Abstract:
There is provided a centrifugal separator for solid-liquid separations. The centrifugal separator comprises (a) an accelerator rotatable at an angular velocity,ω about an axis, and having an inside surface with a point on the axis, and (b) a nozzle for introducing a feed stream at a volumetric flow rate (Q) into the accelerator via an orifice. The orifice is substantially centered about the point, and the orifice has an inner diameter (d) within the range of approximately 
     0 &lt;d ≦4δ, 
     where δ=1.414 [(4Q/π 2 ω) ⅓ ].

Description:
CROSS REFERENCE TO RELATED APPLICATIONS  
       [0001]    The present application is claiming priority of U.S. Provisional Patent Application Serial No. 60/205,955, filed on May 19, 2000. 
     
    
     
       BACKGROUND OF THE INVENTION  
         [0002]    1. Field of the Invention  
           [0003]    The present invention relates to centrifuges, and more particularly, to a centrifugal separator for solid liquid separation having a low-shear feeding system.  
           [0004]    2. Description of the Prior Art  
           [0005]    In a continuous flow centrifugal separator, a solid-liquid suspension in a feed stream is introduced into a rotating bowl. Various feeding systems have been employed to accelerate the velocity of the feed stream to the angular velocity of the bowl. Some prior art feeding systems were designed without consideration of the sensitivity of the solid particles in the feed to shear stresses. When a separator that incorporates such a feeding system is used to separate a solid from a solid-liquid suspension, the solid particles are typically subjected to high levels of shear stress. If the suspended particles are shear-sensitive, as in the case of precipitated proteins or living cells, the particles may be broken or otherwise damaged.  
           [0006]    U.S. Pat. No. 5,674,174, issued to Carr (hereinafter “the &#39;174 patent”), describes a feeding system that is intended to minimize shear stresses. The &#39;174 patent describes applying a feed stream to a rotating distributor cone by an applicator head in such a way that the velocity of the feed stream exiting the applicator head attempts to match the velocity of an adjacent rotating conical surface. However, in practice, as the feed stream contacts the rotating conical surface, it is subjected to a multi-dimensional velocity profile. There is a longitudinal component, e.g., a component parallel to the surface and normal to the direction of rotation, and one or more tangential components, i.e., components in the direction of rotation. In the &#39;174 patent, the applicator head imparts only a tangential velocity on the feed stream, and in many cases, shear stresses due to the longitudinal velocity component exceed those due to the tangential velocity component. Consequently, the applicator head of the &#39;174 patent does not produce sufficiently low shear stresses for use with mammalian cells. Also, in the system of the &#39;174 patent, the point on the rotating distributor cone at which the feed stream is applied is at a significant radial distance from the axis of rotation of the distributor cone, and as such, typical surface velocities are also significant. For example, if a feed stream is applied at a radius of 5 cm and the distributor cone is rotating at 10,000 rpm, the surface velocity that must be matched by the feed stream is approximately 5236 cm/sec. Imparting such a high velocity to the feed stream subjects the feed stream to a high level of shear stress in conduits leading to the applicator head. Additionally, a small mismatch in velocities between the feed stream from the applicator head and the spinning surface of the distributor cone, resulting either from the directional difference mentioned above, i.e., longitudinal versus tangential components, or from flow rate control tolerances, produces substantial shear stresses. Consequently, the system described in the &#39;174 patent appears to be best suited for suspended solids that are only moderately sensitive to shear, such as yeast cells or compact precipitates, but it is not suitable for more shear-sensitive materials, such as mammalian cells.  
           [0007]    Another system that addresses the shear stress problem is disclosed in U.S. Pat. No. 5,823,937, issued to Carr (hereinafter “the &#39;937 patent”). While the &#39;937 patent generally teaches placing a feed applicator off-center to an axis of rotation of a centrifuge bowl, it also describes a feed applicator that applies a feed stream concentric with the axis of rotation. The concentric approach, as compared to that of the &#39;174 patent, may reduce the radius from the axis of rotation at which the feed stream contacts the rotating surface and therefore potentially reduce shear stress. However, tests have revealed that concentric application of the feed stream, alone, does not guarantee that shear-sensitive materials are preserved.  
           [0008]    Consequently, there is a need for a separator that is capable of processing the most shear-sensitive cells and precipitates. The present invention overcomes the problems associated with the conventional separator devices by providing a separator that is capable of processing ultra shear-sensitive cells and precipitates.  
