System and method for blood separation using centrifugal separation or rotation film separation technique

Abstract

To provide a system and method for blood separation using both centrifugal separation and a rotation film separation technique.SOLUTION: A centrifugal separation device includes a prismatic reflecting body 108. The prismatic reflecting body includes an inner wall 110 and an outer wall 112, and a first end wall 114 and a second end wall 116. The first end wall is inclined at about 45° with respect to the second end wall. The prismatic reflecting body is formed of a light transmissive material. The inner wall is configured to receive the light traveling along an initial path, and to transmit the light to the first end wall. The first end wall is configured to receive the light that has passed through the inner wall, and divert the light toward the second end wall in a direction inclined with respect to the initial path. The second end wall is configured to receive the light from the first end wall, and transmits the light to outside of the prismatic reflecting body.SELECTED DRAWING: Figure 22

Description

[Technical field]

[0001] [Related Applications] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 62 / 395,536, filed September 16, 2016, and U.S. Provisional Patent Application No. 62 / 447,478, filed January 18, 2017, which are incorporated herein by reference.

[0002] [Technical field] The present subject matter relates to systems and methods for processing and collecting blood, blood components, or other suspensions of cellular material. More particularly, the present subject matter relates to blood separation systems and methods that employ both centrifugation and spinning membrane separation techniques. [Background technology]

[0003] Currently, various blood processing systems allow for the collection of specific blood components from a blood source instead of whole blood. Typically, in such systems, whole blood is drawn from the blood source, the specific blood component or components are separated, removed, and collected, and the remaining blood components are returned to the blood source. When the blood source is a human donor, removing only the specific components is advantageous because it potentially requires less time for the donor's body to return to pre-donation levels, allowing for more frequent donations than if whole blood were collected. This increases the overall supply of blood components, such as plasma and platelets, that are made available for transport and / or therapeutic treatment.

[0004] According to one approach, whole blood can be separated into its components by centrifugation. This requires that the whole blood passes through a centrifuge after it is drawn from the blood source and before it is returned to the blood source. To reduce contamination and possible infection (if the blood source is a human donor or patient), the blood is preferably processed in a sealed, sterile fluid flow circuit during the centrifugation process. The operator attaches a new sterile disposable flow circuit to the centrifuge before processing, and removes and discards it afterwards. A typical disposable flow circuit is sealed and sterile, and includes a separation chamber portion cooperatively attached to a durable, reusable assembly that includes hardware (such as a centrifuge, a drive system, pumps, valve actuators, programmable controls, etc.) that rotates the separation chamber and controls the flow through the fluid circuit. The separation chamber may be formed from an entirely rigid material (e.g., molded plastic), in which case the chamber itself defines a flow path or channel through which the blood is separated into two or more components, or may be formed from a more flexible material (e.g., a belt or annulus), which relies on system hardware to support the chamber and define the shape of the chamber as blood flows through it.

[0005] With the disposable circuit loaded into the centrifuge (or immediately prior to or during loading), an operator typically inputs, for example by a touch screen or other user interface system, the particular processing protocol to be executed by the system (e.g., the procedure in which platelets are to be separated from whole blood and collected) and other parameters (e.g., donor weight, desired volume of separated blood components to be collected, etc.). Once the system is programmed, the operator phlebotomizes the donor, and the system performs the procedure under the operator's supervision.

[0006] The centrifuge spins the separation chamber of the disposable flow circuit during processing, causing heavier (higher specific gravity) components of the whole blood in the separation chamber, such as red blood cells, to move radially outward from the center of rotation toward the outer or "high G" wall of the separation chamber. Lighter (lower specific gravity) components, such as plasma, move toward the inner or "low G" wall of the separation chamber. The boundary that forms between the heavier and lighter components in the separation chamber is commonly referred to as the interface. By providing appropriately positioned channeling structures and outlet ports in the flow circuit, various of these components can be selectively removed from the whole blood. For example, in one blood separation procedure, plasma is separated from the cellular blood components and collected, and the cellular blood components and replacement fluid are returned to the blood source. Alternatively, red blood cells can be harvested from the separation chamber and the remaining blood components returned to the donor. Other methods are possible, including but not limited to platelet harvesting, red blood cell exchange, plasma exchange, etc.

[0007] While many blood separation systems and procedures employ centrifugation principles, there is another type of device that is used for plasma exchange (i.e., separation of plasma from whole blood) that is based on the use of membranes. More specifically, this type of device uses relatively rotating surfaces, at least one of which carries a porous membrane. Typically, the device uses an outer stationary housing and an inner rotating rotor that is covered with a porous membrane.

[0008] Well-known plasma exchange devices include the Autopheresis-C® and Aurora separators sold by Fenweil, Inc., Lake Zurich, Illinois, an affiliate of Fresenius Kabi AG, Bad Homburg, Germany. A detailed description of an exemplary rotating membrane separator can be found in U.S. Pat. No. 5,194,145, which is hereby incorporated by reference. This patent describes a membrane-coated spinner with an internal collection system disposed within a stationary shell. Blood is fed into the annular space or gap between the spinner and the shell. The blood travels along the longitudinal axis of the shell toward an outlet region, and plasma passes through the membrane and out of the shell into a collection bag. The remaining blood components, primarily red blood cells, platelets, and white blood cells, travel to the outlet region between the spinner and the shell before typically being returned to the donor.

[0009] Spinning membrane separators have been found to provide superior plasma filtration rates, primarily due to a unique flow pattern (the "Taylor vortex") induced in the gap between the spinning membrane and the shell. The Taylor vortex helps prevent blood cells from adhering to the membrane and fouling or clogging it.

[0010] Since both types of separators have their advantages, it would be advantageous to provide an integrated system that can utilize the advantages of both centrifugation and spinning membrane separation. Summary of the Invention

[0011] There are several aspects of the present subject matter that may be embodied separately or together in the devices, systems, and methods described and / or claimed below. These aspects may be used alone or in combination with other aspects of the subject matter described herein, and the description of these aspects together is not intended to exclude the separate use of these aspects, nor the claiming of such aspects separately, nor the various combinations described in the claims appended hereto or later amended thereto.

[0012] In one aspect, the blood separation device includes a centrifuge and a spinning membrane separator drive unit. The controller is configured and / or programmed to control the operation of the centrifuge and the spinning membrane separator drive unit. The blood separation device further includes a case, and the centrifuge and the spinning membrane separator drive unit are integrated into the case.

[0013] In another aspect, a fluid flow circuit for use in combination with a blood separation device includes a centrifuge system and a spinning membrane separator in fluid communication with the centrifuge chamber.

[0014] In yet another aspect, a blood separation system includes a blood separation device including a centrifuge and a spinning membrane separator drive unit mounted within a case. The system also includes a fluid flow circuit having a centrifuge chamber configured to be mounted to the centrifuge and / or a spinning membrane separator configured to be mounted to the spinning membrane separator drive unit.

[0015] In another aspect, a method of blood separation includes providing a blood separation device including a centrifuge and a spinning membrane separator drive unit. A fluid flow circuit is attached to the blood separation device, and blood is conveyed through the fluid flow circuit. At least a portion of the blood in the fluid separation circuit is separated into two or more blood components using the centrifuge and / or the spinning membrane separator drive unit.

[0016] In yet another aspect, a method of controlling a blood separation procedure includes providing a blood separation device including a pump, a centrifuge, and a spinning membrane separator drive unit. A fluid flow circuit is attached to the blood separation device, and the pump is controlled to convey blood through the fluid flow circuit. The centrifuge and / or the spinning membrane separator drive unit are controlled to separate at least a portion of the blood in the fluid flow circuit into two or more blood components.

[0017] In another aspect, a method of separating blood includes conveying blood through a fluid flow circuit and separating at least a portion of the blood into two or more blood components using a centrifuge, wherein at least a portion of one of the separated blood components is further separated into two or more subcomponents using a spinning membrane separator drive unit.

[0018] In yet another aspect, a method of controlling a blood separation procedure includes controlling a pump to convey blood through a fluid flow circuit, a centrifuge is controlled to separate at least a portion of the blood in the fluid flow circuit into two or more blood components, and a spinning membrane separator drive unit is controlled to further separate at least a portion of one of the separated blood components into two or more subcomponents.

[0019] In another aspect, a method of separating blood includes attaching a fluid flow circuit to a blood separation device including a centrifuge and a spinning membrane separator drive unit, and conveying blood through the fluid flow circuit, red blood cells are separated from at least a portion of the blood in the fluid flow circuit using the spinning membrane separator drive unit, and at least a portion of the separated red blood cells are collected.

[0020] In yet another aspect, a method of controlling a blood separation procedure includes attaching a fluid flow circuit including a fluid container to a blood separation device including a plurality of pumps, a centrifuge, and a spinning membrane separator drive unit. The at least one pump is controlled to convey blood through the fluid flow circuit, and the spinning membrane separator drive unit is controlled to separate red blood cells from at least a portion of the blood in the fluid flow circuit. The at least one pump is controlled to convey at least a portion of the separated red blood cells to the fluid container.

[0021] In another aspect, a method of separating blood includes attaching a fluid flow circuit to a blood separation device including a centrifuge and a spinning membrane separator drive unit, and conveying blood through the fluid flow circuit, red blood cells and plasma are separated from at least a portion of the blood in the fluid flow circuit using the spinning membrane separator drive unit, and at least a portion of the separated red blood cells and separated plasma are collected.

[0022] In yet another aspect, a method of controlling a blood separation procedure includes attaching a fluid flow circuit including a plurality of fluid containers to a blood separation device including a plurality of pumps, a centrifuge, and a spinning membrane separator drive unit. At least one pump is controlled to transport blood through the fluid flow circuit, and the spinning membrane separator drive unit is controlled in at least one fluid flow path to separate red blood cells and plasma from at least a portion of the blood in the fluid flow circuit. At least a portion of the separated red blood cells and separated plasma are transported to the fluid container.

[0023] In another aspect, a method of separating blood includes attaching a fluid flow circuit to a blood separation device including a centrifuge and a spinning membrane separator drive unit, conveying blood through the fluid flow circuit, plasma is separated from at least a portion of the blood in the fluid flow circuit using the spinning membrane separator drive unit, and at least a portion of the separated plasma is collected.

[0024] In yet another aspect, a method of controlling a blood separation procedure includes attaching a fluid flow circuit including a fluid container to a blood separation device including a plurality of pumps, a centrifuge, and a spinning membrane separator drive unit. The at least one pump is controlled to transport blood through the fluid flow circuit, and the spinning membrane separator drive unit is controlled to separate plasma from at least a portion of the blood in the fluid flow circuit. The at least one pump is controlled to transport at least a portion of the separated plasma to the fluid container.

[0025] In another aspect, a method of blood separation includes conveying blood through a fluid flow circuit and separating at least a portion of the blood in the fluid flow circuit into a first blood component and a second blood component. At least a portion of the first blood component is conveyed into a container. At least a portion of the second blood component is further separated into a first subcomponent and a second subcomponent, and at least a portion of the first subcomponent is conveyed into the container to form a mixture with the first blood component in the container. At least a portion of the second subcomponent is collected. At least a portion of the mixture is separated into the first blood component and the second blood component, and at least a portion of the second blood component separated from the mixture is further separated into the first subcomponent and the second subcomponent. At least a portion of the second subcomponent separated from the at least a portion of the second blood component separated from the mixture is collected.

[0026] In yet another aspect, a method of controlling a blood separation procedure includes controlling a pump to transport blood through a fluid flow circuit, controlling a first separator to separate at least a portion of the blood in the fluid flow circuit into a first blood component and a second blood component, and transporting at least a portion of the first blood component into a container. The second separator is controlled to further separate at least a portion of the second blood component into a first subcomponent and a second subcomponent, and the second pump is controlled to transport at least a portion of the first subcomponent to the container to form a mixture with the first blood component in the container. At least a portion of the second subcomponent is collected. The first separator is controlled to separate at least a portion of the mixture into the first blood component and the second blood component, and the second separator is controlled to separate at least a portion of the second blood component separated from the mixture into the first subcomponent and the second subcomponent. At least a portion of the second subcomponent separated from the second blood component separated from the mixture is collected.

[0027] In another aspect, a centrifuge chamber includes a body including a low-g sidewall portion and a high-g sidewall portion extending circumferentially about an axis of rotation and spaced apart to define a generally annular groove therebetween. A plurality of radially inner walls define an inlet and at least one outlet associated with the groove, while a ramp is defined by one of the sidewalls and extends across at least a portion of the groove to indicate an interface between separated fluid components within the groove. At least a portion of the ramp and at least a portion of the other sidewall portion angularly aligned with the ramp are formed from an optically transparent material.

[0028] In yet another aspect, a prismatic reflector for incorporation into a centrifuge chamber includes an inner wall, an outer wall, a first end wall, and a second end wall. The prismatic reflector is formed of an optically transparent material. The inner wall is configured to receive light traveling along an initial path and transmit the light to the first end wall, which receives and directs the light toward the second end wall in a direction angled relative to the initial path. The second end wall is configured to receive the light from the first end wall and transmit it out of the prismatic reflector.

[0029] In another aspect, an interface monitoring system for detecting a location of an interface between separated fluid components in a groove of a centrifuge chamber having an axis of rotation includes a light source and a light detector. The light source is configured to transmit light into the centrifuge chamber along an initial path toward the axis of rotation and through the groove of the centrifuge chamber. The light detector is configured to receive at least a portion of the light as it exits the centrifuge chamber and generate a signal indicative of a location of the interface between the separated fluid components in the groove of the centrifuge chamber. The light detector is oriented to receive light traveling in a direction generally perpendicular to the initial path of the light.

[0030] In yet another aspect, a blood separation system includes a blood separation device and a fluid flow circuit. The blood separation device includes a centrifuge and an interface monitoring system. The fluid flow circuit includes a centrifuge chamber with a groove defined between a low-g sidewall and a high-g sidewall, the chamber configured to be mounted to the centrifuge. The interface monitoring system includes a light source and a light detector. The light source is configured to transmit light into the centrifuge chamber along an initial path toward the axis of rotation and through the groove of the centrifuge chamber. The light detector is configured to receive at least a portion of the light as it exits the centrifuge chamber, the light detector being oriented to receive light traveling in a direction generally perpendicular to the initial path of the light.

[0031] In another aspect, a method for detecting a location of an interface between separated fluid components in a groove of a centrifuge chamber having an axis of rotation includes separating fluid in the groove of the centrifuge chamber into at least two fluid components. Light is directed along an initial path through the groove to intersect at least one of the fluid components. The light exiting the groove is directed out of the centrifuge chamber in a direction that is generally perpendicular to the initial path of the light. At least a portion of the light exiting the centrifuge chamber is detected and a signal is generated indicative of a location of an interface between the separated fluid components in the groove.

