Abstract:
A fluid processing assembly can be easily inserted into and removed from a rotatable centrifuge channel. The processing assembly comprises a processing container and a carrier. The processing container has flexibility and, in use, occupies the channel to receive fluids for separation in the centrifugal field. The carrier retains the processing container outside the channel in a flexed condition conforming to the channel. The carrier resists deformation of the processing container during its insertion into or removal from the channel.

Description:
FIELD OF THE INVENTION 
     The invention relates to blood processing systems and apparatus. 
     BACKGROUND OF THE INVENTION 
     Today, people routinely separate whole blood by centrifugation into its various therapeutic components, such as red blood cells, platelets, and plasma. 
     Conventional blood processing methods use durable centrifuge equipment in association with single use, sterile processing systems, typically made of plastic. The operator loads the disposable systems upon the centrifuge before processing and removes them afterwards. 
     The centrifuge chamber of many conventional centrifuges takes the form of a relatively narrow arcuate slot or channel. Loading a flexible processing container inside the slot prior to use, and unloading the container from the slot after use, can often be time consuming and tedious. 
     SUMMARY OF THE INVENTION 
     The invention makes possible improved liquid processing systems that provide easy loading and unloading of disposable processing components. The invention achieves this objective without complicating or significantly increasing the cost of the disposable components. The invention allows relatively inexpensive and straightforward disposable components to be used. 
     The invention provides a processing assembly for insertion into and removal from a channel which, in use, is rotated to create a centrifugal field. The processing assembly comprises a generally flexible processing container and a carrier, to which the processing container is attached. The carrier shapes the processing container to generally match the configuration of the channel. The carrier limits deformation of the processing container during its insertion into and removal from the channel. Inside the channel, the processing container receives fluids, e.g., blood, for separation in the centrifugal field. 
     The features and advantages of the invention will become apparent from the following description, the drawings, and the claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a side view, partly in section, of a centrifuge having a channel into which a flexible processing container carried by a generally stiff carrier have been inserted for use, the centrifuge being shown in an operational condition; 
         FIG. 2  is a side view of the centrifuge shown in  FIG. 1 , also partly in section, having been rotated by about 90° to reveal other structural features not shown in  FIG. 1 ; 
         FIG. 3  is a side view, partly in section, of the centrifuge shown in  FIG. 1 , except that the channel has been swung upward to receive the flexible processing container and carrier as a unit; 
         FIG. 4  is a front plan view of the flexible processing container shown in  FIG. 1 ; 
         FIG. 5  is a schematic, perspective view of the interior of the processing container shown in  FIG. 4 , showing details of the separation of whole blood into red blood cells and platelet-rich plasma in the whole blood entry region of the container; 
         FIG. 6  is a top sectional view of the processing container shown in  FIG. 4 , showing various contours formed along the high-G and low-G sides of the separation zone to enhance centrifugal separation of blood; 
         FIGS. 7 and 8  are perspective views, taken along the low-G side of the channel, showing further details of one of the contours shown in  FIG. 6 , which comprises an inclined ramp used to help govern the collection of platelet-rich plasma from the container; 
         FIG. 9  is a schematic view of the separation of blood within the processing container shown in  FIG. 4 , showing the dynamic flow conditions which the various contours shown in  FIG. 6  develop. 
