Centrifugal separation apparatus and method for separating fluid components

An apparatus and method are provided for separating components of a fluid or particles. A separation vessel having a barrier dam is provided to initially separate an intermediate density components of a fluid, and a fluid chamber is provided to further separate these intermediate density components by forming an elutriative field or saturated fluidized particle bed. The separation vessel includes a shield for limiting flow into the fluid chamber of relatively high density substances, such as red blood cells. The separation vessel also includes a trap dam with a smooth, gradually sloped downstream section for reducing mixing of substances. Structure is also provided for adding additional plasma to platelets and plasma flowing from the fluid chamber. The system reduces clumping of platelets by limiting contact between the platelets and walls of the separation vessel.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to an apparatus and method for separating components of a fluid. The invention has particular advantages in connection with separating blood components.

2. Description of the Related Art

In many different fields, liquids carrying particle substances must be filtered or processed to obtain either a purified liquid or purified particle end product. In its broadest sense, a filter is any device capable of removing or separating particles from a substance. Thus, the term “filter” as used herein is not limited to a porous media material but includes many different types of processes where particles are either separated from one another or from liquid.

In the medical field, it is often necessary to filter blood. Whole blood consists of various liquid components and particle components. Sometimes, the particle components are referred to as “formed elements”. The liquid portion of blood is largely made up of plasma, and the particle components include red blood cells (erythrocytes), white blood cells (including leukocytes), and platelets (thrombocytes). While these constituents have similar densities, their average density relationship, in order of decreasing density, is as follows: red blood cells, white blood cells, platelets, and plasma. In addition, the particle constituents are related according to size, in order of decreasing size, as follows: white blood cells, red blood cells, and platelets. Most current purification devices rely on density and size differences or surface chemistry characteristics to separate and/or filter the blood components.

Numerous therapeutic treatments require groups of particles to be removed from whole blood before either liquid or particle components can be infused into a patient. For example, cancer patients often require platelet transfusions after undergoing ablative, chemical, or radiation therapy. In this procedure, donated whole blood is processed to remove platelets and these platelets are then infused into the patient. However, if a patient receives an excessive number of foreign white blood cells as contamination in a platelet transfusion, the patient's body may reject the platelet transfusion, leading to a host of serious health risks.

Typically, donated platelets are separated or harvested from other blood components using a centrifuge. The centrifuge rotates a blood reservoir to separate components within the reservoir using centrifugal force. In use, blood enters the reservoir while it is rotating at a very rapid speed and centrifugal force stratifies the blood components, so that particular components may be separately removed. Centrifuges are effective at separating platelets from whole blood, however they typically are unable to separate all of the white blood cells from the platelets. Historically, blood separation and centrifugation devices are typically unable to consistently (99% of the time) produce platelet product that meets the “leukopoor” standard of less than 5×106white blood cells for at least 3×1011platelets collected.

Because typical centrifuge platelet collection processes are unable to consistently and satisfactorily separate white blood cells from platelets, other processes have been added to improve results. In one procedure, after centrifuging, platelets are passed through a porous woven or non-woven media filter, which may have a modified surface, to remove white blood cells. However, use of the porous filter introduces its own set of problems. Conventional porous filters may be inefficient because they may permanently remove or trap approximately 5–20% of the platelets. These conventional filters may also reduce “platelet viability,” meaning that once passed through a filter a percentage of the platelets cease to function properly and may be partially or fully activated. In addition, porous filters may cause the release of brandykinin, which may lead to hypotensive episodes in a patient. Porous filters are also expensive and often require additional time consuming manual labor to perform a filtration process.

Although porous filters are effective in removing a substantial number of white blood cells, they have drawbacks. For example, after centrifuging and before porous filtering, a period of time must pass to give activated platelets time to transform to a deactivated state. Otherwise, the activated platelets are likely to clog the filter. Therefore, the use of at least some porous filters is not feasible in on-line processes.

Another separation process is one known as centrifugal elutriation. This process separates cells suspended in a liquid medium without the use of a membrane filter. In one common form of elutriation, a cell batch is introduced into a flow of liquid elutriation buffer. This liquid which carries the cell batch in suspension, is then introduced into a funnel-shaped chamber located in a spinning centrifuge. As additional liquid buffer solution flows through the chamber, the liquid sweeps smaller sized, slower-sedimenting cells toward an elutriation boundary within the chamber, while larger, faster-sedimenting cells migrate to an area of the chamber having the greatest centrifugal force.

When the centrifugal force and force generated by the fluid flow are balanced, the fluid flow is increased to force slower-sedimenting cells from an exit port in the chamber, while faster-sedimenting cells are retained in the chamber. If fluid flow through the chamber is increased, progressively larger, faster-sedimenting cells may be removed from the chamber.

Thus, centrifugal elutriation separates particles having different sedimentation velocities. Stoke's law describes sedimentation velocity (SV) of a spherical particle as follows:

SV=29⁢r2⁡(ρp-ρm)⁢gη
where, r is the radius of the particle, ρpis the density of the particle, ρmis the density of the liquid medium, η is the viscosity of the medium, and g is the gravitational or centrifugal acceleration. Because the radius of a particle is raised to the second power in the Stoke's equation and the density of the particle is not, the size of a cell, rather than its density, greatly influences its sedimentation rate. This explains why larger particles generally remain in a chamber during centrifugal elutriation, while smaller particles are released, if the particles have similar densities.

As described in U.S. Pat. No. 3,825,175 to Sartory, centrifugal elutriation has a number of limitations. In most of these processes, particles must be introduced within a flow of fluid medium in separate discontinuous batches to allow for sufficient particle separation. Thus, some elutriation processes only permit separation in particle batches and require an additional fluid medium to transport particles. In addition, flow forces must be precisely balanced against centrifugal force to allow for proper particle segregation.

Further, a Coriolis jetting effect takes place when particles flow into an elutriation chamber from a high centrifugal field toward a lower centrifugal field. The fluid and particles turbulently collide with an inner wall of the chamber facing the rotational direction of the centrifuge. This phenomenon mixes particles within the chamber and reduces the effectiveness of the separation process. Further, Coriolis jetting shunts flow along the inner wall from the inlet directly to the outlet. Thus, particles pass around the elutriative field to contaminate the end product.

Particle mixing by particle density inversion is an additional problem encountered in some prior elutriation processes. Fluid flowing within the elutriation chamber has a decreasing velocity as it flows in the centripetal direction from an entrance port toward an increased cross sectional portion of the chamber. Because particles tend to concentrate within a flowing liquid in areas of lower flow velocity, rather than in areas of high flow velocity, the particles concentrate near the increased cross-sectional area of the chamber. Correspondingly, since flow velocity is greatest adjacent the entrance port, the particle concentration is reduced in this area. Density inversion of particles takes place when the centrifugal force urges the particles from the high particle concentration at the portion of increased cross-section toward the entrance port. This particle turnover reduces the effectiveness of particle separation by elutriation.

For these and other reasons, there is a need to improve particle separation.