[0032] In yet another aspect, a method of controlling a fluid separation procedure includes controlling a pump to deliver fluid into a groove in a centrifuge chamber. The centrifuge is controlled to rotate the centrifuge chamber about an axis of rotation to separate the fluid in the groove into at least two fluid components. The light source is controlled to direct light along an initial path through the groove to intersect at least one fluid component and to direct the light exiting the groove outside the centrifuge chamber in a direction generally perpendicular to the initial path of the light. The light detector is controlled to detect at least a portion of the light exiting the centrifuge chamber and generate a signal indicative of a location of an interface between the separated fluid components in the groove. [Brief description of the drawings]

[0033] FIG. 1 is a perspective view of an exemplary blood separation device including components of a blood separation system according to one aspect of the present disclosure. 2-11 are schematic diagrams of exemplary disposable fluid flow circuits that can be attached to the blood separation apparatus of FIG. 1 to complete a blood separation system according to one aspect of the present disclosure. FIG. 12 is a perspective view of an exemplary centrifuge of the blood separation device of FIG. 1 with the centrifuge chamber of the fluid flow circuit mounted therein. FIG. 12A is a perspective view of the centrifuge of FIG. 12 with selected portions thereof broken away to show the light sources of the interface monitoring system. FIG. 12B is a perspective view of the centrifuge of FIG. 12 with the light source operative to transmit a light beam to a photodetector of the interface monitoring system. FIG. 12C is a perspective view of the centrifuge of FIG. 12 with selected portions thereof broken away to show the light sources and light detectors of the interface monitoring system. FIG. 13 is a plan view of an exemplary cassette of a fluid flow circuit that can be programmed to perform a variety of different blood processing procedures in conjunction with the blood separation device shown in FIG. FIG. 14 is a perspective view of an exemplary spinning membrane separator in a fluid flow circuit. FIG. 15 is a perspective view of a portion of the spinning membrane separator and spinning membrane separator drive unit of FIG. 14, with portions of both cut away for illustration purposes. FIG. 16 is a perspective view of an exemplary centrifuge chamber of a fluid flow circuit. FIG. 16A is a front view of the centrifuge chamber of FIG. 16B is a bottom perspective view of the fluid flow path through the centrifuge chamber of FIG. FIG. 17 is a perspective view of another embodiment of a centrifuge chamber of a fluid flow circuit. FIG. 17A is a front view of the centrifuge chamber of FIG. 17B is a top perspective view of the fluid flow path through the centrifuge chamber of FIG. FIG. 18 is a perspective view of a third embodiment of a centrifuge chamber of a fluid flow circuit. FIG. 18A is a front view of the centrifuge chamber of FIG. FIG. 19 is an enlarged perspective view of a portion of a groove in one of the centrifuge chambers of FIGS. 16-18A, in which the interface between separated blood components is positioned at a desired location on a ramp defined in the groove. FIG. 20 is an enlarged perspective view of the groove and ramp of FIG. 19, with the interface at an undesirably high position on the ramp. FIG. 21 is an enlarged perspective view of the groove and ramp of FIG. 19 with the interface at an undesirably low point on the ramp. FIG. 22 is a perspective view of a prismatic reflector that may be used in combination with any of the centrifuge chambers of FIGS. 16-18A. FIG. 22A is a perspective view of the prismatic reflector of FIG. 22 showing light transmitted through it. 23-23C are schematic diagrams of the ramp and prismatic reflector of the centrifuge chamber that pass through the path of light from the light source during the calibration phase. 24-24C are schematic diagrams of the voltage outputs or signals transmitted by the photodetector during the states shown in FIGS. 23-23C, respectively. FIG. 25 is a schematic diagram of a ramp rotating to align with a small diameter light beam from a light source. FIG. 25A is a schematic diagram of a ramp rotating to align with a large diameter light beam from a light source. FIG. 26 is a schematic diagram of the voltage output or signal transmitted by the photodetector during the conditions shown in FIG. FIG. 26A is a schematic diagram of the voltage output or signal transmitted by the photodetector during the condition shown in FIG. 25A. 27-27C are schematic diagrams of a ramp and a prismatic reflector passing through the path of light from a light source during a separation procedure. 28-28C are schematic diagrams of the voltage outputs or signals transmitted by the photodetector during the states shown in FIGS. 27-27C, respectively. 29-29A are schematic diagrams of separated blood components on a ramp and the pulse width of the signal generated by the photodetector for each state. FIG. 29C is a schematic diagram of saline on a ramp and the pulse width of the signal generated by the photodetector for such a condition. FIG. 30 is a schematic illustration of the position of the interface between separated blood components on a ramp compared to the target interface position. FIG. 31 is a chart illustrating a control protocol for moving an interface between separated blood components on a ramp from a current position to a target interface position. 32 and 33 are schematic diagrams of the fluid flow circuit of FIG. 2 installed in the blood separation device of FIG. 1, illustrating a system performing different fluid flow tasks in connection with separating and collecting red blood cells from blood. FIG. 34 is a schematic diagram of the fluid flow circuit of FIG. 3 installed in the blood separation device of FIG. 1, illustrating the system performing different fluid flow tasks in connection with separating and collecting red blood cells from blood. 35-38 are schematic diagrams of the fluid flow circuit of FIG. 4 installed in the blood separation device of FIG. 1, illustrating the system performing different fluid flow tasks in connection with the separation and collection of red blood cells and plasma from blood. 39 and 40 are schematic diagrams of the fluid flow circuit of FIG. 5 installed in the blood separation device of FIG. 1 and illustrate the system performing different fluid flow tasks in connection with separating and collecting red blood cells and plasma from blood. 41 and 42 are schematic diagrams of the fluid flow circuit of FIG. 6 installed in the blood separation device of FIG. 1, illustrating the system performing different fluid flow tasks in connection with the separation and collection of plasma from blood. FIG. 43 is a schematic diagram of the fluid flow circuit of FIG. 7 installed in the blood separation device of FIG. 1, illustrating the system performing different fluid flow tasks in connection with the separation and collection of plasma from blood. 44-49 are schematic diagrams of the fluid flow circuit of FIG. 8 installed in the blood separation device of FIG. 1, illustrating the system performing different fluid flow tasks in connection with the separation and collection of platelets, plasma, and red blood cells from blood. 50-53 are schematic diagrams of the fluid flow circuit of FIG. 9 installed in the blood separation device of FIG. 1, illustrating the system performing different fluid flow tasks in connection with the separation and collection of platelets or platelets and plasma from blood. 54-56 are schematic diagrams of the fluid flow circuit of FIG. 10 installed in the blood separation device of FIG. 1, illustrating the system performing different fluid flow tasks in connection with the separation and collection of platelets or platelets and plasma from blood. 57-60 are schematic diagrams of the fluid flow circuit of FIG. 11 mounted on the blood separation device of FIG. 1, showing the system performing different fluid flow tasks in connection with the separation and collection of platelets or platelets and plasma from lower processing / extracorporeal volumes of blood. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0034] The embodiments disclosed herein are intended to provide an exemplary description of the subject matter. However, they are exemplary only and not exhaustive, as the subject matter may be embodied in various forms. Thus, the specific details disclosed herein should not be construed as limiting the subject matter defined in the appended claims.

[0035] 1-60 illustrate components of a blood or fluid separation system embodying various aspects of the present subject matter. The system may be referred to herein as a "blood processing system" or "blood separation system" and illustrates examples of various ways in which the system may be used to separate blood into its component parts, although it should be understood that systems according to the present disclosure may be used to process a variety of fluids, which may include bodily and non-bodily fluids.

[0036] Generally speaking, the system includes two major components: a durable, reusable blood separation device 10 (FIG. 1) and disposable fluid flow circuits 12A-12J (sometimes collectively referred to herein as elements 12). Blood separation device 10 includes a spinning membrane separator drive unit 14 (FIG. 1), a centrifuge or centrifugal separator 16 (FIG. 12), additional components that control the flow of fluid through disposable flow circuit 12, and a controller 18 (FIG. 2), which governs the operation of the other components of blood separation device 10 to perform blood processing and collection procedures selected by an operator, as will be described in more detail.

[0037] I. Durable Blood Separator Blood separation device 10 (FIG. 1) is constructed as a durable item capable of extended use. It should be understood that blood separation device 10 of FIG. 1 is merely illustrative of one possible configuration, and blood separation devices according to the present disclosure may have different configurations.

[0038] In the illustrated embodiment, blood separation device 10 is embodied within a single housing or case 20. The illustrated case 20 includes a generally horizontal portion 22 (which may include sloped or angled faces or tops to improve visibility and ergonomics) and a generally vertical portion 24. The spinning membrane separator drive unit 14 and centrifuge 16 are shown mounted in the generally horizontal portion 22 of the case 20, while the control unit 18 is shown mounted in the generally vertical portion 24. The construction and operation of the spinning membrane separator drive unit 14, centrifuge 16, control unit 18, and selected other components of blood separation device 10 will now be described in more detail.

[0039] In the illustrated embodiment, generally horizontal portion 22 is intended to rest on an elevated, generally horizontal support surface (e.g., a countertop or tabletop), however, it is also within the scope of this disclosure for case 20 to include a support base that allows case 20 to be properly positioned and oriented when placed on a floor or ground. It is also within the scope of this disclosure for case 20 to be attached to a generally vertical surface (e.g., a wall) by fixedly or removably fastening generally vertical portion 24 of case 20 to the surface.

[0040] Case 20 may be configured to assume only the position or configuration of FIG. 1 or may be configured to move between two or more positions or configurations. For example, in one embodiment, generally horizontal portion 22 and generally vertical portion 24 are joined by a hinge or pivot such that case 20 can be moved between a functional or open configuration ( FIG. 1 ) in which generally horizontal portion 22 and generally vertical portion 24 are oriented approximately 90 degrees relative to generally horizontal portion 22, and a transport or closed configuration in which generally vertical portion 24 is rotated about the hinge to approach generally horizontal portion 22. In such a reconfigurable embodiment, generally vertical portion 24 can be considered to be a lid for case 20 and generally horizontal portion 22 can be considered to be a base. If case 20 is so reconfigurable, it may include a latch for releasably locking case 20 in its closed configuration and / or a handle that an operator can grasp to transport case 20 in its closed configuration.

[0041] Although it may be advantageous to embody blood separation device 10 in a small portable case 20, it is also within the scope of the invention to embody blood separation device 10 in a larger case or fixture so that it is installed in a single location and remains there for an extended period of time. When the blood separation device is provided as a fixture, more components and functionality may be provided than in more portable versions.

[0042] A. Rotating membrane separation drive unit Blood separation apparatus 10 includes a spinner support or spinning membrane separator drive unit 14 (FIG. 1) for housing a generally cylindrical spinning membrane separator 26 in fluid flow circuit 12 (FIGS. 14 and 15). Although U.S. Pat. No. 5,194,145 describes an exemplary spinning membrane separator drive unit suitable for incorporation into blood separation apparatus 10, it should be understood that spinning membrane separator drive unit 14 may be of different configurations without departing from the scope of the present invention.

[0043] The illustrated spinning membrane separator drive unit 14 has a base 28 configured to receive a lower portion of the spinning membrane separator 26 and an upper end cap 30 for receiving an upper portion of the spinning membrane separator 26. Preferably, the upper end cap 30 is disposed directly above the base 28 to vertically orient the spinning membrane separator 26 received by the spinning membrane separator drive unit 14 and define a vertical axis about which the spinning membrane separator 26 rotates. Although it may be advantageous for the spinning membrane separator drive unit 14 to vertically orient the spinning membrane separator 26, it is within the scope of the present disclosure for the spinning membrane separator 26 to be oriented differently when installed in the blood separation device 10.

[0044] In one embodiment, one of the components of the spinning membrane separator drive unit 14 is movable relative to the other components, thereby allowing the spinning membrane separator drive unit 14 to accommodate spinning membrane separators 26 of different sizes. For example, the top end cap 30 can be translated vertically relative to the base 28 and fixed to a number of different positions, each fixed position corresponding to a different sized spinning membrane separator 26. As will be explained in more detail, a smaller spinning membrane separator 26 may be sufficient for selected separation procedures, while a larger spinning membrane separator 26 may be necessary or advantageous for other separation procedures (particularly when red blood cells are separated from plasma).

[0045] At least one of the base 28 and the top end cap 30 is configured to rotate one or more components of the spinning membrane separator 26 around an axis defined by the spinning membrane separator drive unit 14. The mechanism by which the spinning membrane separator drive unit 14 rotates one or more components of the spinning membrane separator 26 may vary without departing from the scope of the present disclosure. In one embodiment, the component of the spinning membrane separator 26 that is rotated includes at least one element (e.g., a metallic material) configured to be acted upon by a magnet, while the spinning membrane separator drive unit 14 includes a magnet (e.g., a series of magnetic coils or a semicircular arc magnet). By modulating the magnetic field acting on the aforementioned elements of the spinning membrane separator 26, one or more components of the spinning membrane separator 26 can be rotated in different directions and at different speeds. In other embodiments, different mechanisms can be used to rotate one or more components of the spinning membrane separator 26.

[0046] Regardless of the mechanism by which the rotating membrane separator drive unit 14 rotates one or more components of the rotating membrane separator 26, the one or more components of the rotating membrane separator 26 are preferably rotated at a speed sufficient to generate Taylor vortices in a gap between the rotating and stationary elements (or elements rotating at different speeds) of the rotating membrane separator 26. Fluids to be separated in the rotating membrane separator 26 flow through this gap, and filtration can be dramatically improved by the generation of Taylor vortices.

[0047] B. Centrifuge With respect to the centrifuge 16, it includes a centrifuge compartment 32 that can house the other components of the centrifuge 16 (FIG. 12). The centrifuge compartment 32 may include a lid 34 that is opened to insert and remove a centrifuge chamber 36 from the fluid flow circuit 12. During a separation procedure, the lid 34 may be closed with the centrifuge chamber 36 located within the centrifuge compartment 32 as the centrifuge chamber 36 is rotated about an axis 38 under the power of an electric drive motor or rotor 40 of the centrifuge 16.

[0048] The particular configuration and operation of the centrifuge 16 depends on the particular configuration of the centrifuge chamber 36 of the fluid flow circuit 12. In one embodiment, the centrifuge 16 is similar in construction and operation to that of the ALYX system manufactured by Fenwall, Inc. of Lake Zurich, Illinois, an affiliate of Fresenius Kabi AG Bad Homburg, Germany, as described in detail in U.S. Patent No. 8,075,468, which is incorporated herein by reference. More specifically, the centrifuge 16 may include a carrier or support 42 that holds the centrifuge chamber 36 and a yoke member 44. The yoke member 44 engages an umbilicus 46 of the fluid flow circuit 12 that extends between the centrifuge chamber 36 and a cassette 48 of the fluid flow circuit 12 (FIG. 13). The yoke member 44 causes the umbilicus 46 to orbit around the centrifuge chamber 36 at a rotational speed of 1 omega. The umbilix 46 twists about its own axis as it orbits around the centrifuge chamber 36. The twisting of the umbilix 46 about its axis as it rotates at 1 omega with the yoke member 44 imparts a rotation of 2 omega to the centrifuge chamber 36, in accordance with known designs. The relative rotation of the yoke member 44 at a rotational speed of 1 omega and the centrifuge chamber 36 at a rotational speed of 2 omega keeps the umbilix 46 from twisting, avoiding the need for a rotational seal.

[0049] Blood is introduced into the centrifuge chamber 36 by the umbilix 46, and the blood separates within the centrifuge chamber 36 (e.g., into a layer of less dense components, such as platelet-rich plasma, and a layer of denser components, such as packed red blood cells) as a result of centrifugal forces as the centrifuge chamber rotates. To monitor the separation of the blood within the centrifuge chamber 36, components of an interface monitoring system can be disposed within the centrifuge compartment 32. As shown in Figures 12A-12C, the interface monitoring system can include a light source 50 and a photodetector 52 positioned and oriented to receive at least a portion of the light emitted by the light source 50. Preferably, the light source 50 and the photodetector 52 are disposed on a stationary surface of the centrifuge compartment 32, although it is within the scope of the present disclosure for one or both to be attached to a moving component of the centrifuge 16 (e.g., the yoke member 44, which rotates at a speed of 1 omega).

[0050] The orientation of the various components of the interface monitoring system will depend at least in part on the particular configuration of the centrifuge chamber 36, which will be described in more detail herein. In general, however, the light source 50 emits a light beam (e.g., a laser light beam) through the separated blood components in the centrifuge chamber 36 (formed by a material that substantially transmits without absorbing light or at least certain wavelengths of light). A portion of the light reaches the photodetector 52, which transmits a signal to the controller 18 indicative of the location of the interface between the separated blood components. If the controller 18 determines that the interface is in the wrong position (which may affect the separation efficiency of the centrifuge 16 and / or the quality of the separated blood components), the controller 18 can issue commands to the appropriate components of the blood separation device 10 to modify operation to move the interface to the proper position.

[0051] C. Other Components of the Blood Separator In addition to the spinning membrane separator drive unit 14 and the centrifuge device 16, the blood separation device 10 may include other components compactly arranged to aid in blood processing.

[0052] The generally horizontal portion 22 of the case 20 of the illustrated blood separation device 10 includes a cassette station 54 that houses a cassette 48 of the fluid flow circuit 12 (FIG. 13). In one embodiment, the cassette station 54 is configured similarly to the cassette station of U.S. Pat. No. 5,868,696 (incorporated herein by reference), but is adapted to include additional components and functionality. The illustrated cassette station 54 includes a plurality of clamps or valves V1-V9 (FIG. 1) that move between a plurality of positions (e.g., between a retracted or lowered position and an actuated or raised position) to selectively contact or interact with corresponding valve stations C1-C9 (FIGS. 2-11 and 13) of the cassette 48 of the fluid flow circuit 12. Depending on the configuration of fluid flow circuit 12, the cassette 48 may not include a valve station C1-C9 for each valve V1-V9 of cassette station 54, in which case less than all valves V1-V9 are used in the separation procedure, as described below.

[0053] In the actuated position, the valves V1-V9 engage the associated valve station C1-C9 (e.g., by closing one or more ports associated with the valve station C1-C9, thereby preventing fluid flow through the port(s). In the retracted position, the valves V1-V9 are disengaged from the associated valve station C1-C9 (or contact the associated valve station C1-C9 with less force than when in the actuated position) and allow fluid flow through the associated valve station C1-C9 (e.g., by opening one or more ports associated with the valve station C1-C9, thereby allowing fluid flow through the one or more ports). Additional clamps or valves V10 and V11 are positioned outside of the cassette station 52 and interact with portions of the fluid flow circuit 12 or valve stations C10 and C11 (which may be lengths of tubing) to selectively allow and prevent fluid flow therethrough. Valves V1-V9 and corresponding valve stations C1-C9 of cassette station 54 and cassette 48 may be configured and operate differently than valves V10 and V11 and valve stations C10 and C11 remote from cassette station 54.