         FIG. 10  is a plan view of the processing container shown in  FIG. 4  with an integrally attached, multiple lumen umbilicus to conduct fluids to and from the container in a seal less system; 
         FIG. 11  is a section view of the umbilicus taken generally along line  11 — 11  in  FIG. 10 ; 
         FIG. 12A  is a perspective, exploded view of the processing container and a generally stiff carrier, which aids its insertion into and removal from the channel of the centrifuge shown in  FIG. 1 ; 
         FIG. 12B  is a perspective, assembled view of the processing container and carrier shown in  FIG. 12A ; 
         FIG. 13 and 14  are perspective views of a processing container shown in  FIG. 4  when carried by a generally stiff carrier, which can be placed in a generally lay-flat condition for storage ( FIG. 13 ) and rolled into a curved condition for insertion into the channel (FIG.  14 ); 
         FIG. 15  is a perspective view of a slotted carrier, which carries a processing container shown in  FIG. 4 , to aid in its insertion into and removal from the channel of the centrifuge shown in  FIG. 1 ; 
         FIG. 16  is a perspective view of a tool intended to be fitted over the top of a processing container, as shown in  FIG. 4 , to aid its insertion into and removal from the channel of the centrifuge shown in  FIG. 1 ; and 
         FIG. 17  is a perspective view of the tool shown in  FIG. 16 , when fitted to the processing chamber for use in inserting and removing the chamber into and from the channel of the centrifuge shown in FIG.  1 . 
       The invention may be embodied in several forms without departing from its spirit or essential characteristics. The scope of the invention is defined in the appended claims, rather than in the specific description preceding them. All embodiments that fall within the meaning and range of equivalency of the claims are therefore intended to be embraced by the claims. 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       FIGS. 1 and 2  show a centrifugal processing system  10  that embodies the features of the invention. The system  10  can be used for processing various fluids. The system  10  is particularly well suited for processing whole blood and other suspensions of biological cellular materials. Accordingly, the illustrated embodiment shows the system  10  used for this purpose. 
     The system  10  includes a centrifuge assembly  12  and a fluid processing assembly  14 , which is used in association with the centrifuge assembly  12 , as  FIGS. 1 and 2  show. The centrifuge assembly  12  is intended to be a durable equipment item capable of long term use. The fluid processing assembly  14  is intended to be a single use, disposable item, which is loaded into the centrifuge assembly  12  at time of use and unloaded and discarded after use. 
     A stationary platform  16  carries the rotating components of the centrifuge assembly  12 . The rotating components of the centrifuge assembly  12  include a yoke assembly  18  and a chamber assembly  20 . 
     The yoke assembly  18  includes a yoke base  22 , a pair of upstanding yoke arms  24  (best shown in FIG.  2 ), and a yoke bowl  26 . The yoke base  22  is attached to a first axle  28 , which spins on a bearing element  30  about the stationary platform  16 . An electric drive  32 , e.g., a permanent magnet, brushless DC motor, rotates the yoke assembly  18  on the first axle  28 . 
     The chamber assembly  20  is attached to a second axle  34 , which spins on a bearing element  36  within the yoke bowl  26 . The yoke bowl  26  is pivotally carried by pins  38  on the yoke arms  24 . The yoke bowl  26  and, with it, the chamber assembly  20  it carries, swing as a unit on the pins  38  between a downward facing position for operation (shown in  FIGS. 1 and 2 ) and an upward facing position for loading the fluid processing assembly  14  (shown in FIG.  3 ).  FIG. 3  shows the centrifuge assembly  12  before loading in the fluid processing assembly  14 , whereas  FIGS. 1 and 2  show the centrifuge assembly  12  after loading in the fluid processing assembly  14 . 
     A latch mechanism  40  releasably locks the yoke bowl  26  in the downward operating position. When the yoke bowl  26  is in the downward operating position, the axis of rotation  60  for the yoke assembly  18  (about axle  28 ) is generally aligned with the axis of rotation  62  of the chamber assembly  20  (about the axle  34 ). 
     The latch mechanism  40  can take various forms. In the illustrated embodiment (see FIG.  2 ), a pin  160  is carried by the yoke arm  24 . The pin  160  is spring-biased to normally project into a key way  162  in the yoke bowl  26  when the yoke bowl  26  is located in its downward operating position. The interference between the pin  160  and the key way  162  retains the yoke bowl  26  in the downward position. The pin  160  includes a handle end  164 , allowing the operator to manually pull the pin  160  outward, against its spring bias. This frees the pin  160  from the key way  162 . With the pin  160  withdrawn, the operator can pivot the yoke bowl  26  into its upward facing position. 
