embodiment may be compatible with, combined with, included in, and / or incorporated into other embodiments of the present disclosure. Thus, the disclosure of a particular feature with respect to a particular embodiment of the present disclosure should not be construed as limiting the application or inclusion of that feature to the particular embodiment. Rather, it will be understood that other embodiments may also include that feature without necessarily departing from the scope of the pres...

Claims

1. 1. A skid for use in separating biological components, said skid comprising: an enclosure bounding a compartment, the compartment being bounded in part by a mounting platform; a loading assembly secured to the housing in communication with the compartment, an alignment plate having a top surface with a cavity recessed therein, said cavity communicating with said compartment; a drive rotor rotatably disposed below the alignment plate and at least partially surrounding the cavity, the drive rotor including one or more magnets; a motor coupled to the drive rotor for selectively rotating the drive rotor about the cavity; a loading assembly comprising: a mounting portion at least partially surrounding the drive rotor and in communication with the compartment, the mounting portion having one or more mounting elements including an upstanding mounting plate movable between a raised position in which the mounting plate is aligned with the alignment plate and a second lowered position in which the mounting plate is disposed at a lower height than the alignment plate.

2. a door formed in the housing and communicating with the compartment; 10. The skid of claim 1, further comprising a door mounted to the enclosure, the door being movable between an open position in which the door opening is exposed and a closed position in which the door covers the door opening.

3. 3. The skid of claim 2, further comprising a notch recessed in an exterior surface of the enclosure and extending between a side of the enclosure and the door opening, the notch bounding a channel communicating with the compartment whether the door is in the open position or the closed position.

4. the mounting platform includes an opening extending therethrough; The skid of claim 1 , wherein the loading assembly is secured to the chassis such that the alignment plate is aligned with the opening extending through the mounting platform.

5. 5. The skid of claim 4, wherein at least a portion of the top surface of the mounting platform, the top surface of the alignment plate, and the top surface of the mounting plate are horizontally aligned when the mounting is in the raised position.

6. The loading assembly includes: an annular inner sleeve surrounding the opening, the annular inner sleeve having an upper end to which the alignment plate is attached; a receiver extending from a bottom surface of the alignment plate and projecting into the opening of the annular inner sleeve, the receiver bounding the cavity; The skid of claim 1 further comprising: the drive rotor disposed at least partially within the opening of the inner sleeve.

7. 7. The skid of claim 6, wherein the loading assembly further comprises an annular outer sleeve surrounding the inner sleeve, the outer sleeve having an upper end on which the mounting plate is mounted, the outer sleeve and the mounting plate being movable relative to the inner sleeve.

8. a support from which the inner sleeve stands; a pivotal mounting block secured to the support at a location spaced from the inner sleeve; a pair of pivot arms each having a first end pivotally mounted to the pivot mounting block such that the pair of pivot arms extend along opposite sides of the outer sleeve; 8. The skid of claim 7, further comprising a pair of support pins projecting outwardly from the opposite sides of the outer sleeve and connecting with corresponding ones of the pair of pivot arms.

9. The skid of claim 7 further comprising a linear actuator positioned to selectively raise and lower the outer sleeve relative to the inner sleeve.

10. The skid of claim 1 , wherein the one or more mounting elements comprise one or more L-shaped clips upstanding from the mounting plate and facing toward the cavity.

11. The skid of claim 1 further comprising one or more peristaltic pumps mounted on an exterior surface of the enclosure.

12. The skid of claim 1 further comprising one or more pinch valves mounted on an exterior surface of the housing.

13. The skid of claim 1 further comprising one or more of a pressure sensor, a conductivity sensor, a flow meter sensor, a pH sensor, a temperature sensor, or a turbidity sensor mounted on an exterior surface of the enclosure.

14. 1. A system for separating a biological component, the system comprising: A skid according to claim 1; a centrifuge removably disposed within the compartment of the skid, the centrifuge being supported on the mounting plate of the loading assembly.

15. 15. The system of claim 14, further comprising a first fluid line fluidly coupled to the centrifuge within the compartment of the skid, the first fluid line exiting the compartment and being removably secured to an exterior surface of the enclosure.

16. 16. The system of claim 15, wherein the first fluid line is removably coupled to a peristaltic pump and / or pinch valve secured to the exterior surface of the housing.

17. 16. The system of claim 15, further comprising a sensor mounted in the first fluid line, the sensor removably plugged into an electrical outlet formed in the exterior surface of the housing.

18. 15. The system of claim 14, wherein the centrifuge is at least partially secured to the mounting plate by magnetic forces generated by the one or more magnets in the drive rotor.

19. The centrifuge comprises: a separate stator bounding a chamber, the separate stator having a floor from which a receiving portion projects outwardly, the receiving portion bounding a recess in the separate stator communicating with the chamber; a split rotor rotatably disposed within the chamber of the split stator; a drive coupling portion coupled to the separation rotor and extending from the separation rotor so as to protrude into the recess of the receiving portion; a driver sleeve projecting outwardly from a floor of the split stator and at least partially surrounding the receiving portion of the split stator; 15. The system of claim 14, wherein the centrifuge is positioned such that the receiver of the separation rotor is aligned with the cavity of the alignment plate and the one or more mounting elements engage the driver sleeve.

