Abstract:
A novel centrifuge bowl for processing particles suspended in a fluid is disclosed. The centrifuge bowl includes an annular cavity concentrically located about the rotation axis for suitably separating particles of similar densities but of different diameters. The cavity is preferably configured to have an annular cross sectional area, which is parallel to the rotation axis, that increases from a centrifugal side of the cavity toward a centripetal side of the cavity. This configuration allows to generate an almost rigidly rotating field upon rotation of the centrifuge bowl, which field helps to uniformly disperse Coriolis force throughout the circumference of the cavity to avoid turbulent mixing of the particles. In an alternative embodiment, the cavity is surrounded by an outer cavity for separating particles according to density before processing them through the inner cavity. This construction is particularly suitable for processing whole blood to harvest platelet-rich-plasma with reduced level of white blood cell contamination.

Description:
TECHNICAL FIELD  
         [0001]    The present invention relates to the field of separating particles, in particular to a centrifuge bowl for separating particles of differing size and/or density suspended in a fluid. More specifically, when applied to the medical field, the present invention relates to an improved centrifuge bowl which enables to produce a blood product with a substantially lower level of contamination with white blood cells.  
         BACKGROUND ART  
         [0002]    In many fields of technology, it is desired to separate particles suspended in a fluid. For example, in the medical field, it is desired to fractionate whole human blood for transfusion purposes. Specifically, whole human blood includes blood cells such as red blood cells, white blood cells and platelets and these cells are suspended in plasma, an aqueous solution of proteins and other chemicals. Today, blood transfusions are widely given by transfusing only those blood components required by a particular patient instead of using a transfusion of whole blood. Transfusing only those blood components necessary saves the available supply of blood, and in many cases, is convenient for the patient.  
           [0003]    To this end, whole human blood is separated into its various blood components with a procedure called apheresis. According to a typical apheresis process, whole blood is separated into a higher density component such as red blood cells, at least one intermediate density component such as platelets and white blood cells, including lymphocytes and granulocytes, and a lower density component such as plasma, and a desired blood component or components are harvested. Among various blood component products or fractionates obtainable through apheresis, the demand for concentrated platelet products is rapidly growing. This is particularly because, with the improvement in cancer therapy, there is a need to administrate more and more platelets to patients whose hemopoietic function is often lowered after undergoing chemical or radiation therapy.  
           [0004]    As is well known, platelets have a short half-life of 4-6 days and the number of donors is usually limited. Therefore, in the production of concentrated platelet products, i.e., platelet-rich-plasma, it is important to harvest platelets from the whole blood supplied by a donor at a maximum yield. Further, it is known that contamination of concentrated platelet products with white blood cells can lead to serious medial complications, such as GVH reactions. Therefore, it is also very important to keep the level of contamination with white blood cells as low as possible, while maximizing platelet yields.  
           [0005]    Recent immunology studies have revealed that side effects of contaminant white blood cells can be substantially reduced, if not completely obviated, when the level of contamination is sufficiently low. For example, it has been reported that non-hemolytic febrile reaction (NHFR) rarely takes place if the number of white blood cells contained in a 200 ml transfusion bag, which may contain 2.0-3.0×10 −11  platelets, is 5.0×10 7  or less. Likewise, it has been recognized that complications such as CMV viral infection and alloimmunization rarely take place if the level of white blood cells in a bag is 1.0×10 7  and 1.0×10 6 , respectively, or lower (Kazuo Tsubaki,  Saishin Igaku  Vol. 48, No. 7, pp. 989-996 (1993)). In view of these, it is desired to consistently produce, through apheresis, concentrated platelet products having 1.0×10 6  or less white blood cells.  
           [0006]    Among several apheresis methods available, an intermittent flow method and a continuous flow method have been widely used. Further, centrifugation has been widely accepted as a technique for separating blood components according to density or specific gravity. A centrifuge bowl of the type disclosed in U.S. Pat. No. 4,300,717, herein referred to as “Latham” bowl, typifies a centrifuge bowl for use in the intermittent flow method. The bowl comprises a rotor portion in which blood components are separated and a stator portion having inlet and outlet ports, and these are combined by a rotary seal. The rotor portion comprises a generally frustoconical body and a similarly shaped core is coaxially disposed therein to form a fractionation chamber therebetween. In use, anticoagulated whole blood is introduced to the bowl through the inlet port. The rotor rotates at a fixed or variable speed and blood components are separated within the fractionation chamber by centrifugation in accordance with density. With blood continuously entering the bowl through the inlet port, the separated blood components are progressively displaced inwardly from the radially outward portion of the bowl and successively reach the outlet port. Blood components exiting through the outlet port are retained and stored, while components remaining in the bowl are usually returned to the patient or donor.  
           [0007]    To maximize the yield of platelets while decreasing white blood cell contaminants, various excellent techniques have been developed in connection with the Latham bowl. For example, in Schoendorfer et al. U.S. Pat. Nos. 4,416,654 and 4,416,654 assigned to the same assignee of the present application, a “surge” technique is disclosed. According to the surge technique, when whole blood is collected and separated within the fractionation chamber into a red blood cell layer, a buffy coat layer which is a mixture of platelets and white blood cells and a plasma layer, a low density fluid, preferably plasma, is pumped through the centrifuge at a relatively high flow rate. The platelets and white blood cells in the buffy coat layer, which are of similar densities but of different effective diameters, are centrifugally elutriated and the yield of platelets is improved thereby.  
