Patent Publication Number: US-2022212207-A9

Title: Centrifuge system for separating cells in suspension

Description:
TECHNICAL FIELD 
     This disclosure relates to centrifugal processing of materials. Exemplary embodiments relate to devices for separating cells in suspension through centrifugal processing. 
     BACKGROUND 
     Devices and methods for centrifugal separation of cells in suspension are useful in many technological environments. Such systems may benefit from improvements. 
     SUMMARY 
     The exemplary embodiments described herein include apparatus and methods for centrifugal separation of cells in large-scale cell culture with a high cell concentration using pre-sterilized, single-use fluid path components. The exemplary centrifuges discussed herein may be solid wall centrifuges that use pre-sterilized, single-use components, and may be capable of processing cell suspensions, with high cell concentrations. 
     The exemplary embodiments use rotationally fixed feed and discharge components. Single use components include a flexible membrane mounted on a rigid frame including a core with an enlarged diameter. The single use components may further include at least one centripetal pump. The single use structures may be supported within a multiple use rigid bowl having an internal truncated cone shape. These structures permit the exemplary systems to maintain a sufficiently high angular velocity to create a settling velocity suited to efficiently processing highly concentrated cell culture streams. Features which minimize feed turbidity, and others which permit the continuous or semi-continuous discharge of cell concentrate, increase the overall production rate over the rate which can be achieved. Exemplary structures and methods provide for effective operation and reduce risks of contamination. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic view of an exemplary embodiment of a centrifuge system including single use and multiple use components. 
         FIG. 2  is a close-up view of the upper flange area of the centrifuge of  FIG. 1 , which shows a method of sealing the flexible chamber material to the surface of the flange. 
         FIG. 3  is an isometric cutaway view of the core and upper flanges of the single use component of the embodiment the centrifuge system of  FIG. 1 . 
         FIG. 4  is a schematic view of the embodiment illustrated in  FIG. 1 , in which the pump chamber of the centrifuge system includes accelerator fins. 
         FIG. 5  is an isometric view of the top of the pump chamber of the example embodiment of the centrifuge system illustrated in  FIG. 4 . 
         FIG. 6  is an isometric cutaway view of the core, upper flanges and lower flanges, of a single use centrifuge system with an enlarged core diameter (to create a shallow pool centrifuge), and a feed accelerator. 
         FIG. 7  is an isometric view of the feed accelerator of  FIG. 6 . 
         FIG. 8  is an isometric cutaway view of the core and upper flanges of a single use centrifuge system with a standard core diameter, and a feed accelerator with curved vanes and an elliptical bowl. 
         FIG. 9  is an isometric view of the feed accelerator of  FIG. 8 . 
         FIG. 10  is a schematic view of a portion of a continuous concentrate discharge centrifuge system. 
         FIG. 11  is a schematic view of a portion of a second embodiment which includes a continuous concentrate discharge centrifuge system. 
         FIG. 12  is a schematic view of a continuous concentrate discharge centrifuge system with diluent injection. 
         FIG. 13  is schematic view of a portion of a third example embodiment of a continuous concentrate discharge system, with a throttle mechanism for the centripetal pumps. 
         FIG. 14  is an isometric cutaway view of the core and upper flanges of a single use centrifuge system with a core, and a feed accelerator with straight vanes. 
         FIG. 15  is an isometric view of the feed accelerator of  FIG. 14 . 
         FIG. 16  is an isometric cutaway view of an alternative continuous concentrate discharge centrifuge system. 
         FIG. 17  is an isometric exploded view of an alternative centripetal pump. 
         FIG. 18  is an isometric view of a plate of the alternative centripetal pump including the volute passages therein. 
         FIG. 19  is a schematic view of a centrifuge system which operates to assure that positive pressure is maintained in the centrifuge core cavity. 
         FIG. 20  is a schematic view showing simplified exemplary logic flow executed by at least one control circuit of the system shown in  FIG. 19 . 
         FIG. 21  is a cross-sectional schematic view of an alternative continuous centrate and concentrate discharge centrifuge system. 
         FIG. 22  is a cross-sectional schematic view of a further alternative continuous centrate and concentrate discharge centrifuge system. 
         FIG. 23  is a cross-sectional schematic view of a further alternative continuous centrate and concentrate discharge centrifuge system. 
         FIG. 24  is a schematic view of the control system for an exemplary continuous centrate and concentrate discharge centrifuge system. 
         FIG. 25  is a schematic representation of logic flow associated with an exemplary control system of  FIG. 24 . 
         FIG. 26  is a cross-sectional view of an exemplary upper portion of a single use centrifuge structure that includes concentrate and centrate dams in the separation chamber. 
         FIG. 27  is a cross-sectional view of an exemplary upper portion of a single use structure that includes vanes in the centrate pump chamber and the concentrate pump chamber for purposes of controlling the radial position of the air/liquid interface. 
         FIG. 28  is a perspective view of a chamber surface of an exemplary concentrate or centrate pump chamber and that includes a plurality of chamber vanes. 
         FIG. 29  is a cross-sectional view of an exemplary upper portion of a single use structure similar to that shown in  FIG. 27  showing a position of an air/liquid interface. 
         FIG. 30  is a cross-sectional view of an exemplary upper portion of a single use structure including an air passage for maintaining pressurized air in the air pocket. 
         FIG. 31  is a schematic view of an exemplary system for controlling a centrifuge system including centrate flow back pressure control. 
     
    
    
     DETAILED DESCRIPTION 
     In the field of cell culture as applied to bio-pharmaceutical processes there exists a need to separate cells from fluid media such as fluid in which cells are grown. The desired product from the cell culture may be a molecular species that the cell excretes into the media, a molecular species that remains within the cell, or it may be the cell itself. At production scale, the initial stages of cell culture process typically take place in bioreactors, which may be operated in either batch or continuous mode. Variations such as repeated batch processes may be practiced as well. The desired product often must eventually be separated from other process components prior to final purification and product formulation. Cell harvest is a general term applied to these cell separations from other process components. Clarification is a term denoting cell separations in which a cell-free supernatant (or centrate) is the objective. Cell recovery is a term often applied to separations wherein a cell concentrate is the objective. The exemplary embodiments herein are directed to cell harvest separations in large-scale cell culture systems. 
     Methods for cell harvest separations include batch, intermittent, continuous and semi-continuous centrifugation, tangential flow filtration (TFF) and depth filtration. Historically, centrifuges for cell harvest of large volumes of cell culture at production scale are complex multiple use systems that require clean-in-place (CIP) and steam-in-place (SIP) technology to provide an aseptic environment to prevent contamination by microorganisms. At lab scale and for continuous cell harvest processes, smaller systems may be used. The UniFuge centrifuge system, manufactured by Pneumatic Scale Corporation, described in published application US 2010/0167388, the entire disclosure of which is incorporated herein by reference, successfully processes culture batches for cell harvest in the range of 3-30 liters/minute in quantities of up to about 2000 liters using intermittent processing. Also incorporated herein in their entirety are U.S. patent application Ser. No. 15/886,382 filed Feb. 1, 2018; and U.S. Pat. No. 9,222,067, which are also owned by Pneumatic Scale Corporation, the assignee of the present application. Intermittent processing generally requires periodically stopping both rotation of the centrifuge bowl and the feed flow in order to discharge concentrate. This approach usually works well with lower concentration, high viability cultures, in which large batches can be processed, and the cell concentrate discharged relatively quickly and completely. 
     There is sometimes a requirement to harvest cells from highly concentrated and/or low viability cell cultures, which contain a high concentration of cells and cell debris in the material feed, which are sometimes referred to as “high turbidity feeds.” Such high turbidity feeds can slow down the processing rate in some centrifugal separation systems, because:
         1. a slower feed flow rate is required to provide increased residence time in the centrifuge in order to separate small cell debris particles, and   2. the higher concentrations of both cells and cell debris may result in the bowl filling rapidly with cell concentrate, which requires the bowl to be stopped to discharge concentrate.
 
These combined factors may result in a reduced net throughput rate, and unacceptably long cell harvest processing times. In addition to the increased costs which may be associated with a longer processing time, increased time in the centrifuge may also result in a higher degree of product contamination and loss in the harvesting low viability cell cultures.
       

     A high concentration of cell and cell debris in a material feed may also result in a cell concentrate with a very high viscosity. This may make it more difficult to completely discharge the cell concentrate from the centrifuge, even with a prolonged discharge cycle. In some cases, an additional buffer rinse cycle may be added to obtain a sufficiently complete discharge of concentrate. The need to make either or both of these adjustments to the discharge cycle further increases the processing time, which can make the challenges of processing a large volume of cell culture more complex and costly. 
     Scaling up the size of systems, by increasing the bowl size to increase the length of the feeding portion of the intermittent processing cycle is sometimes not practical because it also results in a proportionately longer discharge cycle for the cell concentrate. Another limitation that may preclude simple geometric scale-up is variation in scaling of the pertinent fluid dynamic factors. The maximum processing rate of any centrifuge depends on the settling velocity of the particles being separated. The settling velocity is given by a modification of Stokes&#39; law defined by Equation 1: 
     
       
         
           
             
               
                 
                   v 
                   = 
                   
                     
                       Δ 
                       ⁢ 
                       
                           
                       
                       ⁢ 
                       
                         p 
                         · 
                         r 
                         · 
                         
                           d 
                           2 
                         
                         · 
                         
                           ω 
                           2 
                         
                       
                     
                     
                       18 
                       · 
                       μ 
                     
                   
                 
               
               
                 
                   Equation 
                   ⁢ 
                   
                       
                   
                   ⁢ 
                   1 
                 
               
             
           
         
       
     