20. 20. The system of claim 19, wherein the receiving portion of the isolated stator is received within the cavity of the alignment plate when the mounting plate is moved to the lowered position, and the receiving portion of the isolated stator is removed from within the cavity of the alignment plate when the mounting plate is moved to the raised position.

21. 20. The system of claim 19, wherein the driver sleeve has one or more holes or recesses into which portions of the one or more mounting elements are received.

22. 20. The system of claim 19, wherein the centrifuge is rigidly secured to the housing of the skid by moving the mounting plate to the lowered position with the one or more mounting elements engaged with the driver sleeve.

23. 1. A method for separating a biological component, the method comprising: Positioning a centrifuge on the top surface of the mounting platform of the skid of claim 1; moving the centrifuge laterally within the compartment of the housing so that the centrifuge is supported on the mounting plate of the mounting portion and the mounting element engages the centrifuge; moving the mounting plate to the lowered position so that the centrifuge is lowered relative to the alignment plate, wherein a drive coupling of the centrifuge is received within the cavity of the alignment plate when the mounting plate is moved to the lowered position; and operating the motor to rotate the drive rotor which magnetically rotates a separation rotor of the centrifuge.

24. 24. The method of claim 23, wherein laterally moving the centrifuge includes sliding the centrifuge laterally on the mounting platform into proximity with a magnetic field produced by the one or more magnets of the drive rotor, the magnetic field assisting in positioning the centrifuge.

25. 24. The method of claim 23, wherein moving the mounting plate to the lowered position rigidly secures the centrifuge to the housing of the skid.

26. The step of positioning the centrifuge on the top surface of the mounting platform comprises: Passing the centrifuge into the compartment through a doorway formed on the housing; and closing a door covering the access opening after the centrifuge is inside the compartment.

27. 24. The method of claim 23, wherein the centrifuge is positioned on the top surface of the mounting platform such that a first fluid line coupled to the centrifuge exits the compartment of the housing, the method further comprising removably securing the first fluid line to a pinch valve and / or a peristaltic pump mounted to an exterior surface of the housing.

28. 1. A method for separating a biological suspension, the method comprising: Culturing biological cells or microorganisms in a suspension in a biological production vessel, the suspension further comprising a culture medium; and passing the inlet stream of the suspension from the bioproduction vessel through an inlet opening of a centrifuge, the centrifuge separating the inlet stream into a first outlet stream that exits the centrifuge through a first outlet opening and a second outlet stream that exits the centrifuge through a second outlet opening, the first outlet stream having a higher density or percent of solids than the second outlet stream.

29. 1. A centrifuge comprising: a separate stator bounding the chamber, the separate stator having an inlet opening, a first outlet opening, and a second outlet opening; a separation rotor bounding a compartment, the separation rotor being at least partially disposed within the chamber of the separation stator and rotatable within the chamber about an axis of rotation, a heavy component collection recess and a light component collection recess being disposed at spaced apart positions between the separation stator and the separation rotor, the heavy component collection recess being in communication with the first outlet opening and the light component collection recess being in communication with the second outlet opening, the separation rotor comprising: A floor portion and a sidewall assembly upstanding from the floor and surrounding the compartment, the sidewall assembly including a plurality of separated heavy component fluid paths, each of the plurality of separated heavy component fluid paths communicating upstream with the inlet opening and downstream with the heavy component collection recess; a separation rotor comprising a plurality of upper partitions projecting radially inwardly from a sidewall assembly into the compartment to at least partially divide the compartment into a plurality of separated light component fluid paths, each of the plurality of separated light component fluid paths communicating upstream with the inlet opening and downstream with the light component collection recess; a centrifuge, wherein each light component fluid path is in communication with at least two of the separated heavy component fluid paths but is isolated from at least some of the plurality of separated heavy component fluid paths.

30. 1. A centrifuge comprising: a separate stator bounding the chamber, the separate stator having an inlet opening, a first outlet opening, and a second outlet opening; a separation rotor bounding a compartment, the separation rotor being at least partially disposed within the chamber of the separation stator and rotatable within the chamber about an axis of rotation, the separation rotor having a floor with an inner surface and an opposite bottom surface, a bowl formed on the bottom surface of the floor and projecting outwardly from the bottom surface, the bowl bounding a recess formed on the inner surface of the floor and in communication with the compartment of the separation rotor; an annular bearing assembly extending between the separation stator and the separation rotor to enable the separation rotor to rotate relative to the separation stator, the annular bearing assembly surrounding an exterior surface of the bowl so as to surround at least a portion of the recess and disposed directly adjacent to the exterior surface.

31. 31. The centrifuge of claim 30, wherein during operation, fluid flowing between the inlet opening and the first and second outlet openings passes through the recess in the bowl to form a heat sink for the bearing.

32. 31. The centrifuge of claim 30, further comprising a plurality of fins projecting downwardly from the bottom surface of the floor and projecting radially outwardly away from the bowl.

Images