           [0008]    Further, according to Latham et al. U.S. Pat. No. 5,607,579 also assigned to the assignee hereof, the separation between platelets and white blood cells is further improved by stopping withdrawal of whole blood and recirculating plasma through the centrifuge prior to the surge phase. This technique is called “dwell”, during which platelets and white blood cells are effectively separated and arranged in the order of size, before being displaced from the centrifuge using the surge technology. The &#39;579 patent also teaches to recirculate plasma while the withdrawal of whole blood so as to dilute the same and to promote separation among the blood components.  
           [0009]    In accordance with the dwell technology, the level of contamination with white blood cells is decreased to the order of 1.0×10 7  per transfusion bag containing platelets at the usually required dosage. To meet the demanding therapeutic needs of today, however, it is desirable to further decrease the level of contamination.  
           [0010]    In the field of continuous flow apheresis method, on the other hand, centrifugal elutriation has also been widely employed. For example, U.S. Pat. Nos. 4,268,393; 4,269,718; 4,350,283 and 4,798,579 describe a funnel-shaped or cone-shaped chamber rotatable with a centrifuge around a rotation axis for performing centrifugal elutriation. Generally, the chamber diverges from an inlet disposed at a centrifugal side toward an outlet disposed at a centripetal side. As a low density fluid, such as plasma, is pumped through the chamber, smaller cells having a slower sedimentation velocity are allowed to exit from the chamber through the outlet, while larger cells having a faster sedimentation velocity are retained within the chamber. By appropriately controlling the speed of rotation, cells having a desired diameter can be successively elutriated from the chamber.  
           [0011]    However, the centrifugal elutriation with this type of chamber suffers from a number of inherent disadvantages. Specifically, when cells enter the chamber rotating around the centrifuge axis and plasma is pumped through the chamber, Coriolis force which is known to give rise to a whirling flow is generated and the cells and the plasma turbulently flow along the chamber wall facing the direction of rotation of the centrifuge. This mixes the cells being separated within the chamber, and also directly routes the cells from the inlet to the outlet without passing through the region where the centrifugal elutriation theoretically should take place. This reduces the effectiveness of the centrifugal elutriation considerably. Another problem with the prior art centrifugal elutriation is cell mixing by density inversion. As the chamber is diverging from the inlet to the outlet, the velocity of the cells entering the chamber decreases as they move from the inlet to the outlet. This leads to a high concentration near the outlet and a low concentration near the inlet. This condition is unstable and may lead to turnover and turbulent mixing when the centrifugal force urges the cells in the high concentration region near the outlet toward the inlet region.  
           [0012]    Hlavinka et al. U.S. Pat. No. 5,674,173 describes a technique for mitigating the aforementioned problems while benefiting from centrifugal elutriation. According to the &#39;173 patent, a chamber having a kite-shaped axial cross section is mounted on a centrifuge for rotation therewith. The interior of the chamber converges from a maximum cross-sectional area near an outlet toward an inlet. The interior includes one or more grooves surrounding the longitudinal axis of the chamber for dispersing Coriolis force in a circumferential direction around the longitudinal axis. However, the shape of the chamber of the &#39;173 patent is still generally conical and Coriolis force may not be sufficiently dispersed through the grooves and may still cause turbulent mixing of the separated cells along the chamber wall facing rotation. Further, while the &#39;173 patent describes that a saturated bed of platelets is established at the maximum cross-sectional area and this bed rejects white blood cells, circular current could be formed between the platelet bed and upstream plasma and this may also cause whirl mixing of the cells.  
         OBJECTS OF THE INVENTION  
         [0013]    Accordingly, an object of the present invention is to provide an improved centrifuge bowl for separating particles suspended in a fluid, in particular blood components or cells of whole blood.  
           [0014]    Another object of the present invention is to provide a centrifuge bowl for separating or harvesting platelets at a high yield, with a sufficiently low level of contamination with white blood cells.  
           [0015]    A further object of the present invention is to provide a centrifuge bowl which can be mounted to a conventional apheresis machine and can be operated in accordance with conventional protocols, while providing the aforementioned advantages.  
           [0016]    A further object of the present invention is to provide a centrifuge bowl which is simple in structure and less costly in manufacture.  
         SUMMARY OF THE INVENTION  
         [0017]    According to one aspect of the present invention, a centrifuge bowl comprises an inlet port, an outlet port and at least one annular cavity concentrically located about the rotation axis of the centrifuge bowl. The annular cavity communicates with the inlet and outlet ports at its centripetal and centrifugal peripheries, respectively, so that fluid entering the inlet port flows through the cavity toward the rotation axis before exiting the outlet port.  
           [0018]    Preferably, the bowl comprises a hollow bowl body having an aperture at one axial end and the inlet and outlet ports fluidly communicate with the interior of the bowl body through the aperture, for example by way of tubing. A rotary seal is disposed to cover the aperture if needed. A core may be disposed within the hollow interior of the bowl body for rotation therewith, and the annular cavity is defined between the bowl body and the core. The bowl body and the core may also form an axial gap therebetween to define a passageway for directing fluid from the inlet port radially outwardly to the centrifugal periphery of the cavity.  
