Patent Description:
Various blood processing systems now make it possible to collect particular blood constituents, rather than whole blood, from a blood source. Typically, in such systems, whole blood is drawn from a source, the particular blood component or constituent is removed and collected, and the remaining blood constituents are returned to the source.

Whole blood is typically separated into its constituents through centrifugation. This requires that the whole blood be passed through a centrifuge after it is withdrawn from, and before it is returned to, the source. To avoid contamination and possible infection of the source, the blood is preferably contained within a sealed, sterile fluid flow circuit during the entire centrifugation process. Typical blood processing systems thus include a permanent, reusable centrifuge assembly containing the hardware (drive system, pumps, valve actuators, programmable controller, and the like) that spins and pumps the blood, and a disposable, sealed and sterile fluid flow circuit that is mounted in cooperation on the hardware. The centrifuge assembly engages and spins a disposable centrifuge chamber of the fluid flow circuit during a collection procedure. The blood, however, makes actual contact only with the fluid flow circuit, which assembly is used only once and then discarded.

As the whole blood is spun by the centrifuge, the heavier (greater specific gravity) components, such as red blood cells, move radially outwardly away from the center of rotation toward the outer or "high-g" wall of the separation chamber. The lighter (lower specific gravity) components, such as plasma, migrate toward the inner or "low-g" wall of the separation chamber. Various ones of these components can be selectively removed from the whole blood by forming appropriately located channeling seals and outlet ports in the separation chamber.

Separation efficiency and the hematocrit of a separated packed red blood cell product depend upon a number of factors, including the rate at which blood is conveyed into the centrifuge. For example, an increased inflow rate will result in a relatively low hematocrit at a given rotation rate. While it is typically preferred for the hematocrit to remain uniform throughout the course of a separation procedure, it is not uncommon for the flow rate of blood entering the centrifuge to vary throughout a procedure. The inflow rate may change for any of a number of reasons, including a change resulting from venous flow control for a living blood source), such that separation efficiency and the hematocrit of a separated packed red blood cell product may vary throughout a procedure when the rotation rate of the centrifuge remains constant. This may lead to inaccurate yields, inconsistent products, and longer procedure times. Accordingly, it would be advantageous to provide systems and methods in which the rotation rate of a centrifuge changes in response to a change in the rate at which blood is conveyed into the centrifuge during a separation procedure so as to maintain a substantially constant separation efficiency and red blood cell product hematocrit throughout the procedure.

Relevant prior art is for instance disclosed in documents <CIT>, <CIT> and <CIT>.

A fluid processing device according to the present invention comprises the technical features as defined in independent claim <NUM>. A method of separating a bodily fluid according to the present invention comprises the technical features as defined in independent claim <NUM>.

There are several aspects of the present disclosure which may be embodied separately or together in the devices and systems described below. These aspects may be employed alone or in combination with other aspects of the present disclosure, and the description of these aspects together is not intended to preclude the use of these aspects separately.

In one aspect, a fluid processing device includes a controller and a centrifuge configured to receive and rotate a continuous-flow centrifuge chamber of a fluid flow circuit so as to separate a fluid in the centrifuge chamber into at least first and second constituents. The device also includes a pump system configured to convey the fluid through the fluid flow circuit and into the centrifuge chamber at first and second rates. The controller is configured to control the centrifuge to rotate the centrifuge chamber at a first rotation rate when the pump system is conveying the fluid into the centrifuge chamber at the first rate. The controller is further configured to control the centrifuge to rotate the centrifuge chamber at a second rotation rate when the pump system is conveying said fluid into the centrifuge chamber at the second rate. The first and second rotation rates are different, with each of the first and second rotation rates being based at least in part on a concentration of a fluid component within the fluid, the rate at which the pump system is conveying the fluid into the centrifuge chamber, and a target concentration of the fluid component in one of the first and second constituents.

In another aspect, a method of separating a fluid includes conveying the fluid into a continuous-flow centrifuge chamber of a fluid flow circuit at first and second rates and rotating the centrifuge chamber with a centrifuge so as to separate the fluid in the centrifuge chamber into at least first and second constituents. The centrifuge rotates the centrifuge chamber at a first rotation rate when the fluid is being conveyed into the centrifuge chamber at the first rate and at a different second rotation rate when the fluid is being conveyed into the centrifuge chamber at the second rate. Each of the first and second rotation rates is based at least in part on a concentration of a fluid component within the fluid, the rate at which the fluid is being into the centrifuge chamber, and a target concentration of the fluid component in one of the first and second constituents.

These and other aspects of the present subject matter are set forth in the following detailed description of the accompanying drawings.

Therefore, specific designs and features disclosed herein are not to be interpreted as limiting the present disclosure.

<FIG> show components of a blood or fluid processing system that embodies various aspects of the present subject matter. While the system may be described herein in terms of its use in separating blood into two or more components, it should be understood that systems according to the present disclosure can be used for processing a variety of biological or bodily fluids (including fluids containing both bodily and non-bodily fluids, such as anticoagulated blood), as well as non-bodily fluids. It should be further emphasized that when using bodily fluids such as blood the methods using said systems are applied offline; i.e. bodily fluid previously collected (from any patient) is used.

Fluid processing systems according to the present disclosure typically include two principal components, a durable and reusable fluid processing device <NUM> (<FIG>) and a disposable fluid flow circuit <NUM> (<FIG>). The illustrated fluid processing device <NUM> includes a spinning membrane separator drive unit <NUM> (<FIG>), a centrifuge or centrifugal separator <NUM> (<FIG>), additional components that control fluid flow through the disposable flow circuit <NUM>, and a controller <NUM> (<FIG>), which governs the operation of the other components of the fluid processing device <NUM> to perform a procedure selected by the operator. The principles described herein regarding setting the rotation rate of a continuous-flow centrifuge are not limited to any particular fluid processing systems or procedures, so no complete fluid processing devices or procedures will be described in detail herein. However, reference may be made to <CIT> for a detailed description of the fluid processing device <NUM> of <FIG>, along with various exemplary procedures that may be carried out using such a system.

The fluid processing device <NUM> (<FIG>) is configured as a durable item that is capable of long-term use. It should be understood that the fluid processing device <NUM> of <FIG> is merely exemplary of one possible configuration and that fluid processing devices according to the present disclosure may be differently configured. For example, it is within the scope of the present disclosure for the fluid processing device to omit a spinning membrane separator drive unit <NUM>.

In the illustrated embodiment, the fluid processing device <NUM> is embodied in a single housing or case <NUM>. The illustrated case <NUM> includes a generally horizontal portion <NUM> (which may include an inclined or angled face or upper surface for enhanced visibility and ergonomics) and a generally vertical portion <NUM>. The spinning membrane separator drive unit <NUM> and the centrifugal separator <NUM> are shown as being incorporated into the generally horizontal portion <NUM> of the case <NUM>, while the controller <NUM> is shown as being incorporated into the generally vertical portion <NUM>.