[0054] The cassette station 54 may be provided with additional components such as pressure sensors A1-A4 that interact with the sensor stations S1-S4 of the cassette 48 to monitor the pressure at various locations in the fluid flow circuit 12. For example, if the blood source is a human donor, one or more pressure sensors A1-A4 may be configured to monitor the pressure in the donor's veins during blood collection and return. Other pressure sensors A1-A4 may monitor the pressure in the spinning membrane separator 26 and the centrifuge chamber 36. The controller 18 may receive signals from the pressure sensors A1-A4 indicative of the pressure in the fluid flow circuit 12, and if the signal indicates a low or high pressure condition, the controller 18 may initiate an alarm or error condition to alert an operator of the condition and / or to attempt to bring the pressure to an acceptable level without operator intervention.

[0055] The blood separation device 10 may also include a number of pumps P1-P6 for pumping fluid through the fluid flow circuit 12. The pumps P1-P6 may be configured differently or similarly to one another and / or may function the same or differently from one another. In the illustrated embodiment, the pumps P1-P6 are configured as peristaltic pumps, which may be configured generally as described in U.S. Pat. No. 5,868,696. Each pump P1-P6 engages a different tubing loop T1-T6 (FIG. 13) extending from a side of the cassette 48 and may be selectively actuated under command of the controller 18 to pump fluid through a portion of the fluid flow circuit 12, as will be described in more detail. In one embodiment, all or a portion of the cassette station 54 may be capable of translational movement in and out of the case 20 to allow for automatic loading of the tubing loops T1-T6 into the associated pumps P1-P6.

[0056] The illustrated blood separation device 10 also includes a spinner inlet sensor M1 mounted within the spinning membrane separator drive unit 14 for determining one or more characteristics of the fluid entering the spinning membrane separator 26. If the fluid entering the spinning membrane separator 26 is whole blood (which may include anticoagulated whole blood), the spinner inlet sensor M1 may be configured to determine the hematocrit of the blood entering the spinning membrane separator 26. If the fluid entering the spinning membrane separator 26 is platelet-rich plasma, the spinner inlet sensor M1 may be configured to determine the platelet concentration of the platelet-rich plasma entering the spinning membrane separator 26. The spinner inlet sensor M1 may detect one or more characteristics of the fluid by optically monitoring the fluid as it flows through the tubes of the fluid flow circuit 12, or by any other suitable technique. The controller 18 may receive a signal from the spinner inlet sensor M1 indicative of one or more characteristics of the fluid entering the spinning membrane separator 26 and use the signal to optimize the separation procedure based on the characteristics. If one or more characteristics are outside of an acceptable range, the controller 18 may initiate an alarm or error condition to alert an operator of the condition. Suitable apparatus and methods for monitoring hematocrit and / or platelet concentration are described in U.S. Patent No. 6,419,822, which is incorporated herein by reference, although it should be understood that different approaches may be used to monitor the hematocrit and / or platelet concentration of the fluid entering the spinning membrane separator 26.

[0057] The illustrated blood separation device 10 further includes a spinner outlet sensor M2 that houses a tube of the fluid flow circuit 12 that carries the separated blood components out of the spinning membrane separator 26. The spinner outlet sensor M2 monitors the fluid to determine one or more properties of the fluid, and may do so by optically monitoring the fluid as it flows through the tube, or by any other suitable technique. In one embodiment, separated plasma flows through the tube, 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 U.S. Pat. No. 8,556,793 (incorporated herein by reference), or by any other suitable device and / or method.

[0058] The illustrated blood separation device 10 also includes an air detector M3 (e.g., an ultrasonic air bubble detector) that houses the tubing of the fluid flow circuit 12 that flows fluid to the recipient. It may be advantageous to prevent air from reaching the recipient, whether a human recipient (e.g., the same human who serves as the blood source) or a non-human recipient (e.g., a storage bag or container), and the air detector M3 can send a signal to the controller 18 indicative of the presence or absence of air in the tubing. If the signal indicates that air is present in the tubing, the controller 18 can initiate an alarm or error condition to alert an operator of the condition and / or to address (e.g., by reversing the flow of fluid through the tubing or by diverting the position of the vent) to prevent air from reaching the recipient.

[0059] The generally vertical portion 24 of the case 18 can include a plurality of weigh scales W1-W6 (six shown, but more or less may be provided), each capable of supporting one or more fluid containers F1-F12 of the fluid flow circuit 12 (FIGS. 2-11). The containers F1-F12 receive separated blood components or intravenous or additive fluids during processing. Each weigh scale W1-W6 transmits a signal indicative of the weight of fluid in the associated container F1-F12 to the controller 18 for tracking weight changes over the course of processing. This enables the controller 18 to process incremental weight changes to derive fluid throughput and flow rates, and subsequently generate signals to control processing events based at least in part on the derived throughput rates. For example, the controller 18 can diagnose and alert an operator to leaks and blockages in the fluid flow circuit 12.

[0060] The illustrated case 20 also includes a number of hooks or supports H1 and H2 capable of supporting various components of the fluid flow circuit 12 or other objects of suitable size and configuration.

[0061] D. Control Unit According to one aspect of the present disclosure, blood separation device 10 includes a controller 18 suitably configured and / or programmed to control the operation of blood separation device 10. In one embodiment, controller 18 includes a main processing unit (MPU), which may include, for example, a Pentium™ type microprocessor manufactured by Intel Corporation, although other types of conventional microprocessors may be used. In one embodiment, controller 18 may be mounted inside generally vertical portion 24 of case 20 adjacent to or incorporated within an operator interface station (e.g., a touch screen). In other embodiments, controller 18 and operator interface station may be associated with generally horizontal portion 22 or may be incorporated into a separate device that is connected (physically, by cable, etc., or wirelessly) to blood separation device 10.

[0062] The controller 18 is configured and / or programmed to perform at least one blood processing application, but more advantageously is configured and / or programmed to perform a variety of different blood processing applications. For example, the controller 18 may be configured and / or programmed to perform one or more of a dual 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, and a platelet / plasma collection procedure. Details of various exemplary procedures that may be performed by the controller 18 are described in further detail. Additional or alternative procedure applications may be included without departing from the scope of the present disclosure.

[0063] More specifically, in performing any one of these blood processing applications, the controller 18 is configured and / or programmed to control one or more of the following tasks: drawing blood into a fluid flow circuit 12 carried by the blood separation device 10, transporting the blood through the fluid flow circuit 12 to a location for separation (i.e., in the spinning membrane separator 26 or centrifuge chamber 36 of the fluid flow circuit 12), separating the blood into two or more components as needed, and transporting the separated components to a storage container, a second location for further separation (e.g., to either the spinning membrane separator 26 or the centrifuge chamber 36 that was not used in the initial separation step), or to a recipient (which may be the donor from whom the blood was originally drawn).

[0064] This may include directing the spinning membrane separator drive unit 14 and / or the centrifuge 16 to operate at a particular rotational speed, and directing the pumps P1-P6 to deliver fluid at a particular flow rate through a portion of the fluid flow circuit 12. Thus, although a particular component of the blood separation device 10 (e.g., the spinning membrane separator drive unit 14 or the centrifuge 16) may be described herein as performing a particular function, it should be understood that the component is controlled by the controller 18 to perform that function.

[0065] As will be described below, some procedures require the use of both the centrifuge 16 and the spinning membrane separator drive unit 14, in which case a properly programmed control unit 18 is particularly important to coordinate the operation of these two components, among others, to ensure that flow to and from the centrifuge 16 and spinning membrane separator drive unit 14 is at appropriate levels and that the components are functioning properly to process the blood circulating through the fluid flow circuit 12.

[0066] Before, during, and after treatment, controller 18 may receive signals from various components of blood separation device 10 (e.g., pressure sensors A1-A4) to monitor various aspects of the operation of blood separation device 10 and the characteristics of the blood and separated blood components as they flow through fluid flow circuit 12. If the operation of any of the components and / or one or more characteristics of the blood or separated blood components are outside of acceptable ranges, controller 18 may initiate an alarm or error condition to alert an operator and / or take action to correct the condition. Appropriate corrective actions will depend on the particular error condition and may include actions performed with or without operator involvement.

[0067] For example, the controller 18 may include an interface control module that receives a signal from the optical detector 52 of the interface monitoring system. The signal that the controller 18 receives from the optical detector 52 is indicative of the location of the interface between the separated blood components within the centrifuge chamber 36. If the controller 18 determines that the interface is in the wrong location, it may issue commands to appropriate components of the blood separation device 10 to modify their operation to move the interface to the appropriate location. For example, the controller 18 may direct one of the pumps P1-P6 to flow blood into the centrifuge chamber 36 at a different rate and / or to remove separated blood components from the centrifuge chamber 36 at a different rate and / or to cause the centrifuge 16 to spin the centrifuge chamber 36 at a different rate. The specific protocols executed by the interface control module in adjusting the location of the interface within the centrifuge chamber 36 are described in more detail with respect to an exemplary centrifuge chamber 36.

[0068] Such control typically occurs whether the blood is derived from a container or directly from a donor, and whether the components are directed to a storage container or returned to the donor or other living recipient.

[0069] If provided, an operator interface station associated with the control unit 18 allows an operator to view information regarding the operation of the system on a screen or display (in alphanumeric format and / or as graphic images). The operator interface station also allows the operator to select applications to be executed by the control unit 18, as well as to change certain functions and performance criteria of the system. If configured as a touch screen, the screen of the operator interface station can receive input from the operator via touch actuation. Alternatively, if the screen is not a touch screen, the operator interface station can receive input from the operator via a separate input device, such as a computer mouse or keyboard. It is also within the scope of this disclosure for the operator interface station to receive input from both a touch screen and a separate input device, such as a keypad.

[0070] II. Disposable Fluid Flow Circuits A. Overview With regard to the fluid flow circuit or flow set 12 (FIGS. 2-11), it is intended to be a sterile, single-use, disposable item. Prior to initiating a given blood processing and collection procedure, an operator loads the various components of the fluid flow circuit 12 into the case 20 in association with the blood separation device 10. The control unit 18 executes the procedure based on a preset protocol, taking into account other inputs from the operator. Once the procedure is completed, the operator disassociates the fluid flow circuit 12 from the blood separation device 10. The portion of the fluid flow circuit 12 that holds the collected blood component or components (e.g., a collection container or bag) is removed from the case 20 and retained for storage, transfusion, or further processing. The remaining portion of the fluid flow circuit 12 is removed from the case 20 and discarded.

[0071] A variety of different disposable fluid flow circuits 12A-12J can be used in combination with blood separation device 10, with the appropriate fluid flow circuit depending on the separation procedure to be performed using the system. Accordingly, the different fluid flow circuits will be described in relation to specific separation procedures. Generally speaking, however, fluid flow circuit 12 includes a cassette 48 (FIG. 13) to which other components of fluid flow circuit 12 are connected by flexible tubing. The other components may include a number of fluid containers F1-F12 (for holding blood, separated blood components, intravenous fluids, or additive solutions), one or more blood source access devices (e.g., a phlebotomy needle or connector for accessing the blood in the fluid containers), and a spinning membrane separator 26 (FIGS. 14 and 15) and / or a centrifuge chamber 36 (FIG. 16).

[0072] B. Cassette and tube Cassette 48 (FIG. 13) provides a centralized, programmable, integrated platform for all pumping and many of the valve functions required for a given blood processing procedure. In one embodiment, cassette 48 is configured similarly to the cassette of U.S. Pat. No. 5,868,696, but includes additional components (e.g., more tubing loops T1-T6) and functionality.

[0073] In use, cassette 48 is mounted in cassette station 54 of blood separation device 10 and positioned such that the flexible diaphragm of cassette 48 contacts cassette station 54. The flexible diaphragm covers an array of interior cavities formed by the body of cassette 48. The different interior cavities define sensor stations S1-S4, valve stations C1-C9, and a plurality of flow paths. The side of cassette 48 opposite the flexible diaphragm may be sealed by another flexible diaphragm or a rigid cover, thereby sealing off fluid flow through cassette 48 from the external environment.

[0074] Each sensor station S1-S4 is aligned with an associated pressure sensor A1-A4 of the cassette station 54, and each pressure sensor A1-A4 can monitor the pressure within the associated sensor station S1-S4. Each valve station C1-C9 is aligned with an associated valve V1-V9 and can define one or more ports that allow fluid communication between the valve station C1-C9 and other internal cavities (e.g., flow paths) of the cassette 48. As described above, each valve V1-V9 is movable under command of the controller 18 and moves between a plurality of positions (e.g., between a retracted or lowered position and an actuated or raised position) to selectively contact the valve station C1-C9 of the cassette 48. In the actuated position, the valve V1-V9 engages the associated valve station C1-C9 to close one or more ports thereof to prevent fluid flow therethrough. In the retracted position, the valves V1-V9 are disengaged from (or contact) their associated valve stations C1-C9 with less force than when they are in the actuated position, opening one or more ports associated with the valve stations C1-C9, thereby allowing fluid flow therethrough.

[0075] As described, a number of tubing loops T1-T6 extend from the side of cassette 48 to interact with pumps P1-P6 of blood separation device 10. In the illustrated embodiment, six tubing loops T1-T6 extend from cassette 48 to be received by different ones of the six pumps P1-P6, however, in other embodiments, a procedure does not require the use of all of pumps P1-P6. In this case, cassette 48 may include fewer than six tubing loops. Different pumps P1-P6 may interact with tubing loops T1-T6 of cassette 48 to perform different tasks during a separation procedure (described in more detail below), however, in one embodiment, different ones of pumps P1-P6 may be configured to function as a source pump, an anticoagulant pump, a spinner pump, a separation component pump, an additive pump, and a substitution fluid pump. As described, it should be understood that certain procedures may require less than all of the sensor stations, valve stations, and / or tubing loops shown in the exemplary cassette 48 of FIG. 13, such that the cassettes of different fluid flow circuits 12 may be configured differently (e.g., with fewer sensor stations, valve stations, and / or tubing loops) without departing from the scope of the present disclosure.

[0076] Additional tubes extend from the sides of the cassette 48 to connect to other components of the fluid flow circuit 12, such as the various fluid containers F1-F12, the spinning membrane separator 26 (if provided), and the centrifuge chamber 36 (if provided). The number and contents of the various fluid containers F1-F12 depend on the procedure for which the fluid flow circuit 12 is used, so they will be described in more detail with respect to the particular procedure. If the fluid flow circuit 12 includes a centrifuge chamber 36, the tubes connected thereto (including one inlet tube and two outlet tubes) may be aggregated to the umbilicus 46 (FIG. 12) which is engaged by a yoke member 44 of the centrifuge 16 (as described above) to orbit the umbilicus 46 and rotate the centrifuge chamber 36 during a separation procedure.

[0077] Various additional components may be incorporated into the tubing leading from cassette 48 or into one of the cavities of cassette 48. For example, as shown in Figures 2-11, a manual clamp 56 may be associated with one or more lines leading to a blood source and / or a fluid recipient, a return line filter 58 (e.g., a microaggregate filter) may be associated with a line leading to a fluid recipient, a filter 60 may be positioned upstream of one or more fluid containers to remove material (e.g., white blood cells) from separated components (e.g., red blood cells or platelets) flowing into the fluid containers (as in Figures 2-5,8), and / or an air trap 62 may be positioned on the line upstream of centrifuge chamber 36 (as in Figures 8-11).

[0078] C. Rotating membrane separator 14 and 15, the spinning membrane separator 26 is shown. As will be described in more detail, the spinning membrane separator 26 is used to separate plasma from cellular blood components of whole blood or any other plasma-containing fluid (e.g., platelet-rich plasma) obtained from a blood source. The spinning membrane separator 26 (if provided) is associated with the remainder of the fluid flow circuit 12 by an inlet port 64 and two outlet ports 66 and 68. Although the inlet port 64 is shown as being associated with the lower or bottom end of the spinning membrane separator 26, while the outlet ports 66 and 68 are associated with the upper or top end of the spinning membrane separator 26, it is not within the scope of this disclosure to invert the spinning membrane separator 26 such that fluid enters the upper or top end of the spinning membrane separator 26 and fluid exits the lower or bottom end of the spinning membrane separator 26.

[0079] The illustrated rotating membrane separator 26 includes a generally cylindrical housing 70 mounted concentrically about a longitudinal vertical central axis. An internal member or rotor 72 is mounted concentrically about the central axis. As described above with respect to the rotating membrane separator drive unit 14, the housing 70 and the rotor 72 are relatively rotatable. In a preferred embodiment, the housing 70 is stationary and the rotor 72 is a rotary spinner that is concentrically rotatable within the cylindrical housing 70. In such an embodiment, the housing 70 (or at least its upper and lower ends) is formed with a non-cylindrical shape, while the rotor 72 includes elements (e.g., metallic materials) that interact with the magnets of the rotating membrane separator drive unit 14 to rotate the rotor 72 within the housing 70, as described above.