         SUMMARY OF THE INVENTION  
         [0009]    A centrifugal separator comprising (a) an accelerator rotatable at an angular velocity, ω about an axis, and having an inside surface with a point on the axis, and (b) a nozzle for introducing a feed stream at a volumetric flow rate, Q into the accelerator via an orifice. The orifice is substantially centered about the point, and the orifice has an inner diameter, d within the range of approximately 
           0 &lt;d≦ 4δ, 
           [0010]    where δ=1.414[(4Q/π 2 ω) ⅓ ]. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0011]    [0011]FIG. 1 is a cross-sectional view of a feed applicator and accelerator of a centrifuge separator in accordance with the present invention.  
         [0012]    [0012]FIG. 1A is a detailed view of a nozzle used in the centrifuge separator of FIG. 1.  
         [0013]    [0013]FIG. 1B is a detailed view of a portion of the centrifuge separator of FIG. 1 onto which a feed stream is discharged.  
         [0014]    [0014]FIG. 1C shows a detailed view of a portion of the centrifuge separator of FIG. 1 for approximating an average tangential velocity.  
         [0015]    [0015]FIG. 2 is a cross-sectional view of a second embodiment of a feed applicator of a centrifuge separator in accordance with the present invention.  
         [0016]    [0016]FIG. 2A is an enlarged view of a nozzle used in the centrifuge separator of FIG. 2.  
         [0017]    [0017]FIG. 3 is a graph for determining an orifice diameter for various combinations of feed flow rate and bowl speed in accordance with the present invention. 
     
    
     DESCRIPTION OF THE INVENTION  
       [0018]    The present invention provides for a centrifugal separator for solid-liquid separation of ultra shear-sensitive material, such as, mammalian cells. In addition to mammalian cells, materials, such as, precipitated proteins, are extremely sensitive to, and may be damaged by, shear stress. The particles of precipitated protein can break down under shear to form smaller particles that are more difficult to separate. The present invention is suitable for use with such materials.  
         [0019]    The present invention enables a significant reduction in shear stress in a centrifuge feed zone as compared with prior art designs. This is accomplished by delivering a feed stream as a narrow jet through a nozzle orifice, where the feed stream is applied along an axis of rotation of a dome-shaped feed accelerator. The nozzle orifice is spaced apart from the dome-shaped feed accelerator by an adjustable gap. An average feed stream velocity through the orifice matches a tangential surface velocity on the dome-shaped feed accelerator averaged over an area on the accelerator upon which the feed stream is discharged. By sizing the orifice such that the average velocity of the feed stream flowing from the orifice matches the tangential velocity of the accelerator surface, shear forces on solid constituents within the feed stream are minimized.  
         [0020]    Making the orifice an arbitrary size without considering other parameters can aggravate the situation with respect to the shear forces. For example, if the orifice size is reduced while keeping the centrifuge speed and flow rate the same, then the feed stream will impinge on a smaller diameter target on the accelerator and experience reduced shear rates due to the tangential motion of the accelerator. However, the feed stream will now be moving faster in the nozzle and will experience higher shear rates both within the nozzle and upon impingement of the jet on the surface of the accelerator.  
         [0021]    Conversely, if the orifice size is increased, then the feed stream will experience lower shear rates in the nozzle and upon impingement of the jet on the surface of the accelerator. However, because the radius of the area onto which the feed stream is discharged is greater, the larger target area will subject the feed stream to higher shear rates due to the higher tangential velocities at the points of impingement that are further from the axis of rotation of the accelerator.  
         [0022]    [0022]FIG. 1 illustrates a centrifugal separator  5  in accordance with the present invention. Centrifugal separator  5  includes a hemispherical dome-shaped feed accelerator  10  and a centrifuge bowl  12 . For clarity and ease of understanding, FIG. 1 shows only a small portion of centrifuge bowl  12 .  
         [0023]    Feed accelerator  10  is rotatable about an axis of rotation  18 , and has an inside surface  24  with a point  26  on axis of rotation  18 . Feed accelerator  10  is attached to bowl  12  by a screw arrangement  13 . During conventional operation, bowl  12  contains a pool of liquid, and more specifically, a solid-liquid suspension. Bowl  12  has conventional circumferential baffles  14  that dampen axial wave motions of the liquid when bowl  12  is rotating. A feed tube  16  is held in place by a fitting (not shown). Feed tube  16  is preferably centered with respect to axis of rotation  18 .  