     where v=settling velocity, Δρ is solid-liquid density difference, d is particle diameter, r is radial position of the particle, w is angular velocity, and μ is liquid viscosity. With respect to scale-up geometry, changing the radius of the bowl changes the maximum radial position r that particles can occupy. Therefore, if the other parameters in Equation 1 are held constant, an increase in bowl radius leads to an increase in average settling velocity and a gain in throughput for a given separation efficiency. However, as the radius increases it becomes more difficult to maintain the angular velocity of the bowl because of the increased material strength that may be required, and other engineering limitations. If a decrease in angular velocity is larger than the square root of the proportional increase in radius, then the average settling velocity and the gain in throughput (which is proportional to radius) both decline. 
     One of the engineering limitations that must be considered is that the angular velocity needed to rotate the larger bowl may not be practical to achieve because of the more massive and costly centrifuge drive platform that would be needed. 
     In addition if the angular velocity is held constant as the radius increases, the forces urging the cells toward the walls of the centrifuge also increase. When the bowl is rotated at sufficiently high angular velocity to create the desired processing efficiency, the walls of the container and the cells which accumulate there, experience added stress. As to the cells, this can cause cell damage by packing the cells to excessively high concentrations. Cell damage is a drawback in applications wherein cell viability needs to be maintained and can lead to contamination of products that are present in solution in the centrate. The higher viscosity resulting from excessively high cell concentrations is also sometimes a drawback for complete discharge of the cell concentrate. 
     Exemplary embodiments include apparatus and methods for continuous or semi-continuous centrifugal separation of low viability cell suspension cultures containing a high concentration of cells and cell debris, at a rate suitable for processing large volumes of cell suspensions on a commercial scale. Some exemplary centrifuges are of pre-sterilized, single-use designs and are capable of processing such cell suspensions at flow rates exceeding 20 liters per minute. This flow capacity enables total run times in the range of 2 to 3 hours for a 2000 liter bioreactor. Exemplary embodiments of the single-use centrifuge systems may be capable of processing about 300 to 2,000 liters of fluid while operating at a rate of about 2 to 40 liters per minute. 
       FIG. 1  discloses a single use centrifuge structure  1000 . The centrifuge structure  1000  includes a core structure  1500  (best shown in  FIG. 3 ) comprising a core  1510 , upper flanges  1300 , lower flanges  1200 , and a flexible liner  1100  sealed to both an upper flange  1300  and a lower flange  1200 . The centrifuge structure  1000  also includes a centripetal pump  1400 , comprising a pair of stationary paring disks  1410  in a rotating pump chamber  1420 , and a rotating mechanical seal  1700 . 
     Centrifuge structure  1000  also includes a feed/discharge assembly  2000 . The assembly  2000  comprises a plurality of concentric tubes about the rotational axis  1525  (labeled in  FIG. 12 ) of the centrifuge  1000 . The innermost portion of feed/discharge assembly  2000  includes a feed tube  2100 . A plurality of additional tubes concentrically surround the feed tube  2100 , and may include tubes or fluid pathways to permit centrate discharge  2200 , concentrate discharge  2500  (see, for example,  FIG. 12 ), or diluent feed  5000  (see, for example,  FIG. 12 ). Each portion of the feed/discharge connection may be in fluid connection with a portion of the interior of the centrifuge  1000 , and a collection or feed chamber (not shown) via appropriate fluid connections, and may include further tubes which are in fluid connection with the concentric tubes to remove or add the centrate, concentrate, or diluents from or to the system. 
     The upper and lower flanges  1300 ,  1200 , as illustrated in  FIG. 1 , comprise conical bowls, axially aligned with and concave toward the core  1510 . Core  1510  comprises a generally cylindrical body with a hollow cylindrical center large enough to accept feed tube  2100  having an axis  1525  (labeled in  FIG. 12 ). The upper flange  1300 , the core  1510  and the lower flange  1200  may be a unitary structure to provide a stronger support structure for flexible liner  1100  which is alternatively referred to herein as a membrane. In other embodiments, the core structure  1500  may be formed from a plurality of component parts. In further embodiments, the core  1510  and upper flange  1300  may comprise a single component, with a lower flange  1200  comprising a separate component, or the core  1510  and lower flange  1200  may comprise a single component with the upper flange  1300  comprising a separate component. 
     An embodiment of a unitary core  1510  and upper flange  1300  is illustrated in  FIG. 3 . This unitary component would be joined to lower flange  1200  to create the internal supporting structure  1500  of the single use components of centrifuge  1000 . This structure anchors the flexible liner  1100  around a fixed internal rigid or semi-rigid support structure  1500  at both the top and bottom. When the centrifuge system is in use, the flexible liner  1100  is also supported externally by the walls and cover of the multiple use structure  3000 . 
     The exemplary separation chamber  1550  is an open chamber which is roughly cylindrical in shape, bounded roughly by the exterior surface  1515  of the core  1510  and the flexible liner  1100 , and by the upper surface  1210  of the lower flanges  1200  and the lower surface  1310  of the upper flanges  1300 . 
     The separation chamber  1550  is in fluid connection with the feed tube  2100  via holes  1530  extending from the central cavity  1520  of the core  1510  to the exterior surface  1515  of the core  1510 . The separation chamber  1550  is also in fluid connection with the pump chamber  1420  via similar holes  1540  through the core structure  1500 . In this example, holes  1540  angle upward, toward the pump chamber  1420 , opening into the separation chamber  1550  just below the junction between the core  1510  and upper flanges  1300 . 
     As shown in  FIG. 12 , holes  1420  or  4420  may enter pump chambers at an angle other than upward, including horizontally or at a downward angle. In addition, in some embodiments holes  1420 ,  4420  may be replaced by slits, or gaps between accelerator fins. 
       FIG. 1  also shows a feed/discharge assembly  2000  which includes a feed tube carrier  2300 , through which feed tube  2100  extends into the position shown in  FIG. 3 , close to the bottom of centrifuge structure  1000 . In this position the feed tube  2100  can perform both feed and discharge functions without being moved. Shearing forces during the feeding process may be minimized by careful design of the gap between the nozzle  2110  of the feed tube  2100  and the upper surface  1210  of the lower flanges  1200 , the diameter of the nozzle  2110  of the feed tube  2100 , and the angular velocity of the centrifuge. U.S. Pat. No. 6,616,590, the disclosure of which is incorporated herein by reference in its entirety, describes how to select appropriate relationships to minimize the shearing forces. Other suitable feed tube designs which minimize the shearing forces associated with feeding a liquid cell culture into a rotating centrifuge which are known to those skilled in the art may also be used. 
       FIG. 1  further includes a centripetal pump  1400  for discharging centrate through a centrate discharge path  2200 . In the embodiment shown in  FIG. 1 , the centrate pump  1400  is located above the upper flange  1300  in a pump chamber  1420 . Pump chamber  1420  is a chamber defined by the upper surface  1505  of the core  1510  and the inner surfaces  1605 ,  1620  of a centrifuge cover  1600 . The centrifuge cover  1600  may include cylindrical walls  1640  and a mating cap portion  1610  shaped like a generally circular disk (shown in  FIG. 5 ). The centrifuge cover  1600  may be formed as a unitary body, or from separate components. 
     As discussed in more detail below, in other embodiments, the shape and position of the centrate pump chamber  1420  may vary. Chamber  1420  will generally be an axially symmetric chamber near the upper end of the core structure  1500  which is in fluid connection with the separation chamber  1550  via holes or slits  1530  which extend from adjacent the exterior of the core  1515  into the centrate pump chamber  1420 . In some embodiments, as shown most clearly in  FIGS. 11 and 12 , centrate pump chamber  1420  may be located in a recess within chamber  1550 . 
     Exemplary centrate pump  1400  comprises a pair of paring disks  1410 . Paring disks  1410  are two thin circular disks (plates), which are axially aligned with the axis  1525  of core structure  1500 . In the embodiment illustrated in  FIGS. 1-5 , paring disks  1410  are held stationary relative to the centrifuge structure  1000 , and are separated from each other by a fixed gap  1415  (labeled  1415  in  FIG. 10 ). The gap  1415  between the paring disks  1410  forms part of a fluid connection for removing centrate from the centrifuge  1000 , which permits centrate to flow between the paring disks  1410  into a hollow cylindrical centrate discharge path  2200  surrounding the feed tube carrier  2300 , terminating in centrate outlet  2400 . 
     The exemplary single use centrifuge structure  1000  is contained within a multiple use centrifuge structure  3000 . The structure  3000  comprises a bowl  3100  and a cover  3200 . The walls of the centrifuge bowl  3100  support the flexible liner  1100  of centrifuge structure  1000  during rotation of the centrifuge  1000 . In order to do so, the external structure of the single use structure  1000  and the internal structure of the multiple use structure conform to each other. Similarly, the upper surface of upper flanges  1200 , the exterior of an upper portion of core  1510 , and a lower portion of the walls  1640  of the centrifuge cover  1600  conform to the inner surface of the multiple use bowl cover  3200 , which is also adapted to provide support during rotation. Features of the multiple use bowl  3100  and bowl cover  3200 , discussed in more detail below, are designed to ensure that shear forces do not tear the liner  1100  free from the single use centrifuge structure  1000 . In some instances, an existing multiple use structure  3000  may be retrofitted for single use processing by selecting a conforming single use structure  1000 . In other instances, the multiple use structure  3000  may be specially designed for use with single use structure inserts  1000 . 
       FIG. 2  shows a portion of an exemplary structure for upper flanges  1300 , plastic liner  1100 , and the cover  3200  of a multiple use centrifuge structure  3000  to illustrate sealing the flexible liner  1100  to the upper flanges  1300 . The flexible liner  1100  may be a thermoplastic elastomer such as a polyurethane (TPU) or other stretchable, tough, non-tearing, bio-compatible polymer, while the upper and lower flanges  1300 ,  1200  may be fabricated from a rigid polymer such as polyetherimide, polycarbonate, or polysulfone. The flexible liner  1100  is a thin sleeve, or envelope, which extends between and is sealed to the upper and lower flanges  1300 ,  1200 , and forms the outer wall of separation chamber  1550 . The composition of the liner  1100  and of the upper and lower flanges  1300 ,  1200 , and core  1510  described herein are exemplary only. Those skilled in the art may substitute suitable materials with properties similar to those suggested which are, or may become, known. 
     A thermal bonding attachment process may be used to bond the dissimilar materials in the area shown in  FIG. 2 . The thermal bond  1110  is formed by preheating the flange material, placing the elastomeric polymer atop the heated flange, and applying heat and pressure to the elastomeric film liner  1100  at a temperature above the film&#39;s softening point. The plastic liner  1100  is bonded to lower flange  1200  in the same manner. Although a thermal bond  1110  is described herein, it is merely exemplary. Other means of creating a similarly strong relatively permanent bond between the flexible film and the flange material may be substituted, such as by temperature, chemical, adhesive, or other bonding means. 
     The exemplary single-use components are pre-sterilized. During the removal of these components from their protective packaging and installation into a centrifuge, the thermal bonds  1110  maintain sterility within the single-use chamber. The stretchable flexible liner  1100  conforms to the walls of reusable bowl  3100  when in use. Reusable bowl  3100  provides sufficient support, and the flexible liner  1100  is sufficiently elastic, to permit the single use structure  1000  to withstand the increased rotational forces which are generated when the larger radius centrifuge  1000  is filled with a liquid cell culture or other cell suspension and is rotated with a sufficient angular velocity to reach a settling velocity that permits processing at a rate of about 2-40 liters a minute. 
     In addition to the thermal bond  1110 , sealing ridges or “nubbins”  3210  may be present on bowl cover  3200  to compress the thermoplastic elastomeric film against the rigid upper flanges  1300 , forming an additional seal. The same compression seals may also be used at the bottom of the bowl  3100  to seal the thermoplastic elastomeric film against the rigid lower flanges  1200 . These compression seals support the thermal bonded areas  1110 , by isolating them from shearing forces created by the hydrostatic pressure that develops during centrifugation when the chamber is filled with liquid. The combination of the thermal bond  1110  and the compression nubbin  3210  seals has been tested at 3000×g, which corresponds to a hydrostatic pressure of 97 psi at the bowl wall. The lining should be sufficiently thick and compressible to permit the nubbins  3210  to compress and grip the flexible liner  1100  yet minimize the risk of tearing near the thermal bond  1110  or compression nubbins  3210 . In one example embodiment, a flexible TPU liner 0.010 inch thick sealed without tearing or leaking. 
     An embodiment corresponding to the illustrations of  FIGS. 1-2  has been tested within a bowl that was 5.5 inches in diameter. At 2000×g it had a hydraulic capacity &gt;7 liters/min and successfully separated mammalian cells to 99% efficiency at a rate of 3 liter/min. 
     In most instances, the upper and lower flanges  1300 ,  1200  may have a shape similar to that illustrated  FIG. 1 , but in some instances the upper surface of the single use centrifuge structure may have a different shape, as is illustrated in  FIGS. 10 and 11 . In the embodiments illustrated in  FIGS. 10 and 11 , rather than having a generally conical bowl cover  3200 , to conform to generally conical upper flanges  1300 , both the upper flanges and the bowl cover are relatively disk-shaped. Those skilled in the art will be able to adapt the sealing techniques described herein for use with differently shaped sealing surfaces. 
       FIGS. 4-5  illustrate an example embodiment with features to improve the efficiency of the centripetal pump  1400 . As shown in detail in  FIG. 5 , this embodiment of an internal structure for single use components similar to that illustrated in  FIGS. 1 and 2  includes a plurality of radial fins  1630  on the inner face  1620  of a cap portion  1610  of the pump chamber  1420 .  FIG. 5  shows the inner face  1620  of the cap portion  1610  of centrifuge cover  1600 . The radial fins  1630 , may be thin, generally rectangular, radial plates, extending perpendicularly from the inner surface  1620  of the cap portion  1610 . In the exemplary embodiment, six (6) fins  1630  are illustrated, but other embodiments may include fewer or more fins  1630 . In this embodiment, fins  1630  form part of the inner face of cap  1620 , but in other embodiments may comprise the upper surface  1620  of pump chamber  1420 , which may take a form other than cap  1610 . When the centrifuge system  1000  is in use, fins  1630  are located above the paring disks  1410  of the centripetal pump  1400  in the chamber  1420 . These fins  1630  transmit the angular rotation of the centrifuge  1000  to the centrate within in the pump chamber  1420 . 
     This increases the efficiency of the centripetal pump  1400 , stabilizing the gas to liquid interface in the pump chamber  1420  above the paring disks  1410 , and increasing the size of the gas barrier. The gas barrier is a generally cylindrical column of gas extending from the exterior of the feed/discharge mechanism  2000  outward into the pump chamber  1420  to the inner surface of the rotating centrate. This increase in the size of the barrier occurs because the resulting increase in angular velocity of the centrate forces the centrate toward the wall of the centrifuge. When rotating centrate within the pump chamber  1420  comes into contact with the stationary paring disks  1410  the resulting friction may decrease the efficiency of the pump  1400 . The addition of a plurality of radial fins  1630 , which rotate with the same angular velocity as the centrate, overcomes any reduction in velocity that might otherwise result from the encounter between the rotating centrate and the stationary paring disks  1410 . 