           [0019]    This type of centrifuge bowl is suitable for processing a fluid containing first particles and second particles, which are of similar densities but of different diameters. A fractionated whole blood containing platelets and white blood cells suspended in plasma is a good example of such fluid. The bowl may be employed, for example, as a secondary centrifuge in an apheresis machine and operable for receiving from a primary centrifuge platelet-rich-plasma and purifying the same by decreasing the level of contamination with white blood cells. However, other uses may be readily apparent to those skilled in the art and they are within the scope of the present invention. For example, other blood fractions may be suitably processed through the bowl. Also, the bowl may be appropriately scaled and configured to process whole blood rather than blood fractions. Further, it is also within the skill of an artisan to provide, where necessary, two or more such annular cavities in succession.  
           [0020]    Principally, it is believed that particles suspended in a fluid are separated by centrifugal elutriation as the fluid flows through the annular cavity while the centrifuge bowl is rotating. Specifically, in the case of plasma containing platelets and white blood cells, the particles are of similar densities. As the white blood cells have a greater diameter, however, they have a faster sedimentation velocity than the platelets, according to Stoke&#39;s law. Therefore, by pumping such plasma suspension from the inlet port to the outlet port through the cavity, the platelets are collected at a high yield while the white blood cells remain within the cavity. From this point of view, the present invention may have something in common with the prior art centrifugal elutriators discussed above.  
           [0021]    However, the cavity in accordance with the present invention is annular in shape, while the chambers of the prior art centrifugal elutriators are not. As mentioned previously, the prior art centrifugal elutriators suffer from adversarial effects of Coriolis force which causes turbulent mixing of separated particles along the chamber wall facing rotation. In accordance with the present invention, it is believed that Coriolis force is not localized and uniformly dispersed around the cavity because of the annular configuration of the cavity. Therefore, the prior art problems associated with localization of Coriolis force can be obviated by the present invention.  
           [0022]    Further, while the inventors do not wish to be bound by a particular theory or function, it is also believed that a phenomenon known as almost rigidly rotating flow is created within the annular cavity. Specifically, when a fluid containing suspended particles is introduced into and fills the cavity while the centrifuge bowl is rotating, flow of the fluid mostly takes place through thin layers known as Stewartson and Ekman layers formed along cavity walls. These layers are considered to be established rapidly when the centrifuge bowl is accelerated sufficiently, and disperse the angular momentum of the system throughout the cavity. Because of this, a turbulent flow is not generated within the cavity. The particles are separated by centrifugal elutriation as they move through the Stewartson and Ekman layers, and particles having a faster sedimentation velocity are either prevented from exiting the cavity or deviated out of these layers and taken into an interior flow region formed between the layers. It is also speculated that a portion of the particles somehow circulate with fluid within the cavity and this promotes separation between the particles.  
           [0023]    The annular cavity may assume various different configurations within the frame of the present invention. One suitable configuration of the annular cavity is such that its annular cross sectional area, which is taken along an imaginary cylinder extending in a direction parallel to the rotation axis, increases as the diameter of the imaginary cylinder decreases. This means that the value described as 2πrh, wherein r is a radial distance from the rotation axis and h is the height of the cavity parallel to the rotation axis at that radial distance, increases as the value of r decreases. If the annular cavity suffices this condition, the flow velocity through the cavity decreases as the fluid entering the cavity at the centrifugal periphery thereof, i.e., radially outer side of the annular cavity, flows toward the centripetal periphery, i.e., radially inner side of the annular cavity. This is usually preferable for separating particles suspended in a fluid by centrifugal elutriation. As an example, the annular cavity may have a triangular or quadrangular shape in axial cross section, but it should be understood that other geometrical shapes are also possible. Preferably, the maximum annular cross sectional area is located near the cavity outlet, but this does not preclude to provide an annular transition area, in which the annular cross sectional area decreases from the maximum annular cross sectional area toward the cavity outlet.  
           [0024]    Further, it may be preferable if the centrifugal periphery of the annular cavity, which is in fluid communication with the inlet port of the centrifuge bowl and defining a peripheral slot for fluid entry into the cavity, is vertically offset along the rotation axis from the centripetal periphery of the annular cavity, which is in fluid communication with the outlet port of the centrifuge bowl and defining a peripheral slot for fluid exit from the cavity. This configuration may prevent fluid flow from radially directly routed from the centrifugal periphery to the centripetal periphery before the particles are sufficiently separated through the cavity. More preferably, the axial cross section of the cavity is asymmetric with respect to a line drawn to pass through the cavity inlet and outlet. It is also preferable that the cavity terminates at its centripetal side with a cylindrical wall extending along the rotation axis and the peripheral cavity outlet is formed intermediate between the upper and lower peripheral edges of the cylindrical wall.  
           [0025]    In accordance with another aspect of the present invention, a centrifuge bowl having a radially outer cavity and a radially inner cavity is provided. This is particularly suitable for processing a liquid including particles of different densities, as well as particles of similar densities but of different diameters. Whole blood is a typical example that is amenable to processing with this bowl. With this type of centrifuge bowl, it is possible to advantageously replace a conventional centrifuge bowl, such as the Latham bowl, and an improved separation can thereby be achieved without necessitating substantial modification to the existing apheresis machines that utilize the Latham bowl.  