The illustrated fluid processing device <NUM> includes a spinner support or spinning membrane separator drive unit <NUM> (<FIG>) for accommodating a generally cylindrical spinning membrane separator <NUM> of a fluid flow circuit <NUM> (<FIG>). <CIT> describes an exemplary spinning membrane separator drive unit that would be suitable for incorporation into the fluid processing device <NUM>, but it should be understood that the spinning membrane separator drive unit <NUM> may be differently configured without departing from the scope of the present disclosure. The principles described herein are specific to setting the rotation rate of the centrifugal separator <NUM>, so the spinning membrane separator drive unit <NUM> is not described in detail herein.

Principles of setting the rotation rate of a continuous-flow centrifuge are described herein in the context of a particularly configured centrifugal separator <NUM> and associated continuous-flow centrifuge chamber or centrifugal separation chamber <NUM> for illustrative purposes, but it should be understood that such principles may be practiced in combination with differently configured centrifugal separators and/or continuous-flow centrifuge chambers, and that the principles described herein are not specific to the illustrated centrifuge chamber <NUM> and/or centrifugal separator <NUM>.

The illustrated centrifugal separator <NUM> includes a centrifuge compartment <NUM> that may receive the other components of the centrifugal separator <NUM> (<FIG>). The centrifuge compartment <NUM> may include a lid <NUM> that is opened to insert and remove a centrifuge chamber <NUM> of the fluid flow circuit <NUM>. During a separation procedure, the lid <NUM> may be closed with the centrifuge chamber <NUM> positioned within the centrifuge compartment <NUM>, as the centrifuge chamber <NUM> is spun or rotated about an axis <NUM> under the power of an electric drive motor or rotor <NUM> of the centrifugal separator <NUM>.

The particular configuration and operation of the centrifugal separator <NUM> depends upon the particular configuration of the centrifuge chamber <NUM> of the fluid flow circuit <NUM>. In one embodiment, the centrifugal separator <NUM> is similar in structure and operation to that of the ALYX system manufactured by Fenwal, Inc. of Lake Zurich, Illinois, which is an affiliate of Fresenius Kabi AG of Bad Homburg, Germany, as described in greater detail in <CIT>. More particularly, the centrifugal separator <NUM> may include a carriage or support <NUM> that holds the centrifuge chamber <NUM> and a yoke member <NUM>. The yoke member <NUM> engages an umbilicus <NUM> of the fluid flow circuit <NUM>, which extends between the centrifuge chamber <NUM> and a cassette <NUM> of the fluid flow circuit <NUM> (<FIG>). The yoke member <NUM> causes the umbilicus <NUM> to orbit around the centrifuge chamber <NUM> at a one omega rotational speed. The umbilicus <NUM> twists about its own axis as it orbits around the centrifuge chamber <NUM>. The twisting of the umbilicus <NUM> about its axis as it rotates at one omega with the yoke member <NUM> imparts a two omega rotation to the centrifuge chamber <NUM>, according to known design. The relative rotation of the yoke member <NUM> at a one omega rotational speed and the centrifuge chamber <NUM> at a two omega rotational speed keeps the umbilicus <NUM> untwisted, avoiding the need for rotating seals.

A fluid is introduced into the centrifuge chamber <NUM> by the umbilicus <NUM>, with the fluid being separated (e.g., into a layer of less dense components, such as platelet-rich plasma, if the fluid is blood, and a layer of more dense components, such as packed red blood cells, if the fluid is blood) within the centrifuge chamber <NUM> as a result of centrifugal forces as it rotates. Components of an interface monitoring assembly may be positioned within the centrifuge compartment <NUM> to oversee separation of fluid within the centrifuge chamber <NUM>. As shown in <FIG>, the interface monitoring assembly may include a light source <NUM> and a light detector <NUM>, which is positioned and oriented to receive at least a portion of the light emitted by the light source <NUM>. The illustrated light source <NUM> and light detector <NUM> are associated with stationary surfaces of the centrifuge compartment <NUM>, but either or both may instead be associated with a movable structure or component of the fluid processing device <NUM>, as in <CIT>.

The orientation of the various components of the interface monitoring system depends at least in part on the particular configuration of the centrifuge chamber <NUM>, which will be described in greater detail herein. In general, though, the light source <NUM> emits a light beam "L" (e.g., a laser light beam) through the separated fluid components within the centrifuge chamber <NUM> (which may be formed of a material that substantially transmits the light L or at least a particular wavelength of the light L without absorbing it). A portion of the light L reaches the light detector <NUM>, which transmits a signal to the controller <NUM> that is indicative of the location of an interface between the separated fluid components. If the controller <NUM> determines that the interface is in the wrong location (which can affect the separation efficiency of the centrifugal separator <NUM> and/or the quality of the separated blood components), then it can issue commands to the appropriate components of the fluid processing device <NUM> to modify their operation so as to move the interface to the proper location.

In addition to the spinning membrane separator drive unit <NUM> and the centrifugal separator <NUM>, the fluid processing device <NUM> may include other components compactly arranged to aid fluid processing.

The generally horizontal portion <NUM> of the case <NUM> of the illustrated fluid processing device <NUM> includes a cassette station <NUM>, which accommodates a cassette <NUM> of the fluid flow circuit <NUM> (<FIG>). In one embodiment, the cassette station <NUM> is similarly configured to the cassette station of <CIT>, but is adapted to include additional components and functionality. The illustrated cassette station <NUM> includes a plurality of clamps or valves V1-V9 (<FIG>), which move between a plurality of positions (e.g., between a retracted or lowered position and an actuated or raised position) to selectively contact or otherwise interact with corresponding valve stations C1-C9 of the cassette <NUM> of the fluid flow circuit <NUM> (<FIG> and <FIG>). Depending on the configuration of the fluid flow circuit <NUM>, its cassette <NUM> may not include a valve station C1-C9 for each valve V1-V9 of the cassette station <NUM>, in which case fewer than all of the valves V1-V9 will be used in a separation procedure.

In the actuated position, a valve V1-V9 engages the associated valve station C1-C9 to prevent fluid flow through that valve station C1-C9 (e.g., by closing one or more ports associated with the valve station C1-C9, thereby preventing fluid flow through that port or ports). In the retracted position, a valve V1-V9 is disengaged from the associated valve station C1-C9 (or less forcefully contacts the associated valve station C1-C9 than when in the actuated position) to allow fluid flow through that valve station C1-C9 (e.g., by opening one or more ports associated with the valve station C1-C9, thereby allowing fluid flow through that port or ports). Additional clamps or valves V10 and V11 may be positioned outside of the cassette station <NUM> to interact with portions or valve stations C10 and C11 (which may be lengths of tubing) of the fluid flow circuit <NUM> to selectively allow and prevent fluid flow therethrough. The valves V1-V9 and corresponding valve stations C1-C9 of the cassette station <NUM> and cassette <NUM> may be differently configured and operate differently from the valves V10 and V11 and valve stations C10 and C11 that are spaced away from the cassette station <NUM>.

The cassette station <NUM> may be provided with additional components, such as pressure sensors A1-A4, which interact with sensor stations S1-S4 of the cassette <NUM> to monitor the pressure at various locations of the fluid flow circuit <NUM>. Other pressure sensors A1-A4 may monitor the pressure of the spinning membrane separator <NUM> and the centrifuge chamber <NUM>. The controller <NUM> may receive signals from the pressure sensor A1-A4 that are indicative of the pressure within the fluid flow circuit <NUM> and, if a signal indicates a low- or high-pressure condition, the controller <NUM> may initiate an alarm or error condition to alert an operator to the condition and/or to attempt to bring the pressure to an acceptable level without operator intervention.