       FIG. 6  shows an exemplary embodiment of an improved core structure  1500  for use in high turbidity feeds. Core structure  1500  includes a core  1510 , upper flange  1300 , and lower flange  1200 . Core  1510  has a cylindrical central cavity  1520  adapted to permit feed tube  2100  to be inserted into the central cavity  1520 . The distance from the central axis  1525  to the exterior of core  1515  (the core width, represented by dashed line  6000  in  FIG. 6 ) is larger than the corresponding distance in the embodiment illustrated in  FIG. 3 . The larger diameter core  1510  decreases the depth (represented by dashed line  6010 ) of the separation chamber  1550 , making centrifuge  1000  operate as a shallow pool centrifuge. The depth  6010  of a separation chamber  1550  is generally the distance between the exterior of the core  1510  and the flexible liner  1100 , labeled in  FIGS. 1 and 12 . A shallow pool centrifuge is one which has a depth  6010  which is small, relative to the diameter of the centrifuge. As can be seen in the exemplary embodiment illustrated in  FIG. 12 , in order to facilitate removal of the cell concentrate, the shallow pool depth  6010  may vary from shallower at the bottom of separation chamber  1550  to somewhat deeper the top of the separation chamber  1550 . In some embodiments illustrated herein, the ratio of the average separation pool depth  6010  to the core width is 1:1 or lower. An example of a shallow pool centrifuge is offered as an optional model of the VIAFUGE® which is a centrifuge system, manufactured by Pneumatic Scale Corporation. The advantage of a shallow pool centrifuge is that it enables separation at higher feed flow rates. This is accomplished by virtue of a higher average g-force for a given inner bowl diameter, which creates a higher sedimentation velocity at a given angular velocity. The resulting enhanced separation performance is beneficial when separating highly turbid feeds containing a high concentration of cell debris. 
     The example embodiment of the core structure  1500  which is illustrated in  FIG. 6  also includes accelerator vanes  1560  as part of the lower flange  1200 . Accelerator vanes  1560  (as shown in  FIG. 12 ), rather than holes  1530  through a solid core  1510  (as shown in  FIG. 10-11 ), comprise an alternate embodiment of a fluid connection between the central cavity  1520  of the core  1510  and the separation chamber  1550 . 
     In the exemplary embodiment of a core structure  1500  shown in  FIG. 6 , accelerator vanes  1560  comprise a plurality of radially, generally rectangular, spaced thin plates  1580  extending upward from the upper conical surface of the lower flange  1200 . Plates  1580  extend upward orthogonal to the base of the core  1510 . Plates  1580  generally extend radially outward from near the axis  1525  of the core  1510 . In the exemplary embodiment, there are 12 plates  1580 , as shown most clearly in  FIG. 7 . In other embodiments there may be fewer or more than 12 plates  1580 . In addition, in other embodiments the plates  1580  may be curved in the direction of rotation of the centrifuge  1000 , as shown in an exemplary embodiment in  FIG. 9 . The interior surface of lower flange  1200  may be modified to form an elliptical accelerator bowl  1590 , with the curved plates extending upward therefrom. These embodiments are intended to be exemplary, and those skilled in the art may combine them in different ways or may modify these embodiments to further benefit from the turbidity reduction these plates and the shape of the lower flange  1200  and/or an embedded accelerator bowl create. 
     Further features of an example embodiment of a single use centrifuge  1000  which is designed to operate continuously or semi-continuously are illustrated in  FIGS. 10-12 . The exemplary embodiment illustrated in  FIG. 10  includes a second centripetal pump  4400  for removal of cell concentrate. Centripetal pump  4400  for the removal of cell concentrate is located above the centripetal pump  1400  for removal of centrate. Centripetal pump  4400  includes a pump chamber  4420  and paring disks  4410 . A plurality of holes or continuous slits  4540  extend from the upper outer circumference of the separation chamber  1550  into pump chamber  4420 , providing fluid connection from outer portion of the separation chamber  1550  to the second pump chamber  4420 . As with pump chamber  1400 , pump chamber  4400  may have a different shape than that illustrated in  FIGS. 10-12 , but will generally be an axially symmetric chamber near the upper end of the core structure  1500  which is in fluid connection with the separation chamber  1550 . As with pump chamber  1400 , the pump chamber may be partially or entirely recessed within core structure  1500 . If a centrate pump chamber  1400  is present near the upper end of the core structure  1500 , the cell concentrate pump chamber  4400  will generally be located above it. A pump chamber  4400 , for the removal of cell concentrate, will be in fluid connection with separation chamber  1550  via holes or slits  4540  which extend from adjacent the outer upper wall of separation chamber  1550 , in order to collect the heavier cell concentrate which is urged there by centrifugal forces. 
     In the embodiment illustrated in  FIG. 10 , the paring disks  4410  used in the concentrate discharge pump  4400  are approximately the same radius as those used in the centrate discharge pump  1400 , and are rotationally fixed. In other embodiments, such as the one shown in  FIG. 11 , the paring disks  4410  in the concentrate discharge pump  4400  may have a larger radius than those in the centrate discharge pump  1400 , with a correspondingly larger pump chamber  4420 . Paring disks of various intermediate diameters may be used as well. The optimum diameter will depend on the properties of the cell concentrate that is to be discharged. Larger diameter paring disks have a higher pumping capacity, but create greater shear. 
     In the embodiments illustrated in  FIGS. 1, 4, and 10 , the paring disks  4410  in the concentrate discharge pump  4400  are rotationally fixed. In other embodiments, such as the one shown in  FIG. 11 , paring disks in  4410  may be adapted to rotate with an angular velocity between zero and the angular velocity of the centrifuge  1000 . The desired angular velocity can be controlled by a number of mechanisms that are known to those skilled in the art. An example of a means of control is an external slip clutch that allows the paring disks  4410  to rotate at an angular velocity that is a fraction of that of the centrifuge  1000 . Other means of controlling the angular velocity of the paring disks will be apparent to those skilled in the art. 
     In the embodiments illustrated in  FIGS. 1, 4, 10-12 , the gaps  1415 ,  4415  between paring disks  1410  and  4410  are fixed. In other embodiments, such as the embodiment in  FIG. 13 , the gaps  1415 ,  4415  between paring disks  1410  and  4410  may be adjustable, in order to control the flow rate at which centrate or concentrate are removed from the centrifuge  1000 . One of each pair of paring disks  1410  and  4410  is attached to a vertically moveable throttle tube  6100 . Throttle tube  6100  may be moved up or down in order to narrow or widen the gap  1415 ,  4415  between each pair of the paring disks  1410 ,  4410 . In addition, an external peristaltic pump  2510  (not shown) may be added to the concentrate removal line  2500  (not shown) to aid in removal of concentrate. This pump  2510  may be controlled by a sensor  4430  in the pump chamber  4420 . The sensor  4430  (not shown) may also be used to control a diluent pump  5150  in order to synchronize concentrate removal with the addition of diluents. 
     Also illustrated in  FIG. 13  is an embodiment in which the centrate pump  1400  is located at the base of the centrifuge  1000 . In the embodiment illustrated in  FIG. 13 , a centrate well  1555  is created between the pump chamber  1420  and the flexible liner  1100 . Holes  1530  extend from the core  1510 , below the pump chamber  1420 , into the centrate well  1555 . In addition, in the exemplary embodiment illustrated, holes  1540  extend from the separation chamber  1550 , adjacent the exterior surface  1515  of the core  1510 , into the pump chamber  1420  to permit the centrate to be removed using centrate pump  1400 . Holes  4540  may also extend between the separation chamber  1550 , adjacent its outer upper surface, into pump chamber  4420  to permit cell concentrate to flow into pump chamber  4420  to be removed using centripetal pump  4400 . 
     As noted above, in the exemplary embodiment illustrated, the gaps  1415 ,  4415  between the paring disks  4410  and  1410  may be adjustable by use of a throttle tube  6100  connected to one of each pair of paring disks  4410 ,  1410 . Throttle tube  6100 , and the attached one of each paring disk pair  4410 ,  1410 , may be moved up or down to narrow or widen gaps  1415 ,  4415 . In the exemplary embodiment illustrated, the throttle tube  6100  is attached to the lower and upper paring disk of paring disk pairs  4410 ,  1410 , respectively. In other embodiments the attachment may be reversed, may be used to throttle a single centripetal pump, or may be used to throttle both in parallel (rather than opposition as illustrated in  FIG. 13 ). 
     As can be seen in the embodiments illustrated in  FIGS. 10-12 , the wall of the solid multiple use bowl  3100  is thicker at the base than it is in the upper portion, in order to create an internal truncated cone shape to support single use centrifuge structure  1000  which has a smaller radius at the lower end than at the upper end. This larger radius at the upper end of the separation chamber  1550  moves the denser cell concentrate toward the upper outer portion of the separation chamber  1550  and into centripetal pump chamber  4420 . In the embodiment illustrated, the truncated cone shape is created by a multiple use bowl  3100  with a wall which is thicker at the base than it is in the upper portion. Those skilled in the art will recognize that a multiple use bowl  3100  having an internal truncated cone shape may also include walls of uniform thickness, and that there may be other variations which create the desired internal shape for the multiple use bowl  3100 . 
     In the example embodiments illustrated in  FIGS. 10-12 , feed mechanism  2000  also includes an additional pathway for the removal of cells, or cell concentrate. In the embodiment illustrated in  FIG. 1 , the cylindrical pathway  2200  around the feed tube  2100  is used to remove centrate. The embodiments illustrated in  FIGS. 10-12  also include, a concentric cylindrical pathway for the removal of cells or cell concentrate, referred to as a cell discharge tube  2500 . Cell discharge tube  2500  surrounds the centrate removal pathway  2200 . If the centrifuge is designed to be used with a concentrate that is expected to be very viscous, an additional concentric cylindrical fluid pathway  5000  may be added around the feed tube  2100  to permit the diluents to be introduced into the cell concentrate pump chamber  4420  in order to decrease the viscosity of the concentrate. The diluent pathway  5000 , in the exemplary embodiment illustrated in  FIG. 12 , comprises a concentric tube surrounding the cell discharge pathway, and opens at the lower end into a thin disk-shaped fluid pathway  5100  above paring disks  4410 , discharging near the outer edge of the paring disks  4410  to provide fluid communication with the pump chamber  4420 . Injecting the diluent by this means, and in this location, limits the diluent to mixing with, and being discharged with, the concentrate rather than being introduced into the centrate, which may be undesirable in some applications. In alternative embodiments, the diluents may be introduced directly onto the upper surface of the paring disks and allowed to spread radially outward, or onto a separate disk located above the paring disks. 
     The choice of diluent will depend on the objectives of the separation process and the nature of the cell concentrate that is to be diluted. In some cases a simple isotonic buffer or deionized water can serve as the diluent. In other cases, diluents that are specific to the properties of a cell concentrate may be advantageous. For example, in production scale batch cell culture operated at low cell viability, flocculants are commonly added to the culture as it is being fed to a centrifuge to cause cells and cell debris to flocculate or agglomerate into larger particles, which facilitates their separation by increasing their rate of sedimentation. Since both cells and cell debris carry negative surface charges, the compounds used as flocculants are typically cationic polymers, which carry multiple positive charges, such as polyethyleneimine By virtue of their multiple positive charges, such flocculants can link negatively charged cells and cells debris into large agglomerates. An undesirable consequence of the use of such flocculants is that they further increase the viscosity of cell concentrates. Therefore, a particularly useful diluent in this application is a deflocculant that will disrupt the bonds that increase the viscosity of the cell concentrate. Examples of deflocculants include high salt buffers such as sodium chloride solutions ranging in concentration from 0.1 M to 1.0 M. Other deflocculants that may be useful in reducing the viscosity of cell concentrate are anionic polymers such as polymers of acrylic acid. 
     In the case of a cell concentrate wherein cell viability is to be maintained, a diluent can be chosen that is a shear protectant, such as dextran or Pluronic F-68. The use of a shear protectant, in combination with an isotonic buffer, will enhance the survival and viability of cells as they are being discharged from the centrifuge. 
     The exemplary centrifuge illustrated in  FIG. 4  operates as described below. During a feed cycle, a feed suspension flows into the rotating bowl assembly through feed tube  2100 . As the feed suspension enters the central cavity  1520  of core  1510  near lower flange  1200 , it is urged outward along the upper surface of lower flange  1200  by centrifugal forces, passing into the separation chamber  1550  through holes  1530  in core  1510 . 
     Centrate collects in the separation chamber  1550 , a hollow, roughly cylindrical space below the upper flange  1300  surrounding core  1510 . The centrate flows upward from its entrance into the separation chamber through holes  1530  until it encounters holes  1540  between the separation chamber  1550  and the pump chamber  1420  in the upper portion of the separation chamber  1550 , adjacent the core  1410 . Particles of density higher than that of the liquid are moved toward the outer wall of the separation chamber  1550  by sedimentation (particle concentrate), away from holes  1530 . When the rotation of the centrifuge  1000  is stopped, the particle concentrate moves downward under the influence of gravity to the nozzle  2110  of the feed tube  2100  for removal via the combined feed/discharge mechanism  2000 . 
     During rotation, the centrate enters the centrate pump chamber  1420  through holes  1540 . Within the pump chamber  1420 , the rotating centrate encounters stationary paring disks  1410 , which convert the kinetic energy of the rotating liquid into pressure which urges the centrate being discharged upward through the centrate discharge path  2200  within the feed/discharge mechanism  2000  and out through the centrate discharge tube  2400 . 
     The efficiency of the centripetal pump  1400  is increased by adding radial fins  1630  on the inner surface  1620  of the cap portion  1610  of the rotating pump  1400 . These fins  1630  impart the angular momentum of the rotating assembly to the centrate in the pump chamber  1420 , which might otherwise slow because of friction when the rotating centrate encounters the stationary paring disks  1410 . The centripetal pump  1400  provides an improved means of centrate discharge, over mechanical seals, because of the gas liquid interface within the pump chamber  1420 . The gas within the pump chamber  1420  is isolated from contamination by the external environment by the rotating seal  1700 . Because the centrate being discharged between the paring disks  1410  does not come into contact with air, either during the feed or discharge process, it avoids the excessive foaming that often occurs when the discharge process introduces air into the cell culture. 
     In the centrifuge  1000  embodiment illustrated in  FIGS. 4-5 , cell concentrate is discharged by periodically stopping bowl rotation and the feed flow and then pumping out the cell concentrate that has been collected along the outer walls of the separation chamber  1550 . This process is known as intermittent processing. When the volumetric capacity of the separation chamber  1550  is reached, centrifuge rotation is stopped. The cell concentrate moves downward toward nozzle  2110  of feed tube  2100 , where the concentrate is withdrawn by pumping it out through the feed tube  2100 . Appropriate valving (not shown) external to the centrifuge  1000  is used to direct the concentrate into a collection vessel (not shown). If the entire bioreactor batch has not yet been completely processed, then bowl rotation and feed flow are resumed, and is followed by additional feed and discharge cycles until the full batch has been processed. 
     As noted above, when the cell culture is concentrated or contains significant cell debris, the process described above slows down because residence time must be increased to capture small debris particles, which necessitates a slower feed flow rate and the separation chamber  1550  fills rapidly and rotation must be halted frequently and repeatedly for each culture batch. In addition, the cell concentrate tends to be more viscous so gravity does not work as efficiently to drain the cell concentrate to the bottom of the centrifuge  1000  so it takes longer and, in some instances, may require a wash to remove the remaining cells. 
     The single use centrifuge, as modified in the exemplary embodiments illustrated in  FIGS. 6-13 , creates a higher average settling velocity without an increase in angular velocity, permits the centrifuge  1000  to run continuously or semi-continuously, and allows a diluent to be added to the cell concentrate during the cell removal process so that the removal of cells is more easily and more completely accomplished. 
     Embodiments of a single use centrifuge structure  1000  shown in  FIGS. 6-12  operate as discussed herein. Feed suspension enters the single use centrifuge structure  1000  via feed tube  2100 . As the feed suspension encounters accelerator vanes  1560 , the vanes  1560  impart an angular velocity to the feed suspension which approaches the angular velocity of the single use centrifuge  1000 . The use of vanes  1560 , rather than holes  1530 , provides for a greater volume of feed suspension to enter the separation chamber  1550  at a slower radial velocity, avoiding the jetting which occurs when the feed suspension is forced through holes  1530  having smaller cross sectional openings than the openings between the vanes  1560 . This reduction in velocity of the feed stream as it enters the separation zone, or pool, minimizes disruption of the liquid contents of the pool, which allows for more efficient sedimentation. 