[0080] The boundaries of the blood flow pathway are generally defined by a gap 74 between the inner surface of the housing 70 and the outer surface of the rotor 72, which may be referred to as the shear gap. A typical shear gap 74 may be about 0.025 to 0.050 inches (0.067 to 0.127 cm) and may be of uniform dimension along the axis, e.g., when the axes of the housing 70 and rotor 72 are coincident. Alternatively, the width of the shear gap 74 may also vary along the axial direction, e.g., the width of the gap 74 increases in the direction of flow to limit hemolysis. Such gap widths may range from about 0.025 to about 0.075 inches (0.06 to 0.19 cm). For example, in one embodiment, the axes of the housing 70 and rotor 72 are coincident and the outer diameter of the rotor 72 decreases in the direction of flow while the inner diameter of the housing 70 remains constant. In other embodiments, the inner diameter of the housing 70 may increase while the diameter of the outer rotor remains constant, or the diameters of both sides may vary. In one exemplary embodiment, the gap width may be approximately 0.035 inches (0.088 cm) at the upstream or inlet end of gap 74 and approximately 0.059 inches (0.15 cm) at the downstream or terminal end of gap 74. The gap width may vary linearly or in steps or in any other manner as desired. In any event, the width dimension of gap 74 is preferably selected such that at the desired relative rotational speed, a Taylor-Couette flow, such as a Taylor vortex, is generated within gap 74 to limit hemolysis.

[0081] The plasma-containing fluid is supplied to the gap 74 by an inlet port 64 (FIG. 14), which directs the fluid to the bottom end of the spinning membrane separator 26 or to a blood inlet area adjacent the bottom end. The spinning membrane separator drive unit 14 rotates the housing 70 and the rotor 72 relative to one another to create Taylor vortices within the gap 74. The outer surface of the rotor 72 and / or the inner surface of the housing 70 are at least partially (and more preferably substantially or entirely) covered by a cylindrical porous membrane 76 (shown in FIG. 15 as being attached to the outer surface of the rotor 72). It should thus be understood that the term "spinning membrane separator" does not necessarily require that the membrane 76 be attached to a component of the spinning membrane separator 26 that rotates, but may also include devices in which the membrane 76 is attached to a stationary element, including another element within which the membrane 76 rotates relative to the stationary element 76.

[0082] Membrane 76 typically has a nominal pore size of 0.65-0.8 microns, although other pore sizes may alternatively be used. Membranes useful for the methods described herein may be fiber mesh membranes, cast membranes, track-etched membranes, or other types of membranes known to those of skill in the art. For example, in one embodiment, membrane 76 may have a polyester mesh (substrate) with nylon particles solidified thereon, thereby creating a tortuous path through which only components of a particular size pass. In another embodiment, membrane 76 may be formed of a thin (approximately 15 micron thick) sheet of polycarbonate with, e.g., defined pores or holes therein, sized and configured to allow only one or more selected blood components to pass therethrough.

[0083] In embodiments in which the rotor 72 rotates within the housing 70 and the membrane 76 is attached to the outer surface of the rotor 72, the outer surface of the rotor 72 may be shaped to define ribs 78 separated by a series of spaced circumferential grooves or annular lands 80 (FIG. 15). The surface grooves defined by the circumferential grooves 78 are interconnected by longitudinal grooves 82. At one or both ends of the rotor 72, these grooves 78 communicate with a central orifice or manifold 84. Pumping fluid into and out of the rotating membrane separator 26 causes the plasma to flow through the membrane 76 and grooves 78 while the cellular blood components remain within the gaps 74 as the fluid flows from the inlet port 64 at the bottom of the rotating membrane separator 26 toward the top. The relative rotation of the rotor 72 and the housing 70 creates a particular flow pattern (described above) within the gaps 74, which allows the cellular blood components to be filtered from the plasma without clogging the membrane 76.

[0084] At the top of the rotating membrane separator 26, plasma exits the rotating membrane separator 26 via an outlet port 66 that is concentric with the axis of rotation and in fluid communication with a central orifice 84 of the rotor 72 (FIG. 15), where the plasma flows into a line associated with the outlet port 66. The separated cellular blood components exit the gap 74 via an outlet port 68 defined at the top end or upper portion of the housing 70 and oriented approximately tangentially to the gap 74 (FIG. 14), where the cellular blood components flow into a line associated with the outlet port 68.

[0085] As mentioned above, depending on the particular blood separation procedure being performed, it may be advantageous to use different sized spinning membrane separators 26. FIG. 14 shows a spinning membrane separator 26 having a rotor 72 with a spinner diameter D, a filtration length FL, and an overall length LOA. An exemplary smaller spinning membrane separator may have a spinner diameter D of about 1.1 inches, a filtration length FL of about 3 inches, and an overall length LOA of about 5.0 inches. In comparison, an exemplary larger spinning membrane separator may have a spinner diameter D of about 1.65 inches, a filtration length FL of about 5.52 inches, and an overall length LOA of about 7.7 inches. An exemplary smaller spinning membrane separator is described in more detail in U.S. Pat. No. 5,194,145, which is incorporated herein by reference, while an exemplary larger spinning membrane separator is described in more detail in U.S. Pat. App. Pub. No. 2015 / 0218517, which is incorporated herein by reference.

[0086] D. Centrifugation chamber If platelets and / or white blood cells are to be separated and collected, the fluid flow circuit 12 may comprise a centrifuge chamber 36. An exemplary centrifuge chamber 36 is shown in Figures 16 and 16A, while Figure 16B illustrates the fluid flow path defined by the centrifuge chamber 36. In the illustrated embodiment, the body of the centrifuge chamber 36 is preformed (e.g., by injection molding) into the desired shape and configuration from a rigid biocompatible plastic material, such as unplasticized medical grade acrylonitrile-butadiene-styrene (ABS). All contours, ports, grooves, and walls that affect the blood separation process are performed in a single injection molding operation. Alternatively, the centrifuge chamber 36 may be formed by separate molded parts, by nesting a cup-shaped subassembly or two symmetrical halves.

[0087] The underside of the centrifuge chamber 36 includes a shaped container 86 suitable for receiving the end of the Umbilix 46 in the fluid flow circuit 12 (FIG. 12). A suitable container 86 and the manner in which the Umbilix 46 may cooperate with the container 86 to deliver fluid to and remove fluid from the centrifuge chamber 36 are described in further detail in U.S. Patent No. 8,075,468.

[0088] The illustrated centrifuge chamber 36 has radially spaced inner (low g) and outer (high g) sidewall portions 88 and 90, a bottom or first end wall portion 92, and a cover or second end wall portion 93. The cover 93 includes a simple flat portion that can be easily welded or otherwise secured to the body of the centrifuge chamber 36. Tolerances between the cover 93 and the body of the centrifuge chamber 36 will not affect the separation efficiency of the centrifuge chamber 36, since all features that affect the separation process are incorporated into one injection molded part. The wall portions 88 and 90, the bottom portion 92, and the cover 93 together define a closed, approximately annular groove 94 (FIG. 16B).

[0089] A (whole blood) inlet 96 in communication with groove 94 is defined between opposing inner radial walls 98 and 100. One of the inner walls 98 joins the outer (high g) wall 90 and separates the upstream and downstream ends of groove 94. The inner walls 98 and 100 define an inlet passage 96 to the centrifuge chamber 36, which in one flow configuration allows fluid to flow from Umbilix 46 to the upstream end of groove 94.

[0090] The illustrated centrifuge chamber 36 further includes a first outlet 102 and a second outlet 104, which may be defined by opposing surfaces of the radially inner wall. Both the first outlet 102 and the second outlet 104 extend radially inward from the groove 94. The first (platelet-rich plasma) outlet 102 extends radially inward from an opening located in the inner wall 88 in the illustrated embodiment, and the second (red blood cell) outlet 104 extends radially inward from an opening associated with the outer wall 90. The illustrated first outlet 102 may be located adjacent to the inlet 96 (near the upstream end of the groove 94), and the second outlet 104 may be located at the opposite downstream end of the groove 94.

[0091] It should be understood that the centrifuge chamber 36 illustrated in FIG. 16 is merely exemplary, and that the centrifuge chamber may be configured differently without departing from the scope of the present disclosure. For example, FIGS. 17 and 17A show an alternative embodiment of the centrifuge chamber 36a, and FIG. 17B shows the fluid flow path defined by the centrifuge chamber 36a. The centrifuge chamber 36a is similar to the centrifuge chamber 36 except for the location where the inlet 96 opens into the groove 94. As best shown in FIGS. 16A and 16B, in the centrifuge chamber 36 of FIG. 16, the inlet 96 opens into the groove 94 adjacent the first end wall 92 (the outlets 102 and 104 open into the groove 94 adjacent the second end wall 93). In contrast, as best shown in FIGS. 17A and 17B, the inlet 96 of the centrifuge chamber 36a of FIG. 17 opens (along with the outlets 102 and 104) into the groove 94 adjacent the second end wall 93. The location where the inlet 96 opens into the groove 94 may affect the separation of fluids within the groove 94, so that the centrifuge chamber 36 of FIG. 16 may be preferred for particular procedures or for use in combination with particular blood separation devices, while the centrifuge chamber 36a of FIG. 17 may be preferred for other procedures or for use in combination with other blood separation devices.

[0092] 18 and 18A show another exemplary embodiment of a centrifuge chamber 36b suitable for incorporation into the fluid flow circuit 12. The centrifuge chamber 36b is similar to the centrifuge chambers 36 and 36a of FIGS. 16 and 17, except for the position where the inlet 96 opens into the groove 94. In contrast to the inlet 96 of the centrifuge chambers 36 and 36a of FIGS. 16 and 17, the inlet 96 of the centrifuge chamber 36b of FIG. 18 opens into the groove 94 at a median axial position spaced apart from the first and second end walls 92 and 93 (whereas the outlets 102 and 104 open into the groove adjacent to the second end wall 93). The inlet 96 may open into the groove 94 at a position closer to the first end wall 92 than the second end wall 93, closer to the second end wall 93 than the first end wall, or at a position equally spaced between the first end wall 92 and the second end wall 93. Because the axial position at which the inlet 96 opens into the groove 94 can affect the separation of the fluids within the groove 94, the preferred position at which the inlet 96 opens into the groove 94 (which may also depend on the nature of the blood separation device that is paired with the centrifuge chamber 36b) can be determined experimentally.

[0093] 1. Centrifugation and interface detection principle As the centrifuge chamber 36 is rotated about the axis of rotation 38, blood flowing into the grooves 94 separates into an optically dense layer RBC and an optically less dense layer PRP (FIGS. 19-21). The optically dense layer RBC is formed as larger and / or heavier blood particles move toward the outer (high g) wall 90 under the influence of centrifugal force. The optically dense layer RBC typically contains red blood cells (and thus may be referred to herein as the "RBC layer"), although depending on the speed at which the centrifuge chamber 36 rotates, other cellular components (e.g., larger white blood cells) may also be present in the RBC layer RBC.

[0094] The low optical density layer PRP typically comprises platelet rich plasma (and thus is referred to herein as the "PRP layer"). Depending on the speed at which the centrifuge chamber 36 is rotated and the length of time the blood resides therein, other components (e.g., smaller white blood cells and anticoagulants) may also be present in the PRP layer PRP. In one embodiment, blood introduced into the channel 94 via the inlet 96 travels in a generally clockwise direction (in the orientation of FIG. 16) as the RBC layer RBCs separate from the PRP layer PRP. The RBC layer RBCs continue to move in a clockwise direction as they travel the length of the channel 94 along the outer wall 90 from the upstream end to the downstream end, where they exit the channel 94 via a second outlet 104. The PRP layer PRP, separated from the RBC layer RBCs, reverses direction and travels counterclockwise along the inner wall 88 to a first outlet 102 adjacent the inlet 96. The inner sidewall 88 tapers inwardly as it approaches the second outlet 104 to force plasma released at or near the downstream end of the groove 94 back up the interface toward the upstream end of the groove 94, where the lower surface hematocrit resuspends platelets that have settled at the interface.

[0095] As mentioned above, the transition between the RBC layer RBC and the PRP layer PRP may be referred to as the interface INT. The location of the interface INT in the groove 94 of the centrifuge chamber 36 may dynamically move during blood processing, as shown in Figures 19-21. If the location of the interface INT is too high (i.e., too close to the inner wall 88 and the first outlet 102 as in Figure 20), the red blood cells may flow into the first outlet 102, which may adversely affect the quality of the low density component (platelet-rich plasma). On the other hand, if the location of the interface INT is too low (i.e., too far from the inner wall 88 as shown in Figure 21), the collection efficiency of the system may be compromised. The ideal or target interface INT may be determined experimentally, and it may vary depending on any of several factors (e.g., the configuration of the centrifuge chamber 36, the speed at which the centrifuge chamber 36 rotates about the rotation axis 38).

[0096] As discussed above, the blood separation device 10 can include an interface monitoring system and a controller 18 having an interface control module for monitoring and, if necessary, correcting the position of the interface INT. In one embodiment, the centrifuge chamber 36 is formed with a ramp 106 that extends from the high-g wall 90 across at least a portion of the groove 94 at an angle α (FIGS. 16 and 19-21). In one embodiment, the angle α measured relative to the axis of rotation 38 is about 25°. FIGS. 19-21 show the orientation of the ramp 106 as viewed from the low-g side wall 88 of the centrifuge chamber 36. Although it describes a flexible separation chamber, the general structure and function of the ramp 106 can be better understood by reference to U.S. Pat. No. 5,632,893, which is incorporated herein by reference. The ramp 106 may be positioned at any number of positions between the upstream and downstream ends of the groove 94, but in one embodiment, the ramp 106 may be positioned within the fluid passage approximately adjacent to the first outlet 102 in the path of the flow path and / or fluid components traveling from the inlet 96 to the first outlet 102.

[0097] The ramp 106 makes the interface INT between the RBC layer RBC and the PRP layer PRP more detectably identifiable and displays the RBC layer RBC, the PRP layer PRP, and the interface INT for viewing through a light-transmitting portion of the centrifuge chamber 36. To that end, the ramp 106 and at least a portion of the centrifuge chamber 36 angularly aligned with the ramp 106 can be formed of a light-transmitting material, although it may be advantageous to form the entire centrifuge chamber 36 of the same light-transmitting material.

[0098] In the illustrated embodiment, the light source 50 of the interface monitoring system is secured to a fixture or wall of the centrifuge compartment 32 and is arranged to emit light that is directed toward the axis of rotation 38 of the centrifuge 16, as shown in FIGS. 12A-12C. If the light detector 52 is positioned at an angle to the light source 50 (as in the illustrated embodiment), the light L emitted by the light source 50 must be redirected from its initial path before reaching the light detector 52. In the illustrated embodiment, the light L is redirected by a reflector associated with a light-transmitting portion of the inner wall 88, as shown in FIGS. 12A and 12B. The reflector may be a separate piece that is secured to the inner wall 88 (e.g., by being glued thereto) or may be integrally formed with the body of the centrifuge chamber 36.

[0099] In one embodiment, the reflector can be a reflective surface such as a mirror oriented to direct the light L emitted by the light source 50 toward the light detector 52 (e.g., at a 45° angle). In another embodiment, the reflector is provided as a prismatic reflector 108 (FIGS. 12C, 22, and 22A) formed of an optically transparent material (e.g., a clear plastic material) and having an inner wall 110 and an outer wall 112 and first and second end walls 114 and 116 (FIG. 22). The inner wall 110 is disposed against the inner wall portion 88 of the centrifuge chamber 36 and is oriented substantially perpendicular to the initial path of the light L from the light source 50. This allows the light L from the light source 50 to enter the prismatic reflector 108 through the inner wall 110 while following its initial path. The light L passes through the prismatic reflector 108 along its initial path until it hits the first end wall 114. The first end wall 114 is oriented at an angle (e.g., about a 45° angle) relative to the first surface 110 and the second end wall 116 such that light is redirected within the prismatic reflector 108 via the first end wall 114 rather than exiting the prismatic reflector prism 108.