The fluid processing device <NUM> may also include a plurality of pumps P1-P6 (which may be collectively referred to as a pump system) to cause fluid to flow through the fluid flow circuit <NUM>. The pumps P1-P6 may be differently or similarly configured and/or function similarly or differently from each other. In the illustrated embodiment, the pumps P1-P6 are configured as peristaltic pumps, which may be generally configured as described in <CIT>. Each pump P1-P6 engages a different tubing loop T1-T6 extending from a side surface of the cassette <NUM> (<FIG>) and may be selectively operated under command of the controller <NUM> to cause fluid to flow through a portion of the fluid flow circuit <NUM>, as will be described in greater detail. In one embodiment, all or a portion of the cassette station <NUM> may be capable of translational motion in and out of the case <NUM> to allow for automatic loading of the tubing loops T1-T6 into the associated pump P1-P6.

The illustrated fluid processing device <NUM> also includes an optical detection assembly or centrifugal separator sensor M1 for determining one or more properties of fluids flowing out of and/or into the centrifugal separator <NUM>. If the fluid flowing out of the centrifugal separator <NUM> includes red blood cells, the centrifugal separator sensor M1 may be configured to determine the hematocrit of the fluid. If the fluid flowing out of the centrifugal separator <NUM> is platelet-rich plasma, the centrifugal separator sensor M1 may be configured to determine the platelet concentration of the platelet-rich plasma. The centrifugal separator sensor M1 may detect the one or more properties of a fluid by optically monitoring the fluid as it flows through tubing of the fluid flow circuit <NUM> or by any other suitable approach. The controller <NUM> may receive signals from the centrifugal separator sensor M1 that are indicative of the nature of flow into and out of the centrifuge separator <NUM> (e.g., whether air or a liquid flow is flowing through an inlet or outlet conduit connected to the centrifuge chamber <NUM>, whether fluid is flowing through such conduit or is stagnant, etc.) and use the signals to optimize the separation procedure. If one or more properties of a fluid flowing into or out of the centrifuge chamber <NUM> is outside of an acceptable range, then the controller <NUM> may initiate an alarm or error condition to alert an operator to the condition. Exemplary optical detection assemblies are described in <CIT> and <CIT>, but it should be understood that a different approach may also be employed for optically monitoring fluid flow into and out of the centrifugal separator <NUM>.

The illustrated fluid processing device <NUM> further includes a spinner outlet sensor M2, which accommodates tubing of the fluid flow circuit <NUM> that flows a separated substance out of the spinning membrane separator <NUM>. The spinner outlet sensor M2 monitors the substance to determine one or more properties of the substance, and may do so by optically monitoring the substance as it flows through the tubing or by any other suitable approach. In one embodiment, separated plasma flows through the tubing, in which case the spinner outlet sensor M2 may be configured to determine the amount of cellular blood components in the plasma and/or whether the plasma is hemolytic and/or lipemic. This may be done using an optical monitor of the type described in <CIT> or by any other suitable device and/or method.

The illustrated fluid processing device <NUM> also includes an air detector M3 (e.g., an ultrasonic bubble detector), which accommodates tubing of the fluid flow circuit <NUM> that flows fluid to a recipient. It may be advantageous to prevent air from reaching the recipient, so the air detector M3 may transmit signals to the controller <NUM> that are indicative of the presence or absence of air in the tubing. If the signal is indicative of air being present in the tubing, the controller <NUM> may initiate an alarm or error condition to alert an operator to the condition and/or to take corrective action to prevent the air from reaching the recipient (e.g., by reversing the flow of fluid through the tubing or diverting flow to a vent location).

The generally vertical portion <NUM> of the case <NUM> may include a plurality of weight scales W1-W6 (six are shown, but more or fewer may be provided), each of which may support one or more fluid containers F1-F7 of the fluid flow circuit <NUM> (<FIG>). The containers F1-F7 receive fluid components or waste products separated during processing or assorted non-biological fluids (e.g., priming fluids, intravenous fluids, or additive fluids). Each weight scale W1-W6 transmits to the controller <NUM> a signal that is indicative of the weight of the fluid within the associated container F1-F7 to track the change of weight during the course of a procedure. This allows the controller <NUM> to process the incremental weight changes to derive fluid processing volumes and flow rates and subsequently generate signals to control processing events based, at least in part, upon the derived processing volumes. For example, the controller <NUM> may diagnose leaks and obstructions in the fluid flow circuit <NUM> and alert an operator.

The illustrated case <NUM> is also provided with a plurality of hooks or supports K1 and K2 that may support various components of the fluid flow circuit <NUM> or other suitably sized and configured objects.

As described above, the fluid processing device <NUM> includes a controller <NUM>, which is suitably configured and/or programmed to control operation of the fluid processing device <NUM>. In one embodiment, the controller <NUM> comprises a main processing unit (MPU), which can comprise, e.g., a Pentium™ type microprocessor made by Intel Corporation, although other types of conventional microprocessors can be used. In one embodiment, the controller <NUM> may be mounted inside the generally vertical portion <NUM> of the case <NUM>, adjacent to or incorporated into an operator interface station (e.g., a touchscreen). In other embodiments, the controller <NUM> and operator interface station may be associated with the generally horizontal portion <NUM> or may be incorporated into a separate device that is connected (either physically, by a cable or the like, or wirelessly) to the fluid processing device <NUM>.

The controller <NUM> is configured and/or programmed to execute at least one fluid processing application but, more advantageously, is configured and/or programmed to execute a variety of different fluid processing applications. For example, the controller <NUM> may be configured and/or programmed to carry out one or more of the following: a double unit red blood cell collection procedure, a plasma collection procedure, a plasma/red blood cell collection procedure, a red blood cell/platelet/plasma collection procedure, a platelet collection procedure, a platelet/plasma collection procedure, and a mononuclear cell collection procedure. Additional or alternative procedure applications (e.g., plasma exchange, red blood cell exchange, and photopheresis) can be included without departing from the scope of the present disclosure.

More particularly, in carrying out any one of these fluid processing applications, the controller <NUM> is configured and/or programmed to control one or more of the following tasks: drawing fluid into a fluid flow circuit <NUM> mounted to the fluid processing device <NUM>, conveying fluid through the fluid flow circuit <NUM> to a location for separation (i.e., into the spinning membrane separator <NUM> or the centrifuge chamber <NUM> of the fluid flow circuit <NUM>), separating the fluid into two or more components as desired, and conveying the separated components into storage containers, to a second location for further separation (e.g., into whichever of the spinning membrane separator <NUM> and centrifuge chamber <NUM> that was not used in the initial separation stage), or to a recipient (which may be the source from which the fluid was originally drawn).