     As the centrifuge  1000  rotates, the particles which are denser than the centrate are urged toward the outside of the separation chamber  1550 , leaving the particle free centrate near the core  1510 . The centrifuge bowl  3100  has the shape of an inverted truncated cone, with a wider radius at the upper end than the lower end. The centrifugal force causes the particles to collect in the upper and outer portion of the chamber. The centrifuge  1000  may operate with semi-continuous discharge of concentrate. The centrate discharge works, generally, as described with respect to  FIG. 4 . The cell concentrate discharge works similarly, with the cell concentrate collecting near the upper outer portion of the separation chamber  1550  and entering the concentrate discharge pump chamber  4400  via holes  4540  adjacent the upper outer wall of the separation chamber  1550 . 
     The rate of feed of suspension, as well as the angular velocity of rotation, may be monitored using a vibration sensor system such as the one described in U.S. Pat. No. 9,427,748, incorporated by reference herein in its entirety. Such a sensor system permits the centrifuge to be filled at a lower rate until the vibrations indicate the centrifuge is nearly full, then to adjust the feed rate and angular velocity appropriately in response to this information. Typically, the feed rate will be decreased or stopped once the centrifuge is nearly full and the angular velocity will be increased in order to increase the settling velocity and once the settling and discharge is essentially complete, the cycle will be repeated. If the system is optimized using the additional features described herein to diminish the need to interrupt the process, it may be possible to operate the system continuously, or nearly continuously, at the angular velocity needed for settling. 
     With semi-continuous concentrate discharge, the suspension continues to be fed into the centrifuge  1000 , using concentrate pump  4400  operating intermittently to remove concentrate. The operation of concentrate pump  4400  may be controlled by an optical sensor in the concentrate discharge line that indicates the presence or absence of concentrate being discharged. In lieu of a concentrate pump  4400 , the discharge cycle may be managed electronically using a controller and sensors which determine when to open and shut a valve for the most efficient processing of the fluid suspension. 
     The average rate of discharge may further be controlled by using a centrifuge  1000  with an adjustable gap between the paring disks  4410 ,  1410 . It should be noted that it may only be desired or necessary for one set of paring disks  4410 ,  1410  to be adjustable. The gap between paring disks  4410 ,  1410  (which forms a part of the fluid pathway out of the centrifuge  1000 ) may be opened to permit flow, or closed to shut the flow off, acting as an internal valve. Depending on the desired product, or the characteristics of the product, it may also be useful to widen or narrow the gap  4415 ,  1415  between paring disks  4410 ,  1410 . Changing the gap affects both pumping and shear rates associated with the pairing disks. 
     The rate of removal of concentrate and centrate from the centrifuge  1000 , and the viability of the concentrate removed, may be further controlled using a number of features of exemplary embodiments shown in  FIGS. 4-13 . Accelerator fins  4630 , similar to those in the centrate pump chamber  1420 , may be added to concentrate pump chamber  4420 . The addition of accelerator fins  4630  increases the rate at which the concentrate may be removed, by overcoming some of the slow down due to friction between the moving concentrate and the paring disks  4410 . In addition to accelerator fins  4630  in the upper surface of the pump chamber  4420 , such fins  4630  may also be added to a lower surface in the pump chamber  4420  to increase their effectiveness. A further feature may be the substitution of slits for holes  1540 ,  4540 , which minimizes the shear on material entering the pump chambers  1420 ,  4420 . 
     If viability of the concentrate is a concern, rotatable paring disks  4410  may be included in pump chamber  4420 , which reduce the shear imparted to the concentrate as it contacts the surfaces of the paring disks  4410 . The rotation rate of paring disks  4410  may be adjusted to a rate somewhat between stationary and the rate of rotation of the separation chamber  1550  to balance concentrate viability against the rate of discharge. The desired angular velocity can be controlled by a number of mechanisms that are known to those skilled in the art. An example of a means of control is an external slip clutch that allows the paring disks to rotate at an angular velocity that is a fraction of that of the centrifuge. The use of slip clutches is well known to those skilled in the art. In addition, there may be means other than slip clutches to adjust the angular velocity that will be apparent to those skilled in the art. 
     A peristaltic pump  2510  may be also used to make removal of the concentrate more efficient and reliable, particularly with very concentrated feed suspensions. Using a peristaltic pump  2510  permits the user to more precisely control the rate of flow of the concentrate from the centrifuge  1000  than is possible relying on centripetal pumps  4400 , alone, because the rate of centripetal pumps are not as easily adjustable as the rate of a peristaltic pump  2510 . 
     In addition, a diluent, such as sterile water or a buffer, may be pumped into the concentrate pump chamber  4420  through the diluent pathway  5000  using a diluent pump  5150  in order to cut the viscosity of the concentration. A more complete discussion of useful diluents can be found above. The rate at which either or both of the peristaltic pump  2510  or the diluent pump  5150  operates may be controlled by an automated controller (not shown) responsive to a concentration sensor  4430  located in the concentrate discharge connection  2500 . The controller may be programmed to start, stop, or modify the pump rate for both diluent addition and concentrate removal responsive to the particle concentration in the concentrate, either independently, responsive to a concentration sensor  4430 , in conjunction with a standard feed/discharge cycle, or as a combination. 
       FIG. 16  shows an alternative example embodiment of a core used in connection with a centrifuge that provides continuous separation processing to produce continuous concentrate and centrate feeds. The core  10  is similar to those previously discussed that is configured to be positioned in the rotatable bowl of a centrifuge. The centrifuge bowl and the core rotate about an axis  12  during processing. The apparatus includes a stationary assembly  14  and a rotatable assembly  16 . 
     As with the previously described embodiments, the stationary assembly  14  includes a feed tube  18 . The feed tube  18  is coaxial with the axis  12  and terminates in an opening  20  adjacent the bottom of the separation chamber or cavity  22  of the core. The stationary assembly further includes a centrate centripetal pump  24 . The exemplary embodiment of the centrate centripetal pump  24 , which is described in greater detail hereafter, includes inlet opening  26  and an annular outlet opening  28 . The annular outlet opening is in fluid connection with a centrate tube  30 . The centrate tube extends in coaxial surrounding relation with the feed tube  18 . 
     In this exemplary embodiment, the centrate centripetal pump  24  is positioned in a centrate pump chamber  32 . The centrate pump chamber is defined by walls which are part of the rotatable assembly, and which during operation provide for the inlet openings  26  of the centrate centripetal pump to be exposed to a pool of liquid centrate. 
     The exemplary embodiment further includes a concentrate centripetal pump  34 . The concentrate centripetal pump  34  of the exemplary embodiment may also be of a construction like that later discussed in detail. In the exemplary arrangement the concentrate centripetal pump  34  includes inlet openings  36  positioned in a wall that bounds the annular periphery of the centripetal pump. It should be noted that the concentrate centripetal pump  34  has a greater peripheral diameter than the peripheral diameter of the centrate pump. The concentrate pump further includes an annular outlet opening  38 . The annular outlet opening  38  is in fluid connection with a concentrate outlet tube  40 . The concentrate outlet tube extends in coaxial surrounding relation with the centrate tube  30 . 
     In the exemplary embodiment the inlet openings  36  of the concentrate centripetal pump are positioned in a concentrate pump chamber  42 . The concentrate pump chamber is defined by walls of the rotatable assembly  16 . During operation, the inlet openings  36  of the concentrate centripetal pump are exposed to concentrate in the concentrate pump chamber  42 . The concentrate pump chamber  42  is bounded vertically by a top portion  44 . At least one fluid seal  46  extends between the outer circumference of the outlet tube  40  and the top portion  44 . The exemplary seal  46  is configured to reduce the risk of fluid escaping from the interior of the separation chamber and to prevent introduction of contaminants from the exterior area of the core therein. 
     During operation of the centrifuge, the bowl and the core including the cavity or separation chamber is rotated about the axis  12  in a rotational direction. Rotation in the rotational direction is operative to separate cell suspension that is introduced through the feed tube  18 , into centrate which is discharged through the centrate tube  30  and concentrate which is discharged through the concentrate outlet tube  40 . 
     Cell suspension enters the separation chamber  22  through the tube opening  20  at the bottom of the separation chamber. The cell suspension is moved outwardly via centrifugal force and a plurality of accelerator vanes  48 . As the suspension is moved outwardly by the accelerator vanes, the cell suspension material is acted upon by the centrifugal force such that the cell material is caused to be moved outwardly toward the annular tapered wall  50  that bounds the outer side of the separation chamber. The concentrated cellular material is urged to move outwardly and upwardly as shown against the tapered wall  50  and through a plurality of concentrate slots  52 . The concentrate material moves upwardly beyond the concentrate slots and into the concentrate pump chamber  42  from which the concentrate is discharged by the concentrate centripetal pump  34 . 
     In the exemplary arrangement, during operation the cell free centrate is positioned in proximity to a vertical annular wall  54  which bounds the inside of the separation chamber  22 . The centrate material moves upwardly through centrate holes  56  in the annular base structure that bounds the centrate pump chamber  32 . The centrate moves upwardly through the centrate holes  56  and forms a pool of liquid centrate in the centrate chamber. From the centrate chamber, the centrate is moved through operation of the centrate centripetal pump  24  and delivered from the core through the centrate tube  30 . 
     In the exemplary embodiment of  FIG. 16 , the concentrate and centrate pumps may have a configuration generally like that shown in  FIG. 17 . In  FIG. 17 , the centrate centripetal pump  24  is represented in an isometric exploded view. As shown in  FIG. 17 , the exemplary centripetal pump has a disk-shaped body that is comprised of a first plate  58  and a second plate  60 . During operation, the first plate and the second plate are held in releasable engaged relation via fasteners which are represented by screws  62 . Of course it should be understood that in other embodiments, other configurations and fastening methods may be used. 
     In the exemplary arrangement, the second plate  60  includes walls that bound three sides of curved volute passages  64 . It should be understood that while in the exemplary arrangement, the centripetal pump includes a pair of generally opposed volute passages  64 . In other arrangements, other numbers and configurations of volute passages may be used. 
     In the exemplary arrangement, the first and second plates make up the disk-shaped body of the centripetal pump which has a annular vertically extending wall  67  which defines an annular periphery  66 . Inlet openings  68  to the volute passages  64  extend in the annular periphery. An annular collection chamber  70  extends in the body radially outwardly from the axis  12  and is fluidly connected to the volute passages. The annular collection chamber  70  receives the material that enters the inlet openings  68 . The annular collection chamber  70  is in fluid connection with an annular outlet opening that is coaxial with the axis  12 . In the exemplary arrangement for the centrate centripetal pump, the annular outlet opening is an annular space which extends between the outer wall of feed tube  18  and the inner wall of second plate  60  which outlet is fluidly connected to the centrate outlet tube  30 . 
     In the exemplary arrangement each of the volute passages  64  is configured such that the volute passages are curved toward the rotational direction of the bowl and separation chamber, the rotational direction is represented by Arrow R in  FIG. 17 . In the exemplary arrangement, the vertically extending walls  74  which bound the volute passages and which face the rotational direction, are each curved toward the rotational direction. The curved configuration of the walls  74  which bound the volute passages horizontally, provide for the enhanced pumping properties of the exemplary arrangement. Further, the opposed bounding wall  76  of each volute passage in the exemplary arrangement has a similar curved configuration. The curved configuration of the vertically extending walls that bound the volute passages horizontally provide for a constant cross-sectional area of each volute passage from the respective inlet to the collection chamber. This consistent cross-sectional area is further achieved through the use of a generally flat wall  78  which extends between walls  74  and  76  and which bounds the volute passage vertically on one side. Further in the exemplary embodiment the first plate  58  includes a generally planar circular face  80  on its side which faces inwardly when the plates are assembled to form the disk-shaped body of the centripetal pump. In this exemplary arrangement, the face  80  serves to vertically bound the sides of both volute passages  64  of the centripetal pump. 
     Of course it should be understood that this exemplary arrangement which includes a pair of plates, one of which includes a recess with walls which bound three of the four sides of the curved volute passages and the other of which includes a surface that bounds the remaining side of the volute passages is exemplary. It should be understood that in other arrangements, other configurations and structures may be used. 
     In the exemplary centripetal pump structure shown in  FIG. 16 , the centripetal pump structures are utilized and have the capability for moving more liquid than comparably sized paring disk-type centripetal pumps. Further, the exemplary configuration produces less heating of the liquid than comparable paring disks. 
     Further in the exemplary arrangement as previously discussed, the annular periphery of the centrate centripetal pump  24  has a smaller outer diameter than the periphery of the concentrate centripetal pump  34 . This configuration is used in the exemplary arrangement to avoid the centrate centripetal pump removing too much liquid from the pool of liquid centrate which forms in the centrate pump chamber  32 . Assuring that there is sufficient liquid centrate within the centrate pump chamber, helps to assure that waves do not form in the centrate adjacent to the inlets of the centrate centripetal pump. The formation of waves which could result from less than sufficient liquid centrate, may cause vibration and other undesirable properties of the centrifuge and core. 
     The larger annular periphery of the concentrate pump of the exemplary arrangement causes material to preferentially flow out of the core via the concentrate centripetal pump. In exemplary arrangements, the flow of concentrate downstream of the concentrate output tube  40  can be controlled to control the ratio of centrate flow to concentrate flow from the core. 
     Further in exemplary embodiments, utilizing centripetal pumps having the configurations described, the properties and flow characteristics of the centrifuge may be tailored to the particular materials and requirements of the separation processing being performed. Specifically the diameters of the annular periphery of the centripetal pumps may be sized so as to achieve optimum properties for the particular processing activity. For example, the larger the diameter of the periphery of the centripetal pump, the greater flow and pressure at the outlet that can be achieved. Further the larger diameter tends to produce greater mixing than a relatively smaller diameter. However, the larger diameter also results in greater heating than a smaller peripheral diameter of a centripetal pump. Thus to achieve less heating, a smaller diameter periphery may be used. Further it should be understood that different sizes, areas and numbers of inlet openings and different volute passage configurations may be utilized to vary flow and pressure properties as desired for purposes of the particular separation process. 
       FIG. 19  shows schematically an exemplary system which is utilized to help assure positive pressure within a separation chamber which is alternatively referred to herein as a cavity, during cell suspension processing. As discussed in connection with previous exemplary embodiments, it is generally desirable to assure positive pressure above atmospheric pressure at all times within the separation chamber. Doing so reduces the risk that contaminants are introduced into the separation chamber by infiltrating past the one or more fluid seals which operatively extend between the stationary assembly and the rotatable assembly of the core. Further as previously discussed, it is also generally desirable to maintain air at positive pressure within the separation chamber in contact with the interior face of the fluid seal. The presence of an air pocket adjacent the seal avoids the seal coming into contact with the material being processed and further helps to reduce the risk of contaminant introduction into the processed material as well as the escape of any material from the separation chamber. 