SUMMARY OF THE INVENTION

The present invention is directed to an apparatus and method that substantially obviate one or more of the limitations and disadvantages of the related art. To achieve these and other advantages and in accordance with the purpose of the invention, as embodied and broadly described herein, the invention includes an apparatus for use with a centrifuge having a rotatable rotor including a retainer. The apparatus comprises a separation vessel for placement in the retainer. The separation vessel has an inlet portion, an outlet portion, and a flow path extending between the inlet portion and the outlet portion. The inlet portion has an inlet port for supplying to the separation vessel a fluid to be separated into components. The outlet portion includes a first wall, a second wall spaced from the first wall, at least three outlet ports for removing separated components of the fluid from the separation vessel, and a shield between one of the outlet ports and the second wall for limiting entry into said one outlet port of at least one relatively high density component of the fluid. The shield has a surface facing said one outlet port. When the separation vessel is placed in the retainer, the surface of the shield is located closer than two of the other outlet ports to the axis of rotation to maintain the surface of the shield out of a layer of the relatively high density fluid component formed in the outlet portion.

In one other aspect, the invention includes a centrifugal separation apparatus having a centrifuge rotor, a retainer on the centrifuge rotor, and a separation vessel in the retainer. The separation vessel includes an inlet portion, an outlet portion, and a trap dam. The outlet portion has a barrier for substantially blocking passage of at least one of the separated components of the fluid, and at least one outlet port for removing at least the blocked component of the fluid from the vessel. The trap dam is located between the outlet port and the inlet portion. The trap dam extends away from the axis of rotation of the rotor to trap relatively low density substances and includes a downstream portion having a relatively gradual slope.

In an additional aspect, the separation vessel further includes a gradual sloped segment across from the trap dam. The gradual sloped segment increases thickness of a layer of the relatively high density fluid component formed across from the trap dam.

In another aspect, the invention includes an apparatus having a separation vessel and a fluid chamber. The separation vessel includes an inlet port, a first outlet port for removing at least relatively intermediate density components of fluid, and a second outlet port for removing at least one relatively low density component of the fluid. A first line is coupled to the first outlet port and also is coupled to an inlet of a fluid chamber for separating the components of the fluid flowing through the first line. A second line is coupled to the second outlet port and is also in flow communication with an outlet of the fluid chamber to mix the relatively low density component of the fluid with substances flowing from the outlet of the fluid chamber.

In yet another aspect, the invention includes a method of separating components of a fluid. In the method, a separation vessel rotates about an axis of rotation and fluid to be separated passes into the vessel. The fluid separates into at least a relatively high density component, a relatively intermediate density component, and a relatively low density component. At least the relatively intermediate density component is removed from the separation vessel via an outlet port. Passage of the relatively high density component into the outlet port is limited with a shield having a surface facing the outlet port. The position of an interface between the high density component and the intermediate density component is controlled so that the surface of the shield is between the interface and the outlet port.

In still another aspect, the high density component includes red blood cells, the intermediate density component includes platelets, and the low density component includes plasma.

In an additional aspect, the invention includes a method wherein at least relatively intermediate density components are removed from the separation vessel via a first outlet port; and at least some of a low density component is removed from the separation vessel via a second outlet port. The removed intermediate density components are flowed into a fluid chamber. At least some of a first subcomponent of the intermediate density components is retained in the fluid chamber, and at least some of a second subcomponent of the intermediate density components is permitted to flow from an outlet of the fluid chamber. The low density component removed from the separation vessel is combined with the second subcomponent flowing from the outlet of the fluid chamber.

In a further aspect of the invention, the first subcomponent includes white blood cells, the second subcomponent includes platelets, and the low density component includes plasma.

In an even further aspect of the invention, an apparatus for use with a centrifuge includes a separation vessel having an outlet portion including at least one outlet port and a shield having a surface facing the outlet port. Structure is provided for controlling the position of an interface between at least one relatively high density component of a fluid and at least one other separated component of the fluid so that the surface of the shield is between the interface and the outlet port.

In another aspect, the invention includes a method of reducing clumping of platelets during separation of blood components. The method includes introducing blood components into a rotating separation vessel such that the blood components stratify in the separation vessel to form at least a radial outer layer including red blood cells, an intermediate layer including at least platelets, and a radial inner layer including low density substances. To substantially limit contact between the platelets and at least one of the radial inner and outer walls of the separation vessel, the radial outer layer of red blood cells is maintained between the intermediate layer and the radial outer wall of the separation vessel and/or the radial inner layer of low density substances is maintained between the intermediate layer and the radial inner wall of the separation vessel. This reduces platelet clumping.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The embodiments of the present invention preferably include a COBE® SPECTRA™ single stage blood component centrifuge manufactured by Cobe Laboratories of Colorado. The COBE® SPECTRA™ centrifuge incorporates a one-omega/two-omega sealless tubing connection as disclosed in U.S. Pat. No. 4,425,112 to Ito, the entire disclosure of which is incorporated herein by reference. The COBE® SPECTRA™ centrifuge also uses a single-stage blood component separation channel substantially as disclosed in U.S. Pat. No. 4,094,461 to Kellogg et al. and U.S. Pat. No. 4,647,279 to Mulzet et al., the entire disclosures of which are also incorporated herein by reference. The embodiments of the invention are described in combination with the COBE® SPECTRA™ centrifuge for purposes of discussion only, and this is not intended to limit the invention in any sense.

As will be apparent to one having skill in the art, the present invention may be advantageously used in a variety of centrifuge devices commonly used to separate blood into its components. In particular, the present invention may be used with any centrifugal apparatus that employs a component collect line such as a platelet collect line or a platelet rich plasma line, whether or not the apparatus employs a single stage channel or a one-omega/two-omega sealless tubing connection.

As embodied herein and illustrated inFIG. 1, the present invention includes a centrifuge apparatus10having a centrifuge rotor12coupled to a motor14so that the centrifuge rotor12rotates about its axis of rotation A—A. The rotor12has a retainer16including a passageway or annular groove18having an open upper surface adapted to receive a separation vessel28,28a, or28bshown respectively inFIGS. 2,4–6, and7. The groove18completely surrounds the rotor's axis of rotation A—A and is bounded by an inner wall20and an outer wall22spaced apart from one another to define the groove18therebetween. Although the groove18shown inFIG. 1completely surrounds the axis of rotation A—A, the groove could be partially around the axis A—A when the separation vessel is not generally annular. As compared to previous designs of the COBE® SPECTRA™ blood component centrifuge, the outer wall22is preferably spaced closer to the axis of rotation A—A to reduce the volume of the separation vessel28,28a,28band to increase flow velocity in the vessel28,28a,28b.

Preferably, a substantial portion of the groove18has a constant radius of curvature about the axis of rotation A—A and is positioned at a maximum possible radial distance on the rotor12. As described below, this shape ensures that substances separated in the separation vessel28,28a,28bundergo relatively constant centrifugal forces as they pass from an inlet portion to an outlet portion of the separation vessel28,28a,28b.

The motor14is coupled to the rotor12directly or indirectly through a shaft24connected to the rotor12. Alternately, the shaft24may be coupled to the motor14through a gearing transmission (not shown).