     The chamber assembly  20  includes an arcuate channel  42 , which is defined between an outer wall  44 , an inner wall  46 , and a bottom wall  48 . The channel  42  spins about the rotational axis  62 . During rotation, the outer wall  44  becomes a high-G wall and the inner wall  46  becomes a low-G wall. The high-G wall and low-G wall together define the high and low limits of the centrifugal field. 
     The fluid processing assembly  14  includes a disposable processing container  64 , which, in use, is carried within the channel  42  for common rotation, as  FIGS. 1 and 2  show. While rotating with the channel  42 , fluids introduced into the container  64  separate as a result of centrifugal forces. Once the separation procedure is completed, the processing chamber  64  is intended to be removed from the channel  42  and disposed of. 
     The construction of the processing container  64  can vary, according to the separation objectives. In the illustrated embodiment, the container  64  is used to separate packed red blood cells (PRBC) and platelet-rich plasma (PRP) from whole blood (WB) drawn from a donor. 
     With this separation objective in mind (see FIG.  4 ), the processing container  64  comprises two elongated sheets  66 A and  66 B of a flexible, biocompatible plastic material, such as plasticized medical grade polyvinyl chloride, heat sealed together about their periphery. The fluid processing assembly  14  includes three tubing branches  68 ,  70 , and  72  that communicate directly with the processing container  64 . In the illustrated embodiment, the tubing branches  68 ,  70 , and  72  are integrally connected to the processing container  64 , so that the processing assembly  14  can be manufactured as a sterile, closed system. 
     The first tubing branch  68  carries WB through an inlet port  74  into the container  64 . The container  64  includes interior seals  76  and  78 , which form a WB inlet passage  80  that leads into a WB entry region  82 . WB follows a circumferential flow path in the container  64 , as it spins inside the channel  42  about the rotational axis  62 . The side walls of the containers  64  expand within the confines of the channel  42  against the low-G wall  46  and high-G wall  44 . 
     As  FIG. 5  shows, WB separates in the centrifugal field within the container  64  into PRBC  84 , which move toward the high-G wall  44 , and PRP  86 , which are displaced by movement of the PRBC  84  toward the low-G wall  46 . An intermediate layer  88 , called the interface, forms between the PRBC  84  and PRP  86 . 
     The second tubing branch  70  carries separated PRP through a first outlet port  90  from the container  64 . The interior seal  78  also creates a PRP collection region  92  in the container  64 . The PRP collection region  92  is adjacent to the WB entry region  82 . The velocity at which the PRBC  84  settle toward the high-G wall  44  in response to centrifugal force is greatest in the WB entry region  82  than elsewhere in the container  64 . There is also relatively more plasma volume to displace toward the low-G wall  46  in the WB entry region  82 . As a result, relatively large radial plasma velocities toward the low-G wall  46  occur in the WB entry region  82 . These large radial velocities toward the low-G wall  46  elute large numbers of platelets from the PRBC  84  into the close-by PRP collection region  92 , for collection through the second tubing branch  70 . 
     The third tubing branch  72  carries separated PRBC  84  through a second outlet port  94  from the container  64 . The interior seal  76  also forms a dog-leg  96  that defines a PRBC collection passage  98 . A stepped-up barrier  100  (see  FIG. 6 ) extends into the PRBC mass along the low-G wall  46 , creating a restricted passage  102  between it and the facing high-G wall  44 . The restricted passage  102  allows PRBC present along the high-G wall  44  to move beyond the barrier  100  into the PRBC collection passage  98  to the PRBC port  94 . Simultaneously, the stepped-up barrier  100  blocks the passage of the PRP beyond it. 