           [0026]    Preferably, the centrifuge bowl in accordance with this aspect comprises a bowl body concentrically located about the rotation axis and a core disposed within the bowl body for rotation therewith, and the outer and inner annular cavities are defined therebetween. The outer cavity includes a centrifugal peripheral slot which is in fluid communication with an inlet port and the inner cavity includes a centripetal peripheral slot which is in fluid communication with an outlet port. The inner and outer annular cavities fluidly communicate with each other through an annular restriction channel formed between the cavities. Preferably, the annular restriction channel communicates the cavities solely in the radial direction so that the overall height of the centrifuge bowl can be decreased. The annular channel has a short axial height and flow from the outer cavity is throttled through the annular channel. Generally, the inner cavity is constructed to perform the same function as the annular cavity previously discussed, and thus the description regarding the annular cavity set forth above may equally be applied to the inner cavity. The outer cavity usually serves to separate particles according to density, and its configuration may be limited only from this point of view. To enable easy manufacture, the outer cavity is preferably formed to have a simple shape, for example a rectangular shape in axial cross section.  
           [0027]    The bowl body may include an aperture at one axial end thereof and a rotary seal assembly which includes the inlet and outlet ports may be affixed to the bowl body to cover the aperture. The bowl body may have a two-part construction including a disc-like bottom wall and a shaped upper part which may be formed by injection molding. To assemble a bowl, the core is positioned on the bottom wall so as to define a radial gap or passageway between a lower surface of the core and an upper surface of the bottom wall, and the upper part is then placed over the core. The upper part is then integrated with the bottom wall by hermetically sealing them together at the periphery, and a rotary seal assembly is inserted through the axial aperture of the bowl body to cover the same. This type of centrifuge bowl is simple in structure and can be inexpensively manufactured.  
           [0028]    The inlet port fluidly communicates with the radial passageway formed along the bottom wall of the bowl body, and a fluid pumped into the inlet port is directed radially outwardly through the passageway to enter the outer annular cavity at the centrifugal periphery thereof. The fluid then enters the annular inner cavity through the annular channel and exits from the outlet port which is in fluid communication with the annular inner cavity.  
           [0029]    When whole blood is pumped through the inlet port and guided into the centrifuge bowl, it is led through the radial passageway and enter the outer annular cavity from the centrifugal peripheral slot. Within the outer annular cavity, the whole blood is separated by a centrifugal force and stratified in accordance with density. At this point, a layer of red blood cells, a buffy coat layer and a plasma layer are formed. With continued withdrawal of whole blood, the separated blood components enter, with the plasma layer first, into the inner cavity via the restricting annular channel. In the inner cavity, the components of the buffy coat layer are separated by centrifugal elutriation, and perhaps under the influence of an almost rigidly rotating flow, as described above.  
           [0030]    Preferably, the centrifuge bowl in accordance with this aspect of the present invention is dimensioned to have the same diametrical size as the conventional Latham bowl, so that it can be mounted to a conventional apheresis machine such as MCS, Multi or CCS manufactured by Haemonetics Corporation of 400 Wood Road, Braintree, Mass. 02184, U.S.A., the assignee hereof. Further, the radial position of the cavities and annular channel is adjusted so that the bowl would be compatible with the existing optics and/or electronics of the conventional apheresis machines.  
           [0031]    In accordance with a typical protocol for harvesting platelet-rich-plasma, anti-coagulated whole blood is drawn into the bowl at a speed of 20 to 200 ml/min, preferably 50 to 150 ml/min. When the whole blood is separated within the outer cavity and the front end of the buffy coat layer has approached or entered the annular channel, blood drawing is stopped and plasma is recirculated at a surge flow rate, e.g., at a speed in the range of 120 to 240 ml/min for effectively separating platelets and white blood cells. By this process, platelets are selectively pumped out of the inner cavity through the outlet, while white blood cells are retained in the inner cavity. The remaining blood fraction in the centrifuge bowl is then returned to the patient or donor. Prior to the surge step, a dwell step may be performed, in which plasma is recirculated at a constant or gradually increasing speed within a range of 60 to 160 ml/min without causing platelets to egress from the outlet port. Further, during the drawing of whole blood into the bowl, it is possible to dilute or compensate for the flow by circulating plasma. This is known as the critical flow technology.  
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0032]    The foregoing and other objects, features and advantages of the present invention will be apparent from the following detailed description of preferred embodiments shown in the drawings. The drawings are not necessarily to scale, and emphasis might have been placed to illustrate the principles of the present invention.  
         [0033]    [0033]FIG. 1 is an axial sectional view of one embodiment of the centrifuge bowl comprising a single annular cavity in accordance with the present invention;  
         [0034]    [0034]FIG. 2 is an axial sectional view explaining the expected function of the annular cavity of FIG. 1;  
         [0035]    [0035]FIG. 3 is a partial cutaway elevational view illustrating the rotary seal assembly used for the centrifuge bowl of FIG. 1;  
         [0036]    [0036]FIG. 4 is an axial sectional view of another embodiment of the centrifuge bowl comprising inner and outer annular cavities in accordance with the present invention; and  
         [0037]    [0037]FIG. 5 is an explanatory view showing a dimensional relationship of the centrifuge bowl of FIG. 4 with the conventional Latham bowl. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0038]    Referring now to FIG. 1, an embodiment of a centrifuge bowl  10  having a single annular cavity  20  is shown. In the following, the bowl will be described as a disposable centrifuge bowl adapted for the processing of a fractionated whole blood, e.g., platelets and white blood cells suspended in plasma (hereinafter “platelet-rich-plasma fraction”, or “PRP fraction”), but it should be understood that the invention will not be limited thereto in any way. For example, the bowl of FIG. 1 may be employed, with or without modification, for processing other whole blood fractions or whole blood per se.  