[0100] The first end wall 114 directs the light L at an angle to its initial path (which may be at an angle of approximately 90°, directing the light L from a path toward the axis of rotation 38 to a path generally parallel to the axis of rotation 38) toward the second end wall 116 ( FIG. 22A ). The first end wall 114 and the inner and outer walls 110 and 112 of the prismatic reflector 108 may be configured to transmit the redirected light L from the first end wall 114 to the second end wall 116 by total internal reflection. The second end wall 116 is oriented substantially perpendicular to the redirected path of the light L through the prismatic reflector 108, such that the light L exits the prismatic reflector 108 along the redirected path via the second end wall 116. In one embodiment, the second end wall 116 is roughened or textured or otherwise treated or conditioned to diffuse the light L as it exits the prismatic reflector 108, which may make it more likely that the light L will reach the photodetector 52 (FIG. 12C).

[0101] The prismatic reflector 108 may be aligned at an angle with the ramp 106, such that light L from the light source 106 will only enter the prismatic reflector 108 when the ramp 106 has been rotated into the path of the light L. At all other times (when the ramp 106 is not in the path of the light L), the light L will not reach the prismatic reflector 108 and therefore the photodetector 52. This is illustrated in Figures 23-23C, which show the ramp 106 and prismatic reflector 108 (with the light source 50 in a fixed position) as the centrifuge chamber 36 rotates about the axis of rotation 38. In Figure 23, the ramp 106 and prismatic reflector 108 have not yet rotated into the initial path of the light L from the light source 50. At this point, no light is transmitted to the photodetector 52, so the output voltage of the photodetector 52 (i.e., the signal transmitted from the photodetector 52 to the control unit 18) is in a low or zero state. (Figure 24).

[0102] As the ramp 106 is first rotated into the initial path of light L from light source 50 (FIG. 23A), the light L begins to reach the prismatic reflector 108, which directs the light L toward the photodetector 52. This causes the voltage output of the photodetector 52 (i.e., the signal sent from the photodetector 52 to the controller 18) to increase to a non-zero value or state, as shown in FIG.

[0103] During the calibration phase, the groove 94 is filled with a fluid that transmits light L rather than absorbing or reflecting light or preventing it from reaching the prismatic reflector 108, and the voltage output of the photodetector 52 remains generally constant as the ramp 106 and prismatic reflector 108 are rotated through the initial path of light L from the light source 50 (FIGS. 23B and 24B). Such a calibration phase may coincide with a priming phase during which saline is pumped through the fluid flow circuit 12 to prime the fluid flow circuit 12, or may comprise a separate phase. The calibration phase is useful to ensure proper operation of the light source 50 and the photodetector 52, to standardize readings made during a separation procedure in the event that there are any irregularities or imperfections in the centrifuge chamber 36, and to establish a baseline value for the signal transmitted from the photodetector 52 to the controller 18 when the ramp 106 and prismatic reflector 108 are aligned with the light source 50. As will be explained in more detail, different layers of fluid presented on the ramp 106 allow different amounts of light L to reach the prismatic reflector 108, so that the voltage output of the photodetector 52 does not typically remain constant as the ramp 106 and the prismatic reflector 108 rotate through the initial path of the light L from the light source 50.

[0104] The ramp 106 and prismatic reflector 108 eventually rotate out of alignment with the light source 50 (FIG. 23C), at which point light L does not reach the prismatic reflector 108 and the voltage output of the photodetector 52 returns to its low or zero state (FIG. 24C).

[0105] To improve the resolution of the signal generated by the photodetector 52, it may be advantageous for the light L to have a relatively small diameter. For example, FIG. 25 shows the ramp 106 displaying the separated blood components rotated into the path of the small diameter light L, and FIG. 25A shows the ramp 106 rotated into the path of the large diameter light L'. Ideally, the voltage output of the photodetector 52 (i.e., the signal it sends to the control unit 18) increases instantaneously from its zero state to a higher state as soon as the ramp 106 and prismatic reflector 108 rotate into the initial path of the light L from the light source 50. When a small diameter light L is used (FIG. 25), the entire light L is aligned with the ramp 106 and prismatic reflector 108 very quickly, resulting in a very rapid change in the voltage output of the photodetector 52 (FIG. 26). In contrast, when a larger diameter light L' is used (FIG. 25A), it takes longer for the entire light L' to become aligned with the ramp 106 and prismatic reflector 108, resulting in a slower change in the voltage output of photodetector 52 (FIG. 26A). Thus, by comparing FIGS. 26 and 26A, it can be seen that a smaller diameter light better approximates the idealized instantaneous change in the voltage output of photodetector 52.

[0106] The diameter of the light L can be reduced by providing the light source 50 to emit a focused light L having a relatively small diameter, such as by providing the light source 50 as a laser rather than a typical light emitting diode. To effectively reduce the diameter of the light L, the light source 50 can include a lens 118 (FIG. 12C) that focuses the light L to a point P (which may be a few thousandths of an inch in diameter) within the centrifuge chamber 36. In one embodiment, this focal point P is approximately the midpoint of the surface of the ramp 106 where the interface INT is displayed (i.e., the inclined surface of the ramp 106 facing the inner wall 88 or the last surface of the ramp 106 that the light L passes through before exiting the ramp 108). As the ramp 106 rotates past the light L, the circumferential displacement of the ramp 106 can be about 0.25 inches, in which case the resolution can be about 0.5%.

[0107] 2. Exemplary Interface Detection and Correction Procedure During separation of blood in the channel 94, light L from the light source 50 passes through the light-transmitting portion of the outer wall 90 and the ramp 106 to intersect the separated blood components as the ramp 106 rotates into an initial path of the light L. After passing through the ramp 106, the light continues to pass through the channel 94 and the fluid within the channel 94. At least a portion of the light L (i.e., the portion that is not absorbed or reflected by the fluid) exits the channel 94 by impinging upon and entering the light-transmitting portion of the inner wall 88. The light L passes through the inner wall 88 and enters the prismatic reflector 108, which redirects the light L from its initial path to the photodetector 50, as described above. Thus, in contrast to known systems in which light from a light source travels through a ramp and a fluid-filled channel before being reflected back through the channel to reach the photodetector, the light L reaches the photodetector 52 after intersecting and passing through the separated blood components in the channel 94 only once. Requiring the light L to pass through the fluid-filled groove 94 only once, rather than twice, before reaching the photodetector 52 tends to increase the intensity of the light L reaching the photodetector 52, which can be advantageous in terms of improving monitoring and correction of the interface position.

[0108] The photodetector 52 generates a signal that is sent to the interface control module of the control unit 18, which can determine the position of the interface INT on the ramp 106. In one embodiment, the position of the interface INT is related to a change in the amount of light L transmitted through the PRP layer PRP and the RBC layer RBC. For example, the light source 50 may be configured to emit light L, such as red visible light (from a laser or a differently configured light source 50), which is substantially absorbed by red blood cells, but is more easily transmitted by platelet-rich plasma than red blood cells. The PRP layer PRP and the RBC layer RBC each occupy a certain portion of the ramp 106, and the photodetector 52 receives a different amount of light L depending on whether the light L passes through the PRP layer PRP on the ramp 106 or the RBC layer RBC on the ramp 106. The percentage of the ramp 106 occupied by each layer is related to the position of the interface INT within the groove 94. Thus, by measuring the amount of time that the voltage output or signal from the photodetector 52 is relatively high (corresponding to the time during which the light L passes only through the PRP layer PRP on the ramp 106), the control unit 18 can determine the location of the interface INT and, if necessary, take steps to correct the location of the interface INT.

[0109] 27-27C show a portion of the ramp 106 rotating into and through the initial path of the light L from the light source 50. Four specific events are shown: just before the ramp 106 rotates into the path of the light L (FIG. 27), the ramp 106 initially rotating into the path of the light L (FIG. 27A), just before the interface INT displayed on the ramp 106 rotates into the path of the light L (FIG. 27B), and just after the interface INT has rotated into the path of the light L (FIG. 27C). FIGS. 28-28C show the voltage output of the photodetector 52 (which corresponds to the signal it sends to the controller 18) during each of these events.

[0110] As discussed above, when the prismatic reflector 108 is not aligned with the initial path of the light L from the light source 50, as shown in Figure 27, the photodetector 52 does not receive the light L from the light source 50. Figure 28 shows that the output voltage of the photodetector 52 (i.e., the signal sent from the photodetector 52 to the control unit 18) at this time is in a low or zero state.

[0111] When the ramp 106 is initially rotated into the path of the light L from the light source 50 (FIG. 27A), the photodetector 52 can begin to receive the light L. The amount of light L received by the photodetector 52 depends on the fluid on the ramp 106 that the light L encounters (i.e., the fluid in the groove 94 between the ramp 106 and the inner wall 88 that the light L must traverse before being directed to the photodetector 52). As noted above, the PRP layer PRP occupies a percentage of the groove 94 adjacent the inner wall 88, while the RBC layer RBC occupies a percentage of the groove 94 adjacent the outer wall 90 (the interface INT is located at the transition between the two separated blood component layers). The illustrated ramp 106 is closest to the inner sidewall 88 at its left end, but is further away from the inner sidewall 88 at its right end (as oriented in FIGS. 27-27C). 27-27C, at a position adjacent its left end, the ramp 106 will only display fluid closest to the inner wall 88 (i.e., the PRP layer PRP), and at a position adjacent its right end, the ramp 106 will only display fluid closest to the outer wall 90. At some point between its ends, the angled ramp 106 will be at a radial position where it will display the transition (i.e., the interface INT) between the PRP layer PRP and the RBC layer RBC. Thus, the location of the interface INT on the ramp 106 will depend on the percentage of the width of the ramp 106 that displays the PRP layer PRP (which indicates the percentage of the groove 94 that is occupied by the PRP layer PRP) and the percentage of the width of the ramp 106 that displays the RBC layer RBC (which indicates the percentage of the groove 94 that is occupied by the RBC layer RBC). It should be understood that the percentage of the ramp 106 occupied by the PRP layer PRP and the RBC layer RBC may not necessarily be equal to the percentage of the groove 94 occupied by the PRP layer PRP and the RBC layer RBC, but the percentage of the ramp 106 occupied by a separated blood component layer may simply be indicative of the percentage of the groove 94 occupied by that separated blood component layer.

[0112] In such an embodiment, as shown in FIG. 27A, when the ramp 106 rotates into the path of the light L from the light source 50, the light L first encounters the portion of the ramp 106 closest to the inner wall 88 (i.e., the portion of the ramp 106 that most restricts the groove 94). As described above, the PRP layer PRP is adjacent to the inner wall 88 as it separates from the RBC layer RBC, such that the fluid displayed in this radially innermost portion of the ramp 106 (i.e., the fluid present in the groove 94 between the ramp 106 and the inner wall 88) becomes the PRP layer PRP. The light travels substantially through the PRP layer PRP to the inner wall 88 and through the optically transparent inner wall 88 to the prismatic reflector 108, which redirects the light L to the photodetector 52. This causes the voltage output of the photodetector 52 (i.e., the signal transmitted from the photodetector 52 to the controller 18) to increase to a non-zero value or state, as shown in FIG. 28A. Depending on the properties of the light L, the amount of light L (and therefore the magnitude of the voltage output) received by the photodetector 52 after the light L passes through the PRP layer PRP may be greater than, less than, or equal to the amount of light L received by the photodetector 52 after passing through the saline solution during the calibration stage described above.

[0113] Further rotation of the ramp 106 through the path of the light L from the light source 50 exposes the light L to a portion of the ramp 106 that is progressively further away from the inner wall 88 (i.e., the light L travels through a portion of the groove that is less restricted by the ramp 106 as it rotates through the light L). Until the interface INT on the ramp 106 rotates into the path of the light L (as shown in FIG. 27B), the only fluid in the groove 94 through which the light L would have passed is the PRP layer PRP, and a generally uniform level of light reaches the photodetector 52 during the conditions shown in FIGS. 27A and 27B. Thus, the voltage output of the photodetector 52 is generally uniform (at a high level) throughout the entire passage of the light L before the ramp 106 is exposed to the interface INT, as shown in FIG. 28B. The controller 18 can be programmed and / or configured to consider a signal that deviates from the maximum signal level (e.g., a 10% decrease) as part of a rising signal for purposes of calculating the pulse width of the signal. The control unit 18 treats a larger deviation (ie, a larger decrease in signal magnitude) as the end of a rising signal for purposes of calculating the pulse width of the signal.

[0114] As soon as the interface INT is rotated from the light source 50 into the path of the light L, the light L will begin to encounter the RBC layer RBC in the groove 94, as shown in FIG. 27C. As described above, the RBC layer RBC is disposed adjacent to the outer wall 90 as it separates from the PRP layer PRP, so that the RBC layer RBC is not visible on the ramp 106 until the ramp 106 is moved farther away from the inner wall 88 (i.e., toward the right end of the ramp 106 in the orientation of FIGS. 27-27C). Because less light passes through the RBC layer RBC than through the PRP layer PRP (which may include all or substantially all of the light L absorbed by the RBC layer RBC), the amount of light L reaching the photodetector 52 is reduced compared to the amount of light L reaching the photodetector 52 while passing only through the PRP layer PRP in the flow channel 94 (FIGS. 27A and 27B).

[0115] When less light L is received, the voltage output or signal from the photodetector 52 decreases to a lower level than when the light L passed only through the PRP layer PRP in the groove 94, as shown in FIG. 28C. When the light L encounters the RBC layer RBC in the groove 94, the photodetector 52 generates a signal or voltage output approximately equal to its zero state (when the photodetector 52 is not receiving, as in FIG. 28) or generates a signal or voltage output that is somewhat less in magnitude than the signal or voltage output generated while the light L encountered only the PRP layer PRP in the groove 94. The controller 18 can be programmed and / or configured to recognize this low level signal as indicative of the presence of the RBC layer RBC on the ramp 106 (and in the portion of the groove 94 traversed by the light 94) and to treat this low level signal as a signal that is the end of the rising signal generated by the photodetector 52 while the light L passed only through the PRP layer PRP in the groove 94.

[0116] Thus, the pulse width of the rising signal from the photodetector 52 to the control unit 18 (i.e., the time that the light L is only crossing the PRP layer PRP in the groove 94) is determined by the percentage of the ramp 106 that is occupied by the PRP layer PRP and the RBC layer RBC. Thus, a signal from the photodetector 52 to the control unit 18 with a larger pulse width is associated with a PRP layer PRP occupying a larger portion of the ramp 106 (as shown in FIG. 29 from the perspective of the light source 50, which may correspond to the state shown in FIG. 20), indicating a thinner RBC layer RBC on the ramp 106 (and in the groove 94). Conversely, a signal from the photodetector 52 to the control unit 18 with a narrower pulse width is associated with a PRP layer PRP occupying a smaller portion of the ramp 106 (as shown in FIG. 29A), indicating a thicker RBC layer RBC on the ramp 106 (and in the groove 94).

[0117] The control unit 18 can compare the pulse width of the signal to the pulse width generated during the calibration phase (discussed above and shown in FIG. 29C), which corresponds to the pulse width when light L is sent to the photodetector 52 across the entire width of the ramp 106. The pulse width of the signal generated by the photodetector 52 during the calibration phase is sometimes referred to as the saline calibration signal. Comparing these two pulse widths indicates the percentage of the ramp 106 that is occupied by the PRP layer PRP and the RBC layer RBC, information that the control unit 18 can use to determine the location of the interface INT within the groove 94. In particular, the interface location can be calculated as follows: Interface position (%) = ((Saline calibration pulse width - current plasma pulse width) / Saline calibration pulse width) x 100 [Equation 1]

[0118] It will be appreciated that since the difference between the two pulse widths corresponds to the length of time that the ramp 106 rotates through the path of the light without the photodetector 52 receiving a high level of light L (i.e., the amount of time that the ramp 106 rotates through the path of the light L while the RBC layer RBCs are present on the ramp 106), equation 1 effectively calculates the percentage of the ramp 106 that is occupied by the RBC layer RBCs.

[0119] Once the position of the interface INT on the ramp 106 has been determined, the interface control module compares the actual interface position to the desired interface position, which may be referred to as the set point S. The difference between the set point S and the calculated interface position may be referred to as the error signal E, as shown in Figure 30. It should be understood that this representation of the error signal E in terms of the targeted red blood cell percentage (i.e., the percentage of the ramp 106 that is actually occupied by the RBC layer RBCs versus the percentage of the ramp 106 that should be occupied by the RBC layer RBCs) is merely exemplary, and that the error signal E may be expressed or calculated in any of many other ways.

[0120] When the control value is expressed in terms of a targeted red blood cell percentage, a negative error signal E indicates that the RBC layer RBC on the ramp 106 is too large (as shown in FIG. 20). The interface control module of the controller 18 generates signals to adjust the operating parameters accordingly, such as by decreasing the rate at which platelet-rich plasma is removed through the first outlet 102 under the action of the pump of the blood separation device 10. The interface INT moves toward the desired control position where the error signal is zero (as shown in FIG. 19).