     As  FIGS. 5 ,  7 , and  8  show, the high-G wall  44  also projects toward the low-G wall  46  to form a tapered ramp  104  in the PRP collection region  92 . The ramp  104  forms a constricted passage  106  along the low-G wall  46 , along which the PRP  86  extends. The ramp  104  keeps the interface  88  and PRBC  84  away from the PRP collection port  90 , while allowing PRP  86  to reach the PRP collection port  90 . 
     In the illustrated embodiment (see FIG.  7 ), the ramp  104  is oriented at a non-parallel angle α of less than 45° (and preferably about 30°) with respect to the axis of the PRP port  90 . The angle α mediates spill-over of the interface  88  and PRBC  84  through the constricted passage  106 . 
     As  FIGS. 7 and 8  show, the ramp  104  also displays the interface  88  for viewing through a side wall of the container  64  by an associated interface controller  108  (shown schematically in FIG.  5 ). The interface controller  108  controls the relative flow rates of WB, PRP, and PRBC through their respective ports  74 ,  90 , and  94 . In this way, the controller  108  maintains the interface  88  at a prescribed control location on ramp  104  close to the constricted passage  106  (as  FIG. 7  shows), and not spaced away from the constricted passage  106  (as  FIG. 8  shows). The controller  108  thereby controls the platelet content of the PRP collected through the port  90 . The concentration of platelets in the plasma increases with proximity to the interface  88 . By maintaining the interface  88  at a high position on the ramp  104  (as  FIG. 7  shows), the plasma conveyed by the port  90  is platelet-rich. 
     Further details of a preferred embodiment for the interface controller are described in U.S. Pat. No. 5,316,667, which is incorporated herein by reference. 
     As  FIG. 5 and 6  show, radially opposed surfaces in the container  64  form a flow-restricting region  114  along the high-G wall  44  of the WB entry region  82 . The region  114  restricts WB flow in the WB entry region  82  to a reduced passage, thereby causing more uniform perfusion of WB into the container  64  along the low-G wall  46 . The constricted region  114  also brings WB into the entry region  82  at approximately the preferred, controlled height of the interface  88  on the ramp  104 . 
     As  FIG. 6  shows, the low-G wall  46  tapers outward away from the axis of rotation  62  toward the high-G wall  44  in the direction of WB flow, while the facing high-G wall  44  retains a constant radius. The taper can be continuous (as  FIG. 6  shows) or can occur in step fashion. These contours along the high-G and low-G walls  44  and  46  produce a dynamic circumferential plasma flow condition generally transverse the centrifugal force field in the direction of the PRP collection region  92 . As depicted schematically in  FIG. 9 , the circumferential plasma flow condition in this direction (arrows  214 ) continuously drags the interface  88  back toward the PRP collection region  92 , where the higher radial plasma flow conditions already described exist to sweep even more platelets off the interface  88 . Simultaneously, the counterflow patterns (arrow  216 ) serve to circulate the other heavier components of the interface  88  (the lymphocytes, monocytes, and granulocytes) back into the PRBC mass, away from the PRP stream. 
     As  FIG. 10  best shows, the three tubing branches  68 ,  70 , and  72  are coupled to an umbilicus  116 . As  FIG. 11  shows, the umbilicus  116  includes a coextruded main body  118  containing three interior lumens  120 , which each communicates with one of the tubing branches  68 ,  70 , and  72 . The main body  118  is made, e.g., from HYTREL® 4056 Plastic Material (DuPont), which withstands high speed flexing. 
     As  FIG. 10  shows, an upper support block  122  and a lower support block  124  are secured, respectively, to opposite ends of the umbilicus body  118 . Each support block  122  and  124  is made, e.g., of a HYTREL® 8122 Plastic Material (DuPont), which are injection over-molded about the main umbilicus body  118 . The over-molded blocks  122  and  124  include formed lumens, which communicate with the three umbilicus lumens  120 . The three tubing branches  68 ,  70 , and  72  (made from polyvinyl chloride material) are solvent bonded to the upper block  122  in communication with the umbilicus lumens  120 . Additional tubing branches  126  (also made from polyvinyl chloride material) are solvent bonded to the lower block  124  in communication with the umbilicus lumens  120 . The additional tubing branches  126 , in use, are placed in operative association with conventional peristaltic pumps, sensors, and clamps (not shown). 