         [0039]    As shown in FIG. 1, the bowl comprises a rotary seal assembly, or seal and header assembly, shown generally at  30 , a bowl body shown generally at  12  and a core  14 . The seal and header assembly  30  is shown in more detail in FIG. 3. It provides a rotary seal and a fluid communication pathway between the interior of the rotatable bowl body  12  and stationary conduits  41  and  42  connected respectively to an inlet port  31  and an outlet port  32 . The assembly  30  is comprised of a stationary header, shown generally at  33 , a feed tube assembly, shown generally at  34 , an effluent tube  35 , and a rotary seal, shown generally at  36 . The rotary seal  36  comprises a fixed seal ring  37 , a diaphragm member  38  and a rotatable seal ring  39  which is disposed on an outside seal member, or crown  16 . The diaphragm member  38  is affixed about its outer periphery to the periphery of the seal ring  37 . The seal ring  37  includes an annular lip which slidably contacts against an opposing surface of the seal ring  39 . The crown  16  may include an axially open groove on its periphery or may otherwise be appropriately configured to establish a fluid-tight coupling with the bowl body  12 . The crown  16  is provided with a central opening, through which the effluent tube  35  extends. The inner periphery of the diaphragm member  38  is joined to the effluent tube  35 .  
         [0040]    The header  33  is comprised of an integrally formed member having the inlet port  31 , extending radially into an axial passageway  43 . The passageway  43  is coupled to the inner, stationary conduit  41  formed by an axially extending bore of the feed tube assembly  34  and, in turn, to a feed tube stem  18 , thereby forming a non-rotating inlet path for a PRP fraction to enter the interior of the bowl body  12 . The header  33  also includes the outlet port  32 , which extends radially into a channel  44  extending about the feed tube assembly  34  in coaxial relationship. The channel  44  then couples to the stationary conduit  42  to form an outlet passageway. An outer shield member  40  is formed on the header  33  and extends over the rotary seal  36 .  
         [0041]    The feed tube assembly  34  is formed with a radial flange  34  A integral therewith and a radial flange  35 A is also integrally formed on the effluent tube  35 , thereby forming a radially outwardly opening collection port  45  fluidly communicating with the outlet port  32 . The header and seal assembly  30 , as thus described, is formed and assembled as an individual unit and, after the core  14  has been disposed within the bowl body  12  as shown in FIG. 1, inserted through the opening  12 A of bowl body  12  and fixed thereto by appropriate means such as welding or threading.  
         [0042]    The bowl body  12  is of a two-part construction, comprising a molded upper part  11  having axial openings and a molded lower part or bottom disc  13 . Theses parts are made of any suitable plastic materials such as acrylics or styrene, which are compatible with physiological fluid. After the core  14  has been positioned on the bottom disc  13 , the upper mold part  11  and the disc  13  are assembled and hermetically sealed together, for example by ultrasonic welding. The disc  13  or the core  14  includes spacers  15  which are circumferentially disposed at predetermined intervals, say at every 60°, so that the disc  13  and the core  14  are separated by an axial gap G which serves as a radial passageway  17  for guiding the PRP fraction introduced from the feed tube stem  18  to the cavity  20 .  
         [0043]    The annular cavity  20  is formed between and bounded by the lower surface of the upper bowl part  11  and the upper surface of the core  14 . The cavity  20  includes a cavity inlet  21 , which is a peripheral slot formed at the centrifugal side thereof, and a cavity outlet  23 , which is a peripheral slot formed at the centripetal side thereof. The inlet slot  21  communicates with the radial passageway  17  through an axially extending, circumferentially continuous slit  19  and the outlet slot  22  communicates with the collection port  45  through a radially extending passageway  23  formed between the upper bowl part  11  and the core  14 .  
         [0044]    The annular cavity  20  has a generally triangular shape in axial cross section. The height of the cavity  20  increases from the inlet slot  21  toward the outlet slot  22  so that the annular cross sectional area given by 2πrh, wherein r is a radial distance from the rotation axis and h is the height of the cavity  20  parallel to the rotation axis at that radial distance, increases as the value of r decreases. The cavity  20  has an upper annular wall  24  which horizontally extends radially inwardly from the inlet slot  21  toward the rotation axis of the centrifuge  10  and terminates at an upper peripheral wall  25  which extends downwardly therefrom to the upper peripheral edge of the outlet slot  22 . From the lower peripheral edge of the outlet slot  22 , a lower peripheral wall  26  begins and extends generally in parallel to the rotation axis until it meets an inclined wall  27  extending from the inlet slot  21  radially inwardly and axially downwardly. The inclined wall  27  contains an acute angle with the rotation axis. This angle may range from 20 to 60 degrees, preferably is in a range of 30 to 50 degrees. The annular wall  24  may be modified to contain an obtuse angle with the rotation axis. Further, while the inclined wall  27  and the annular wall  24  are illustrated as a radially extending planar surface, they can alternatively be formed as a convexly or concavely curved surface insofar as smooth transitions of fluid and/or particles along the wall surfaces are maintained.  