This may include instructing the spinning membrane separator drive unit <NUM> and/or the centrifugal separator <NUM> to operate at a particular rotational speed and instructing a pump to convey fluid through a portion of the fluid flow circuit <NUM> at a particular flow rate. Hence, while it may be described herein that a particular component of the fluid processing device <NUM> (e.g., the spinning membrane separator drive unit <NUM> or the centrifugal separator <NUM>) performs a particular function, it should be understood that that component is being controlled by the controller <NUM> to perform that function.

Before, during, and after a procedure, the controller <NUM> may receive signals from various components of the fluid processing device <NUM> to monitor various aspects of the operation of the fluid processing device <NUM> and characteristics of the fluid and separated fluid components as they flow through the fluid flow circuit <NUM>. If the operation of any of the components and/or one or more characteristics of the fluid or separated fluid components is outside of an acceptable range, then the controller <NUM> may initiate an alarm or error condition to alert the operator and/or take action to attempt to correct the condition. The appropriate corrective action will depend upon the particular error condition and may include action that is carried out with or without the involvement of an operator.

For example, the controller <NUM> may include an interface control module, which receives signals from the light detector <NUM> of the interface monitoring assembly and the centrifugal separator sensor M1. The signals that the controller <NUM> receives from the light detector <NUM> are indicative of the location of an interface between the separated fluid components within the centrifuge chamber <NUM>, while the signals from the centrifugal separator sensor M1 indicate whether the target interface location should be adjusted. If the controller <NUM> determines that the interface is in the wrong location, then it can issue commands to the appropriate components of the fluid processing device <NUM> to modify their operation so as to move the interface to the proper location. For example, the controller <NUM> may instruct the pump system to cause fluid to flow into the centrifuge chamber <NUM> at a different rate and/or for a separated fluid component to be removed from the centrifuge chamber <NUM> at a different rate and/or for the centrifuge chamber <NUM> to be spun at a different speed by the centrifugal separator <NUM>.

If provided, an operator interface station associated with the controller <NUM> allows the operator to view on a screen or display (in alpha-numeric format and/or as graphical images) information regarding the operation of the system. The operator interface station also allows the operator to select applications to be executed by the controller <NUM>, as well as to change certain functions and performance criteria of the system. If configured as a touchscreen, the screen of the operator interface station can receive input from an operator via touch-activation. Otherwise, if the screen is not a touchscreen, then the operator interface station may receive input from an operator via a separate input device, such as a computer mouse or keyboard. It is also within the scope of the present disclosure for the operator interface station to receive input from both a touchscreen and a separate input device, such as a keypad.

As for the fluid flow circuit or flow set <NUM> (<FIG>), it is intended to be a sterile, single use, disposable item. Before beginning a given procedure, the operator loads various components of the fluid flow circuit <NUM> in the case <NUM> in association with the fluid processing device <NUM>. The controller <NUM> implements the procedure based upon preset protocols, taking into account other input from the operator. Upon completing the procedure, the operator removes the fluid flow circuit <NUM> from association with the fluid processing device <NUM>. The portions of the fluid flow circuit <NUM> holding the collected fluid component or components (e.g., collection containers or bags) are removed from the case <NUM> and retained for storage, immediate use, or further processing. The remainder of the fluid flow circuit <NUM> is removed from the case <NUM> and discarded.

A variety of different disposable fluid flow circuits may be used in combination with the fluid processing device <NUM>, with the appropriate fluid flow circuit depending on the procedure to be carried out using the system. Generally speaking, though, the fluid flow circuit <NUM> includes a cassette <NUM> (<FIG>) to which the other components of the fluid flow circuit <NUM> are connected by flexible tubing or conduits. The other components may include a plurality of fluid containers F1-F7 (for holding fluid to be processed, a separated fluid component, a priming fluid, or an additive solution, for example), one or more fluid source access devices (e.g., a connector for accessing fluid within a fluid container), a centrifuge chamber <NUM> (<FIG>), and (optionally) a spinning membrane separator <NUM>.

<FIG> illustrates an exemplary fluid flow circuit <NUM> having a single fluid access device (e.g., a phlebotomy needle) for alternately drawing fluid into the fluid flow circuit <NUM> and conveying fluid out of the fluid flow circuit <NUM>. It should be understood that the illustrated fluid flow circuit <NUM> is merely exemplary and that the principles described herein may be employed with differently configured fluid flow circuits. This may include fluid flow circuits having a pair of fluid access devices, with one dedicated to drawing fluid into the fluid flow circuit and other being dedicated to conveying fluid out of the fluid flow circuit.

The cassette <NUM> (<FIG>) provides a centralized, programmable, integrated platform for all the pumping and many of the valving functions required for a given fluid processing procedure. In one embodiment, the cassette <NUM> is similarly configured to the cassette of <CIT>, but is adapted to include additional components (e.g., more tubing loops T1-T6) and functionality.

In use, the cassette <NUM> is mounted to the cassette station <NUM> of the fluid processing device <NUM>, with a flexible diaphragm of the cassette <NUM> placed into contact with the cassette station <NUM>. The flexible diaphragm overlays an array of interior cavities formed by the body of the cassette <NUM>. The different interior cavities define sensor stations S1-S4, valve stations C1-C9, and a plurality of flow paths or conduits. The side of the cassette <NUM> opposite the flexible diaphragm may be sealed by another flexible diaphragm or a rigid cover, thereby sealing fluid flow through the cassette <NUM> from the outside environment.

Each sensor station S1-S4 is aligned with an associated pressure sensor A1-A4 of the cassette station <NUM>, with each pressure sensor A1-A4 capable of monitoring the pressure within the associated sensor station S1-S4. Each valve station C1-C9 is aligned with an associated valve V1-V9, and may define one or more ports that allow fluid communication between the valve station C1-C9 and another interior cavity of the cassette <NUM> (e.g., a flow path). As described above, each valve V1-V9 is movable under command of the controller <NUM> to move between a plurality of positions (e.g., between a retracted or lowered position and an actuated or raised position) to selectively contact the valve stations C1-C9 of the cassette <NUM>. In the actuated position, a valve V1-V9 engages the associated valve station C1-C9 to close one or more of its ports to prevent fluid flow therethrough. In the retracted position, a valve V1-V9 is disengaged from the associated valve station C1-C9 (or less forcefully contacts the associated valve station C1-C9 than when in the actuated position) to open one or more ports associated with the valve station C1-C9, thereby allowing fluid flow therethrough.

As described, a plurality of tubing loops T1-T6 extend from the side surface of the cassette <NUM> to interact with pumps P1-P6 of the fluid processing device <NUM>. In the illustrated embodiment, six tubing loops T1-T6 extend from the cassette <NUM> to be received by a different one of six pumps P1-P6, but in other embodiments, a procedure may not require use of all of the pumps P1-P6, in which case the cassette <NUM> may include fewer than six tubing loops. The different pumps P1-P6 may interact with the tubing loops T1-T6 of the cassette <NUM> to perform different tasks during a separation procedure, as will be described in greater detail. Certain procedures require fewer than all of the sensor stations, valve stations, and/or tubing loops illustrated in the exemplary cassette <NUM> of <FIG>, such that it should be understood that the cassettes of different fluid flow circuits <NUM> may be differently configured (e.g., with fewer sensor stations, valve stations, and/or tubing loops) without departing from the scope of the present disclosure.