         [0024]    A nozzle  22  provides a feed stream in a narrow jet from feed tube  16  via an orifice  50  (see FIG. 1A), which is preferably circular with a radius (r), onto surface  24  at point  26 . Orifice  50  is substantially centered about point  26  and is spaced apart from surface  24  by a gap  20 .  
         [0025]    In operation, for a given flow rate of feed stream flowing via orifice  50 , and for a given angular velocity of feed accelerator  10 , the diameter of orifice  50  is selected such that an average feed stream velocity in orifice  50  is equal to a tangential velocity of accelerator  10  averaged over an area  55  (see FIG. 1B), which is preferably circular, on surface  24  onto which the feed stream is discharged. In other words, the average velocity, v of the feed stream is approximately equal to an average tangential velocity, vt of surface  24  in area  55  of surface  24  being centered at point  26  and having radius, r. Thus, area  55  is approximately equal to the area of orifice  50 . The tangential velocity of surface  24  averaged over area  55  can be approximated by using the tangential velocity at a point on surface  24  located 0.707 r from point  26 , that is, 0.707 of the length of the radius (r) from point  26  (see FIG. 1C).  
         [0026]    Nozzle  22  is interchangeable, and thus attachable to, and removable from, feed tube  16 . The dimension of gap  20  is set by adjusting the relative position between feed tube  16  and surface  24 . For example, assume that the portion of nozzle  22  protruding from the feed tube has a length (L). Gap  20  (g) is set by the steps of (a) substituting, in place of nozzle  22  on feed tube  16 , a member, e.g., a solid gauge or a dummy orifice plug (not shown), having a length (m) of approximately m=L+g, (b) adjusting the relative position between feed tube  16  and surface  24  so that the dummy plug contacts surface  24  at point  26 ; and (c) installing nozzle  22  on feed tube  16  in place of the dummy orifice plug. The dimension of orifice  50  is set by selecting nozzle  22  so that it has a desired orifice dimension, as described below in association with FIG. 3.  
         [0027]    For practical reasons it is desirable to minimize the dimension of gap  20 . For example, to minimize drips when feed accelerator  10  is operated in a downward-facing orientation (as shown in FIG. 1), or to minimize a hold-up of the feed stream when feed accelerator  10  is operated in an upward-facing orientation (not shown). In the case of ultra shear-sensitive feeds, a minimal dimension for gap  20  should be used as a starting point for empirical studies, and thereafter adjusted to minimize damage to the shear-sensitive cells or particles.  
         [0028]    By reducing the width of the feed stream to a narrow jet “d” that impinges on a small target area at the center of the dome of feed accelerator  10 , i.e., at point  26 , shear rates resulting from the tangential velocity of feed accelerator  10  are reduced to the same order as those resulting from the impingement of the jet of the feed stream from nozzle  22 . To minimize shear, it is preferable to center the feed tube  16  with respect to the axis of rotation  18  of bowl  12  as accurately as possible. For this purpose, the accelerator  10  can be provided with a centering target (not shown) etched on its surface. A fitting that holds the feed tube in place allows some lateral adjustment for centering as well as axial adjustment for setting the width of gap  20 .  
         [0029]    [0029]FIG. 2 shows another embodiment of the present invention employed in a centrifugal separator  200 . Centrifugal separator  200  includes an elliptical dome-shaped feed accelerator  205  and centrifuge bowl  210 . FIG. 2 shows only a small portion of centrifuge bowl  210 .  
         [0030]    Feed accelerator  205  is rotatable about an axis of rotation  215 , and has an inside surface  220  with a point  225  on axis of rotation  215 . Feed accelerator  205  is attached to bowl  210  by a screw arrangement  230 . Bowl  210  has a co-axial baffle  235 . A feed tube  240  is preferably centered with respect to axis of rotation  215 .  
         [0031]    Feed tube  240  includes a nozzle  245  that provides a feed stream in a narrow jet from feed tube  240  via an orifice  250  (see FIG. 2A) onto surface  220  at point  225 . The orifice is substantially centered about point  225  and is spaced apart from surface  220  by a gap  255 .  