As shown inFIG. 1, a holder26is provided on a top surface of the rotor12. The holder26releasably holds a fluid chamber30on the rotor12so that an outlet32of the fluid chamber30is positioned closer to the axis of rotation A—A than an inlet34of the fluid chamber30. The holder26preferably orients the fluid chamber30on the rotor12with a longitudinal axis of the fluid chamber30in a plane transverse to the rotor's axis of rotation A—A. In addition, the holder26is preferably arranged to hold the fluid chamber30on the rotor12with the fluid chamber outlet32facing the axis of rotation A—A. Although the holder26retains the fluid chamber30on a top surface of the rotor12, the fluid chamber30may also be secured to the rotor12at alternate locations, such as beneath the top surface of the rotor12.

FIG. 2schematically illustrates a portion of the separation vessel28and fluid chamber30mounted on the rotor12. The separation vessel28has a generally annular flow path46and includes an inlet portion48and outlet portion50. A wall52prevents substances from passing directly between the inlet and outlet portions48and50without first flowing around the generally annular flow path46(e.g., counterclockwise as illustrated by arrows inFIG. 2).

In the portion of the separation vessel28between the inlet and outlet portions48and50, a radial outer wall65of the separation vessel28is preferably positioned closer to the axis of rotation A—A than the radial outer wall65in the outlet portion50. During separation of blood components in the separation vessel28, this arrangement causes formation of a very thin and rapidly advancing red blood cell bed in the separation vessel28between the inlet and outlet portions48and50. The red blood cell bed reduces the amount of blood components required to initiate a separation procedure, and also decrease the number of unnecessary red blood cells in the separation vessel28. As explained below, the radially outer red blood cell bed substantially limits, or more preferably prevents, platelets from contacting the radial outer wall65of the separation vessel28. This is believed to reduce clumping of platelets caused when platelets contact structural components of centrifugal separation devices, which are normally formed of polymer materials.

As shown inFIG. 2, the inlet portion48includes an inflow tube36for conveying a fluid to be separated, such as whole blood, into the separation vessel28. The outlet portion50, on the other hand, includes first, second, and third outlet lines38,40,42for removing separated substances from the separation vessel28and an interface control line44for adjusting the level of an interface F between separated substances in the vessel28. Preferably, the separation vessel28forms what is known as a single stage component separation area rather than forming a plurality of such stages. In other words, each of the components separated in the vessel28preferably are collected and removed in only one area of the vessel28, namely the outlet portion50. In addition, the separation vessel28preferably includes a substantially constant radius except in the region of the outlet portion50where the outer wall of the outlet portion50is preferably positioned farther away from the axis of rotation A—A to allow for outlet ports56,58,60, and61of the lines38,40,42, and44, respectively, to be positioned at different radial distances and to create a collection pool with greater depth for the high density red blood cells.

Although the lines38,40, and42are referred to as being “collection” lines, the substances removed through these lines can be either collected or reinfused back into a donor. In addition, the invention could be practiced without one or more of the lines40,42, and44.

AlthoughFIG. 2shows the inlet portion48as having a wide radial cross-section, the outer wall of the inlet portion48can be spaced closer to the inner wall of the inlet portion48and/or be tapered. An inlet port54of inflow tube36allows for flow of a substance to be separated, such as whole blood, into the inlet portion48of separation vessel28. During a separation procedure, substances entering the inlet portion48follow the flow path46and stratify according to differences in density in response to rotation of the rotor12. Preferably, the flow path46between the inlet and outlet portions48and50is curved and has a substantially constant radius. In addition, the flow path46is placed at the maximum distance from the axis A—A. This shape ensures that components passing through the flow path46encounter a relatively constant gravitational field and a maximum possible gravitational field for the rotor12.

The separated substances flow into the outlet portion50where they are removed via first, second, and third outlet ports56,58, and60respectively, of first, second, and third collection lines38,40, and42. Separated substances are also removed by an interface controlling outlet port61of the interface control line44.

As shown inFIG. 2, the first, second, and third ports56,58, and60and interface port61are positioned at varying radial locations on the rotor12to remove substances having varying densities. The second outlet port58is farther from the axis of rotation A—A than the first, third, and interface ports56,60and61to remove higher density components H separated in the separation vessel28, such as red blood cells. The third port60is located closer to the axis of rotation A—A than the first, second, and interface ports56,58, and61to remove the least dense components L separated in the separation vessel28, such as plasma. Preferably, the first port56is about 0.035 inch to about 0.115 inch closer than the interface port61to the axis of rotation A—A.

As shown inFIG. 2, the outlet portion50includes a barrier62for substantially blocking flow of intermediate density components1, such as platelets and some mononuclear cells (white blood cells). Preferably, the barrier62is a skimmer dam extending completely across the outlet portion50in a direction generally parallel to the axis of rotation A—A. The first outlet port56is positioned immediately upstream from barrier62, downstream from the inlet portion48, to collect at least the intermediate density components I blocked by the barrier62and, optionally, some of the lower density components L.

Radially inner and outer edges of the barrier62are spaced from radially inner and outer walls63,65of the separation vessel28to form a first passage64for lower density components L, such as plasma, at a radially inner position in the outlet portion50and a second passage66for higher density components H, such as red blood cells, at a radially outer position in the outlet portion50. The second and third collection ports58and60are preferably positioned downstream from the barrier62to collect the respective high and low density components H and L passing through the second and first passages66and64.

The interface control outlet port61is also preferably positioned downstream from the barrier62. During a separation procedure, the interface port61removes the higher density components H and/or the lower density components L in the outlet portion50to thereby control the radial position of the interface F between the intermediate density components I and higher density components H in the outlet portion50so that the interface F and the interface port61are at about the same radial distance from the rotational axis A—A. Although the interface port61is the preferred structure for controlling the radial position of the interface F, alternative structure could be provided for performing this function. For example, the position of the interface F could be controlled without using an interface port by providing an optical monitor (not shown) for monitoring the position of the interface and controlling flow of liquid and/or particles through one or more of the ports54,56,58, and60in response to the monitored position.

Preferably, the second collection line40is flow connected to the interface control line44so that substances removed via the second collection port58and the interface control port61are combined and removed together through a common line. Although the second and third outlet ports58and60and the interface outlet port61are shown downstream from the barrier62, one or more of these ports may be upstream from the barrier62. In addition, the order of the outlet ports56,58,60, and the control port61along the length of the outlet portion50could be changed. Further details concerning the structure and operation of the separation vessel28are described in U.S. Pat. No. 4,094,461 to Kellogg et al. and U.S. Pat. No. 4,647,279 to Mulzet et al., which have been incorporated herein by reference.

A shield96is positioned between the first outlet port56and the outer wall65to limit entry into the first outlet port56of the higher density components H. The shield96is preferably a shelf extending from an upstream side of the dam62. In the preferred embodiment, the shield96is at least as wide (in a direction parallel to the axis A—A) as the first outlet port56and extends upstream at least as far as the upstream end of first outlet port56so that the shield96limits direct flow into the first outlet port56of components residing between the shield96and the outer wall65, including the higher density components H. In other words, the shield96ensures that a substantial amount of the substances flowing into the first outlet port56originate from radial locations which are not further than the shield96from the axis of rotation A—A.