Additional tubing or conduits extend from the side surface of the cassette <NUM> to connect to the other components of the fluid flow circuit <NUM>, such as the various fluid containers F1-F7, the spinning membrane separator <NUM>, and the centrifuge chamber <NUM>. The number and content of the various fluid containers F1-F7 depends upon the procedure for which the fluid flow circuit <NUM> is used, so they will be described in greater detail with respect to an exemplary procedure. The tubing connected to the centrifuge chamber <NUM> (which includes one inlet conduit and two outlet conduits) may be aggregated into an umbilicus <NUM> (<FIG>) that is engaged by the yoke member <NUM> of the centrifugal separator <NUM> (as described above) to cause the umbilicus <NUM> to orbit around and spin or rotate the centrifuge chamber <NUM> during a separation procedure.

Various additional components may be incorporated into the tubing leading out of the cassette <NUM> or into one of the cavities of the cassette <NUM>. For example, as shown in <FIG>, a manual clamp <NUM> may be associated with a line or lines leading to the fluid source and/or fluid recipient, a return line filter <NUM> (e.g., a microaggregate filter) may be associated with a line leading to a fluid recipient, filters may be positioned upstream of one or more of the fluid containers to remove a substance (e.g., leukocytes) from a separated component (e.g., red blood cells) flowing into the fluid container, and/or an air trap <NUM> may be positioned on a line upstream of the centrifuge chamber <NUM>.

An exemplary centrifuge chamber <NUM> is shown in <FIG> and <FIG>, while <FIG> illustrates the fluid flow path defined by the centrifuge chamber <NUM>. In the illustrated embodiment, the body of the centrifuge chamber <NUM> is pre-formed in a desired shape and configuration (e.g., by injection molding) from a rigid, biocompatible plastic material, such as a non-plasticized medical grade acrylonitrile-butadiene-styrene (ABS). All contours, ports, channels, and walls that affect the fluid separation process are preformed in a single, injection molded operation. Alternatively, the centrifuge chamber <NUM> can be formed by separate molded parts, either by nesting cup-shaped subassemblies or two symmetric halves.

The underside of the centrifuge chamber <NUM> includes a shaped receptacle <NUM> that is suitable for receiving an end of the umbilicus <NUM> of the fluid flow circuit <NUM> (<FIG>). A suitable receptacle <NUM> and the manner in which the umbilicus <NUM> may cooperate with the receptacle <NUM> to deliver fluid to and remove fluid from the centrifuge chamber <NUM> are described in greater detail in <CIT>.

The illustrated centrifuge chamber <NUM> has radially spaced apart inner (low-g) and outer (high-g) side wall portions <NUM> and <NUM>, a bottom or first end wall portion <NUM>, and a cover or second end wall portion <NUM>. The cover <NUM> comprises a simple flat part that can be easily welded or otherwise secured to the body of the centrifuge chamber <NUM>. Because all features that affect the separation process are incorporated into one injection molded component, any tolerance differences between the cover <NUM> and the body of the centrifuge chamber <NUM> will not affect the separation efficiencies of the centrifuge chamber <NUM>. The wall portions <NUM> and <NUM>, the bottom <NUM>, and the cover <NUM> together define an enclosed, generally annular channel <NUM> (<FIG>).

An inlet <NUM> communicating with the channel <NUM> is defined between opposing interior radial walls <NUM> and <NUM>. One of the interior walls <NUM> joins the outer (high-g) wall portion <NUM> and separates the upstream and downstream ends of the channel <NUM>. The interior walls <NUM> and <NUM> define the inlet passageway <NUM> of the centrifuge chamber <NUM> which, in one flow configuration, allows fluid to flow from the umbilicus <NUM> to the upstream end of the channel <NUM>.

The illustrated centrifuge chamber <NUM> further includes first and second outlets <NUM> and <NUM>, respectively, which may be defined by opposing surfaces of interior radial walls. Both the first and second outlets <NUM> and <NUM> extend radially inward from the channel <NUM>. The first (low-g) outlet <NUM> extends radially inward from an opening which, in the illustrated embodiment, is located at the inner side wall portion <NUM>, while the second (high-g) outlet <NUM> extends radially inward from an opening that is associated with the outer side wall portion <NUM>. The illustrated first outlet <NUM> is positioned adjacent to the inlet <NUM> (near the upstream end of the channel <NUM>), while the second outlet <NUM> may be positioned at the opposite, downstream end of the channel <NUM>.

It should be understood that the centrifuge chamber <NUM> illustrated in <FIG> is merely exemplary and that the centrifuge chamber <NUM> may be differently configured without departing from the scope of the present disclosure. For example, <CIT> describes other exemplary centrifuge chamber configurations that may be used in combination with the principles described herein.

Fluid flowed into the channel <NUM> separates into an optically dense layer "R" and a less optically dense layer "P" (<FIG>) as the centrifuge chamber <NUM> is rotated about the rotational axis <NUM>. The optically dense layer R forms as larger and/or heavier fluid particles move under the influence of centrifugal force toward the outer (high-g) wall portion <NUM>. If the fluid being separated is blood, the optically dense layer R will typically include red blood cells but, depending on the speed at which the centrifuge chamber <NUM> is rotated, other cellular components (e.g., larger white blood cells) may also be present in the optically dense layer R.

If the fluid being separated is blood, the less optically dense layer P typically includes a plasma constituent, such as platelet-rich plasma or platelet-poor plasma. Depending on the speed at which the centrifuge chamber <NUM> is rotated and the length of time that the blood is resident therein, other components (e.g., smaller white blood cells and anticoagulant) may also be present in the less optically dense layer P.

In one embodiment, fluid introduced into the channel <NUM> via the inlet <NUM> will travel in a generally clockwise direction (in the orientation of <FIG>) as the optically dense layer R separates from the less optically dense layer P. The optically dense layer R continues moving in the clockwise direction as it travels the length of the channel <NUM> along the outer side wall portion <NUM>, from the upstream end to the downstream end, where it exits the channel <NUM> via the second outlet <NUM>. The less optically dense layer P separated from the optically dense layer R reverses direction, moving counterclockwise along the inner side wall portion <NUM> to the first outlet <NUM>, adjacent to the inlet <NUM>.

The transition between the optically dense layer R and the less optically dense layer P may be referred to as the interface "N". If the fluid being separated is blood, a buffy coat containing mononuclear cells and peripheral blood stem cells may be located at the interface N. The location of the interface N within the channel <NUM> of the centrifuge chamber <NUM> can dynamically shift during fluid processing, as <FIG> show. If the location of the interface N is too high (that is, if it is too close to the inner side wall portion <NUM> and the first outlet <NUM>, as in <FIG>), red blood cells can flow into the first outlet <NUM>, potentially adversely affecting the quality of the low density components (platelet-rich plasma or platelet-poor plasma). On the other hand, if the location of the interface N is too low (that is, if it resides too far away from the inner wall portion <NUM>, as <FIG> shows), the collection efficiency of the system may be impaired. The ideal or target interface location may be experimentally determined, which may vary depending on any of a number of factors (e.g., the configuration of the centrifuge chamber <NUM>, the rate at which the centrifuge chamber <NUM> is rotated about the rotational axis <NUM>, etc.).