[0121] A positive error signal indicates that the RBC layer RBC on the ramp 106 is too small (as shown in Figures 21 and 30). The interface control module of the controller 18 generates a signal to adjust the operating parameters accordingly, such as by increasing the rate at which the platelet-rich plasma is removed through the first outlet 102 under the action of the pump of the blood separation device 10. The interface INT moves toward the desired control position (Figure 19) where the error signal is again zero.

[0122] The exact change in the rate at which the platelet-rich plasma is removed from the groove 94 can be calculated using a control algorithm in the interface control module. The control algorithm may take any of several forms, including a proportional-integral-derivative ("PID") control system that acts to minimize the difference between the target position of the interface INT on the ramp 106 and the actual position of the interface INT on the ramp 106. A PID control system takes into account the current difference between the two interface positions (the "P term"), the difference between the two interface positions in the past (the "I term"), and a prediction of the future difference between the two interface positions (the "D term"). Alternatively, the interface control module of the control unit 18 may operate in a proportional-integral ("PI") control mode in which the D term is not a factor, which may provide better (i.e., smoother) interface control than a PID control system. FIG. 31 illustrates how the removal rate of the platelet-rich plasma from the groove 94 may be altered to move the interface INT toward a target interface position or set point S. The variation in interface position represents the repeated execution of a control loop that includes (1) calculating the interface position, (2) calculating an error signal, (3) inputting the error signal into a control algorithm of the interface control module, (4) calculating a control signal, (5) sending the control signal to a pump of the blood separation device 10 to remove platelet-rich plasma from the channel 94 at different rates, and (6) returning to step (1) of the control loop. As shown in FIG. 31, the set point S changes during the procedure, with the interface control module functioning to first move the interface INT quickly toward the set point S, and then, once in the vicinity of the set point S, to perform finer adjustments to the position of the interface INT. Although FIG. 31 shows the set point S changing as a step function, it is within the scope of this disclosure for the set point S to change in other ways during the separation procedure or to remain the same for the entire separation procedure.

[0123] It should be understood that this system for controlling the position of the interface INT is merely exemplary, and that systems of different configuration and / or functionality may be employed without departing from the scope of the present disclosure.

[0124] III. Exemplary Separation Procedures An exemplary blood separation procedure that may be performed using the systems and techniques according to the present disclosure will now be described.

[0125] Depending on the blood separation objective, there is an appropriate procedure for separating and collecting any combination of red blood cells, platelets, white blood cells, and (substantially cell-free) plasma. Thus, prior to processing, the operator selects the desired protocol (e.g., using the operator interface station, if provided), which tells the controller 18 how to control the other components of the blood separation device 10 during the procedure.

[0126] If the blood source is a donor, the operator may proceed to input various parameters of the donor such as gender / height / weight, etc. In one embodiment, the operator also inputs the target yields for various blood components (including inputting blood characteristics such as platelet pre-count) or any other collection control system (e.g., amount of whole blood to be processed).

[0127] If there are fluid containers (e.g., platelet storage solution containers) that are not integrally formed with the fluid flow circuit 12, they may be connected to the fluid flow circuit 12 (e.g., by penetrating septa of tubing in the fluid flow circuit 12 or by Luer connectors) and then attached to the blood separation device 10 (including fluid containers F1-F12, which are suspended from weigh scales W1-W6, as appropriate). An integrity check of the fluid flow circuit 12 may be performed by the controller 18 to ensure that the various components are properly connected and functioning. After a successful integrity check, a blood supply may be connected to the fluid flow circuit 12 (e.g., by exsanguining a donor), and the fluid flow circuit 12 may be primed (e.g., with saline pumped from saline bag F2 at one or more of P1-P6 of the blood separation device 10).

[0128] Once fluid flow circuit 12 is primed, blood separation can begin. The stages of blood separation vary depending on the particular procedure and will be described in more detail below.

[0129] A. Red Blood Cell Collection In accordance with one aspect of the present disclosure, red blood cells can be separated and collected from blood using blood separation device 10. When the blood source is a donor, it is generally safe to collect two units of red blood cells (approximately 400 ml total), although it is within the scope of the present disclosure to collect different amounts of red blood cells.

[0130] A blood separation device 10 according to the present disclosure can be used in combination with a fluid flow circuit 12 having a single blood access device (e.g., a single needle that withdraws blood and returns separated blood components to the same location) or two blood access devices (e.g., one needle that withdraws blood from a source and a second needle that flows separated blood components to the same source or to a different recipient). Exemplary fluid flow circuits 12A, 12B and procedures are described for each configuration.

[0131] 1. Single Needle Fluid Flow Circuit and Procedure a. Fluid flow circuit FIGURE 2 is a schematic diagram of an exemplary fluid flow circuit 12A having a single blood access device (e.g., a needle) for separating and collecting red blood cells from blood. Fluid flow circuit 12A includes a cassette 48 of the type described above and shown in FIGURE 13 that connects the various components of fluid flow circuit 12A. The various connections between the components of fluid flow circuit 12 are shown in FIGURE 2, which also shows fluid flow circuit 12A installed on blood separation device 10.

[0132] As will be described below, although the components of fluid flow circuit 12A interact with many of the components of blood separation device 10, there are selected components of blood separation device 10 that are not used in separating and collecting red blood cells using flow circuit 12A of Figure 2. Most notably, centrifuge 16 is not used, only spinning membrane separator drive unit 14. There are also selected valves V3, V4, V5, V8 and pressure sensor A2 of blood separation device 10 that are not used in the procedures described herein.

[0133] B. Retraction phase In the first stage (FIG. 32), blood is drawn from the blood source into the fluid flow circuit 12A. If the blood source is a donor, blood may be drawn into the fluid flow circuit 12A through a single needle connected to the cassette 48 by a line L1. The line L1 may include a manual clamp 56 that may be initially in a closed position to prevent fluid flow through the line L1. When initiating processing, an operator moves the manual clamp 56 from its closed position to an open position to allow fluid to flow through the line L1. As used herein, the term "line" is used to refer to any fluid flow conduit, whether a flexible tube connected to the cassette 48 or a rigid defined flow path of the cassette 48, and unless otherwise specified, a particular line is not limited to being a flexible tube or a rigid defined conduit.

[0134] Blood is drawn into line L1 by pump P2 of blood separation device 10, which may be referred to as a donor pump. As mentioned above, donor pump P2 may be a peristaltic pump that interacts with tubing loop T2 extending from cassette 48 of fluid flow circuit 12A. Anticoagulant may be added to the blood (the term "blood" as used herein may or may not have anticoagulant added) via line L2 under the action of pump P1 of blood separation device 10, which may be referred to as an anticoagulant pump. Anticoagulant pump P1 may be a peristaltic pump that interacts with tubing loop T1 of fluid flow circuit 12A to draw anticoagulant from fluid container F1 (which may also be referred to as an anticoagulant bag) through line L2 and through the junction of lines L1 and L2, where the anticoagulant is mixed with the blood entering fluid flow circuit 12A.

[0135] In the illustrated embodiment, valve station C10 associated with valve V10 is open, allowing blood to flow through lines L3 and L4 and sensor station S1 associated with pressure sensor A1 of blood separation device 10. If the blood source is a living organism (e.g., a donor), pressure sensor A1 can communicate with controller 18 to monitor the pressure within the veins of the blood source.

[0136] The cassette 48 includes two valve stations C1 and C2 downstream of the donor pump P2, which are associated with valves V1 and V2 (respectively) of the blood separation device 10. One valve V2 is closed to prevent fluid flow through the associated valve station C2, and the other valve V1 is open to allow fluid flow through the associated valve station C1. Blood flows through line L5 associated with the open valve V1 to the junction, where a portion of the blood is directed through line L6 to a fluid container F3 (which may be referred to as an in-process bag) and the remainder is directed through line L7 to the spinning membrane separator 26. Line L7 is associated with pump P4 (which may be referred to as a spinner pump), which controls the amount of blood that is directed to the spinning membrane separator 26 instead of the in-process bag F3. In particular, the flow rate of the donor pump P2 is greater than the flow rate of the spinner pump P4, and the difference between them is equal to the flow rate of blood to the in-process bag F3. The flow rates may be selected such that the in-process bag F3 is partially or totally filled with blood at the end of the drawing phase.

[0137] Blood flowing through line L7 toward spinning membrane separator 26 passes through spinner inlet sensor M1, associated with pressure sensor A4 (which monitors the pressure in spinning membrane separator 26), and sensor station S4. Spinner inlet sensor M1 can detect the hematocrit of the blood entering spinning membrane separator 26, which can be used to set the flow rate of pump P5 (sometimes referred to as a red blood cell pump) to achieve a desired concentrated red blood cell hematocrit.

[0138] The spinning membrane separator drive unit 14 of the blood separation device 10 operates the spinning membrane separator 26 to separate plasma from cellular blood components (i.e., red blood cells, platelets, and white blood cells). In one embodiment, the spinning membrane separator 26 is a larger spinning membrane separator (as described above) having a stationary housing 70 and a rotatable rotor 72 to which a membrane 76 is attached. In such an embodiment, the spinning membrane separator drive unit 14 spins the rotor 72 at approximately 2,500-3,000 rpm to separate blood entering the bottom of the spinning membrane separator 26 (as described above) into plasma and cellular components.

[0139] Cellular blood components are pumped from the spinning membrane separator 26 via line L8 by red blood cell pump P5. Valve V6 is closed to prevent fluid flow through associated valve station C6 and line L9, thereby directing the flow of cellular blood components through line L10 to the leukoreduction filter 60. Pressure sensor A3 may interact with sensor station S3 of cassette 48 to monitor the pressure of the leukoreduction filter 60. Valve V6 associated with valve station C6 may be selectively opened to allow fluid flow through lines L9 and L11 to a fluid container F4, sometimes referred to as a return bag. This may be advantageous when the controller 18 determines that sufficient red blood cells have been collected and that additional red blood cells may be delivered to the recipient.

[0140] Before the cellular blood components reach the leukoreduction filter 60, they may be mixed with an additive solution, such as Adsol. The additive solution may be drawn from a fluid container F7 (which may be referred to as an additive bag) via line L12 (which has an open valve V9) under the action of pump P6 (which may be referred to as an additive pump) of the blood separation device 10. The additive pump P6 conveys the additive solution through line L12 and open valve station C9 to the junction where it is mixed with the cellular blood components flowing through line L10.

[0141] The mixture of cellular blood components and additive solution is conveyed through line L13 and leukoreduction filter 60, which removes most of the platelets and white blood cells from the mixture. The leukoreduced red blood cells are conveyed through lines L14 and L15, respectively, to fluid containers F5 and F6 (sometimes referred to as red blood cell bags).

[0142] The cell-free plasma exits spinning membrane separator 26 via line L11 and proceeds through valve station C7 associated with spinner outlet sensor M2, open valve V7, and to return bag F4. Spinner outlet sensor M2 cooperates with controller 18 to determine one or more characteristics of the plasma, such as the amount of cellular blood components in the plasma and / or whether the plasma is hemolytic and / or lipemic.

[0143] There is no pump associated with line L11; instead, the flow rate at which plasma exits spinning membrane separator 26 is equal to the difference between the flow rates of spinner pump P4 and red blood cell pump P5. In one embodiment, spinner pump P4 is set to a constant flow rate and red blood cell pump P5 is set to a flow rate that produces a desired hematocrit for the separated cellular blood components, which may be in the range of approximately 75-85%. Additive pump P6 may be commanded to operate at a flow rate that reduces or dilutes the hematocrit to a particular level before the separated cellular blood components enter leukoreduction filter 60, which may be in the range of approximately 60-70%. In one embodiment, the flow rates of red blood cell pump P5 and additive pump P6 may be calculated as follows: Red blood cell pump flow rate = (spinner pump flow rate x hematocrit of blood entering the spinner membrane separator) / target hematocrit of separated cellular blood components [Equation 2]

[0144] Additive pump flow rate = ((red blood cell pump flow rate x target hematocrit of separated cellular blood components) / target hematocrit after dilution) - red blood cell pump flow rate [Equation 3]

[0145] The draw phase may continue until the amount of blood drawn from the blood source reaches a target volume, or until the in-process bag F3 is filled to a particular level (as determined by a weighing scale from which the in-process bag F3 is suspended), or until other conditions are met.

[0146] C. Return phase As the system transitions to the return phase (FIG. 33), anticoagulant pump P1 stops drawing anticoagulant from anticoagulant bag F1. Valve V10 associated with valve station C10 closes to prevent fluid flow through line L3, and valve V11 associated with valve station C11 opens to allow fluid flow through line L16. Valve V2 associated with valve station C2 also opens to allow flow through line L17, while valve V1 associated with valve station C1 closes to prevent flow through line L5.

[0147] With the valves so positioned, donor pump P2 reverses direction to allow the contents of return bag F4 (typically plasma, but which may include cellular blood components if red blood cells are no longer collected) to be delivered to the recipient (which may be the same blood source) through the same needle that was used to draw blood into fluid flow circuit 12A. On its way to the recipient, the return fluid is pumped through line L17, valve station C2 associated with open valve V2, lines L4 and L18, sensor station S1 associated with pressure sensor A1, return line filter 58, air detector M3, valve station C11 associated with open valve V11, lines L16 and L1. Depending on the user's preference, saline or other substitution fluid is drawn from saline bag F2 through line L19 by pump P3 (sometimes referred to as a saline pump) of blood separation device 10 to the junction where it is mixed and the fluid is delivered to the recipient.

[0148] While the fluid is being delivered to the recipient, the blood in the in-process bag F3 acts as a blood supply for the spinning membrane separator 26. When the system transitions to the return phase, the spinner pump P4 does not change and separation continues in the same manner as described for the draw phase (i.e., blood is separated into plasma and cellular components, plasma flows to the return bag F4, and cellular blood components are diluted, filtered, and collected as leukocyte-reduced red blood cells) until the in-process bag F3 is emptied. Thus, system components downstream of the spinner pump P4 are "blind" as to whether the system is in the draw or return phase. The method described here is preferable to a batch process (which separates blood only during the draw phase and not during the return phase) because separation and collection are continuous, thereby reducing the time required to complete the procedure.

[0149] It will be seen that plasma is delivered to return bag F4 at the same time that the contents of return bag F4 are delivered to the recipient. The rate at which donor pump P2 operates may be greater than the rate at which plasma exits spinning membrane separator 26 to allow return bag F4 to empty during the return phase, even though separation is continuing. Once return bag F4 and / or in-process bag F3 are empty, the system may return to the draw phase if the target amount of red blood cells has not yet been collected.

[0150] 2. Dual Needle Fluid Flow Circuit and Procedure a. Fluid flow circuit FIGURE 3 is a schematic diagram of an exemplary fluid flow circuit 12B having a pair of blood access devices (e.g., needles) for separating and collecting red blood cells from blood. Fluid flow circuit 12B includes a cassette 48 of the type described above and shown in FIGURE 13 that connects the various components of fluid flow circuit 12B. The various connections between the components of fluid flow circuit 12B are shown in FIGURE 3, which also shows fluid flow circuit 12B installed on blood separation device 10.

[0151] Although the components of fluid flow circuit 12B interact with many of the components of blood separation device 10, as described below, there are selected components of blood separation device 10 that are not used to separate and collect red blood cells using fluid flow circuit 12B of FIG. 3. Most notably, centrifuge 16 is not used, only spinning membrane separator drive unit 14 is used. There are also selected valves V1, V3, V5, V8 and donor pump P2 of blood separation device 10 that are not used in the procedure described herein. Fluid flow circuit 12B includes fluid container F8 (which may be referred to as a waste bag), which in the procedure shown in FIG. 34 is used only during a pre-treatment priming stage in which saline from saline bag F2 is pumped through fluid flow circuit 12B before being transported to waste bag F8 for disposal at the end of the procedure.

[0152] b. Procedure In contrast to the separation procedure described above with respect to fluid flow circuit 12A of FIG. 2, fluid flow circuit 12B of FIG. 3 allows for a single stage during which blood is simultaneously drawn and processed and at least a portion of the separated components are delivered to a recipient (FIG. 34). Blood is drawn from a blood source (e.g., using a needle) into fluid flow circuit 12B via line L20. Line L20 may include a manual clamp 56 that may be initially in a closed position to prevent fluid flow through line L20. When processing is to be initiated, an operator moves manual clamp 56 from its closed position to an open position to allow fluid to flow through line L20.