     As further shown in  FIG. 10 , each support block  122  and  124  preferably includes an integral, shaped molded flange  128 , to aid the installation of the umbilicus  116  on the centrifuge assembly  12 , as will be described later. Each support block  122  and  124  further includes a tapered sleeve  130 , which act as strain relief elements for the umbilicus  116  during use. 
     As  FIGS. 12A and 12B  show, in the illustrated and preferred embodiment, the flexible processing container  64  is attached to a carrier  132 . The carrier  132  possesses mechanical properties that limit deformation of the shape of the carrier  32  when subject to linear compression forces. The carrier  32  can be formed, e.g., from molded plastic, thermally formed material vacuum-formed plastic, cardboard, or paper. The processing container  64  is secured to the carrier  132 , e.g., by pinning, gluing, taping, or welding. 
     As  FIG. 12B  shows, the carrier  132  can be shaped to nest within the channel  64 . The carrier provides an added degree of stiffness during handling to aid in the insertion of the processing container  64  into the channel  42 , as well as the removal of the container  64  from the channel  42 , without undue bending or shape deformation. The carrier  132  can include a lubricious surface treatment, to further reduce interference and frictional forces during its insertion into and removal from the channel  42 . 
     As  FIGS. 12  A and  12  B show, the material of the carrier  132  can be pre-shaped in a normally rounded, three-dimensional geometry, which nests within the interior of the channel  42 . Alternatively (as  FIG. 13  shows), the carrier  132  can, if made from semi-rigid material, be maintained before use in a generally lay-flat conditioned. At the time of use (see FIG.  14 ), the carrier  132  is rolled end-to-end and secured, e.g., using end tabs  134  fitting into end slots  135 , to form the rounded, three-dimensional shape, which conveniently slides into the channel  42  in the manner shown in FIG.  12 B. The carrier  132  can include spaced side tabs  136  to aid in grasping, lifting, and lowering the carrier  132  with respect to the channel  42 . 
     As shown in FIGS.  12 A/B to  14 , the carrier  132  extends along only one side of the container  64 . Alternatively, as shown in  FIG. 15 , the carrier  132  can itself form a slotted structure, comprising a front wall  140  and a rear wall  142 , forming a slot  144  between them. In this arrangement, the container  64  is sandwiched in the slot  144  between the front and rear walls  140  and  142 . 
     As  FIG. 15  shows, the carrier walls  140  and  142  can include preformed contoured surfaces, for example, surfaces  146 ,  148 ,  150 , and  152 . When filled with blood and undergoing centrifugation, the sides of the container  64  press against the surfaces  146  to  152 . The contoured surfaces  146  to  152  of the carrier  132  define the high-G and low-G contours desired for the separation zone. 
     For example, a first contoured surface  146  projecting outward from the rear wall  142  can define the PRBC barrier  100 . A second contoured surface  148  projecting from the front wall  140  can define the tapered ramp  104 . Third and fourth contoured surfaces  150  and  152  projecting outward from the front and rear walls  140  and  142  can mutually press against and support the interior seal  78 , to protect the seal  78  against failure or leakage. The other contours shown in  FIG. 6 , and more, can likewise be formed using the carrier  132 . 
       FIGS. 16 and 17  show another alternative embodiment of a carrier  166  for the flexible processing container  64 . In this embodiment, the carrier  166  comprises a cap  168  having a top wall  170  and a depending side wall  172  shaped to nest within the channel  42 . The side wall  172  possesses mechanical properties that limit its deformation when subject to linear compression forces. Like the carrier  32 , the side wall  172  can be formed, e.g., from molded plastic, vacuum-formed plastic, cardboard, or paper. 