As described above, the fluid processing device <NUM> may include an interface monitoring assembly (including the light source <NUM> and the light detector <NUM>), a centrifugal separator sensor M1, and a controller <NUM> with an interface control module to monitor and, as necessary, adjust or correct the position of the interface N. In the illustrated embodiment, the centrifuge chamber <NUM> is formed with a ramp <NUM> extending from the high-g wall portion <NUM> at an angle α across at least a portion of the channel <NUM> (<FIG> and <FIG>). The angle α, measured with respect to the rotational axis <NUM> is about <NUM>° in one embodiment. <FIG> show the orientation of the ramp <NUM> when viewed from the low-g side wall portion <NUM> of the centrifuge chamber <NUM>. Although it describes a flexible separation chamber, the general structure and function of the ramp <NUM> may be better understood with reference to <CIT>. The ramp <NUM> may be positioned at any of a number of locations between the upstream and downstream ends of the channel <NUM>, but in one embodiment, the ramp <NUM> may be positioned generally adjacent to the first outlet <NUM>, in the path of fluid and/or a fluid component moving from the inlet <NUM> to the first outlet <NUM>.

The ramp <NUM> makes the interface N between the optically dense layer R and the less optically dense layer P more discernible for detection, displaying the optically dense layer R, less optically dense layer P, and interface N for viewing through a light-transmissive portion of the centrifuge chamber <NUM>. To that end, the ramp <NUM> and at least the portion of the centrifuge chamber <NUM> angularly aligned with the ramp <NUM> may be formed of a light-transmissive material, although it may be advantageous for the entire centrifuge chamber <NUM> to be formed of the same light-transmissive material.

In the illustrated embodiment, the light source <NUM> of the interface monitoring system is associated with a fixture or wall of the centrifuge compartment <NUM> and oriented to emit a light L that is directed toward the rotational axis <NUM> of the centrifugal separator <NUM>, as shown in <FIG>. If the light detector <NUM> is positioned at an angle with respect to the light source <NUM> (as in the illustrated embodiment), the light L emitted by the light source <NUM> must be redirected from its initial path before it will reach the light detector <NUM>. In the illustrated embodiment, the light L is redirected by a reflector that is associated with a light-transmissive portion of the inner side wall portion <NUM>, as shown in <FIG>. The reflector may be a separate piece that is secured to the inner side wall portion <NUM> (e.g., by being bonded thereto) or may be integrally formed with the body of the centrifuge chamber <NUM>.

In one embodiment, the reflector may be a reflective surface, such as a mirror, that is oriented (e.g., at a <NUM>° angle) to direct light L emitted by the light source <NUM> to the light detector <NUM>. In another embodiment, the reflector is provided as a prismatic reflector <NUM> (<FIG>), which is formed of a light-transmissive material (e.g., a clear plastic material) and has inner and outer walls <NUM> and <NUM> and first and second end walls <NUM> and <NUM> (<FIG>). The inner wall <NUM> is positioned against the inner side wall portion <NUM> of the centrifuge chamber <NUM> and is oriented substantially perpendicular to the initial path of the light L from the light source <NUM>. This allows light L from the light source <NUM> to enter into the prismatic reflector <NUM> via the inner wall <NUM> while continuing along its initial path. The light L continues through the prismatic reflector <NUM> along its initial path until it encounters the first end wall <NUM>. The first end wall <NUM> is oriented at an angle (e.g., an approximately <NUM>° angle) with respect to the inner wall <NUM> and the second end wall <NUM>, causing the light L to be redirected within the prismatic reflector <NUM>, rather than exiting the prismatic reflector <NUM> via the first end wall <NUM>.

The first end wall <NUM> directs the light L at an angle to its initial path (which may be an approximately <NUM>° angle, directing it from a path toward the rotational axis <NUM> to a path that is generally parallel to the rotational axis <NUM>) toward the second end wall <NUM> (<FIG>). The first end wall <NUM> and the inner and outer walls <NUM> and <NUM> of the prismatic reflector <NUM> may be configured to transmit the redirected light L from the first end wall <NUM> to the second end wall <NUM> by total internal reflection. The second end wall <NUM> is oriented substantially perpendicular to the redirected path of the light L through the prismatic reflector <NUM>, such that the light L will exit the prismatic reflector <NUM> via the second end wall <NUM>, continuing along its redirected path. In one embodiment, the second end wall <NUM> is roughened or textured or otherwise treated or conditioned to diffuse the light L as it exits the prismatic reflector <NUM>, which may better ensure that the light L reaches the light detector <NUM> (<FIG>).

The prismatic reflector <NUM> may be angularly aligned with the ramp <NUM>, such that the light L from the light source <NUM> will only enter into the prismatic reflector <NUM> when the ramp <NUM> has been rotated into the path of the light L. At all other times (when the ramp <NUM> is not in the path of the light L), the light L will not reach the prismatic reflector <NUM> and, thus, will not reach the light detector <NUM>.

Upon the ramp <NUM> first being rotated into the path of the light L from the light source <NUM>, the light L will begin to reach the prismatic reflector <NUM>, which directs the light L to the light detector <NUM>. This causes the voltage output of the light detector <NUM> (i.e., the signal transmitted from the light detector <NUM> to the controller <NUM>) to increase to a non-zero value or state. The ramp <NUM> and prismatic reflector <NUM> are eventually rotated out of alignment with the light source <NUM>, at which time no light L will reach the prismatic reflector <NUM> and the voltage output of the light detector <NUM> will return to a low- or zero-state.

During the time that the ramp <NUM> and prismatic reflector <NUM> are rotated through the path of the light L from the light source <NUM>, the light L continues through the channel <NUM> and the fluids in the channel <NUM>. At least a portion of the light L (i.e., the portion not absorbed or reflected by the fluids) exits the channel <NUM> by striking and entering a light-transmissive portion of the inner side wall portion <NUM>. The light L passes through the inner side wall portion <NUM> and enters the prismatic reflector <NUM>, which redirects the light L from its initial path to the light detector <NUM>, as described above.

The light detector <NUM> generates a signal that is transmitted to the interface control module of the controller <NUM>, which can determine the location of the interface N on the ramp <NUM>. In one embodiment, the location of the interface N is associated with a change in the amount of light L that is transmitted through the less optically dense layer P and the optically dense layer R. For example, the light source <NUM> may be configured to emit a light L that is more readily transmitted by platelet-rich plasma or platelet-poor plasma than by red blood cells, such as red visible light (from a laser or a differently configured light source L), which is substantially absorbed by red blood cells. The less optically dense layer P and the optically dense layer R each occupy a certain portion of the ramp <NUM>, with the light detector <NUM> receiving different amounts of light L depending on whether the light L travels through the less optically dense layer P on the ramp <NUM> or the optically dense layer R on the ramp <NUM>. The percentage of the ramp <NUM> occupied by each layer is related to the location of the interface N in the channel <NUM>. Thus, by measuring the amount of time that the voltage output or signal from the light detector <NUM> is relatively high (corresponding to the time during which the light L is passing through only the less optically dense layer P on the ramp <NUM>), the controller <NUM> may determine the location of the interface N and take steps to correct the location of the interface N, if necessary. An exemplary approach to adjustment of the position of the interface N is described in greater detail in <CIT>.