Preferably, the shield96has a radially inner surface98facing the first outlet port56. The inner surface98is spaced radially outward from the first outlet port56by a distance of preferably from about 0.005 inch to about 0.08 inch, and more preferably from about 0.02 inch to about 0.03 inch. The inner surface98is positioned farther than the first and third outlet ports56and60from the axis of rotation A—A. The inner surface98is also positioned closer than the second outlet port58and the interface outlet port61to the axis of rotation A—A. The relative positioning of the inner surface98and interface outlet port61maintains the inner surface98above the interface F, out of the layer of the higher density components H formed in the outlet portion50, and in the layer of intermediate density components1. Because the top surface98is above the interface F, the shield96blocks flow of higher density substances H into the first outlet port56. When the separation vessel28is used in a blood component procedure where the layer of higher density substances H primarily includes red blood cells, preferably the shield96significantly reduces the number of red blood cells which flow into the first outlet port56.

FIG. 3shows a view of a portion of a conventional separation vessel28′ disclosed in above-mentioned U.S. Pat. No. 4,647,279 to Mulzet et al. As shown inFIG. 3, this separation vessel28′ includes a first outlet56′ for intermediate density substances, a second outlet58′ for high density substances, a third outlet60′ for low density substances, and an interface control outlet61′. In addition, the separation vessel28′ includes a barrier62′ having a flow directer100positioned radially outward from the outlet56′. However, the flow directer100does not siginificantly reduce flow of high density substances, such as red blood cells, into the outlet56′ because the flow directer100has a radially inner surface102which is located radially outward from the interface control port61′ to position the inner surface102in a layer of higher density substances. In other words, the radially inner surface102is located radially outward from an interface between higher density substances and intermediate density substances formed in the separation vessel28′.

As shown inFIGS. 1 and 2, the preferred embodiment of the present invention preferably includes a ridge68extending from the inner wall20of the groove18toward the outer wall22of the groove18. When the separation vessel28shown inFIG. 2is loaded in the groove18, the ridge68deforms semi-rigid or flexible material in the outlet portion50of the separation vessel28to form a trap dam70on the radially inner wall63of the separation vessel28, upstream from the first collection port56. The trap dam70extends away from the axis of rotation A—A to trap a portion of lower density substances, such as priming fluid and/or plasma, along a radially inner portion of the separation vessel28located upstream the trap dam70.

When the separation vessel28is used to separate whole blood into blood components, the trap dam70traps priming fluid (i.e. saline) and/or plasma along the inner wall63and these trapped substances help convey platelets to the outlet portion50and first collection port56by increasing plasma flow velocities next to the layer of red blood cells in the separation vessel28to scrub platelets toward the outlet portion50. As explained below, the trapped priming fluid and/or plasma along the inner wall63also substantially limits, or more preferably prevents, platelets from contacting the radial inner wall63. This is believed to reduce clumping of platelets caused when platelets contact structural components of centrifugal separation devices, which are normally formed of polymer materials.

Preferably, the trap dam70has a relatively smooth surface to limit disruption of flow in the separation vessel28, for example, by reducing Coriolis forces. In the preferred embodiment, a downstream portion104of the trap dam70has a relatively gradual slope extending in the downstream direction toward the axis of rotation A—A. During a blood component separation procedure, the relatively gradual slope of the downstream portion104limits the number of platelets (intermediate density components) that become reentrained (mixed) with plasma (lower density components) as plasma flows along the trap dam70. In addition, the gradual sloped shape of the downstream portion104reduces the number of platelets that accumulate in the separation vessel28before reaching the first collection port56.

As shown inFIG. 2, the gradual slope of the downstream portion104preferably extends to a downstream end106located closer than the first outlet port56to the axis of rotation A—A. When the separation vessel28is used for blood component separation, the downstream end106is preferably located radially inward from the layer of platelets formed in the separation vessel28. In contrast, when the downstream end106is located radially outward from the radially innermost portion of the platelet layer, plasma flowing along the surface of the dam70could reentrain (mix) the platelets in plasma downstream from the dam, reducing the efficiency of blood component separation.

In the preferred embodiment shown inFIG. 2, the trap dam70and its downstream portion104preferably have a generally convex curvature. Preferably, the surface of the trap dam70is in the form of a constant radius arc having a center of curvature offset from the axis of rotation A—A. Although the trap dam70could have any radius of curvature, a radius of from about 0.25 inch to about 2 inches is preferred, and a radius of about 2 inches is most preferred.

Although the ridge68preferably deforms the separation vessel28to form the trap dam70, the trap dam70could be formed in other ways. For example, the trap dam70could be a permanent structure extending from a radially inner wall of the separation vessel28. In addition, the trap dam70could be positioned closer to the barrier62and have a small hole passing therethrough to allow for passage of air in a radial inner area of the outlet portion50.

As shown inFIGS. 1 and 2, the outer wall22of the groove18preferably includes a gradual sloped portion108facing the ridge68in the inner wall20. When the separation vessel28shown inFIG. 2is loaded in the groove18, the gradual sloped portion108deforms semi-rigid or flexible material in the outlet portion50of the separation vessel28to form a relatively smooth and gradual sloped segment110in a region of the vessel28across from the trap dam70. In an alternative embodiment, this gradual sloped segment110is a permanent structure formed in the separation vessel28.

In the downstream direction, the segment110slopes gradually away from the axis of rotation A—A to increase the thickness of a layer of high density fluid components H, such as red blood cells, formed across from the trap dam70. The gradual slope of the segment110maintains relatively smooth flow transitions in the separation vessel28and reduces the velocity of high density components H (red blood cells) formed radially outward from the intermediate density components I (platelets).

Preferably, an upstream end112of the gradual sloped segment110is positioned upstream from the trap dam70. This position of the upstream end112reduces the velocity of high density components H, such as red blood cells, as these components flow past the trap dam70and form radially outward from the layer of intermediate density components I blocked by the barrier62.

As shown inFIG. 2, the first collection line38is connected between the first outlet port56and the fluid chamber inlet34to pass the intermediate density components into the fluid chamber30. Preferably, the fluid chamber30is positioned as close as possible to the first outlet port56so that any red blood cells entering the fluid chamber30will be placed in a high gravitational field and compacted. As described below, components initially separated in the separation vessel28are further separated in the fluid chamber30. For example, white blood cells could be separated from plasma and platelets in the fluid chamber30. This further separation preferably takes place by forming an elutriative field in the fluid chamber30or by forming a saturated fluidized bed of particles, such as platelets, in the fluid chamber30.

The fluid chamber30is preferably constructed similar or identical to one of the fluid chambers disclosed in above-mentioned U.S. patent application Ser. No. 08/676,039 and U.S. Pat. No. 5,674,173. As shown inFIG. 2, the inlet34and outlet32of the fluid chamber30are arranged along a longitudinal axis of the fluid chamber30. A wall of the fluid chamber30extends between the inlet34and outlet32thereby defining the inlet34, the outlet32, and an interior of the fluid chamber30.

The fluid chamber30preferably includes two frustoconical shaped sections joined together at a maximum cross-sectional area of the fluid chamber30. The interior of the fluid chamber30preferably tapers (decreases in cross-section) from the maximum cross-sectional area in opposite directions toward the inlet34and the outlet32. Although the fluid chamber30is depicted with two sections having frustoconical interior shapes, the interior of each section may be paraboloidal, or of any other shape having a major cross-sectional area greater than the inlet or outlet area.