     The exemplary system described in connection with  FIG. 19  serves to maintain a consistent positive pressure in the separation chamber and reduces the risk of the introduction of contaminants and the escape of processed material. 
     As schematically shown in  FIG. 19 , the centrifuge includes a rotatable bowl  82 . The centrifuge bowl is rotatable about an axis  84  by a motor  86  or other suitable rotating device. 
     The exemplary centrifuge structure shown includes a rotatable single use core  88  which bounds a cavity  90  which is alternatively referred to herein as a separation chamber. 
     Like other previously described embodiments, the exemplary core includes a stationary assembly which includes a suspension inlet feed tube  92  which has an inlet opening  94  positioned adjacent to the bottom area of the cavity. The stationary assembly further includes at least one centripetal pump  96 . The centripetal pump of the exemplary embodiment includes a disk-shaped body with at least one pump inlet  98  adjacent the periphery thereof and a pump outlet  100  adjacent the center of the centripetal pump. The pump outlet is in fluid connection with a centrate outlet tube  102 . The centrate outlet tube extends in coaxial surrounding relation of the suspension inlet tube in a manner similar to that previously discussed. The rotatable top portion  104  of the fluid containing separation chamber is in operative connection with at least one seal  106  which operates to fluidly seal the cavity of the core with respect to the inlet tube and the outlet tube. The at least one seal  106  extends operatively in sealing relation between the outer annular surface of the centrate outlet tube  102  which is stationary, and the rotatable top portion  104  of the core which has an upper internal wall which internally bounds the cavity  90  as shown. 
     In the exemplary arrangement the inlet tube  92  is fluidly connected to a pump  108 . Pump  108  in an exemplary arrangement is a peristaltic pump which is effective to pump cell suspension without causing damage thereto. Of course it should be understood that this type of pump is exemplary and in other arrangements, other types of pumps may be used. Further in the exemplary arrangement the pump  108  is reversible. This enables the pump  108  to act as a feed pump so as to be able to pump cell suspension from an inlet line  110  and into the inlet tube at a controlled rate. Further in the exemplary arrangement, the pump  108  may operate as a concentrate removal or discharge pump after the cell concentrate has been separated by centrifugal action. In performing this function, the pump  108  operates to pump cell concentrate out of the separation chamber by reversing the flow of material in the inlet tube  92  from that when cell suspension is fed into the separation chamber. The cell concentrate is then pumped to a concentrate line  112 . As represented in  FIG. 19 , the inlet line  110  and concentrate line  112  can be selectively opened and closed by valves  114  and  116  respectively. In the exemplary embodiments, valves  114  and  116  comprise pinch valves which open and close off flow through flexible lines or tubing. Of course it should be understood that this approach is exemplary and in other arrangements, other approaches may be used. 
     In the exemplary system, the centrate outlet tube  102  is fluidly connected to a centrate discharge line  118 . The centrate discharge line is fluidly connected to a centrate discharge pump  120 . In the exemplary arrangement, the centrate discharge pump  120  is a variable flow rate pump which can have the flow rate thereof selectively adjusted. For example in some exemplary arrangements, the pump  120  may include a peristaltic pump which includes a motor, the speed of which may be controlled so as to selectively increase or decrease the flow rate through the pump. The outlet of the centrate discharge pump delivers the processed centrate to a suitable collection chamber or other processing device. 
     In the exemplary arrangement schematically represented in  FIG. 19 , a pressure damping reservoir  122  is fluidly connected to the centrate discharge line  118  fluidly intermediate of the centrate outlet tube  102  and the pump  120 . In the exemplary arrangement, the pressure damping reservoir includes a generally vertically extending vessel with an interior area configured for holding liquid centrate in fluid tight relation. The pressure damping reservoir includes a bottom port  124  which is fluidly connected to the centrate discharge line  118 . 
     On an opposed side of the reservoir  122  is a top port  126 . The top port is exposed to air pressure. In the exemplary arrangement, the top port is exposed to air pressure from a source of elevated air pressure schematically indicated  128 . In exemplary embodiments, the source of elevated pressure may include a compressor, an air storage tank or other suitable device for providing a source of elevated air pressure above atmospheric pressure within the range needed for operation of the system. Air from the source of elevated pressure  128  is passed through a sterile filter  130  to remove impurities therefrom. A regulator  132  is operative to maintain a generally constant air pressure level above atmospheric at the top port of the pressure damping reservoir. In exemplary arrangements, the air pressure regulator comprises an electronic fast acting regulator to help assure that the generally constant air pressure at the desired level is maintained. The exemplary fast acting regulator  132  operates to rapidly increase the pressure acting at the top port  126  when the pressure falls below the desired level, and relieves pressure rapidly through the regulator in the event that the pressure acting at the top port is above the set value of the regulator. 
     In some embodiments the regulator outlet may also be in operative fluid connection with the interior of the top portion  104  of the separation chamber through an air line  143  shown schematically in phantom. In such exemplary arrangements the outlet pressure of the regulator that acts on the top port  126  of the reservoir also acts through the air line  143  on the air pocket inside of the separation chamber which extends downward to a level in the cavity above the centripetal pump inlet and on the interior of the at least one seal  106  and radially from a region proximate to the axis  84  to the upper internal wall on the inside of the top portion  104 . In the exemplary arrangement the line  143  applies the positive pressure to the area within the separation chamber below the at least one seal through at least one segregated passage that extends through the stationary structures of the assembly which includes the centrate outlet tube  102  and the inlet feed tube  92 . The at least one exemplary segregated passage of the air line  143  applies the air pressure to the interior of the top portion  104  through at least one air opening  145  to the separation chamber. The exemplary at least one opening  145  is positioned outside the exterior surface of the outlet tube  102 , above the inlet  98  to the centripetal pump and below the at least one seal  106 . Of course it should be understood that this described structure for the exemplary air line that provides positive air pressure to the air pocket in the separation chamber and on the inner side of the at least one seal is exemplary, and in other embodiments, other structures and approaches may be used. 
     In the exemplary arrangement of the pressure damping reservoir  122 , an upper liquid level sensor  134  is configured to sense liquid centrate within the interior of the pressure damping reservoir. The upper liquid level sensor is operative to sense liquid at an upper liquid level. A lower liquid level sensor  136  is positioned to sense liquid in the reservoir at a lower liquid level. A high liquid level sensor  138  is positioned to detect a high liquid level in the reservoir above the upper liquid level. The high liquid level sensor is positioned so as to sense a liquid level at an unacceptably high level so as to indicate an abnormal condition which may require shutting down the system or taking other appropriate safety actions. In the exemplary arrangement, the liquid level sensors  134 ,  136  and  138  comprise capacitive proximity sensors which are suitable for sensing the level of the liquid centrate adjacent thereto within the pressure damping reservoir. Of course it should be understood that these types of sensors are exemplary and in other arrangements, other sensors and approaches may be used. 
     The exemplary embodiment further includes other components as may be appropriate for the operation of the system. This may include other valves, lines, pressure connections or other suitable components for purposes of carrying out the processing and handling of the suspension, centrate and concentrate as appropriate for the particular system. This may include additional valves such as valve  140  shown schematically for controlling the open and closed condition of the centrate discharge line  118 . The additional lines, valves, connections or other items included may vary depending on the nature of the system. 
     The exemplary system of  FIG. 19  further includes at least one control circuit  142  which may be alternatively referred to as a controller. The exemplary at least one control circuit  142  includes one or more processors  144 . The processor is in operative connection with one or more data stores schematically indicated  146 . As used herein, a processor refers to any electronic device that is configured to be operative via processor executable instructions to process data that is stored in the one or more data stores or received from external sources, to resolve information, and to provide outputs which can be used to control other devices or carry out other actions. The one or more control circuits may be implemented as hardware circuits, software, firmware or applications that are operative to enable the control circuitry to receive, store or process data and to carry out other actions. For example the control circuits may include one or more of a microprocessor, CPU, FPGA, ASIC or other integrated circuit or other type circuit that is capable of performing functions in the manner of an electronic computing device. Further it should be understood that data stores may correspond to one or more of volatile or nonvolatile memory devices such as RAM, flash memory, hard drives, solid state devices, CDs, DVDs, optical memory, magnetic memory or other circuit readable mediums or media upon which computer executable instructions and/or data may be stored. 
     Circuit executable instructions, may include instructions in any of a plurality of programming languages and formats including, without limitation, routines, subroutines, programs, threads of execution, objects, methodologies and functions which carry out the actions such as those described herein. Structures for the control circuits may include, correspond to and utilize the principles described in the textbook entitled Microprocessor Architecture, Programming, and Applications with the  8085  by Ramesh S. Gaonker (Prentice Hall, 2002), which is incorporated herein by reference in its entirety. Of course it should be understood that these control circuit structures are exemplary and in other embodiments, other circuit structures for storing, processing, resolving and outputting information may be used. 
     In the exemplary arrangement, the at least one control circuit  142  is in operative connection through suitable interfaces with at least one sensor such as sensors  134 ,  136  and  138 . The at least one control circuit is also in operative connection with the variable flow rate discharge pump  120 . Further in some exemplary embodiments, the at least one control circuit may also be in operative connection with other devices such as motor  86 , pump  108 , regulator  132 , air pressure source  128 , the fluid control valves and other devices. 
     The exemplary at least one control circuit is operative to receive data and control such devices in accordance with circuit executable instructions stored in the data store  146 . In the exemplary arrangement, the fluid level  147  in the fluid damping reservoir is a property that corresponds to pressure in the centrate discharge tube  102 . In one exemplary implementation which does not utilize air line  143 , the fact that the pressure in the centrate discharge tube is indicative of the pressure in the top portion  104  of the core and the nature of the pressure in the separation chamber adjacent to the seal  106  is utilized to control the operation of the discharge pump and other components. As previously discussed, it is desirable to maintain a positive pressure above atmospheric pressure and a pocket of air adjacent to the at least one seal within the separation chamber to avoid the introduction of contaminants into the separation chamber which could result from negative pressure. However, if the fluid level becomes too high within the separation chamber, the pressure and the suspension material being processed may overflow the seal which may result in potential contamination and undesirable exposure and loss of processed material. This may result from conditions where the back pressure on the centrate line which is in connection with the outlet from the centripetal pump is too high. 
     In the exemplary arrangement the bowl speed produces a corresponding pumping force and a pump output pressure level of the centripetal pump. This pump output pressure level of the centripetal pump varies with the rotational speed of the bowl and the core. The exemplary arrangement without the use of air line  143  provides for a back pressure to be controlled on the centrate outlet tube. Back pressure is provided by controlling the speed of a motor operating the pump  120  and the liquid level  147  in the pressure damping reservoir. The back pressure is maintained so as to be less than the pump output pressure level (so that the centripetal pump may deliver centrate out of the separation chamber) but is maintained at a positive pressure above atmospheric so as to assure that contaminants will not infiltrate into the separation chamber past the seal, and so that air at elevated pressure is maintained in the interior of the separation chamber adjacent to the seal so as to isolate the seal from the components of the suspension being processed. 
     In the exemplary arrangement the elevated pressure applied to the top port  126  of the pressure damping reservoir is maintained by the regulator  132 . Further by the at least one control circuit  142  controlling the speed of pump  120  to maintain the liquid level  147  between the upper liquid level as sensed by the sensor  134  and the lower liquid level  136 , centrate flow out of the separation chamber is controlled so that the pressure of the top area of the separation chamber is maintained at a desired constant value and the centrate does not contact or overflow the seal. 
     In an alternate embodiment with the use of air line  143 , the positive pressure level of the regulator acts on both the fluid in the reservoir  122  and the area of the separation chamber above the centripetal pump inlet. Because the positive pressure level of air applied in both locations is the same, the back pressure on the centrate discharge line (which is the pressure applied above the fluid in the reservoir) is virtually always the same as the pressure in the air pocket at the top of the separation chamber. This enables the centripetal pump to operate without any net effect from either pressure. 
     In this exemplary embodiment the pump  120  and other system components are controlled responsive to the at least one control circuit  142  to assure that there is an adequate volume of air within the interior of the reservoir  122  at all times during centrate production. This assures that the reservoir provides the desired damping effect on changes in centrate discharge line pressure that might otherwise be caused by the pumping action of pump  120 . This is done by maintaining the liquid in the reservoir  122  at no higher than the upper liquid level detected by sensor  134 . Further, the liquid level in the reservoir is controlled to be maintained above the lower liquid level as sensed by sensor  136 . This assures that the centripetal pump is not pumping air and aerating the centrate. 
     In the exemplary arrangement the centrate flow out of the separation chamber is controlled through operation of the at least one control circuit. The exemplary control circuitry may operate the system during processing conditions to maintain the incoming flow of cell suspension by pump  108  to the separation chamber  90  at a generally constant rate, while the separation process is occurring with the motor  86  operating to maintain the constant bowl speed to achieve the separation of the centrate and the cell concentrate. The exemplary arrangement further operates to maintain an ideally constant back pressure on the centrate discharge line from the centripetal pump while maintaining air in the separation chamber above the level of the lower side of the air pocket to isolate the at least one seal  106  from the centrate and concentrate material being processed. 
     In an exemplary arrangement, the pressure maintained through operation of the regulator in the pressure damping reservoir is set at approximately 2 kpa (0.29 psi) above atmospheric. In the exemplary system this pressure has been found to be suitable to assure that the seal integrity and isolation is maintained during all stages of cell suspension processing. Of course it should be understood that this value is exemplary and in other arrangements, other pressure values and pressure damping reservoir configurations, sensors and other features may be utilized. 