Depending on the fluid separation objectives, there is a suitable procedure for separating and collecting any of a variety of different fluid components, either alone or in combination with other fluid components. Accordingly, prior to processing, an operator selects the desired protocol (e.g., using an operator interface station, if provided), which informs the controller <NUM> of the manner in which it is to control the other components of the fluid processing device <NUM> during the procedure.

The operator may also proceed to enter various parameters. In the case of blood separation, this may include information regarding the blood source, along with the target yield for the various blood components (which may also include entering a characteristic of the blood, such as a platelet pre-count) or some other collection control system (e.g., the amount of whole blood to be processed).

If there are any fluid containers (e.g., a storage solution container) that are not integrally formed with the fluid flow circuit <NUM>, they may be connected to the fluid flow circuit <NUM> (e.g., by piercing a septum of a tube of the fluid flow circuit <NUM> or via a luer connector), with the fluid flow circuit <NUM> then being mounted to the fluid processing device <NUM> (including the fluid containers F1-F7 being hung from the weight scales W1-W6 and the hooks or supports H1 and H2, as appropriate). An integrity check of the fluid flow circuit <NUM> may be executed by the controller <NUM> to ensure the various components are properly connected and functioning.

Following a successful integrity check, the fluid flow circuit <NUM> is primed to move air contained in the various conduits and in the centrifuge chamber <NUM> into a more suitable location (e.g., a waste container). The selected procedure then commences, with fluid being conveyed into the fluid flow circuit <NUM> from a source and separated in the centrifuge chamber <NUM> within the centrifugal separator <NUM>.

Conventionally, during a given stage of a multi-stage procedure, the centrifugal separator <NUM> will operate at a uniform or constant rotation rate to separate fluid in the centrifuge chamber <NUM> into two or more constituents. However, the rate at which fluid is conveyed into the centrifuge chamber <NUM> during an individual stage may vary, which will affect the separation efficiency of the fluid processing device <NUM>. To avoid a change in separation efficiency, the rotation rate of the centrifugal separator <NUM> may be adjusted in response to a change in the rate at which fluid is pumped into the centrifuge chamber <NUM>. In general, it has been found that a decrease in inflow rate is best addressed by a corresponding decrease in the rotation rate of the centrifugal separator <NUM> (with an increase in inflow rate being addressed by an increase in the rotation rate), but more precise controls are advantageous to ensure that separation efficiency remains substantially unaffected by a change in inflow rate.

More particularly, the rotation rate per minute ("RPM") of a continuous flow centrifuge determines the centrifugal g-force applied to a fluid within the centrifuge, based on the following relationships:
<MAT> and
<MAT> where g is the acceleration or g-force and r is the radius of the centrifuge.

The g-force is an important aspect in the determination of separation efficiency and may be one of the few parameters controllable by the fluid processing device <NUM>. The following two relationships govern the separation efficiency of a continuous flow centrifuge separating whole blood into packed red blood cells and platelet-rich plasma:
<MAT> and
<MAT> where HRBC is the hematocrit of the packed red blood cells exiting the centrifuge, HWB is the hematocrit of the whole blood being pumped into the centrifuge, β is a shear sensitive constant, QWB is the inlet flow rate, Asep is the separation area of the centrifuge, and SRBC is the sedimentation coefficient of red blood cells. It should be understood that β and SRBC may depend on a variety of factors (which are familiar to those of ordinary skill in the art), but in one exemplary embodiment described in greater detail in <CIT>, the quantity β/SRBC may be expressed as <NUM> x <NUM><NUM> s-<NUM>.

While the relationships of Equations [<NUM>] and [<NUM>] are presented in the context of blood separation, it should be understood that they may be generalized to separation of other types of fluid. For example, HRBC may be replaced by the target concentration of a fluid component in a fluid constituent exiting the centrifuge, with HWB being replaced by the concentration of that fluid component in the fluid being conveyed into the centrifuge, and SRBC being replaced by the sedimentation coefficient of that fluid component.

The variables of most importance in this analysis tend to be the inlet flow rate (QWB) and the g-force (g), which act inversely to one another. Typically, the other variables will remain constant throughout a procedure but, if not, changes may be accounted for by updating the variable(s).

As determined by the above relationships, if the g-force is held constant, then any changes in the inlet flow rate will have a direct impact on the hematocrit of the packed red blood cells exiting the centrifuge and, thus, on the plasma separation efficiency. Therefore, in conventional devices which maintain a standard constant centrifuge rotation rate RPM across procedures, any changes of the inlet flow rate will alter the efficiency of the centrifuge, with significant increases in inflow rate (as may occur in double-needle procedures) significantly decreasing efficiency. In the case of a procedure in which blood is separated into platelet-rich plasma and packed red blood cells, this may lead to inconsistent platelet yields and red blood cell product hematocrit. Therefore, an approach that applies the above relationships to enable adaption of the centrifuge rotation rate in response to inflow rate changes will allow for substantially constant separation efficiencies and outlet hematocrit, leading to more consistent products and faster procedure times.

Rearranging Equation [<NUM>] to solve for g yields Equation [<NUM>]:
<MAT>.

A constant desired or target HRBC (which may be pre-determined or user defined) may be employed, in which case, as the inlet flow rate QWB changes, the required g-force will change accordingly. The g-force output from Equation [<NUM>] can then be inserted into Equation [<NUM>] to determine the centrifuge rotation rate RPM required to ensure that a constant packed red blood cell hematocrit HRBC and, thus, separation efficiency (per Equation [<NUM>]) is achieved.

Any method involving changes to the centrifuge rotation rate during a procedure must also consider the impact of rotation rate changes in the interface monitoring assembly, if employed. For example, in the exemplary embodiment described above, light L from a light source <NUM> may only enter into a prismatic reflector <NUM> and be directed to a light detector <NUM> when a ramp <NUM> angularly aligned with the prismatic reflector <NUM> has been rotated into the path of the light L. During the time that the ramp <NUM> and prismatic reflector <NUM> are rotated through the path of the light L from the light source <NUM>, the light L continues through the channel <NUM> and the fluids in the channel <NUM>. In the case of blood separation, the light source <NUM> may be configured to emit a light L that is more readily transmitted by platelet-rich plasma or platelet-poor plasma than by red blood cells, such as red visible light. The plasma layer and the red blood cell layer each occupy a certain portion of the ramp <NUM>, with the light detector <NUM> receiving different amounts of light L depending on whether the light L travels through the plasma layer on the ramp <NUM> or the red blood cell layer on the ramp <NUM>. The percentage of the ramp <NUM> occupied by each layer is indicative of the radial position of the interface in the channel <NUM>. Thus, by measuring the amount of time that the voltage output or signal from the light detector <NUM> is relatively high (which corresponds to the time during which the light L is passing through only the plasma layer on the ramp <NUM> and which may be referred to as the "pulse width" of the signal), the controller <NUM> may determine the radial position of the interface within the channel <NUM>.