The volume of the fluid chamber30should be at least large enough to accommodate the formation of a saturated fluidized particle bed (described below) for a particular range of flow rates, particle sizes, and rotational speeds of the centrifuge rotor12. The fluid chamber30may be constructed from a unitary piece of plastic or from separate pieces joined together to form separate sections of the fluid chamber30. The fluid chamber30may be formed of a transparent or translucent copolyester plastic, such as PETG, to allow viewing of the contents within the chamber interior with the aid of an optional strobe (not shown) during a separation procedure.

As shown inFIG. 2, a groove72is formed on an inner surface of the fluid chamber30at a position of the maximum cross-sectional area. The groove72is defined by top and bottom wall surfaces oriented substantially perpendicular to the longitudinal axis of the fluid chamber30and an inner surface of the fluid chamber30facing the longitudinal axis. Preferably, the groove72is annular, however, the groove72may also partially surround the longitudinal axis of the fluid chamber30.

The groove72helps to disperse Coriolis jetting within the fluid chamber30, as described below. Sudden increases in liquid flow rate during a particle separation procedure may limit the effectiveness of elutriative particle separation or may limit the ability of the saturated fluidized particle bed to obstruct particle passage. Liquid flowing into the fluid chamber30undergoes a Coriolis jetting effect. This jetting flow reduces the filtration effectiveness of the saturated fluidized particle bed because liquid and particles may pass between the saturated fluidized particle bed and an interior wall surface of the fluid chamber30rather than into the bed itself. The fluid chamber30including groove72counteracts these effects by channeling Coriolis jetting flow in a circumferential direction partially around the axis of fluid chamber30. Therefore, the groove72improves the particle obstruction capability of the saturated bed, especially when liquid flow rates increase.

As shown inFIG. 2, a circumferential lip74extends from a top portion of the groove72toward a bottom portion of the groove72to define an entrance into the groove72. The lip74functions to guide fluid in the groove72.

A plurality of steps76are preferably formed on an inner surface of the fluid chamber30between the maximum cross-section of the chamber30and the inlet34. Although six steps76are illustrated, any number of steps may be provided in the fluid chamber30.

Each step76has a base surface oriented substantially perpendicular to the longitudinal axis of the fluid chamber30, as well as a side surface positioned orthogonal to the base surface. AlthoughFIG. 2depicts a corner where the side surface and the base surface intersect, a concave groove may replace this corner. In a preferred embodiment, each step76is annular and surrounds the axis of the chamber30completely to bound a cylindrical shaped area. Alternative, the steps76may partially surround the axis of the chamber30.

Adding steps76to the fluid chamber30, also improves the particle obstruction characteristics of a saturated fluidized particle bed formed in the fluid chamber30, in particular during increases in the rate of fluid flow. The steps76provide this improvement by providing momentum deflecting and redirecting surfaces to reduce Coriolis jetting in fluid chamber30. When Coriolis jetting takes place, the liquid and particles of the jet travel along an interior surface of the fluid chamber30that faces the direction of centrifuge rotation. Therefore, the jet may transport particles between the fluid chamber interior surface and either a saturated fluidized particle bed or an elutriation field positioned in the fluid chamber30. Thus, particles traveling in the jet may exit the fluid chamber30without being separated.

Steps76direct or alter the momentum of the Coriolis jet flow of liquid and particles generally in a circumferential direction about the axis of the fluid chamber30. Thus, a substantial number of particles originally flowing in the jet must enter the saturated fluidized bed or elutriation field to be separated.

The groove72and steps76are provided to facilitate fluid flow rate increases, as well as to improve steady state performance of the fluid chamber30. During blood component separation, the groove72and steps76greatly reduce the number of white blood cells that would otherwise bypass a saturated fluidized platelet bed formed in the fluid chamber30.

As schematically shown inFIG. 2, a plurality of pumps78,80,84are provided for adding and removing substances to and from the separation vessel28and fluid chamber30. An inflow pump78is coupled to the inflow line36to supply a substance to be separated, such as whole blood, to the inlet portion48. A first collection pump80is coupled to outflow tubing88connected to the fluid chamber outlet32. The first collection pump80draws fluid and particles from the fluid chamber outlet32and causes fluid and particles to enter the fluid chamber30via the fluid chamber inlet34.

A second collection pump84is flow coupled to the second collection line42for removing substances through the third outlet port60. Preferably, the second collection line40and interface control line44are flow connected together, and substances flow through these lines40and44as a result of positive fluid pressure in the vessel outlet portion50.

The pumps78,80,84are preferably peristaltic pumps or impeller pumps configured to prevent significant damage to blood components. However, any fluid pumping or drawing device may be provided. In an alternative embodiment (not shown), the first collection pump80may be fluidly connected to the fluid chamber inlet34to directly move substances into and through the fluid chamber30. The pumps78,80,84may be mounted at any convenient location.

As shown inFIG. 1, the apparatus10further includes a controller89connected to the motor14to control rotational speed of the rotor12. In addition, the controller89is also preferably connected to the pumps78,80,84to control the flow rate of substances flowing to and from the separation vessel28and the fluid chamber30. The controller89preferably maintains a saturated fluidized bed of first particles within the fluid chamber30to cause second particles to be retained in the fluid chamber30. The controller89may include a computer having programmed instructions provided by a ROM or RAM as is commonly known in the art.

The controller89may vary the rotational speed of the centrifuge rotor12by regulating frequency, current, or voltage of the electricity applied to the motor14. Alternatively, the rotational speed can be varied by shifting the arrangement of a transmission (not shown), such as by changing gearing to alter a rotational coupling between the motor14and rotor12. The controller89may receive input from a rotational speed detector (not shown) to constantly monitor the rotation speed of the rotor12.

The controller89may also regulate one or more of the pumps78,80,84to vary the flow rates for substances supplied to or removed from the separation vessel28and the fluid chamber30. For example, the controller89may vary the electricity provided to the pumps78,80,84. Alternatively the controller89may vary the flow rate to and from the vessel28and the fluid chamber30by regulating valving structures (not shown) positioned in the lines36,38,40,42,44and/or88. The controller89may receive input from a flow detector (not shown) positioned within the first outlet line38to monitor the flow rate of substances entering the fluid chamber30. Although a single controller89having multiple operations is schematically depicted in the embodiment shown inFIG. 1, the controlling structure of the invention may include any number of individual controllers, each for performing a single function or a number of functions. The controller89may control flow rates in many other ways as is known in the art.

FIG. 4shows an embodiment of a tubing set90afor use in the apparatus10, andFIG. 5illustrates a cross-sectional view of a portion of the tubing set90amounted in groove18aon rotor12a. The tubing set90aincludes a separation vessel28a, the fluid chamber30, an inflow tube36afor conveying a fluid to be separated, such as whole blood, into the separation vessel28a, first, second, and third outlet lines38a,40a,42afor removing separated components of the fluid from the separation vessel28a, and an interface control line44afor adjusting the level of an interface between separated substances in the vessel28a. When the separation vessel28ais mounted on a rotor12a, the lines36a,38a,42a, and44apreferably pass through slots (not shown) formed on the rotor12a.