       FIG. 20  shows schematically exemplary logic executed through operation of the at least one control circuit  142  in connection with maintaining the desired pressure level in the centrate discharge tube and within the top portion of the separation chamber. It should be understood that the control circuits in some exemplary embodiments may perform numerous additional or different functions other than those represented. These functions may include the overall control of the different processes and steps for operation of the centrifuge in addition to the described pressure control function. As represented in  FIG. 20 , in an initial subroutine step  148 , the at least one control circuit  142  is operative to make a determination on whether the centrifuge operation is currently in a mode where centrate is being discharged from the separation chamber. If so, the at least one control circuit is operative to cause the centrate discharge pump  120  to operate to discharge centrate delivered through the centrate discharge line  118 . This may be done by causing operation of a motor of the pump. In the exemplary arrangement, the flow rate of the pump  120  may be a set value initially or alternatively may be varied depending on particular operating conditions that are determined through control circuit operation during the process. The operation of the centrate discharge pump is represented by a step  150 . 
     The at least one control circuit is then operative to determine in a step  152  whether liquid is sensed at the high level of the high liquid level sensor  138 . If so, this represents an undesirable condition. If liquid is sensed at the level of the sensor  138 , the control circuit then operates to take steps to address the condition. This may include operating the pump  120  to increase its flow rate and making subsequent determinations if the level drops within a period of time while the centrifuge continues to operate. Alternatively or in addition, the at least one control circuit may decrease the speed of pump  108  to reduce the flow of incoming material. If such action does not cause the level to drop within a set period of time, additional steps are taken. Such steps may also include slowing or stopping rotation of the bowl  182 . Such actions may also include stopping the operation of pump  108  so as to avoid the introduction of more suspension material into the separation chamber. These steps which are generally referred to as shutting down normal operation of the system are represented by a step  154 . 
     If liquid is not sensed at the level of the high level sensor  138 , the at least one control circuit is next operative to determine if liquid is sensed at the upper liquid level of sensor  134 . This is represented by step  156 . If liquid is sensed at the upper liquid level sensor, the at least one circuit operates responsive to its stored instructions to increase the speed and therefore the flow rate of discharge pump  120 . This is done in an exemplary embodiment by increasing the speed of the motor that is a part of the pump. This is represented by a step  158 . Increasing the flow rate of the pump causes the liquid level  147  in the pressure damping reservoir to begin to drop as more liquid is moved by the pump  120 . 
     If in step  156  liquid is not sensed at the upper liquid level of sensor  134 , the at least one control circuit then operates to make a determination as to whether liquid is not sensed at the lower liquid level of sensor  136 . This is represented by step  160 . If the liquid level is not at the level of the sensor  136 , the control circuitry operates in accordance with its programming to control the pump  120  to decrease its flow rate. This is done in an exemplary embodiment by slowing the speed of the motor. This is represented by a step  162 . In the exemplary arrangement, slowing the flow rate of the pump  120  causes the liquid level  147  to begin rising in the pressure damping reservoir. In some exemplary arrangements if the level does not rise within the reservoir within a given time, the control circuitry may operate in accordance with its programming to cause additional actions, such as actions associated with shut down step  154  previously discussed. The control circuitry of exemplary embodiments may operate to change the pumping rate of pump  120  to maintain the level  147  within the pressure damping reservoir at a generally constant level between the levels of sensors  134  and  136  during centrate production. 
     In the exemplary arrangement, maintaining the generally constant elevated pressure of sterile air over the liquid in the pressure damping reservoir helps to assure that a similar elevated pressure is consistently maintained in the centrate outlet line and at the seal within the separation chamber. Further in the exemplary arrangements, the pressure is enabled to be controlled at the desired level during different operating conditions of the centrifuge during which the bowl rotates at different speeds. This includes, for example, conditions during which the separation chamber is initially filled at a relatively high rate through the introduction of cell suspension and during which the centrifuge rotates at a relatively lower speed. Pressure can also be maintained during the subsequent condition of final fill in which the flow rate of cell suspension into the separation chamber occurs at a slower rate and during which the rotational speed of the bowl is increased to a higher rotational speed. Further, positive pressure is maintained as previously discussed during the feeding of the suspension into the bowl and during discharge of the centrate from the separation chamber. Further in exemplary embodiments, the at least one control circuit may operate to also maintain the positive pressure during the time period that the concentrate is removed by having it pumped out of the separation chamber. Maintaining positive pressure within the separation chamber during all of these conditions reduces the risk of contamination and other undesirable conditions which otherwise might arise due to negative pressure (below atmospheric pressure) conditions. 
     Of course it should be understood that the features, components, structures and control methodologies are exemplary, and in other arrangements other approaches may be used. Further, although the exemplary arrangement includes a system which operates in a batch mode rather than a mode in which both centrate and concentrate are continuously processed, the principles hereof may also be applied to such other types of systems. 
     While the pressure damping reservoir is useful in exemplary embodiments to help assure that a desired pressure level is maintained in the outlet tube and the separation chamber, other approaches may also be utilized in other exemplary embodiments. For example, in some arrangements pressure may be directly sensed and/or applied in the outlet tube, the separation chamber or in other locations which correspond to the pressure in the separation chamber. In some arrangements, the flow rate of the discharge pump may be controlled so as to maintain the suitable pressure level. In still other arrangements, exemplary control circuits may be operative to control both the discharge pump and a pump that feeds suspension into the core and/or suitable valving or other flow control devices so as to maintain suitable pressure levels. Such alternative approaches may be desirable depending on the particular centrifuge device being utilized and the type of material being processed. 
       FIG. 21  shows schematically an alternative centrifuge system  170  particularly configured to separate cells in a cell culture batch into cell centrate and cell concentrate on a continuous or semi-continuous basis. The exemplary system shows a rigid centrifuge bowl  172  that is rotatable about an axis  174 . The bowl includes a cavity  176  configured for releasably receiving a single use structure  178  therein. The rigid bowl includes an upper opening  180 . An annular securing ring or other securing structure schematically represented  182  enables releasably securing the single use structure  178  within the bowl cavity. 
     The exemplary single use structure  178  of this example embodiment includes a central axially extending feed tube  184 . As later discussed the feed tube is used to deliver the cell culture batch material into the interior area  186  of the single use structure  178 . The feed tube  184  extends from an upper portion at a first axial end  188  of the single use device, to an opening  190  which is in the interior area at a lower portion at a second axial end  192 . The single use structure  178  includes a substantially disc shape portion  194  adjacent the first axial end. Exemplary disc shape portion  194  is generally rigid which means that it is rigid or semi-rigid, and includes an annular outer periphery  196 . The annular outer periphery is configured to engage the upper annular bounding wall  198  of the centrifuge bowl cavity  176 . The annular outer periphery of the disc shape portion  194  is configured to engage the rigid bowl  172  so that the single use structure is rotated therewith. 
     The exemplary single use structure  178  further includes a hollow rigid or at least semi-rigid cylindrical core  200 . Core  200  is operatively engaged with the disc shape portion  194  and is rotatable therewith. The core  200  is axially aligned with the disc shape portion and extends axially intermediate of the upper portion and the lower portion of the single use structure. The core  200  includes an upper opening  202  and a lower opening  204  through which the feed tube  184  extends. 
     Disc shape portion  194  includes a substantially circular centrate centripetal pump chamber  206 . A centrate centripetal pump  208  is positioned in chamber  206 . A substantially annular centrate opening  210  is in fluid connection with the centrate pump chamber  206 . By substantially annular it is meant that the opening may be comprised of discrete openings in an annular arrangement as well as a continuous opening. Centrate centripetal pump  208  is in fluid connection with a centrate discharge tube  212 . Centrate discharge tube  212  extends in coaxial surrounding relation of feed tube  184 . The centrate discharged passes through the substantially annular opening at the periphery of the centrate centripetal pump and through the annular space in the centrate discharge tube  212  on the outside of the feed tube. 
     Disc shape portion  194  further includes a concentrate centripetal pump chamber  214 . Concentrate centripetal pump chamber  214  is a substantially circular chamber that is positioned above centrate centripetal pump chamber  206 . Concentrate centripetal pump chamber  214  has a concentrate centripetal pump  216  positioned therein. The concentrate centripetal pump is in fluid connection with a concentrate discharge tube  220 . The concentrate discharge tube  220  extends in annular surrounding relation of the centrate discharge tube  212 . Concentrate passes through the substantially annular opening at the periphery of the concentrate centripetal pump and through the annular space in the concentrate discharge tube  220  on the outside of the centrate discharge tube. 
     A substantially annular concentrate opening  218  is in fluid connection with the concentrate pump chamber  214 . In the exemplary arrangement the substantially annular concentrate opening and the substantially annular centrate opening are concentric coaxial openings with the concentrate opening disposed radially outward of the centrate opening. Of course this arrangement is exemplary and in other embodiments other approaches and configurations may be used. 
     The exemplary single use structure  178  further includes a flexible outer wall  222 . Flexible outer wall  222  is a fluid tight wall that in the operative position of the exemplary single use structure  178  extends in operatively supported engagement with the wall bounding the rigid bowl cavity  176 . In the exemplary arrangement the flexible outer wall  222  is operatively engaged in fluid tight connection with the disc shape portion  194 . The flexible outer wall has an internal truncated cone shape with a smaller inside radius adjacent to the lower portion of the single use structure which is adjacent to the second axial end  192 . 
     The exemplary flexible outer wall  222  extends in surrounding relation of at least a portion of the core  200 . Wall  222  further bounds an annular separation chamber  224 . The separation chamber  224  extends radially between the outer wall of core  200  and the flexible outer wall  222 . The substantially annular concentrate opening  218  and the substantially annular centrate opening  210  are each in fluid communication with the separation chamber  224 . 
     In the exemplary arrangement the flexible outer wall  222  has a textured outer surface  226 . The textured outer surface is configured to enable air to pass out of the space between the surface bounding the cavity of the rigid bowl  172  and the flexible outer wall  222 . In an exemplary arrangement the textured outer surface may include substantially the entire area of the flexible outer wall that contacts the rigid bowl. In exemplary arrangements the textured outer surface may include one or more patterns of outward extending projections or dimples  228  with spaces or recesses therebetween to facilitate the passage of air. Air may pass out of the bowl cavity  176  when the single use structure  178  is positioned therein either through the upper opening  180  or through a lower opening  230 . In exemplary arrangements the projections may be comprised of resilient deformable material that can decrease in height responsive to force of the liner against the rigid wall of the bowl. The textured outer surface  226  of the flexible outer wall  222  reduces the risk that air pockets will be trapped between the rigid bowl of the centrifuge and the single use structure. Such air pockets may cause irregularities in wall contour which may create imbalances and/or change the contour of the separation chamber in a way that adversely impacts the separation processes. Of course it should be understood that the air release structures described are exemplary and other embodiments other air release structures may be used. 
     The exemplary single use structure shown in  FIG. 21  further includes a lower rigid or semi-rigid disc shape portion  232 . The rigid or semi-rigid material operates to maintain its shape during operation. In the exemplary arrangement lower disc shape portion  232  has a conical shape and is in operative attached connection with the lower end of core  200  by vertically extending wall portions or other structures. A plurality of angularly spaced fluid passages  234  extend between the upper surface of disc shape portion  232  and the radially outward lower portion of the core. Fluid passages  232  extend radially outward and upwardly relative to the bottom of the second axial end  192 , and enable the cells in the cell culture batch material that enters the interior area  186  through the opening  190  in feed tube  184 , to pass radially outwardly and upwardly into the separation chamber  224 . 
     In the exemplary arrangement the flexible outer wall  222  extends below the lower disc shape portion  232  at the second axial end  192  of the single use structure. The flexible outer wall  222  extends intermediate of the lower disc shape portion  232  and the wall surface of the rigid bowl  172  which bounds the cavity in which the single use structure is position. 
     In the exemplary arrangement the feed tube  184 , centrate discharge tube  212  and concentrate discharge tube  220 , as well as with centrate centripetal pump  208  and concentrate centripetal pump  216  remain stationary while the centrifuge bowl  172  and the upper disc shape portion  194 , lower disc shape portion  232  and flexible outer wall  222  rotate relative thereto with the bowl. At least one annular resilient seal  236  extends in sealing engagement operatively between the outer surface of the concentrate discharge tube  220  and the upper disc shape portion  194 . The at least one seal  236  maintains an air tight seal in a manner like that previously discussed, so that an air pocket may be maintained in the interior area  186  during cell processing so as to isolate the seal from the cell culture batch material being processed. The air pocket maintained within the interior area of the single use structure is configured such that the centrate centripetal pump  208  and the concentrate centripetal pump  216  remain in fluid communication with the cell culture batch material. In a manner like that previously discussed, a positive pressure may be maintained within the interior area so as to assure that an air pocket is present to adequately isolate the at least one seal  236  from the cell culture batch material being processed. Alternatively, other approaches may be utilized for purposes of maintaining the isolation of the seal from the material being processed. 
     The exemplary system  170  operates in a manner like that previously discussed. Cells in a cell culture batch material are introduced to the interior area  186  of the single use structure  178  through the feed tube  184 . The cells enter the interior area  186  through the feed tube opening  190  at the lower axial end of the single use structure. Centrifugal forces cause the cells to move outwardly through the openings  234  and into the separation chamber  224 . The outwardly and upwardly tapered outer wall  222  causes the cells or cell material containing cell concentrate to collect adjacent to the radially outward and upper area of the separation chamber  224 . The generally cell free centrate collects in the separation chamber radially inward adjacent to the outer wall of the core  200 . 
     In the exemplary arrangement the cell centrate passes upwardly through the substantially annular centrate opening into the centrate pump chamber. The centrate passes inward through the substantially annular opening of the centrate centripetal pump and then upwardly through the centrate discharge tube  212 . At the same time the cell concentrate passes through the substantially annular concentrate opening  218  and into the concentrate centripetal pump chamber  214 . The cell concentrate passes inwardly through the substantially annular opening of the concentrate centripetal pump  216  and then upwardly through the concentrate discharge tube  220 . This exemplary configuration enables the exemplary system  170  operate on a continuous or semi-continuous basis. The operation of the system  170  may be controlled in a manner like that later discussed so as to facilitate reliable extended operation of the system and delivery of the desired cell concentrate and generally cell free centrate in separate output fluid streams. 