         [0045]    In this configuration, the inlet slot  21  and the outlet slot  22  are axially offset from each other by a distance approximately equal to the axial length of the upper peripheral wall  25 . The amount of this offset may arbitrary be determined and there may be cases where the offset becomes zero. Generally, however, it is preferred not to dispose the inlet and outlet slots  21  and  22  in a coplanar relationship so that a direct radial pathway between these slots will not be formed, as previously mentioned. It may be more preferable to shape the cavity  20  and arrange the inlet and outlet slots  21  and  22  in such a manner that, when viewed in axial cross section, the cavity is not symmetrical with respect to a line drawn through the slots  21  and  22 .  
         [0046]    Referring now to FIG. 2, the expected function of the annular cavity  20  is described. When platelet-rich-plasma, or a PRP fraction is pumped into the bowl  10  through the inlet port  31 , it flows through the conduit  41  and the stem  18  to the bottom portion of the bowl. The PRP fraction is led through the radial passageway  17  and circumferential slit  19  to enter the radial cavity  20  through the inlet slot  21 .  
         [0047]    With continued pumping of the PRP fraction into the bowl  10 , the cavity  20  is filled therewith. Because the bowl  10  is rotated at a sufficient speed, for example at a speed of 2,000 to 7,000 rpm, preferably 3,000 to 5,000 rpm, a field of flow called an almost rigidly rotating flow is created within the annular cavity  20 . The PRP fraction may be pumped into the bowl  10  at a flow rate of 20 to 200 ml/min, preferably 50 to 150 ml/min. The flow rate may substantially be constant over time. Alternatively, it may be increased over time or a combination of constant and increasing flow rates may be used.  
         [0048]    Under the almost rigidly rotating flow field, Stewartson layers S 1 , S 2  are created along the walls  25  and  26  and Ekman layers E 1 , E 2  are created along the walls  24  and  27 . Flow of the PRP fraction mostly takes place through these layers, and flow rarely takes place through an internal region indicated at I. It may be preferable that the outlet slot  22  opens at a position vertically intermediate the inner edges of the upper and lower annular walls  25  and  26  so that any particles moved along the Ekman layers E 1 , E 2  will not directly travel into the outlet slot  22 .  
         [0049]    When platelets and white blood cells contained in the PRP fraction enter the cavity  20 , they first move along the Ekman layers E 1 , E 2  and then the Stewartson layers S 1 , S 2 , and are separated by centrifugal elutriation. In particular, when the PRP fraction flows through the Ekman layers E 1  and E 2 , because platelets have a slower sedimentation velocity than white blood cells, the platelets are dragged by fluid flow more rapidly than the white blood cells toward the outlet slot  22 . Part of the white blood cells, if not most, are retained in the Ekman layers because of their faster sedimentation velocity. In the Stewartson layers S 1  and S 2 , while platelets (represented by “x”) are subjected to an axial dragging force D created by the flow of viscous plasma and allowed to proceed to the outlet slot  22 , larger white blood cells (represented by “o”) are subjected to a centrifugal force C created by the rotation of the centrifuge  10  and taken into the internal region I. The inwardly diverging contour of the cavity  20  decreases the flow velocity of the PRP fraction as it moves inwardly toward the axial walls  25 ,  26 . Because the cells in the PRP fraction are thus centrifugally elutriated through the Ekman and Stewartson layers, and perhaps because of the fact that turbulent flows due to Coriolis force are suppressed or not generated under the almost rigidly rotating flow field, good separation between platelets and white blood cells is considered to be achieved.  
         [0050]    Platelets and plasma exits from the outlet slot  22  and guided through the radial passageway  23  and enter a collection chamber  46 , in which the collection port  45  opens radially outwardly. It should be noted that, when the front end of the plasma displaced from the chamber  20  and the passageway  23  moves radially inwardly and reaches the collection port  45 , air cannot escape from within the bowl and thus the collection chamber will not be overfilled with the plasma.  
         [0051]    Typically, the diameter of the bowl  10  is 10-30 cm, depending upon the required processing volume. Preferably, it is within the range of 15-20 cm so that it can be mounted to a conventional apheresis machine without a substantial modification.  
         [0052]    Turning now to FIG. 4, an embodiment of a centrifuge bowl  110  having an inner annular cavity  120  and an outer annular cavity  150  is shown. The centrifuge bowl  110  comprises a disposable centrifuge rotor, or bowl  112  which has an aperture  1   12  A at one end, a rotary seal assembly  130  and a core  160 . The rotary seal assembly  130  is substantially of the same construction as the rotary seal assembly  30  described above with reference to FIG. 3, and thus is not detailed herein.  
         [0053]    As with the case of the bowl  10 , the bowl body  112  may be formed of any suitable plastic material such as transparent styrene resin or the like and comprises an upper molded part  111  and a lower molded part or bottom disc  113 . The crown  116  of the rotary seal assembly  130  is affixed to the aperture  112 A by threading, welding or the like.  
         [0054]    The core  160  disposed within the bowl body  112  has a stepped profile and comprises a hub  161  including a tapered bore  162 , a radial disc  163  extending radially outwardly from one end of the hub  161 , and an annular shoulder  164  contained between the hub  161  and the disc  163 . Such a core can be easily manufactured by injection molding. Angularly separated spacers  115  are disposed between the bottom disc  113  of the bowl and the core  160  at, for example, intervals of 60°, thereby defining an axial gap G which serves as a radial passageway  117  for guiding fluid pumped into the bowl through the feed tube stem  118 .  