The amount of time that the prismatic reflector <NUM> is in the path of the light L during each rotation of the centrifuge will depend upon the rotation rate of the centrifuge. Thus, when the controller <NUM> is configured to adjust the rotation rate of the centrifuge in response to a change in fluid inflow rate, the controller <NUM> must know both the total length of time that the prismatic reflector <NUM> is in the path of the light L during each rotation of the centrifuge and the pulse width to determine the percentage of the ramp <NUM> occupied by each layer and, hence, the radial position of the interface. In particular, faster centrifuge rotation rates will lead to shorter signal pulse widths due to the following relationship:
<MAT> in which Open Window Circumference is the width or angular extent of the first end wall <NUM> of the prismatic reflector <NUM> (which is the portion of the prismatic reflector <NUM> that is configured to direct light L to the light detector <NUM>) and Chamber Circumference is the circumference of the inner side wall portion <NUM> (i.e., the circumference of the centrifuge chamber <NUM> at the same radial position at which Open Window Circumference is measured). Accordingly, it will be seen that Equation [<NUM>] is indicative of the percentage of each rotation of the centrifuge during which light L can possibly be directed to the light detector <NUM> by the prismatic reflector <NUM>.

In the embodiment presented herein, interface position is determined according to the following relationship:
<MAT> in which Saline Calibration Pulse Width is the maximum possible pulse width of a signal that may be transmitted by the light detector <NUM> (e.g., when only saline is in the channel <NUM>) and Current Plasma Pulse Width is the output of Equation [<NUM>]. It will be seen that, if the centrifuge rotation rate were increased during separation without taking into account the decreasing total time during each rotation when light L can possibly be directed to the light source <NUM>, then a smaller pulse width would be interpreted as a change in the radial position of the interface, rather than being understood as simply reflecting the change in the centrifuge rotation rate. The same would be true for a decrease of the centrifuge rotation rate.

Thus, to account for centrifuge rotation rate changes in the calculation of the Interface Position using Equation [<NUM>], Saline Calibration Pulse Width (which is a reference signal typically taken at the start of a procedure) must be updated in accordance with RPM changes. Saline Calibration Pulse Width is used to determine the baseline width (circumference in time) of the prismatic reflector <NUM> through which the optical signal is measured and accounts for any tolerance discrepancies in the centrifuge chamber <NUM> that may not be considered by simply using Equation [<NUM>] to calculate Saline Calibration Pulse Width with a standard or presumed Open Window Circumference based on designed dimensions of the prismatic reflector <NUM>. It is again emphasized that, while reference is made to a specifically configured centrifuge chamber <NUM> and prismatic reflector <NUM>, these same principals may be applied to differently configured centrifuge chambers and optical monitoring assemblies.

It is possible to update Saline Calibration Pulse Width with respect to centrifuge rotation rate RPM changes by using a theoretical calculation of Equation [<NUM>] as a baseline, where Open Window Circumference would be a constant based on the intended design dimensions. To account for any potential tolerance issues that may alter Open Window Circumference from the designed dimension, Equation [<NUM>] may be rearranged as follows:
<MAT> which can be used to determine the actual Open Saline Window Circumference based on the Saline Calibration Pulse Width measured at the start of the procedure. Then, throughout the procedure as the centrifuge rotation rate RPM changes, Saline Calibration Pulse Width Per RPM may be calculated as follows:
<MAT> and subsequently used in the calculation of Interface Position as follows:
<MAT> which is a variation of Equation [<NUM>].

<FIG> illustrates an application of this approach to adjusting centrifuge rotation rate in response to a change in fluid inflow rate for a procedure in which blood is separated into packed red blood cells and a plasma constituent (e.g., platelet-rich plasma). As explained above, HRBC and HWB will typically remain uniform throughout the course of a procedure and are treated as constants when determining the appropriate centrifuge rotation rate change to implement in response to a change in fluid inflow rate. However, when one or both of HRBC and HWB are subject to change during a procedure, they may be updated at the appropriate times.

During an early stage of a procedure (which may be during a priming stage, for example), Equation [<NUM>] is employed by the controller <NUM> to determine Open Saline Window Circumference (indicated in <FIG> at step <NUM>). HRBC and QWB are then determined (at steps <NUM> and <NUM>, respectively), with HRBC being either determined based on the selected procedure or configurable (e.g., being selected by an operator or calculated by the controller <NUM>) and QWB being either measured or known in view of the selected procedure.

With that information, the controller <NUM> employs Equation [<NUM>] (at step <NUM> of <FIG>) to determine the g-forces required to achieve HRBC. The controller <NUM> then determines the centrifuge rotation rate RPM required to apply the calculated g-forces using Equation [<NUM>] (at step <NUM> of <FIG>). The controller <NUM> commands the centrifugal separator <NUM> to rotate at the calculated rotation rate RPM (at step <NUM> of <FIG>).

When the centrifugal separator <NUM> has been commanded to operate at the calculated rotation rate RPM, the controller <NUM> updates Saline Calibration Pulse Width Per RPM using Equation [<NUM>] (at step <NUM> of <FIG>) and then updates Interface Position using Equation [<NUM>] (at step <NUM> of <FIG>). The controller <NUM> may then return to step <NUM> to determine whether HRBC is to be updated and the process is repeated to ensure that any subsequent change in QWB is addressed by a corresponding change in centrifuge rotation rate RPM, along with Saline Calibration Pulse Width Per RPM and Interface Position being similarly updated.

Again, it should be understood that the principles described herein are not limited to use with any particular centrifugation procedure or any particular fluid to be separated. Additionally, while particularly configured centrifuge chambers and centrifugal separators are shown and described in detail herein, it should be understood that the principles described herein are applicable to differently configured continuous-flow centrifuge chambers and centrifugal separators.

Claim 1:
A fluid processing device (<NUM>), comprising:
a controller (<NUM>) configured to receive input indicative of a concentration of a fluid component within a bodily fluid;
a centrifuge (<NUM>) configured to receive and rotate a continuous-flow centrifuge chamber (<NUM>) of a fluid flow circuit (<NUM>) so as to separate the bodily fluid in the centrifuge chamber (<NUM>) into at least first and second constituents in a separation procedure; and
a pump system configured to convey said bodily fluid through the fluid flow circuit (<NUM>) and into the centrifuge chamber (<NUM>) at first and second rates during said separation procedure, wherein
the controller (<NUM>) is configured to control the centrifuge (<NUM>) to rotate the centrifuge chamber (<NUM>) at a first rotation rate when the pump system is conveying said bodily fluid into the centrifuge chamber (<NUM>) at the first rate during said separation procedure,
the controller (<NUM>) is configured to control the centrifuge (<NUM>) to rotate the centrifuge chamber (<NUM>) at a second rotation rate when the pump system is conveying said bodily fluid into the centrifuge chamber (<NUM>) at the second rate during said separation procedure, and
said first and second rotation rates are different, with each of the first and second rotation rates being based at least in part on the concentration of the fluid component within the bodily fluid, the rate at which the pump system is conveying said bodily fluid into the centrifuge chamber (<NUM>), and a target concentration of the fluid component in one of said first and second constituents and being controlled so as to achieve a substantially uniform separation efficiency.