[0153] Blood is drawn into line L20 by spinner pump P4, rather than donor pump P2 (which is inactive in this procedure). Anticoagulant from anticoagulant bag F1 may be added to the blood via line L21 by the action of anticoagulant pump P1. Valve V10 associated with valve station C10 is opened to allow flow through line L20, while valve V4 associated with valve station C4 is closed to prevent flow through line L22, thereby directing the blood via line L23 to spinning membrane separator 26. Before reaching spinning membrane separator 26, the blood may pass through sensor station S2 associated with pressure sensor A2 (which may be upstream of spinner pump P4 and may monitor venous pressure if the blood source is a live donor), spinner inlet sensor M1, and sensor station S4 associated with pressure sensor A4. Spinner inlet sensor M1 can detect the hematocrit of blood entering spinning membrane separator 26 (which can be used to set the flow rate of red blood cell pump P5 to achieve a desired concentrated red blood cell hematocrit), while pressure sensor A4 can monitor the pressure of spinning membrane separator 26.

[0154] The spinning membrane separator drive unit 14 of the blood separation device 10 operates the spinning membrane separator 26 to separate plasma from cellular blood components (i.e., red blood cells, platelets, and white blood cells). In one embodiment, the spinning membrane separator 26 is a larger spinning membrane separator (as described above) having a stationary housing 70 and a rotatable rotor 72 to which a membrane 76 is attached. In such an embodiment, the spinning membrane separator drive unit 14 spins the rotor 72 at approximately 2,500-3,000 rpm to separate blood entering the bottom of the spinning membrane separator 26 (as described above) into plasma and cellular components.

[0155] Cellular blood components are pumped from the spinning membrane separator 26 via line L24 by red blood cell pump P5. Valve V6 associated with valve station C6 is closed to prevent fluid flow through line L25, thereby directing the flow of cellular blood components through line L24 to the leukoreduction filter 60. Sensor station S3 associated with line L24 can interface with pressure sensor A3 of the blood separation device 10 to monitor the pressure of the leukoreduction filter 60. Valve V6 associated with valve station C6 can be selectively opened to allow fluid flow through lines L25 and L26 to the recipient, which can be advantageous when the controller 18 determines that sufficient red blood cells have been collected.

[0156] Before the cellular blood components reach leukoreduction filter 60, they may be mixed with an additive solution, such as Adsol. The additive solution may be drawn from additive bag F7 (with valve V9 open to allow flow through valve station C9) via line L27 under the action of additive pump P6. Additive pump P6 conveys the additive solution via line L27 to the junction where it is mixed with the cellular blood components flowing through line L24.

[0157] The mixture of cellular blood components and additive solution is conveyed through line L28 to leukoreduction filter 60, which removes the majority of platelets and leukoreduction cells from the mixture. The leukoreduced red blood cells are conveyed through lines L29 and L30 to red blood cell bags F5 and F6, respectively.

[0158] The cell-free plasma exits the spinning membrane separator 26 via line L31 and proceeds through valve station C7 associated with spinner outlet sensor M2, open valve V7, and into line L26. The spinner outlet sensor M2, in cooperation with the controller 18, determines one or more characteristics of the plasma, such as the amount of cellular blood components in the plasma and / or whether the plasma is hemolytic and / or lipemic. There is no pump associated with line L31, so instead, the flow rate at which the plasma exits the spinning membrane separator 26 is equal to the difference between the flow rates of the spinner pump P4 and the red blood cell pump P5. In one embodiment, the spinner pump P4 is set to a constant flow rate and the red blood cell pump P5 is set to a flow rate that produces a desired hematocrit for the separated cellular blood components, which may be in the range of approximately 75-85%. The additive pump P6 may be commanded to operate at a flow rate that reduces or dilutes the hematocrit of the separated cellular blood components to a particular level before entering the leukoreduction filter 60, which may be in the range of approximately 60-70%. The flow rates of the red blood cell pump P5 and the additive pump P6 can be determined using Equations 2 and 3 above.

[0159] Valve V2 associated with valve station C2 is closed to prevent flow through line L32 to waste bag F8, thereby directing the plasma along line L26 through sensor station S1 associated with pressure sensor A1 (which can monitor venous pressure if the fluid recipient is a living organism), return line filter 58, air detector M3, valve station C11 associated with open valve V11, and line L33 on its way back to the recipient (which may be the same as the blood source) through a second needle or blood access device. Depending on user preference, saline or another substitution fluid may be drawn from saline bag F2 via line L34 by saline pump P3 to the junction where it is mixed with the fluid being delivered to the recipient.

[0160] This single-step procedure continues until the target amount of red blood cells is collected.

[0161] B. Collection of red blood cells and plasma In accordance with one aspect of the present disclosure, blood separation device 10 may be used to separate and collect red blood cells and plasma from blood. In contrast to previous applications in which only red blood cells are collected, typically only a single unit of red blood cells is collected along with a target amount of plasma. However, other amounts of red blood cells and plasma can be separated and collected without departing from the scope of the present disclosure.

[0162] A blood separation device 10 according to the present disclosure can be used in combination with a fluid flow circuit 12 having a single blood access device (e.g., a single needle that withdraws separated blood components and returns them to the same location) or two blood access devices (e.g., one needle that withdraws blood from a source and a second needle that flows separated blood components to the same source or to a different recipient). Exemplary fluid flow circuits 12C, 12D and procedures are described for each configuration.

[0163] 1. Single Needle Fluid Flow Circuit and Procedure a. Fluid flow circuit Figure 4 is a schematic diagram of an exemplary fluid flow circuit 12C having a single blood access device (e.g., needle) for separating and collecting red blood cells and plasma from blood. Fluid flow circuit 12C includes a cassette 48 of the type described above and shown in Figure 13 that connects the various components of fluid flow circuit 12C. The various connections between the components of fluid flow circuit 12C are shown in Figure 4, which also shows fluid flow circuit 12C installed on blood separation device 10.

[0164] As will be described below, although the components of fluid flow circuit 12C interact with many components of blood separation device 10, there are selected components of blood separation device 10 that are not used in separating and collecting red blood cells and plasma using fluid flow circuit 12C of Figure 4. Most notably, centrifuge 16 is not used, only spinning membrane separator drive unit 14 is used. There are also selected valves V3 and V6 and pressure sensor A2 of blood separation device 10 that are not used in the procedures described herein.

[0165] b. Entrainment phase - plasma collection only Because the volume of blood required to produce a typical plasma product volume is greater than the volume of blood required to produce a corresponding red blood cell product volume, there can be two draw phases. One phase only collects plasma (while transporting cellular blood components to the recipient), and the other phase collects plasma and red blood cells. The plasma-only draw phase occurs for the majority of the draw phase, while the plasma and red blood cell collection occurs near the end of the procedure. The plasma-only draw phase continues until the volume of collected plasma is within a certain amount of the target product volume, after which the system collects both plasma cells and red blood cells. The transition occurs when the volume of collected plasma is within the range of the volume of plasma that would be produced to obtain the target red blood cell product volume, typically 200 ml of red blood cells. For example, for blood with a hematocrit of 40%, 500 ml of blood would have to be processed to collect 200 ml of red blood cells. Assuming the separated cellular blood components exiting the spinning membrane separator 26 have a hematocrit of 80%, 250 ml of plasma will be produced when processing 500 ml of blood. Thus, collection of plasma only will continue from the start of the procedure until the collected plasma volume is within 250 ml of the target plasma product volume.

[0166] In the plasma-only draw stage (FIG. 35), blood is drawn from the blood source into fluid flow circuit 12C. If the blood source is a donor, blood may be drawn into fluid flow circuit 12C through a single needle connected to cassette 48 by line L40. Line L40 may include a manual clamp 56 that may be initially in a closed position to prevent fluid flow through line L40. When initiating processing, an operator may move manual clamp 56 from its closed position to an open position to allow fluid to flow through line L40.

[0167] Blood is drawn into line L40 by donor pump P2 of blood separation device 10. Anticoagulant can be drawn from anticoagulant bag F1 by anticoagulant pump P1, which transports the anticoagulant through line L41 to the junction where it mixes with blood flowing through line L40 and enters fluid circuit 12C.

[0168] In the illustrated embodiment, valve V10 associated with valve station C10 is open to allow blood to flow through line L42 and sensor station S1 associated with pressure sensor A1. If the blood source is a living organism (e.g., a donor), pressure sensor A1 can communicate with controller 18 to monitor the pressure within the veins of the blood source.

[0169] The cassette 48 includes two valve stations C1 and C2 downstream of the donor pump P2, one of which has the valve V2 closed and the other valve station C1 has the valve V1 open. The blood is pumped by the donor pump P2 through the line L43 to a junction, where it flows through the line L44 and the valve station C1 associated with the open valve V1 to another junction, where a part of the blood is directed through the line L45 to the bag in process F3 and the remaining part is directed through the line L46 to the spinning membrane separator 26. The spinner pump P4 is associated with the line L46 and controls the amount of blood that is directed to the spinning membrane separator 26 instead of the bag in process F3. In particular, the flow rate of the donor pump P2 is greater than the flow rate of the spinner pump P4, the difference between them being equal to the flow rate of blood to the bag in process F3. The flow rates can be selected so that at the end of this drawing phase the bag in process F3 is partially or totally filled with blood.

[0170] Blood flowing through line L46 toward spinning membrane separator 26 passes through sensor station S4, which is associated with spinner inlet sensor M1 and pressure sensor A4. Spinner inlet sensor M1 can detect the hematocrit of the blood entering spinning membrane separator 26, which can be used to set the flow rate of red blood cell pump P5 to achieve a desired concentrated red blood cell hematocrit. Pressure sensor A4 can function to monitor the pressure within spinning membrane separator 26.

[0171] The spinning membrane separator drive unit 14 of the blood separation device 10 operates the spinning membrane separator 26 to separate plasma from cellular blood components (i.e., red blood cells, platelets, and white blood cells). In one embodiment, the spinning membrane separator 26 is a larger spinning membrane separator (as described above) having a stationary housing 70 and a rotatable rotor 72 to which a membrane 76 is attached. In such an embodiment, the spinning membrane separator drive unit 14 spins the rotor 72 at approximately 2,500-3,000 rpm to separate blood entering the bottom of the spinning membrane separator 26 (as described above) into plasma and cellular components.

[0172] Cellular blood components are pumped from spinning membrane separator 26 via line L47 by red blood cell pump P5. Valve V5 associated with valve station C5 is closed to prevent fluid flow through line L48, thereby directing the flow of cellular blood components through line L49 (and valve station C4 associated with open valve V4), line L50 and into return bag F4. Pressure sensor A3, associated with sensor station S3 in communication with line L47, may be inactive during this phase (although it is active during other draw phases as described herein).

[0173] The cell-free plasma exits spinning membrane separator 26 via line L51. Valve V7 associated with valve station C7 is closed to prevent flow through line L50, while valve V8 associated with valve station C8 is open, thereby allowing the separated plasma to flow through spinner outlet sensor M2, valve station C8 associated with open valve V8, and into fluid container F9, which may be referred to as a plasma bag. Spinner outlet sensor M2, in cooperation with controller 18, determines one or more characteristics of the plasma, such as the amount of cellular blood components in the plasma and / or whether the plasma is hemolytic and / or lipemic.

[0174] There is no pump associated with line L51; instead, the flow rate at which plasma exits spinning membrane separator 26 is equal to the difference between the flow rates of spinner pump P4 and red blood cell pump P5. In one embodiment, spinner pump P4 is set to a constant flow rate and red blood cell pump P5 is set to a flow rate that produces a desired hematocrit for the separated cellular blood components, which may be in the range of approximately 75-85%. In one embodiment, the flow rate of red blood cell pump P5 may be determined according to Equation 2 above.

[0175] As described above, the plasma-only drawing phase may continue until the amount of blood drawn from the blood source reaches a target volume, or until the in-process bag F3 is filled to a particular level (as determined by a weigh scale on which the in-process bag F3 is suspended), or other condition is satisfied.

[0176] c. Return phase As the system transitions to the return phase (FIG. 36), anticoagulant pump P1 stops drawing anticoagulant from anticoagulant bag F1. Valve V10 associated with valve station C10 closes to prevent fluid flow through line L42, and valve V11 associated with valve station C11 opens to allow fluid flow through line L52. Valve V2 associated with valve station C2 also opens to allow flow through line L53, while valve V1 associated with valve station C1 closes to prevent flow through line L44.

[0177] With the valves so positioned, donor pump P2 reverses direction to deliver the contents of return bag F4 (typically cellular blood components) to the recipient (which may be the same blood source) through the same needle used to draw blood into fluid flow circuit 12C. On its way to the recipient, the return fluid is pumped through line L53, valve station C2 associated with open valve V2, line L43, sensor station S1 associated with pressure sensor A1, line L54, return line filter 58, air detector M3, valve station C11 associated with open valve 11, lines L52 and L40. Saline or other substitution fluid is drawn by saline pump P3 through line L55 to the junction where it mixes with the fluid being delivered to the recipient, although it is more common that the substitution fluid is not delivered to the recipient until plasma collection is complete.

[0178] While the fluid is being delivered to the recipient, the blood in the in-process bag F3 acts as a blood supply for the spinning membrane separator 26. Once the system transitions to the return phase, the spinner pump P4 does not change and separation continues in the same manner as described for the plasma-only draw phase (i.e., blood is separated into plasma and cellular components, the cellular blood components flow to the return bag F4, and the plasma is collected in the plasma bag F9) until the in-process bag F3 is emptied. Thus, system components downstream of the spinner pump P4 are "blind" as to whether the system is in the plasma-only draw phase or the return phase. The method described here is preferable to a batch process (which separates blood only during the draw phase and not during the return phase) because separation and collection are continuous, thereby reducing the time required to complete the procedure.

[0179] It will be seen that cellular blood components are delivered to the return bag F4 at the same time that the contents of the return bag F4 are delivered to the recipient. The rate at which the donor pump P2 operates may be greater than the rate at which the red blood cell pump P5 operates to allow the return bag F4 to empty during the return phase, even if separation continues. Once the return bag F4 is empty, the system returns to the plasma-only draw phase (FIG. 35) and subsequently alternates between the plasma-only draw phase and the return phase until enough plasma has been collected to begin collecting red blood cells.

[0180] d. Entrainment Phase - Collection of Red Blood Cells and Plasma Once the plasma collection volume in plasma bag F9 falls within a certain amount of target (as explained above), the system transitions to a draw phase where both plasma and red blood cells are collected as shown in FIG. 37. This is the final draw phase of the procedure, collecting the red blood cell product and the remaining plasma volume. This draw phase is the same as the plasma-only draw phase until the cellular blood components exit the red blood cell pump P5. In this phase, valve V4 associated with valve station C4 closes to block flow through line L49 (to return bag F4) and valve V5 associated with valve station C5 opens to allow the separated cellular blood components to flow through lines L48 and L56 toward the leukoreduction filter 60.

[0181] Before the cellular blood components reach the leukoreduction filter 60, they may be mixed with an additive solution, such as Adsol. The additive solution may be drawn from additive bag F7 (with valve V9 associated with valve station C9 open) via line L57 under the action of additive pump P6 of the blood separation device 10. The additive pump P6 conveys the additive solution through line L57 to the junction where it is mixed with the cellular blood components flowing through line L48.

[0182] The mixture of cellular blood components and additive solution is conveyed through line L56 and leukoreduction filter 60, which removes the majority of platelets and leukoreduction filter 60 from the mixture. Pressure sensor A3 associated with sensor station S3 of cassette 48 may monitor the pressure of leukoreduction filter 60. Leukoreduced red blood cells are conveyed through line L58 ​​to red blood cell bag F5.

[0183] Similar to the plasma-only draw stage, acellular plasma exits spinning membrane separator 26 via line L51 and proceeds through spinner outlet sensor M2, valve station C8 associated with open valve V8 and into plasma bag F9. There is no pump associated with line L51; instead, the flow rate at which plasma exits spinning membrane separator 26 is equal to the difference between the flow rates of spinner pump P4 and red blood cell pump P5. In one embodiment, spinner pump P4 is set to a constant flow rate and red blood cell pump P5 is set to a flow rate that produces a desired hematocrit for the separated cellular blood components, which may be in the range of about 75-85%. Additive pump P6 may be commanded to operate at a flow rate that reduces or dilutes the hematocrit of the separated cellular blood components to a particular level before entering leukoreduction filter 60, which may be in the range of about 60-70%. In one embodiment, the flow rates of red blood cell pump P5 and additive pump P6 may be calculated using Equations 2 and 3 above.

[0184] e. Final stage At some point during the draw phase of FIG. 37, donor pump P2 will have pumped enough blood into fluid flow circuit 12C to allow the target red blood cell and plasma product volumes to be reached. However, a certain volume of blood in in-process bag F3 will not yet be processed. At this point, donor pump P2 stops drawing blood and valve V10 associated with valve station C10 closes to prevent fluid flow through line L42. To complete the procedure, the blood remaining in in-process bag F3 is processed by spinning membrane separator drive unit 26, as shown in FIG. 38.