         [0055]    The upper molded part  111  is of a shape such that it cooperates with the stepped profile of the core  160  to define the inner and outer annular cavities  120 ,  150 . Specifically, in the illustrated example, the upper molded part  111  comprises an outer cylindrical portion  151  having inner and outer walls  152 ,  153 , a conical slope portion  154  and a neck portion  155  bridging between the inner wall  152  and the slope portion  154 . With the radial disc  163  of the core  160 , the outer cylindrical portion  151  defines the outer cavity  150  which is generally of an annular shape having a rectangular cross section. The outer cavity  150  communicates at its lower centrifugal periphery with the radial passageway  117 . The neck and slope portions  155 ,  154  cooperate with the shoulder  164  of the core  160  and define the inner annular cavity  120 . The outer and inner cavities  150 ,  130  communicate with each other through an annular channel  121  located between the uprising portion of the shoulder  164  and the neck portion  155 .  
         [0056]    As shown in FIG. 4, the inner cavity  120  is axially bounded between an upper annular wall  124 , which is defined by the slope portion  154  extending radially inwardly and axially upwardly from the upper edge of the annular channel or inlet slot  121 , and a lower annular wall  127  defined by the upper surface of the shoulder  164  which extends radially inwardly and axially upwardly from the lower edge of the annular channel  121 . The upper wall  124  contains an acute angle with the rotation axis and the lower wall  127  contains an obtuse angle with the rotation axis. The upper annular wall  124  is therefore steeper than the lower annular wall  127  and thus the axial height of the inner cavity  120  increases as the distance from the rotation axis decreases. Preferably, the decrement of the radial distance is smaller than the increment of the axial height, Δr&lt;Δh, so that the annular cross sectional area of the annular cavity  120  given by 2πrh increases as the value of r decreases. The upper and lower annular walls  124 ,  127  may be formed to have a curved profile, as in the case of the annular wall  24  and the inclined wall  27  described above in connection with FIG. 1.  
         [0057]    The cavity  120  terminates at its radial inner end with upper and lower peripheral walls  125  and  126 , between which a peripheral outlet slot  122  is defined. In this configuration, the inlet slot  121  and the outlet slot  122  are axially offset as in the embodiment of FIG. 1, but their relative axial positions are reversed.  
         [0058]    The upper peripheral wall  125  is defined by an outer wall  157  of an inner cylindrical portion  156  and the lower peripheral wall  126  is defmed by an outer peripheral wall of the hub  161 . The inner cylindrical portion  156  is spaced from the upper surface of the hub  161  by a radial passageway  123  which communicates the inner cavity  120  with a collection chamber  146  defined between the inner wall  158  of the cylindrical portion  156  and the collection port  145 .  
         [0059]    It is now in order to describe the operation of the centrifuge bowl of FIG. 4. The bowl  110  is particularly suitable for fractionating whole blood and harvesting platelets at a high yield. As shown in FIG. 5, the bowl of FIG. 4 may preferably be comparable with the conventional Latham bowl in diametrical size but has a reduced axial height. Therefore, by attaching an appropriately formed adapter or the like to compensate for the height, the bowl  110  can be mounted to a conventional apheresis machine such as MCS, Multi or CCS mentioned earlier, and operated with existing protocols using the existing optics and/or electronics. Of course, however, this does not exclude other bowl configurations. Broadly, the bowl  110  may have a diameter of 10-30 cm, preferably 15-20 cm.  
         [0060]    First, with the use of a peristaltic pump (not shown), anticoagulated whole blood is drawn from a patient or donor and guided into the bowl  110  via the inlet port  131 , and the bowl is started to rotate. The drawing of blood is usually made at a flow rate of 20 to 150 ml/min, preferably 50 to 100 ml/min, and the bowl may be rotated at a speed of 2,000 to 7,000 rpm, preferably 3,000 to 5,000 rpm. During the drawing of blood, the flow rate may substantially be constant over time. Alternatively, it may be continuously or stepwisely increased over time or a combination of constant and increasing flow rates may be used.  
         [0061]    The whole blood is led from the inlet port  131  to the radial passageway  117  through the feed tube stem  118 , and enter the outer annular cavity  150  at its lower peripheral edge. The whole blood is centrifugally separated and stratified into a layer of red blood cells, which is radially outermost within the outer cavity  150 , and the inner, buffy coat and plasma layers. With continued withdrawal of whole blood, the separated blood components enter, with the plasma layer first, into the inner cavity  120 . The fractionated blood components are then displaced from the inner cavity  120  through the radial passageway  123  and collected by the collection port  145 . As in the case of the bowl of FIG. 1, when the front end of the displaced components reaches the collection port  145 , air is trapped centrally of the bowl and thus the collection chamber  146  will not be overfilled with blood components. The fractionated plasma flows out from the outlet port  132  and collected in a storage bag (not shown).  