Preferably, the separation vessel28ais constructed similar to the centrifugal separator disclosed in above-mentioned U.S. Pat. No. 4,647,279 to Mulzet et al. The separation vessel28aincludes a generally annular channel92aformed of semi-rigid or flexible material and having a flow path46a, shown inFIG. 5. Opposite ends of the channel92aare connected to a relatively rigid connecting structure94including an inlet portion48aand outlet portion50afor the separation vessel28aseparated by a wall52a. An inlet port54aof inflow tubing36ais in fluid communication with the inlet portion48aand allows for flow of a substance to be separated, such as blood, into the separation vessel28a. During a separation procedure, substances entering the vessel28avia the inlet port54aflow around the channel92a(counterclockwise inFIG. 5) via the flow path46aand stratify according to differences in density in response to rotation of the rotor12a.

The separated substances flow into the outlet portion50awhere they are removed through first, second and third outlet ports56a,58a, and60aof respective first, second, and third collection lines38a,40a, and42aand an interface control port61aof the interface control line44a. As shown inFIG. 5, the second collection line40ais preferably connected to the interface control line44aso that substances flowing through the second collection line40aand interface control line44aare removed together through a portion of the interface control line44a.

The first, second and third outlet ports56a,58a, and60aand the interface control port61ahave the same relative radial positioning as that of the first, second, and third outlet ports56,58, and60and the interface control port61shown inFIG. 2, respectively. As shown inFIG. 6, the first port56aand interface port61aare spaced in the radial direction by a distance “d” of from about 0.035 inch to about 0.115 inch so that the first port56ais slightly closer to the axis of rotation A—A.

The outlet portion50aincludes a barrier62afor substantially blocking flow of intermediate density substances, such as platelets and some white blood cells. In the embodiment shown inFIG. 5, the barrier62ais a skimmer dam extending across the outlet portion50ain a direction generally parallel to the axis of rotation A—A. The first collection port56ais positioned immediately upstream from the skimmer dam62a, and downstream from the inlet portion48a, to collect the intermediate density substances blocked by the skimmer dam62a.

A shield96aextends from the upstream side of the skimmer dam62a. The shield96ais preferably configured like the shield96shown inFIG. 2to limit flow of higher density components into the first port56a. As shown inFIG. 6, the radially inward surface98aof the shield96ais spaced radially outward from the first outlet port56aby a gap “g” of preferably from about 0.005 inch to about 0.08 inch, and more preferably from about 0.02 inch to about 0.03 inch.

Radially inner and outer edges of the skimmer dam62aare spaced from radially inner and outer walls of the separation vessel28ato form a first passage64afor lower density substances, such as plasma, at a radially inner position in the outlet portion50aand a second passage66afor higher density substances, such as red blood cells, at a radially outer position in the outlet portion50a. The second and third collection ports58aand60aare preferably positioned downstream from the skimmer dam62ato collect the respective higher and lower density substances passing through the first and second passages66aand64a.

As shown inFIG. 5, a ridge68aextends from the inner wall20aof the groove18atoward the outer wall22aof the groove18a. When the separation vessel28ais loaded in the groove18a, the ridge68adeforms the semi-rigid or flexible material of the separation vessel28ato form a trap dam70aon the radially inner wall of the separation vessel28abetween the first collection port56aand the inlet portion of the separation vessel28a. The trap dam70aextends away from the axis of rotation A—A to trap a portion of lower density substances, such as priming fluid and/or plasma, along a radially inner portion of the separation vessel28a. In addition, the trap dam70ahas a gradual sloped downstream portion104a, and a downstream end106alocated closer than the first outlet port56ato the axis of rotation A—A. The trap dam70apreferably has the same or substantially the same structural configuration and function as the trap dam70shown inFIG. 2and could be permanent structure formed in the vessel28a.

The outer wall22apreferably includes a gradual sloped portion108afor forming a corresponding gradual sloped segment110ain the vessel28awhen the vessel28ais deformed in the groove18. The portion108aand segment110ahave the same or substantially the same structural configuration and function as the portion108and segment110shown inFIG. 2, respectively.

FIG. 7shows an embodiment of a separation vessel28bconstructed substantially the same as the separation vessel28ashown inFIGS. 4–6. In this embodiment, the third collection line42bis flow coupled to the outflow tubing88bextending from the fluid chamber outlet32. This places the third outlet port60ain flow communication with the fluid chamber outlet32to thereby mix substances flowing through the third outlet port60awith substances flowing through the fluid chamber outlet32. During a blood component separation procedure, for example, this structural configuration mixes plasma flowing through third port60awith platelets and plasma flowing from the fluid chamber30. In certain circumstances, this dilution of the platelet collection may be desired to possibly increase shelf life of the platelet collection.

The fluid chamber outlet32and third outlet port60acould be flow coupled in many different ways. For example, the third collection line42bcould coupled to the outflow tubing88bupstream from pump80shown inFIG. 2to reduce the concentration of particles being pumped and possibly eliminate pump84. In the alternative, the outlet of pump84could be flow coupled to the outlet of pump80, for example. Preferably, the flow connection of the third collection line42band outflow tubing88bis not located on the rotatable centrifuge rotor12a.

Methods of separating components or particles of blood are discussed below with reference toFIGS. 1,2, and7. Although the invention is described in connection with blood component separation processes and the structure shown in the drawings, it should be understood that the invention in its broadest sense is not so limited. The invention may be used to separate a number of different particles and/or fluid components, and the structure used to practice the invention could be different from that shown in the drawings. In addition the invention is applicable to both double needle and single needle blood purification or filtration applications. For example, the invention may be practiced with the SINGLE NEEDLE RECIRCULATION SYSTEM FOR HARVESTING BLOOD COMPONENTS of U.S. Pat. No. 5,437,624, the disclosure of which is incorporated herein by reference.

After loading the separation vessel28and fluid chamber30on the rotor12, preferably, the separation vessel28and chamber30are initially primed with a low density fluid medium, such as air, saline solution, plasma, or another fluid substance having a density less than or equal to the density of liquid plasma. Alternatively, the priming fluid is whole blood itself. This priming fluid allows for efficient establishment of a saturated fluidized bed of platelets within the fluid chamber30. When saline solution is used, the pump78shown inFIG. 2pumps this priming fluid through the inflow line36and into the separation vessel28via the inlet port54. The saline solution flows from the inlet portion48to the outlet portion50(counterclockwise inFIG. 2) and through the fluid chamber30when the controller89activates the pump80. Controller89also initiates operation of the motor14to rotate the centrifuge rotor12, separation vessel28, and fluid chamber30about the axis of rotation A—A. During rotation, twisting of lines36,38,40,42, and88is prevented by a sealless one-omega/two-omega tubing connection as is known in the art and described in above-mentioned U.S. Pat. No. 4,425,112.

As the separation vessel28rotates, a portion of the priming fluid (blood or saline solution) becomes trapped upstream from the trap dam70and forms a dome of priming fluid (plasma or saline solution) along an inner wall of the separation vessel28upstream from the trap dam70. After the apparatus10is primed, and as the rotor10rotates, whole blood or blood components are introduced through the inlet port54into the separation vessel28. When whole blood is used, the whole blood can be added to the separation vessel28by transferring the blood directly from a donor through inflow line36. In the alternative, the blood may be transferred from a container, such as a blood bag, to inflow line36.