       FIG. 22  shows an alternative centrifuge system generally indicated  238 . System  238  has a single use structure  240 . Single use structure  240  is similar in most respects the single use structure  178  previously described. Some of the structures and features of single use structure  240  that are generally the same as those described in connection with single use structure  178  are labeled with the same reference numerals as those used to describe single use structure  178 . 
     Single use structure  240  differs from single use structure  178  in that it includes a rigid or semi-rigid lower disc shape portion  242 . Lower disc shape portion  242  is a generally cone shape structure that is in operative connection with the lower end of core  200 . A plurality of radially outward and upward extending fluid passages  244  extend between the lower end of the core  200  and the lower disc shape portion  242 . The exemplary lower disc shape portion  242  further includes a plurality of angularly spaced radially extending vanes  246 . A fluid passage extends radially outward between each immediately angularly adjacent pair of vanes  246 . In this exemplary arrangement the vanes  246  extend upwardly from a bottom portion of disc shape portion  242  and at least some are in operative engagement with the core at radially outer portions thereof. In the exemplary arrangement the vanes  246  accelerate the cell culture batch to facilitate movement and separation within the interior area of the single use structure. 
     An alternative exemplary embodiment of a centrifuge system  248  is shown in  FIG. 23 . This exemplary embodiment includes a single use structure  250 . Single use structure  250  is similar in many respects to the previously described single use structure  178 . Some of the structures and features that are like those in the previously described single use structure  178  are labeled on single use structure  250  with the same reference numbers. 
     The exemplary single use structure  250  differs from single use structure  178  in that it includes a lower disc shape portion  252 . Lower disc shape portion  252  is a rigid or semi-rigid cone shape structure that is in operatively attached connection with the core  200  via wall portions or other suitable structures. Lower disc shape portion  252  includes a plurality of angularly spaced radially outward extending accelerator vanes  254 . Accelerator vanes  254  extend downwardly from a lower conical side of disc shape portion  252 . Each immediately angularly adjacent pair of vanes  254  has a fluid passage extending therebetween. In this exemplary arrangement the flexible outer wall  222  extends in intermediate relation between the lower ends of the vanes  254  and the wall of the rigid bowl  172  bounding the cavity  176 . This exemplary configuration provides a submerged accelerator which is operative to accelerate the cell culture batch material so as to facilitate the separation thereof within the interior area of the single use structure. Of course it should be understood that the single use structural features described herein may be combined in different arrangements so as to facilitate the separation of different types of materials and substances with different properties and to achieve desired output fluid streams. 
       FIG. 26  shows an alternative single use structure  304 . Single use structure  304  is similar to single use structure  178  previously described except as otherwise mentioned herein. Elements that are the same as those in single use structure  178  have been designated using the same reference numbers in  FIG. 26 . 
     Single use structure  304  includes a continuous annular concentrate dam  306 . Concentrate dam  306  extends downward in the separation chamber  224  and is disposed radially inward of the substantially annular concentrate opening  218 . The exemplary annular concentrate dam shown in cross-section extends downward below the concentrate opening and in axial cross-section includes a tapered outward surface  308  that extends outwardly and toward opening  218 . 
     Single use structure  304  further includes a continuous annular centrate dam  310 . Centrate dam  310  extends downward in the separation chamber  224  below the substantially annular centrate opening  210 . Centrate dam  310  is disposed radially outward from the centrate opening  210 . In the exemplary arrangement the downward distance that the concentrate dam  306  and the centrate dam  310  extend in the separation chamber  224  is substantially the same. However in other exemplary arrangements other configurations may be used. Also in other example arrangements a centrifuge structure may include a concentrate dam or a centrate dam, but not both. 
     An annular recess  312  extends in the separation chamber radially between the centrate dam and the concentrate dam. The exemplary annular recess extends upward between the centrate and concentrate dams so as to form an annular pocket therebetween. 
     In exemplary embodiments the concentrate dam  306  helps to assure that primarily cellular material or other solid material to be separated can pass outwardly along the upper portion bounding the separation chamber  224  to reach the concentrate opening  218  and the concentrate centripetal pump chamber  214 . The centrate dam  310  further helps to assure that primarily cell free centrate material is enabled to pass along the upper surface bounding the separation chamber  224  and into the substantially annular centrate opening  210  to reach the centrate pump chamber  206 . It should be understood the numerous different configurations of concentrate and centrate dams may be utilized in different example arrangements depending on the nature of the material being processed and the requirements for handling such materials. 
       FIG. 24  is a schematic view of an exemplary control system for providing generally continuous processing of a cell culture material to produce streams of generally cell free centrate and cell concentrate. In the exemplary arrangement the centrifuge system  170  previously discussed is shown. However it should be understood that the exemplary system features may be used with numerous different types of materials and centrifuge systems and structures such as those discussed herein. 
     In the exemplary embodiment shown, the centrifuge bowl  172  is rotated at a selected speed about axis  174  by a motor  256 . The feed tube  184  is in operative connection with a cell culture feed line  258  through which the cell culture batch material is received. The feed line is in operative connection with a feed pump  260 . In exemplary arrangement feed pump  260  may be a peristaltic pump or other suitable pump for delivering cell culture into the single use structure at a selected flow rate. 
     The centrate discharge tube  212  is in fluid connection with a centrate discharge line  262 . A centrate optical density sensor  264  is in operative connection with an interior area of the centrate discharge line  262 . In the exemplary arrangement the centrate optical density sensor is an optical sensor that is operative to determine the density of cells currently in the centrate passing from the single use structure. This is accomplished in the exemplary embodiment by measuring the reduction in intensity of light output by an emitter that is received by a receiver disposed from the emitter and which has at least a portion of the centrate flow passing there-between. The amount of light from the emitter that is received by the receiver decreases with the increasing density of cells in the centrate. Of course this is only one example of a sensor that may be utilized for purposes of determining the density or amount of cells present in the centrate, and in other arrangement other types of sensors may be used. For example, the light may be near infrared or other visible or non-visible light. In other sensing arrangements other forms of electromagnetic, sonic or other types of signals may be used for sensing. The centrate discharge line is further in operative connection with a centrate pump  266 . In the exemplary embodiment the centrate pump may comprise a peristaltic pump or other variable rate pump suitable for pumping the centrate material. 
     In the exemplary arrangement the concentrate discharge tube  220  is in operative connection with a concentrate discharge line  268 . A concentrate optical density sensor  270  is in operative connection with at least a portion of the interior area of the concentrate discharge line  268 . The exemplary concentrate optical density sensor may operate in a manner like the centrate optical density sensor previously discussed. Of course it should be understood that the concentrate optical density sensor may include different structures or properties, and that different types of cell density sensors may be used in other exemplary embodiments. The concentrate discharge line  268  is in operative connection with a concentrate pump  272 . In the exemplary embodiment the concentrate pump  272  may include a peristaltic pump or other variable rate pump suitable for pumping the concentrate without causing damage thereto. Of course it should be understood that these structures and components are exemplary and alternative systems may include different or additional components. 
     The exemplary control system includes control circuitry  274  which is alternatively referred to herein as a controller. In exemplary embodiments the control circuitry may include one or more processors schematically indicated  276 . The control circuitry may also include one or more data stores schematically indicated  278 . The one or more data stores may include one or more types of tangible mediums which hold circuit executable instructions and data which when executed by the controller cause the controller to carry out operations such as those later discussed herein. Such mediums may include for example, solid-state memory, magnetic memory, optical memory or other suitable non-transitory medium for holding circuit executable instructions and/or data. The control circuitry may include structures like those previously discussed. 
     The operations carried out by the exemplary controller  274  will now be described in connection with the schematic representation of a logic flow shown in  FIG. 25 . In the exemplary arrangement the controller  274  is operative to control the operation of the components in the system so as to maintain the delivery of concurrent output flows of generally cell free centrate and cell concentrate. This is accomplished using the optical density sensors in the respective centrate and concentrate outlet lines to detect the cell density (or turbidity) of the output feeds and to adjust the operation of the system components so as to maintain the output within desired ranges. 
     In the use of the exemplary control system, the cell concentration of cells in the cell culture material to be processed is measured separately prior to initiating the operation of the system. The desired axial rotation speed of the centrifuge is determined as is a speed for operation of the feed pump  260 . In the exemplary arrangement the rotational speed of the centrifuge and the feed rate of the cell material by the feed pump are generally maintained by the controller as constant set values. Of course in other arrangements and systems alternative approaches may be used in which the speeds and feed rates may be adjusted by the controller during cell processing. 
     In the exemplary arrangement, based on the determined cell concentration, the discharge rate (flow rate) of the external concentrate pump  272  is set at an initial value which is referred to herein as a “prime value.” Also preset in the exemplary embodiment is a “prime duration” which corresponds to a time period during which the external concentrate pump  272  will operate initially at the prime value. This duration allows the single use structure  178  to partially fill. Also in the exemplary system a “base speed” is set for the concentrate pump based on the cell density as well as the feed rate from the feed pump  260 . The base speed of the concentrate pump is a speed (which corresponds to flow rate) at which the concentrate pump will operate subsequent to the prime duration. In the exemplary arrangement the set base speed is generally expected to correspond to a concentrate pump speed which will produce centrate with the cell density below a desired set limit and cell concentrate with the cell density generally above a further desired set limit. The set values and limits are received by the controller in response to inputs through suitable input devices and stored in the at least one data store. 
     In the exemplary logic flow represented in  FIG. 25 , the operation of the concentrate pump  272  at the initial prime speed is represented by step  280 . A determination is made at a step  282  by the controller as to whether the concentrate pump has operated at the prime speed for the time period corresponding to the prime duration which is operative to at least partially fill the single use structure  178 . 
     Once the concentrate pump has operated at the prime speed for the prime duration, the controller causes the concentrate pump speed to then increase to the base speed as represented by a step  284 . The controller  274  operates to monitor the cell density in the centrate as detected by sensor  264 . The controller operates to determine if the optical density is higher than the desired set point as represented by step  286 . If the optical density of the centrate is not higher than the set point, then the centrate is sufficiently clear of cells or cell material such that this measurement does not cause a change by the controller in the operating speed of the concentrate pump, and the logic returns to step  284 . 
     If in step  286  the optical density of the centrate is determined to be higher than the set point, then the logic proceeds to a step  288 . In step  288  the controller operates to increase the speed of the concentrate pump by a set incremental step amount. This speed step increase is intended to generally cause the optical density of the centrate to clear as a result of reducing the number of cells therein. 
     After the speed of the concentrate pump  272  is increased in step  288  the controller then operates responsive to the sensor  264  to determine in a step  290  if the optical density of the centrate is still above the set point a set time after the incremental increase in the speed (flow) of the concentrate pump. If it is, then the controller continues to monitor the optical density of the centrate until it is not higher than the set point. In the exemplary arrangement the instructions include a set time period during which the centrate optical density must not be higher than the set point before the concentrate pump speed controller determines that the adjustment to the base speed is sufficient to maintain the optical density of the centrate at a level that is at or below the desired set point. Step  292  is representative of the controller making a determination that the increased concentrate pump speed has maintained the optical density of the centrate at or below the set point for the stored set time period value which corresponds to consistently producing an outflow of sufficiently cell free centrate or reaching the programmed wait time. Responsive to producing the sufficiently cell free centrate for the desired duration or reaching the programmed wait time, the controller next operates in a step  294  to cause the base speed value of the concentrate pump to be adjusted to correspond to the increased base speed. The controller sets the new base speed and the logic returns to the step  284 . It should be noted that if the centrate optical density is still above the set point as determined in step  286 , the concentrate pump speed will again be adjusted. 
     The exemplary controller also concurrently monitors the optical density of the cells in the output concentrate flow. This is done by monitoring the optical density as detected by sensor  270 . As represented by step  296  the controller operates to determine if the optical density in the concentrate is lower than a desired setpoint. If the concentrate optical density is detected at or above the desired set point value that is stored in the data store, then the concentration of cells in the concentrate output flow is at or above the desired level, and the logic returns to the step  284 . However if the optical density of the concentrate is below the desired set point, meaning that the level of cells in the concentrate is less than desired, the controller moves to a step  298 . In step  298  the speed of the concentrate pump is reduced by a predetermined incremental step amount. Reducing the speed of the concentrate pump will reduce output flow rate, generally increase the amount of cells in the concentrate output flow and therefore increase the optical density of the concentrate output flow. 
     The controller then operates the concentrate pump  272  at the new reduced speed as represented in a step  300 . As represented in the step  302  the controller operates the concentrate pump at this reduced speed for a set time period corresponding to a set value stored in the data store so that the concentration of cells in the output concentrate flow may increase before a determination is made as to whether the speed decrease is sufficient. Once the time period is determined to have passed in the step  302 , the controller returns to the step  284  from which the logic flow is then repeated to determine if further speed adjustments are needed. 