         [0062]    When the front end of the buffy coat layer has approached the annular channel or inlet slot  121 , a surge step may be started for separating platelets and white blood cells resident in the buffy coat layer. The surge can be started earlier or later, for example when the front end of the buffy coat layer has entered the inlet slot  121  or the inner cavity  120 . The front end of the buffy coat, as well as other boundaries among the separated blood components can be detected, for example, with an optical sensor which monitors the radius of the region occupied by the separated blood component in the centrifuge and signals when the radius has reached a particular value.  
         [0063]    To perform the surge, withdrawal of whole blood is stopped and part of the collected plasma is recirculated from the storage bag into the bowl  110  at an increased flow rate, for example a flow rate selected within a range of 120 to 240 ml/min, preferably 160 to 220 ml/min. The components in the buffy coat enter the inner cavity  120  and separated by centrifugal elutriation as they migrate through Ekman and Stewartson layers, as in the case of the cavity  20  shown and described in connection with FIG. 2. After most of the platelets have been collected in a storage bag, the plasma introduction is stopped. As can be recognized by those skilled in the art, a dwell step may be performed prior to the surge step, if necessary. The process may be automatically repeated as desired until a sufficient quantity of platelets has been collected. The resultant product contains a high yield of platelets with reduced white blood cell contaminants.  
       EXAMPLES  
     Example 1  
       [0064]    A single cavity centrifuge bowl having the construction shown in FIG. 1 was prepared. The outer diameter of the inner cavity  20  was about 50 mm and the inner diameter was about 33 mm. The maximum height of the cavity  20  was about 20 mm and the axial offset between the inlet and outlet peripheral slots  21  and  22  was about 10 mm. The volume of the cavity  20  was approximately 35 ml. The upper annular wall  24  was generally horizontal but the inclined wall  27  contained about 37 degrees with the axis of rotation.  
         [0065]    The centrifuge bowl was mounted on a centrifuge machine for rotation, with the rotary seal assembly  30  fixedly supported. The bowl was initially filled with saline solution pumped at a predetermined flow rate and the bowl was started to rotate at a predetermined speed. After two minutes of feeding the saline, valves were operated to change the flow from saline to a fractionated whole blood containing platelets and white blood cells suspended in plasma. After switching the flow from saline to plasma, samples of eluted fluid were collected from the outlet port  32  at different points in time, and the collected samples were analyzed. The results are shown in Table 1. The number of platelets and white blood cells shown in Table 1 have been normalized to the volume of a standard platelet transfusion bag.  
                                                             TABLE 1                       Flow           Platelets       WBCs       Rate   Rotation       Number   Yield   Number       (ml/min)   (rpm)   Sample   (/200 ml)   (%)   (/200 ml)                                80   4500   fed plasma   2.4 × 10 11     —   4.8 × 10 7                 1.0 min   1.9 × 10 11     82.3   1.2 × 10 5                 1.5 min   2.0 × 10 11     83.0   4.0 × 10 4                 2.0 min   2.0 × 10 11     83.8   1.6 × 10 5         80   3500   fed plasma   3.2 × 10 11     —   1.4 × 10 8                 1.0 min   2.5 × 10 11     77.8   7.2 × 10 5                 1.5 min   2.6 × 10 11     81.3   5.6 × 10 5                 2.0 min   2.7 × 10 11     82.9   5.6 × 10 5         100   4500   fed plasma   2.4 × 10 11     —   4.8 × 10 7                 0.8 min   1.8 × 10 11     76.6   1.6 × 10 4                 1.2 min   1.8 × 10 11     76.9   4.0 × 10 4                 1.6 min   1.9 × 10 11     78.5   4.0 × 10 4         100   4000   fed plasma   2.4 × 10 11     —   4.8 × 10 7                 0.8 min   1.5 × 10 11     67.2   8.0 × 10 4                 1.2 min   1.7 × 10 11     71.7   &lt;2.0 × 10 4                  1.6 min   1.7 × 10 11     71.4   8.0 × 10 4         100   3500   fed plasma   3.2 × 10 11     —   1.4 × 10 8                 0.8 min   2.7 × 10 11     85.8   8.8 × 10 5                 1.2 min   2.8 × 10 11     87.7   6.8 × 10 5                 1.6 min   2.7 × 10 11     83.9   3.6 × 10 5                 2.0 min   2.8 × 10 11     87.8   4.4 × 10 5                    
 
         [0066]    From the results of Table 1, it is expected that the bowl of FIG. 1 has the ability to produce, from a platelet-rich-plasma fraction of whole blood, a 200 ml leukopoor product which may contain 2.0-3.0×10 −11  platelets, with less than 1×10 6  white blood cell contaminant. Similarly, if the bowl of FIG. 4 is used to separate whole blood in the outer annular cavity  150  and intermediate density blood components enter the inner annular cavity  120  through the annular channel  121  for processing, platelets are harvested at a high yield with a lower level of contamination with white blood cells.  
         [0067]    As has been described above, an improved and highly advantageous centrifuge bowl for processing particles, in particular blood cells such as platelets and white blood cells, is provided in accordance with the present invention. The terms and expressions employed herein are used as terms of description and not of limitation, and there is no intention, in the use of such terms and expressions, of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed.  
         [0068]    The foregoing description has been directed to specific embodiments of this invention. It will be apparent, however, that other variations and modifications may be made to the described embodiments with the attainment of some or all of their advantages. Accordingly, this description should be taken only by way of example and not by way of limitation. It is the object of the appended claims to cover all such variations and modifications as come within the true spirit and scope of the invention.