The blood within the separation vessel28is subjected to centrifugal force causing components of the blood components to separate. The components of whole blood stratify in order of decreasing density as follows: 1. red blood cells, 2. white blood cells, 3. platelets, and 4. plasma. The controller89regulates the rotational speed of the centrifuge rotor12to ensure that this particle stratification takes place. A layer of red blood cells (high density component(s) H) forms along the outer wall of the separation vessel28and a layer of plasma (lower density component(s) L) forms along the inner wall of the separation vessel28. Between these two layers, the intermediate density platelets and white blood cells (intermediate density components I) form a buffy coat layer. This separation takes place while the components flow from the inlet portion48to the outlet portion50. Preferably, the radius of the flow path46between the inlet and outlet portions48and50is substantially constant to maintain a steady red blood cell bed in the outlet portion50even if flow changes occur.

In the outlet portion50, platelet poor plasma flows through the first passage64and downstream of the barrier62where it is removed via the third collection port60. Red blood cells flow through the second passage66and downstream of the barrier62where they are removed via the second collection port58. After the red blood cells, white blood cells, and plasma are thus removed, they are collected and recombined with other blood components or further separated. Alternately, these removed blood components may be reinfused into a donor.

The higher density component(s) H (red blood cells) and lower density component(s) L (plasma) are alternately removed via the interface control port61to control the radial position of the interface F between the higher density component(s) H and intermediate density component(s) I (buffy layer). This interface control preferably maintains the radially inner shield surface98between the interface F and first outlet port56.

A substantial portion of the platelets and some of the white blood cells accumulate upstream from the barrier62. The accumulated platelets are removed via the first outlet port56along with some of the white blood cells and plasma. The shield96limits passage of higher density substances H (red blood cells) into the first outlet port56. Preferably, the shield96substantially reduces the number of red blood cells entering the first outlet port56, thereby improving collection purity.

As the platelets, plasma, white blood cells, and possibly a small number or red blood cells pass through the first outlet port56, these components flow into the fluid chamber30, filled with the priming fluid, so that a saturated fluidized particle bed may be formed. The portion or dome of priming fluid (i.e. saline) trapped along the inner wall of the separation vessel28upstream from the trap dam70guides platelets so that they flow toward the barrier62and the first outlet port56. The trapped fluid reduces the effective passageway volume and area in the separation vessel28and thereby decreases the amount of blood initially required to prime the system in a separation process. The reduced volume and area also induces higher plasma and platelet velocities next to the stratified layer of red blood cells, in particular, to “scrub” platelets, toward the barrier62and first outlet port56. The rapid conveyance of platelets increases the efficiency of collection.

During a blood component separation procedure, the priming fluid trapped upstream from the trap dam70may eventually be replaced by other fluids such as low density, platelet poor plasma flowing in the separation vessel28. Even when this replacement occurs, a dome or portion of trapped fluid is still maintained upstream from the trap dam70.

The relatively gradual slope of the downstream portion104of the trap dam70limits the number of platelets that become reentrained with plasma as plasma flows along the trap dam70. The downstream portion104also reduces the number of platelets accumulated upstream from the barrier62.

The gradually sloped segment110causes formation of a layer of red blood cells across from the trap dam70. The segment110maintains relatively smooth flow transitions in the separation vessel28and reduces the velocity of red blood cells in this region.

During a blood component separation procedure, a bed of red blood cells is preferably maintained along the radial outer wall65of the separation vessel28between the inlet and outlet portions48and50. In addition, the dome or portion of fluid trapped by the trap dam70is preferably maintained along the radial inner wall63of the separation vessel28. The bed of red blood cells and trapped fluid substantially limit, or more preferably prevent, platelets from contacting radially outer and inner walls65and63, respectively, because the platelets are sandwiched between the red blood cell bed and trapped fluid. This is believed to reduce platelet clumping caused when platelets come in contract with structural components of centrifugal separation devices, which are formed of conventional polymer materials. Reduction of platelet clumping is significant because it allows for separation of a greater amount of blood components and does not require the use of as much anticoagulant (AC). For example, the present invention is believed to allow for processing of about 20% more blood, as compared to some conventional dual-stage centrifugal separation devices. In addition, the present invention allows for the use of about a 12 to 1 volume ratio of blood components to AC as compared to a 10 to 1 ratio normally used for some conventional dual-stage centrifugal separation devices, for example.

Accumulated platelets, white blood cells, and some plasma and red blood cells, are removed via the first outlet port56and flow into the fluid chamber30so that the platelets form a saturated fluidized particle bed. The controller89maintains the rotation speed of the rotor12within a predetermined rotational speed range to facilitate formation of this saturated fluidized bed. In addition, the controller89regulates the pump80to convey at least the plasma, platelets, and white blood cells at a predetermined flow rate through the first collection line38and into the inlet34of the fluid chamber30. These flowing blood components displace the priming fluid from the fluid chamber30.

When the platelet and white blood cell particles enter the fluid chamber30, they are subjected to two opposing forces. Plasma flowing through the fluid chamber30with the aid of pump80establishes a first viscous drag force when plasma flowing through the fluid chamber30urges the particles toward the outlet32. A second centrifugal force created by rotation of the rotor12and fluid chamber30acts to urge the particles toward the inlet34.

The controller89preferably regulates the rotational speed of the rotor12and the flow rate of the pump80to collect platelets and white blood cells in the fluid chamber30. As plasma flows through the fluid chamber30, the flow velocity of the plasma decreases and reaches a minimum as the plasma flow approaches the maximum cross-sectional area of the fluid chamber30. Because the rotating centrifuge rotor12creates a sufficient gravitational field in the fluid chamber30, the platelets accumulate near the maximum cross-sectional area of the chamber30, rather than flowing from the chamber30with the plasma. The white blood cells accumulate somewhat radially outward from the maximum cross-sectional area of the chamber30. However, density inversion tends to mix these particles slightly during this initial establishment of the saturated fluidized particle bed.

The larger white blood cells accumulate closer to inlet34than the smaller platelet cells, because of their different sedimentation velocities. Preferably, the rotational speed and flow rate are controlled so that very few platelets and white blood cells flow from the fluid chamber30during formation of the saturated fluidized particle bed.

The platelets and white blood cells continue to accumulate in the fluid chamber30while plasma flows through the fluid chamber30. As the concentration of platelets increases, the interstices between the particles become reduced and the viscous drag force from the plasma flow gradually increases. Eventually the platelet bed becomes a saturated fluidized particle bed within the fluid chamber30. Since the bed is now saturated with platelets, for each new platelet that enters the saturated bed in the fluid chamber30, a single platelet must exit the bed. Thus, the bed operates at a steady state condition with platelets exiting the bed at a rate equal to the rate additional platelets enter the bed after flowing through inlet34.

The saturated bed establishes itself automatically, independent of the concentration of particles flowing into the fluid chamber30. Plasma flowing into the fluid chamber30passes through the platelet bed both before and after the platelet saturation point.