     Of course it should be understood that this schematic simplified logic flow is exemplary and in other embodiments a different logic flow and/or additional operating parameters of system components may be monitored and adjusted for purposes of achieving the desired output flow of centrate and concentrate. For example in other exemplary arrangements the speed of the centrate discharge pump, and thus the centrate discharge flow, may be varied by the controller responsive at least in part to the optical density as detected by the centrate optical density sensor which corresponds to the level of cells in the centrate. For example, the controller may operate to reduce the flow rate of the centrate pump if the level of cells in the centrate is detected as above a set limit. This may be done by the controller as an alternative to or in combination with controlling the concentrate discharge flow rate. The controller may vary the centrate flow as appropriate to assure that the level of cells in the centrate is maintained below set limits or within a set range. 
     Alternatively or in addition the controller may also control the flow rate of cell suspension entering the single use structure. This may be done in conjunction with varying the flow rates of centrate and concentrate from the single use structure, to maintain the level of cells in the centrate and concentrate within the programmed set limits that are stored in memory associated with the controller. Additionally the controller may also operate in accordance with its programming to vary other process parameters such as variation of bowl rotational speed, the introduction of dilutant and dilutant introduction rates as well as other process parameters to maintain the centrate and concentrate properties within programmed limits and desired process rates. Further in other exemplary embodiments other properties or parameters may be monitored and adjusted by the control system for purposes of achieving the desired products. 
       FIG. 27  shows a cross-sectional view of a further alternative single use centrifuge structure  314 . Single use structure  314  is generally similar to single use structure  178  previously discussed except as specifically mentioned. Single use structure  314  includes elements that are operative to help assure that the air/liquid interface of the air pocket that extends in the single use structure and that isolates the seal  236  from the material that is being processed is more stably maintained at a desired radial location. 
     In the single use structure  314  the centrate pump  208  is positioned in a centrate pump chamber  316 . Centrate pump chamber  316  is bounded vertically at the bottom by a circular lower centrate centripetal pump chamber surface  318 . Centrate pump chamber  316  is bounded vertically at the upper side by a circular upper centrate centripetal pump chamber surface  320 . 
     Lower centrate pump chamber surface  318  extends radially outward from a lower centrate centripetal pump chamber opening  322 . In the exemplary arrangement the lower centrate centripetal pump chamber opening  322  extends through a circular top of the core  200  and corresponds to upper opening  202  previously discussed. The feed tube  184  extends through the lower centrate centripetal pump chamber opening. 
     Upper centrate centripetal pump chamber surface  320  extends radially outward from a circular upper centrate centripetal pump chamber opening  324 . The feed tube  184  and the centrate discharge tube  212  extend axially through the upper centrate centripetal pump chamber opening. 
     A plurality of angularly spaced upward extending lower centrate chamber vanes  326  extend on the lower centrate centripetal pump chamber surface  318 . Each of the lower centrate chamber vanes  326  extend radially outward beginning from the lower centrate centripetal pump chamber opening  322 . The lower centrate chamber vanes  326  which are shown in greater detail in  FIG. 28  extend radially outward from the axis of rotation  174  a lower centrate vane distance V. In the exemplary arrangement the lower centrate chamber vanes  326  extend upward in a circular recess on the lower centrate centripetal pump chamber surface  318 . However it should be understood that this arrangement is exemplary and other embodiments other arrangements may be used; for example the radial length of the vanes, vane height, and the depth and diameter of the recess may be varied to achieve desired fluid pressure properties. 
     A plurality of angularly spaced downward extending upper centrate chamber vanes  328  extend from upper centrate centripetal pump chamber surface  320 . Each of the upper centrate chamber vanes  328  extend radially outward beginning from the upper centrate centripetal pump chamber opening  324 . The upper centrate chamber vanes extend radially outward from the axis of rotation  174  an upper centrate vane distance. In the exemplary arrangement the upper centrate vane distance substantially corresponds to the lower centrate vane distance V. In the exemplary arrangement the upper centrate chamber vanes extend downward in a circular recess on the upper centrate centripetal pump chamber surface that has a configuration like that shown for the lower centrate chamber vanes in  FIG. 28 , but in an inverted orientation. 
     In the exemplary arrangement shown the centrate centripetal pump  208  includes a substantially annular centrate centripetal pump opening  330 . The substantially annular centrate centripetal pump opening  330  is disposed radially outward from the axis of rotation  174 , a centrate pump opening distance. The centrate pump opening distance at which the centrate centripetal pump opening  330  is positioned, is a greater radial distance than the lower centrate vane distance and the upper centrate vane distance for reasons that are later discussed. 
     In the exemplary arrangement of the single use structure  314  the concentrate centripetal pump  216  is positioned in a concentrate pump chamber  332 . Concentrate pump chamber  332  is bounded vertically at a lower side by a circular lower concentrate centripetal pump chamber surface  334 . Concentrate pump chamber  332  is bounded vertically at an upper side by a circular upper concentrate centripetal pump chamber surface  336 . 
     The lower concentrate centripetal pump chamber surface  334  extends radially outward from a lower concentrate centripetal pump chamber opening  338 . In the exemplary arrangement the lower concentrate centripetal pump chamber opening corresponds in size to and is continuous with the upper centrate centripetal pump chamber opening  324 . The feed tube  184  and the centrate discharge tube  212  extend through the lower concentrate centripetal pump chamber opening  338 . 
     A plurality of angularly spaced upward extending lower concentrate chamber vanes  340  extend on lower concentrate centripetal pump chamber surface  334 . The lower concentrate chamber vanes  334  extend radially outward beginning from the lower concentrate centripetal pump chamber opening  338 . The lower concentrate chamber vanes  334  extend radially outward from the axis of rotation a lower concentrate vane distance. In the exemplary arrangement the lower concentrate chamber vanes  334  extend on a circular recess portion of the lower concentrate centripetal pump chamber surface similar to the upper and lower centrate chamber vanes previously discussed. Of course it should be understood that this configuration is exemplary. 
     Upper concentrate centripetal pump chamber surface  336  extends radially outward from an upper concentrate centripetal pump chamber opening  342 . The feed tube  184 , the centrate discharge tube  212  and the concentrate discharge tube  220  coaxially extend through the upper concentrate centripetal pump chamber opening  342 . A plurality of angularly spaced upper concentrate chamber vanes  344  extend downward from surface  336 . The upper concentrate chamber vanes extend radially outward from the upper concentrate centripetal pump chamber opening  342  an upper concentrate vane distance. The upper concentrate chamber vanes extend in an upward extending circular recess in the upper concentrate centripetal pump chamber surface. In the exemplary arrangement the upper concentrate chamber vanes are configured in a manner similar to the lower concentrate chamber vanes and the upper and lower centrate chamber vanes previously discussed. Of course it should be understood that this approaches exemplary and other embodiments other approaches may be used. 
     Concentrate centripetal pump  216  includes a substantially annular concentrate pump opening  346 . Concentrate pump opening is radially disposed from the axis of rotation  174  a concentrate pump opening distance. In the exemplary arrangement the upper and lower concentrate vane distances are less than the concentrate pump opening distance. Of course it should be understood that this configuration is exemplary and other embodiments other approaches may be used. 
     In the exemplary single use structure  314  the upper and lower concentrate chamber vanes  344 ,  340 , and the upper and lower centrate chamber vanes  326 ,  328  operate to stabilize and radially position the annular air/liquid interface  348  in the centrate pump chamber  330  and the air/liquid interface  350  in the concentrate pump chamber  332 . As represented in  FIG. 28  the air/liquid interface  348  is positioned radially intermediate along the radial length of the centrate chamber vanes. This is radially inward from the centrate pump opening  330 . The radially extending centrate chamber vanes operate to provide centrifugal pumping force which maintains the annular air/liquid interface  348  at a radial location, both above and below the centrate centripetal pump, that is disposed radially inward of the centrate pump opening  330 . In exemplary arrangements the vanes further help to stabilize the air/liquid interface so that it maintains a coaxial circular configuration both above and below the centrate pump. Further in exemplary arrangements the radial position of the interface relative to the axis of rotation can be controlled as later discussed so that the centrate pump opening  330  is consistently maintained in the liquid centrate and is not exposed to air. 
     The upper concentrate chamber vanes  344  and the lower concentrate chamber vanes  340  work in a similar manner to the centrate chamber vanes. The concentrate chamber vanes maintain the circular air/liquid interface  350  in the concentrate pump chamber  332  at a radial distance that is inward of the substantially annular concentrate pump opening  346 . This configuration assures that the concentrate pump opening is consistently exposed to the concentrate and not to air. It should further be understood that although in the embodiment shown the centrate centripetal pump and the concentrate centripetal pump are of substantially the same size, and other arrangements the centripetal pumps may have different sizes. In such situations the radial distance from the axis of rotation that the centrate chamber vanes and the concentrate chamber vanes extend may be different. Also the radial position relative to the axis of rotation of the air/liquid interface in the centrate pump chamber and the concentrate pump chamber may be different. Numerous different vane configurations and arrangements may be utilized depending on the particular relationships between the components which make up the single use device and the particular material that is processed via the single use structure. 
       FIG. 30  shows an upper portion of a further alternative single use structure  352 . The single use structure  352  is similar to single use structure  304  except as otherwise discussed. Single use structure  352  includes an air tube  354  that extends in coaxial surrounding relation of the concentrate discharge tube  220 . The air tube  354  is in communication with openings  356  inside the single use structure. Openings  356  extend from the interior of the air tube to above the concentrate centripetal pump  216  in the concentrate pump chamber  332 . In this exemplary arrangement the seal  236  as schematically shown, operatively engages the air tube  354  to maintain the air tight engagement with the air tube as well as the concentrate discharge tube, centrate discharge tube and the feed tube. As can be appreciated the air tube may be utilized to selectively maintain the level of the air pressure in the air pocket within the single use structure. Such an arrangement may be utilized in connection with systems like those previously discussed or in other systems, in which an external supply of pressurized air is utilized to isolate the seal of the centrifuge structure from the material being processed and to maintain the air/liquid interface at a desirable location. Of course it should be understood that this structure is exemplary and other embodiments other approaches may be used. 
       FIG. 31  schematically shows a system  358  that may be used for continuously separating cell suspension into substantially cell free centrate and concentrate. System  358  is similar to system  170  previously discussed, except as otherwise mentioned herein. In the exemplary arrangement system  358  operates using a single use structure similar to single use structure  352 . The controller  274  of system  358  operates to control the position of the air/liquid interface within the single use structure to assure that the interface is maintained radially inward relative to the axis of rotation from each of the centrate pump opening and the concentrate pump opening. 
     In the exemplary arrangement a flow back pressure regulator  360  is in fluid connection with the centrate discharge line  262 . In the exemplary arrangement the flow back pressure regulator  360  is fluidly intermediate of the centrate discharge tube  212  and the centrate pump  266 . The exemplary system  358  includes a source of pressurized air schematically indicated  362 . The source of pressurized air  362  is connected to a pilot pressure control valve  364 . The control valve is in operative connection with the controller  274 . Signals from the controller  274  cause selectively variable pressure in a pilot line  366 . The pilot line  366  is in fluid connection with the back pressure regulator  360 . The pressure applied by the pilot pressure control valve  264  in the pilot line  366  is operative to control the centrate flow and consequently the centrate flow back pressure that is applied by the flow back pressure regulator  360 . 
     In the exemplary arrangement a pressure control valve  368  is in fluid communication with the source of pressurized air  362 . Control valve  368  is also in operative connection with the controller  274 . In this exemplary arrangement the control valve  368  is controlled to selectively apply precise pressure to the air tube  354  and the air pocket within the upper portion of the single use structure  352 . 
     In the exemplary arrangement the controller  274  operates in accordance with stored executable instructions to control the operation of the system  358  in a manner like that previously discussed in connection with system  170 . Further in the exemplary arrangement the controller  274  operates to control the pilot pressure valve  364  to vary the back pressure that is applied to the centrate discharge tube  212  by the back pressure regulator  360 . The controller  274  also operates to control valve  368 . The controller operates to maintain and selectively vary the pressure applied in the air pocket at the top of the interior of the single use structure. The controller operates in accordance with its programming to vary the back pressure of the centrate flow and/or the air pocket pressure to maintain the air/liquid interface of the air pocket at a radial distance from the axis of rotation that is inward from the centrate pump opening  330  and the concentrate pump opening  346 . This pressure variation in both the centrate flow back pressure and air pocket pressure, in combination with the action of the centrate chamber vanes and concentrate chamber vanes in the exemplary embodiment, maintain the stability and radially outward extent of the air/liquid interface so as to assure that introduction of air is minimized in the centrate and concentrate outputs from the single use structure. Further the ability to selectively vary the back pressure and flow of the centrate can impact the level of cells and corresponding detected optical density of the discharged concentrate. Thus the controller may operate in accordance with its programming to selectively vary both the concentrate flow rate, centrate back pressure and flow rate, internal air pocket pressure, the feed rate of cell suspension into the single use structure and perhaps other operating variables of the centrifugation process, to maintain the centrate and concentrate properties within the set limits and/or ranges stored in the at least one data store associated with the controller. Further the exemplary arrangement may enable separation of different types of materials and operations at different flow rates while maintaining reliable control of the separation process. Of course while it should be understood that the control of the position of the air/liquid interface is described in connection with features of system  170 , such control may also be utilized in systems of other types which include other or different types of processing elements. 
     Thus the new centrifuge system and method of the exemplary embodiments achieves at least some of the above stated objectives, eliminates difficulties encountered in the use of prior devices and systems, solves problems and attains the desirable results described herein. 
     In the foregoing description certain terms have been used for brevity, clarity and understanding, however, no unnecessary limitations are to be implied there from because such terms are for descriptive purposes and are intended to be broadly construed. Moreover, the descriptions and illustrations herein are by way of examples and the invention is not limited to the exact details shown and described. 
     In the following claims any feature described as a means for performing a function shall be construed as encompassing any means known to those skilled in the filed as capable of performing the recited function, and shall not be limited to the structures shown herein or mere equivalents thereof. 
     Having described the features, discoveries and principles of the new and useful features, the manner in which they are constructed, utilized and operated, and the advantages and useful results attained, the new and useful structures, devices, elements, arrangements, parts, combinations, systems, equipment, operations and relationships are set forth in the appended claims.