         [0032]    Feed tube  240  has superior sanitary properties to that of feed tube  16  shown in FIG. 1. This is because nozzle  245  is an integral part of feed tube  240 . Feed tube  240  is interchangeable and available in a variety of different lengths so that gap  255  can be set to a desired width. For the arrangement in FIG. 1, gap  20  is adjusted through the use of a dummy orifice plug., The method of setting gap  225  involves the steps of (a) inserting a gauge between nozzle  245  and surface  220 , where the gauge has a width approximately equal to a desired width of gap  255 , and (b) adjusting a relative position between nozzle  245  and surface  220 , such as by adjusting a position of feed tube  240  in its fitting (not shown). The gauge for setting of gap  255  may be accomplished by installing a mushroom-shaped temporary plug (not shown) into orifice  250  when feed tube  240  is first inserted into centrifuge separator  200 . Then, after locking feed tube  240  in its fitting, the temporary plug is removed from feed tube  240 . When feed tube  240  and its fitting (not shown) are reinserted, the previously set gap is maintained.  
         [0033]    [0033]FIG. 3 is a graph for determining an orifice diameter for various combinations of feed flow rate and bowl speed in accordance with the present invention. An example is set forth below to illustrate a technique for determining an orifice diameter and gap dimension for given values of bowl speed and feed flow rate.  
         [0034]    Assume a feed tube intended for use with a  6  inch diameter centrifuge bowl is equipped with a set of interchangeable nozzle/orifice plugs of 2.0 though 10 mm I.D. To choose the set up that most closely matches velocities for a given set of operating conditions, refer to the graph of FIG. 3 where orifice diameter is related to combinations of feed flow rate and bowl speed at which average fluid velocity through the orifice and area-averaged tangential velocity within the “target” area of the accelerator are matched according to the following equation: 
         δ=1.414[(4 Q/π   2 ω) ⅓ ]. 
         [0035]    where  
         [0036]    Q=flow rate in ml/min,  
         [0037]    d=nozzle orifice diameter in cm, and  
         [0038]    d=angular velocity in rpm (revolutions per minute).  
         [0039]    Preferably, the orifice diameter, d is set equal to δ, but good results have been achieved over the range of 
         δ/4 ≦d ≦ 2δ, 
         [0040]    and, satisfactory results have been found over the range of 
         0 ≦d≦ 4δ. 
         [0041]    On the x-axis of FIG. 3, find the desired bowl speed, then select a curve whose parameter most closely matches the feed flow rate. For example, for a bowl speed of 5000 rpm and a flow rate of 1000 mL/min, find 5000 rpm on the x-axis, then draw a vertical line  305  that crosses the 1000 mL/min curve at a point  310  corresponding to 5000 rpm. Then draw a horizontal line  315  from point  310  to the y-axis. The intersection of the horizontal line with the y-axis indicates the nozzle diameter to use. In this example, the indicated diameter is between 6.0 mm and 6.5 mm. Assuming that nozzles are provided in 1.0 mm increments, then the 6.0 mm nozzle would be selected.  
         [0042]    As described earlier, the procedure for setting the gap can be facilitated by a solid gauge device that, when substituted for one of the orifice plugs, enables precise depth setting of the feed tube. When any of the orifice plugs are then installed, the gap created between the end of the orifice plug and the surface of the bowl hub can be controlled by the gauge to provide, for example, a relationship g=d/4, where “g” is the gap height and “d” is the inner diameter of the orifice. When this relationship between the orifice inner diameter and the gap height is maintained, the mean feed stream velocity in the orifice is matched by the mean velocity in the annular space immediately adjacent to the orifice.  
         [0043]    The gap height d/4 is the preferred minimum value of gap height, but good results have been achieved over the range of 
           d /4 ≦g≦ 4 d,   
         [0044]    and satisfactory results have been achieved over the range of 
         0 ≦g ≦10 d.   
         [0045]    By selecting the correct orifice diameter for any combination of bowl speed and flow rate, the mean feed stream velocity through the orifice can be closely matched to the surface velocity of the bowl at the point at which the feed stream impinges the feed accelerator. Since the velocity profile of a feed stream has both circumferential, i.e., tangential, and longitudinal components, the above procedure may serve as a starting point, with final operating conditions and gap setting to be determined by trial and error experiments. The range of orifice diameters provided was chosen to provide a good degree of matching over the normal operating range of a centrifuge equipped with a 6 inch diameter bowl.  
         [0046]    By applying the feed in the form of a narrow jet, centered at the axis of rotation of the feed accelerator, shear stresses within the liquid phase are minimized. Thus, even the most shear sensitive cells, such as, mammalian cells, can be processed without significant damage from shear forces. This is an important advantage since an increasing number of applications, such as, for example, in the biotech industry, are based on culturing mammalian cells.  
         [0047]    It should be understood that various alternatives and modifications can be devised by those skilled in the art. The present invention is intended to embrace all such alternatives, modifications and variances that fall within the scope of the appended claims.