The saturated bed of platelets occupies a varying volume in the fluid chamber30near the maximum cross-sectional area of the chamber30, depending on the flow rate and centrifugal field. The number of platelets in the saturated bed depends on a number of factors, such as the flow rate into the fluid chamber30, the volume of the fluid chamber30, and rotational speed. If these variables remain constant, the number of platelets in the saturated fluidized bed remains substantially constant. When the flow rate of blood components into the fluid chamber30changes, the bed self adjusts to maintain itself by either releasing excess platelets or accepting additional platelets flowing into the fluid chamber30. For example, when the plasma flow rate into the fluid chamber30increases, this additional plasma flow sweeps excess platelets out of the now super-saturated bed, and the bed reestablishes itself in the saturated condition at the increased flow rate. Therefore, the concentration of platelets in the bed is lower due to the release of bed platelets.

After the saturated fluidized bed of platelets forms, flowing plasma carries additional platelets into the fluid chamber30and the bed. These additional platelets add to the bed and increase the viscous drag of the plasma flow through the bed. At some point the viscous drag is sufficient to cause platelets near the maximum cross-section area of the fluid chamber30to exit the saturated bed and fluid chamber30. Thus, if the rotational speed and flow rate into the fluid chamber30remain constant, the number and concentration of platelets flowing into the saturated fluidized bed of platelets substantially equals the number and concentration of platelets released from the bed.

Although the bed is saturated with platelets, a small number of white blood cells may be interspersed in the platelet bed. These white blood cells, however will tend to “fall” or settle out of the platelet bed toward inlet34due to their higher sedimentation velocity. Most white blood cells generally collect within the fluid chamber30between the saturated platelet bed and the inlet34.

Red blood cells in the fluid chamber30also settle toward the fluid chamber inlet34, and some of the red blood cells preferably exit the fluid chamber30via the inlet34while blood components are entering the chamber30via the inlet34. In other words, bidirection flow into and out of the fluid chamber30may take place at the fluid chamber inlet34.

The controller89preferably controls the pump80to limit the number of red blood cells accumulating in the fluid chamber30. For example, the controller89can temporarily reverse flow of the pump80to cause red blood cells and other dense substances to be flushed from the fluid chamber outlet34. In addition, the controller89may cycle the pump80to allow for accumulation of relatively sparse components, such as white blood cells, upstream from the barrier62.

The saturated fluidized bed of platelet particles formed in the fluid chamber30functions as a filter or barrier to white blood cells flowing into the fluid chamber30. When blood components flow into the fluid chamber30, plasma freely passes through the bed. However, the saturated fluidized platelet bed creates a substantial barrier to white blood cells entering the fluid chamber30and retains these white blood cells within the fluid chamber30. Thus, the bed effectively filters white blood cells from the blood components continuously entering the fluid chamber30, while allowing plasma and platelets released from the saturated bed to exit the chamber30. This replenishment and release of platelets is referred to as the bed's self-selecting quality. Substantially all of these filtered white blood cells accumulate within the fluid chamber30between the saturated fluidized platelet bed and the inlet34.

The particle separation or filtration of the saturated fluidized particle bed obviates a number of limitations associated with prior art elutriation. For example, particles may be separated or filtered in a continuous steady state manner without batch processing. In addition, an additional elutriating fluid medium is not required. Furthermore, after the saturated fluidized particle bed is established, flow rates may be varied over a range without changing the size of the particles leaving the fluid chamber30. Unlike prior art elutriation, the present invention establishes a saturated particle bed consisting of numerically predominant particles. This bed automatically passes the predominant particles while rejecting larger particles.

The apparatus and method of the invention separate substantially all of the white blood cells from the platelets and plasma flowing through the fluid chamber30. The barrier to white blood cells is created, at least in part, because white blood cells have a size and sedimentation velocity greater than that of the platelets forming the saturated fluidized particle bed. Therefore, particles of similar densities are separated according to different sizes or sedimentation velocities.

Because the initial separation at barrier62and the saturated fluidized bed remove a majority of the red blood cells and some white blood cells, the fluid exiting the fluid chamber30consists mainly of plasma and platelets. Unlike some conventional porous filters, where the filtered white blood cells are retained in the filter, the present invention allows a substantial fraction of white blood cells to be recovered and returned to the donor.

When the blood components are initially separated within the separation vessel28, a substantial number of platelets may become slightly activated. The saturated fluidized platelet bed allows white blood cells to be filtered from plasma and platelets despite this slight activation. Thus, the present invention does not require a waiting period to filter white blood cells after blood components undergo initial separation in a separation vessel28. This is in contrast to methods using some conventional filters.

After separation, the platelets and plasma exiting the fluid chamber30are collected in appropriate containers and stored for later use. The red blood cells and plasma removed from the vessel28may be combined for donor reinfusion or storage. Alternatively, these components may be further separated by the apparatus10.

If dilution of the platelet concentration is desired, the separation vessel28bshown inFIG. 7may be used to combine plasma removed via the third outlet port60awith the platelets and plasma flowing from the fluid chamber outlet32. This allows for the dilution to take place rapidly without significant intervention by a procedurist.

At the completion of a separation procedure, platelets in the saturated fluidized bed are harvested to recover a substantial number of platelets from the fluid chamber30. During bed harvest, the controller89increases the flow rate and/or decreases the rotational speed of the rotor12to release platelets from the bed. This flushes from the fluid chamber30most of the platelets that made up the saturated fluidized bed to substantially increase platelet yield. The harvesting continues until substantially all of the platelets are removed, and just before an unacceptable number of white blood cells begin to flow from the fluid chamber30.

The remainder of contents of the fluid chamber30, having a high concentration of white blood cells, can be separately collected for later use or recombined with the blood components removed from vessel28for return to a donor.

Although the inventive device and method have been described in terms of removing white blood cells and collecting platelets, this description is not to be construed as a limitation on the scope of the invention. The invention may be used to separate any of the particle components of blood from one another. For example, the saturated fluidized bed may be formed from red blood cells to prevent flow of white blood cells through the fluid chamber22, so long as the red blood cells do not rouleau (clump) excessively. Alternatively, the liquid for carrying the particles may be saline or another substitute for plasma. In addition, the invention may be practiced to remove white blood cells or other components from a bone marrow harvest collection or an umbilical cord cell collection harvested following birth. In another aspect, the invention can be practiced to collect T cells, stem cells, or tumor cells. Further, one could practice the invention by filtering or separating particles from fluids unrelated to either blood or biologically related substances.

It will be apparent to those skilled in the art that various modifications and variations can be made to the structure and methodology of the present invention without departing from the scope or spirit of the invention. For example, the fluid chamber30of the invention may be used in a separation process involving elutriation or any other particle separation means without departing from the scope of the invention. Certain aspects of the invention could also be practiced without the fluid chamber. The invention, in its broadest sense, may also be used to separate many different types of particles and/or components from one another. In addition, the above-mentioned separation vessels28,28a, and28bmay be generally belt shaped and have the inlet portion and outlet portion in separate ends spaced from one another without having the inlet portion connected directly to the outlet portion to form a generally annular shape. Thus, it should be understood that the invention is not limited to the examples discussed in this specification. Rather, the invention is intended to cover modifications and variations provided they come within the scope of the following claims and their equivalents.