     The top wall  170  includes an interior groove  174 , which receives the top edge  176  of the container  64 . The groove  174  generally corresponds to the shape of the side wall  172 . Together, the groove  174  and the side wall  172  shape the container  64  into the desired normally rounded, three-dimensional geometry for placement into the interior of the channel  42  (as  FIG. 17  shows). A region  180  of the side wall  172  is cut away to accommodate passage of the tubes  68 ,  70 , and  72  coupled to container  64 . 
     The side wall  172  depends a distance from the top wall  170  sufficient to impart stiffness to the container  42  and thereby prevent buckling or undue bending or shape deformation of the container  42  when inserted into the channel  64 . The cap  168  is intended to be removed once the container  42  has nested in the channel  64 , and can thereafter be re-engaged when it is time to remove the container  42  from the channel  64 . In the illustrated embodiment, the top wall  170  includes an exterior grip  178  for the operator to grasp (see FIG.  17 ), to further facilitate insertion and removal of the container  64  into and from the channel  42 . The carrier  132  can include a lubricious surface treatment, to further reduce interference and frictional forces during its insertion into and removal from the channel  42 . 
     The centrifuge assembly  14  includes upper and lower mounts  156  and  158 . The mounts  156  and  158  receive the umbilicus support blocks  122  and  124 , previously described. The mounts  156  and  158  hold the umbilicus  116  (see  FIGS. 1 and 2 ) in a predetermined orientation during use, which resembles an inverted question mark. 
     As  FIG. 2  best shows, the upper umbilicus mount  156  is located at a non-rotating position above the chamber assembly  20 , aligned with the rotational axis  62  of the assembly  20  when in its downward facing position. The lower umbilicus mount  158  is carried on the top of the chamber assembly  20 , and is also aligned with the rotational axis  62 . The lower umbilicus mount  158  is presented to the operator when the chamber assembly  20  is swung into its upward facing orientation. Thus, with the chamber assembly  20  in its upward facing orientation (shown in FIG.  3 ), the carrier  132  (holding the container  64 ) can be conveniently loaded into the channel  42 . The umbilicus support block  122  can be loaded into the upper mount  156 , just as the umbilicus support block  124  can be loaded into the exposed lower mount  158 . The flanges  128  help orient the blocks  122  and  124  in their respective mounts  156  and  158 . 
     When swung back into the downward facing orientation (see FIG.  2 ), the lower mount  158  holds the lower portion of the umbilicus  116  in a position aligned with the aligned rotational axes  60  and  62  of the yoke assembly  18  and chamber assembly  20 . The mount  158  grips the lower umbilicus support  124  to rotate the chamber assembly  20  as the lower portion of the umbilicus  116  is rotated. 
     The upper mount  156  holds the upper portion of the umbilicus  116  in a non-rotating position above the yoke assembly  18 . Rotation of the yoke base  22  brings a yoke arm  24  into contact with the umbilicus  116 . This, in turn, imparts rotation to the umbilicus  116  about the rotational axis  60 . Constrained by the upper mount  156 , the umbilicus  116  also twists about its own axis  200  as it rotates. For every 180° of rotation of the first axle  28  about its axis  60  (thereby rotating the yoke assembly 180°), the umbilicus  116  will roll or twirl 180° about its axis  200 . This 180° rolling component, when added to the 180° rotating component, cause the chamber assembly  20  to rotate 360° about its axis. The relative rotation of the yoke assembly  18  at a one omega rotational speed and the chamber assembly  20  at a two omega rotational speed, keeps the umbilicus  116  untwisted, avoiding the need for rotating seals. The illustrated arrangement also allows a single drive element  32  to impart rotation, through the umbilicus  116 , to the mutually rotating centrifuge elements  18  and  20 . Further details of this arrangement are disclosed in Brown et al U.S. Pat. No. 4,120,449, which is incorporated herein by reference. 
     Various features of the invention are set forth in the following claims.