[0185] With the valve stations positioned as shown in Fig. 38, the blood in in-process bag F3 acts as the blood supply for spinning membrane separator 26. Until in-process bag F3 is emptied, this stage proceeds in the same manner as described for the final draw stage (i.e., blood is separated into plasma and cellular components, plasma flows to plasma bag F9, and cellular blood components are diluted, filtered, and collected as leukoreduced red blood cells), except that the blood enters spinning membrane separator 26 from a different origin until in-process bag F3 is emptied. Upon emptying of in-process bag F3, a target amount of red blood cell product and plasma product should be contained in the respective collection containers F5 and F9, which can be verified by weight scales from which containers F5 and F9 can be suspended during the procedure.

[0186] 2. Dual-Needle Fluid Flow Circuit and Procedure a. Fluid flow circuit Figure 5 is a schematic diagram of an exemplary fluid flow circuit 12D having a pair of blood access devices (e.g., needles) for separating and collecting red blood cells and plasma from blood. Fluid flow circuit 12D includes a cassette 48 of the type described above and shown in Figure 13 that connects the various components of fluid flow circuit 12D. The various connections between the components of fluid flow circuit 12D are shown in Figure 5, which also shows fluid flow circuit 12D installed on blood separation device 10.

[0187] Although the components of fluid flow circuit 12D interact with many of the components of blood separation device 10, as described below, there are selected components of blood separation device 10 that are not used to separate and collect red blood cells and plasma using fluid flow circuit 12D of FIG. 5. Most notably, centrifuge 16 is not used, only spinning membrane separator drive unit 14. There are also selected valves V1, V3, V6, V7 and donor pump P2 of blood separation device 10 that are not used in the procedure described herein. In the procedure shown in FIGS. 39 and 40, valve V2 (along with waste bag F8 and associated line L59 of fluid bag 12D) is used only during a pre-treatment priming stage, where saline from saline bag F2 is pumped into fluid flow circuit 12D to prime it before being conveyed to waste bag F8 for disposition at the end of the procedure.

[0188] B. Plasma-only phase Similar to the single blood access device or needle procedure, the dual blood access device or needle procedure collects only plasma for a specified period of time from the start of the procedure until the plasma volume collected is within a specified amount of the target volume. Figure 39 shows the plasma-only stage of the procedure.

[0189] Blood is drawn from a blood source (e.g., using a needle) through line L60 into fluid flow circuit 12D. Line L60 may include a manual clamp 56 that may be initially in a closed position to prevent fluid flow through line L60. When processing is initiated, an operator may move manual clamp 56 from its closed position to an open position to allow fluid to flow through line L60.

[0190] Blood is drawn into line L60 by spinner pump P4, rather than donor pump P2 (which is inactive in this procedure). Anticoagulant from anticoagulant bag F1 may be added to the blood via line L61 by the action of anticoagulant pump P1. Valve V10 associated with valve station C10 is opened to allow flow through line L60, while valve V4 associated with valve station C4 is closed to prevent flow through line L62, thereby directing the blood via line L63 to spinning membrane separator 26. Before reaching spinning membrane separator 26, blood may pass through sensor station S2 associated with pressure sensor A2 (which may be upstream of spinner pump P4 and may monitor venous pressure if the blood source is a live donor), inlet sensor M1, and sensor station S4 associated with pressure sensor A4. Spinner inlet sensor M1 can detect the hematocrit of blood entering spinning membrane separator 26 (which can be used to set the flow rate of red blood cell pump P5 to achieve a desired concentrated red blood cell hematocrit), and pressure sensor A4 can monitor the pressure of spinning membrane separator 26.

[0191] The spinning membrane separator drive unit 14 of the blood separation device 10 operates the spinning membrane separator 26 to separate plasma from cellular blood components (i.e., red blood cells, platelets, and white blood cells). In one embodiment, the spinning membrane separator 26 is a larger spinning membrane separator (as described above) having a stationary housing 70 and a rotatable rotor 72 having a membrane 76 mounted thereon. In such an embodiment, the spinning membrane separator drive unit 14 rotates the rotor 72 at approximately 2,500-3,000 rpm to separate blood entering the bottom of the spinning membrane separator 26 (as described above) into plasma and cellular components.

[0192] Cellular blood components are pumped from spinning membrane separator 26 via line L64 by red blood cell pump P5. Valve V5 associated with valve station C5 is closed to prevent fluid flow through line L65, thereby directing the flow of cellular blood components through line L66 to line L66, sensor station S1 associated with pressure sensor A1 (which may monitor intravenous pressure if the fluid recipient is a live donor), return line filter 58, air detector M3, valve station C11 associated with open valve V11, line L67 on the way to the recipient (which may be the same as the blood source) through a second needle or blood access device. Saline or other substitution fluid is drawn from saline bag F2 by saline pump P3 via line L68 to the junction where it mixes with the fluid being delivered to the recipient, although it is more common that the substitution fluid is not delivered to the recipient until plasma collection is complete. Although sensor station S3 is in communication with line L64, pressure sensor A3 associated with sensor station S3 may be inactive during this phase (although it was active in the second phase, as described herein).

[0193] The cell-free plasma exits the spinning membrane separator 26 via line L69, passes through valve station C8 associated with spinner outlet sensor M2, cannulation valve V8, and into plasma bag F9. The spinner outlet sensor M2, in conjunction with controller 18, determines one or more characteristics of the plasma, such as the amount of cellular blood components in the plasma and / or whether the plasma is hemolytic and / or lipemic. There is no pump associated with line L69; instead, the flow rate at which the plasma exits the spinning membrane separator 26 is equal to the difference between the flow rates of the spinner pump P4 and the red blood cell pump P5.

[0194] C. Red blood cell and plasma phase Once the plasma collection volume in plasma bag F9 falls within a certain amount of target (as explained above), the system transitions to a stage where both plasma and red blood cells are collected, as shown in FIG.

[0195] At this stage, valve V11 associated with valve station C11 is closed (to prevent separated cellular blood components from being transported to the recipient through line L67) and valve V5 associated with valve station C5 is opened to allow flow through line L65. With the valves so positioned, separated plasma continues to be transported to plasma bag F9, while separated cellular components are transported through line L65 (but not line L66), valve station C5 associated with open valve V5, and line L70 towards leukoreduction filter L70.

[0196] Before the cellular blood components reach the leukoreduction filter 60, they may be mixed with an additive solution, such as Adsol. The additive solution is drawn from the additive bag F7 via line L71 under the action of the additive pump P6 of the blood separation device 10 (valve V9 associated with valve station C9 is open). The additive pump P6 conveys the additive solution through line L71 to a junction where it is mixed with the cellular blood components flowing through line L65.

[0197] The mixture of cellular blood components and additive solution is conveyed through line L70 and leukoreduction filter 60, which removes most of the platelets and white blood cells from the mixture. Pressure sensor A3 associated with sensor station S3 (in communication with line L65) can monitor the pressure of leukoreduction filter 60. Leukoreduced red blood cells are conveyed through line L72 to red blood cell bag F5.

[0198] There is no pump associated with line L69 leading to plasma bag F9; instead, the flow rate at which the plasma leaves spinning membrane separator 26 is equal to the difference between the flow rates of spinner pump P4 and red blood cell pump P5. In one embodiment, spinner pump P4 is set to a constant flow rate and red blood cell pump P5 is set to a flow rate that produces a desired hematocrit for the separated cellular blood components, which may be in the range of about 75-85%. Additive pump P6 may be commanded to operate at a flow rate that reduces or dilutes the hematocrit of the separated cellular blood components to a particular level before entering leukoreduction filter 60, which may be in the range of about 60-70%. In one embodiment, the flow rates of red blood cell pump P5 and additive pump P6 may be calculated using Equations 2 and 3 above.

[0199] This step continues until the target volume of red blood cells and plasma product is achieved.

[0200] C. Plasma Collection According to one aspect of the present disclosure, blood separation device 10 may be used to separate and collect substantially cell-free plasma from blood. Blood separation device 10 according to the present disclosure may be used in combination with a fluid flow circuit 12 having a single blood access device (e.g., a single needle that withdraws blood and returns separated blood components to the same location) or two blood access devices (e.g., one needle that withdraws blood from a source and a second needle that flows separated blood components to the same source or to a different recipient). Exemplary fluid flow circuits 12E, 12F and procedures are described for each configuration.

[0201] 1. Single Needle Fluid Flow Circuit and Procedure a. Fluid flow circuit Figure 6 is a schematic diagram of an exemplary fluid flow circuit 12E having a single blood access device (e.g., needle) for separating and collecting plasma from blood. The fluid flow circuit 12E includes a cassette 48 of the type described above and shown in Figure 13 that connects the various components of the fluid flow circuit 12E. The various connections between the components of the fluid flow circuit 12E are shown in Figure 6, which also shows the fluid flow circuit 12E installed on a blood separation device 10.

[0202] Although the components of fluid flow circuit 12E interact with many components of blood separation device 10, as described below, there are selected components of blood separation device 10 that are not used in separating and collecting plasma using fluid flow circuit 12E of Figure 6. Most notably, centrifuge 16 is not used, only spinning membrane separator drive unit 14. There are also selected valves V3, V4, V5, V6, V7, V9, pressure sensor A2, and additive pump P6 of blood separation device 10 that are not used in the procedures described herein.

[0203] B. Retraction phase In the first stage (FIG. 41), blood is drawn from the blood source into fluid flow circuit 12E. If the blood source is a donor, blood may be drawn into fluid flow circuit 12E through a single needle connected to cassette 48 by line L80. Line L80 may include a manual clamp 56 that may be initially in a closed position to prevent fluid flow through line L80. When processing is to begin, an operator moves manual clamp 56 from its closed position to an open position to allow fluid to flow through line L80.

[0204] Blood is drawn into line L80 by donor pump P2 of blood separation device 10. Anticoagulant from anticoagulant bag F1 is drawn through line L81 under the action of anticoagulant pump P1 and added to the blood at the junction of lines L80 and L81. Valve V10 associated with valve station C10 opens to allow blood to flow through lines L80 and L82 and sensor station S1 associated with pressure sensor A1. If the blood source is a living organism (e.g., a donor), pressure sensor A1 may monitor the pressure in the veins of the blood source.

[0205] The cassette 48 includes two valve stations C1 and C2 downstream of the donor pump P2 and the line L83, the valve V2 associated with one valve station C2 is closed and the valve V1 associated with the other valve station C1 is open. Blood flows through the line L84 associated with the open valve V1 to a junction where a part of the blood is directed through the line L85 to the in-process bag F3 and the rest is directed through the line L86 to the spinning membrane separator 26. The spinner pump P4 associated with the line L86 controls the amount of blood that is directed to the spinning membrane separator 26 instead of the in-process bag F3. In particular, the flow rate of the donor pump P2 is greater than the flow rate of the spinner pump P4, the difference between them being equal to the flow rate of blood to the in-process bag F3. The flow rates can be selected such that the in-process bag F3 is partially or totally filled with blood at the end of the drawing phase.

[0206] Blood flowing through line L86 toward spinning membrane separator 26 passes through sensor station S4, which is associated with spinner inlet sensor M1 and pressure sensor A4. Spinner inlet sensor M1 can detect the hematocrit of the blood entering spinning membrane separator 26, which can be used to set the flow rate of red blood cell pump P5 to achieve a desired concentrated red blood cell hematocrit. Pressure sensor A4 monitors the pressure in spinning membrane separator 26.

[0207] The spinning membrane separator drive unit 14 of the blood separation device 10 operates the spinning membrane separator 26 to separate plasma from cellular blood components (i.e., red blood cells, platelets, and white blood cells). The spinning membrane separator 26 may be either a smaller spinning membrane separator or a larger spinning membrane separator, as described above. In one embodiment, the spinning membrane separator 26 has a stationary housing 70 and a rotatable rotor 72 to which a membrane 76 is attached. In such an embodiment, the spinning membrane separator drive unit 14 spins the rotor 72 at approximately 2,500-3,000 rpm to separate blood entering the bottom of the spinning membrane separator 26 (as described above) into plasma and cellular components.

[0208] Cellular blood components are pumped from spinning membrane separator 26 via line L87 by red blood cell pump P5. As described above, valve V2 associated with valve station C2 is closed to prevent fluid flow through line L88, thereby directing the flow of cellular blood components through line L87 to return bag F4.

[0209] The cell-free plasma exits spinning membrane separator 26 via line L89, passes through spinner outlet sensor M2, valve station C8 associated with open valve V8, and into plasma bag F9. Spinner outlet sensor M2 cooperates with controller 18 to determine one or more characteristics of the plasma, such as the amount of cellular blood components in the plasma and / or whether the plasma is hemolytic and / or lipemic.

[0210] There is no pump associated with line L89; instead, the flow rate at which plasma exits spinning membrane separator 26 is equal to the difference between the flow rates of spinner pump P4 and red blood cell pump P5. In one embodiment, spinner pump P4 is set to a constant flow rate and red blood cell pump P5 is set to a flow rate that produces a desired hematocrit for the separated cellular blood components, which may be in the range of approximately 75-85%. In one embodiment, the flow rate of red blood cell pump P5 may be determined according to Equation 2 above.

[0211] The draw phase may continue until the amount of blood drawn from the blood source reaches a target volume, or until the in-process bag F3 is filled to a particular level, or until some other condition is met.

[0212] c. Return phase As the system transitions to the return phase (FIG. 42), anticoagulant pump P1 stops drawing anticoagulant from anticoagulant bag F1. Valve V10 associated with valve station C10 closes to prevent fluid flow through line L82, and valve V11 associated with valve station C11 opens to allow fluid flow through line L90. Valve V2 associated with valve station C2 opens to allow flow through line L88, while valve V1 associated with valve station C1 closes to prevent flow through line L84.

[0213] With the valves so positioned, donor pump P2 reverses direction to allow the contents of return bag F4 (typically cellular blood components) to be delivered to the recipient (which may be the same blood source) through the same needle used to draw blood into fluid flow circuit 12E. The return fluid is pumped through line L88, valve station C2 associated with open valve V2, line L83, sensor station S1 associated with pressure sensor A1, line L91, return line filter 58, air detector M3, valve station C11 associated with associated valve V11, lines L90 and L80 on its way to the recipient. Saline or other substitution fluid is drawn by saline pump P3 from saline bag F2 through sensor station S3 associated with pressure sensor A3 via line L92 to the junction where it mixes with the fluid delivered to the recipient, but it is more typical to prevent the substitution fluid from being delivered to the recipient until plasma collection is complete.

[0214] While the fluid is being delivered to the recipient, the blood in the in-process bag F3 acts as a blood supply for the spinning membrane separator 26. When the system transitions to the return phase, the spinner pump P4 does not change and separation continues in the same manner as described for the draw phase (i.e., blood is separated into plasma and cellular components, the separated cellular components flow to the return bag F4, and the separated plasma is collected in the plasma bag F9) until the in-process bag F3 is emptied. Thus, system components downstream of the spinner pump P4 are "blind" as to whether the system is in the draw or return phase. The method described here is preferable to a batch process (which separates blood only during the draw phase and not during the return phase) because separation and collection are continuous, thereby reducing the time required to complete the procedure.

[0215] It will be seen that the separated cellular blood components are delivered to the return bag F4 at the same time that the contents of the return bag F4 are being delivered to the recipient. The rate at which the donor pump P2 operates may be greater than the rate at which the cellular blood components exit the spinning membrane separator 26 to allow the return bag F4 to empty during the return phase, even though separation is continuing. Once the return bag F4 is empty, the system may return to the draw phase if the target amount of plasma has not yet been collected.

[0216] 2. Dual-Needle Fluid Flow Circuit and Procedure a. Fluid flow circuit Figure 7 is a schematic diagram of an exemplary fluid flow circuit 12F having a pair of blood access devices (e.g., needles) for separating and collecting plasma from blood. The fluid flow circuit 12F includes a cassette 48 of the type described above and shown in Figure 13 that connects the various components of the fluid flow circuit 12F. The various connections between the components of the fluid flow circuit 12F are shown in Figure 7, which also shows the fluid flow circuit 12F installed on a blood separation device 10.

[0217] Although the components of fluid flow circuit 12F interact with many components of blood separation apparatus 10, as described below, there are selected components of blood separation apparatus 10 that are not used to separate and collect plasma using fluid flow circuit 12F of FIG. 7. Most notably, centrifuge 16 is not used, only spinning membrane separator drive unit 14 is used. There are also selected valves V1, V3, V5, V6, V7, V9, as well as donor pump P2 and additive pump P6 of blood separation apparatus 10 that are not used in the procedure described herein. Fluid flow circuit 12F includes waste bag F8 and line L100, which in the procedure shown in FIG. 43 are used only during the pre-treatment priming phase, where saline from saline bag F2 is pumped through fluid flow circuit 12F for priming thereof before being conveyed to waste bag F8 for disposal at the end of the procedure.

[0218] b. Procedure In contrast to the separation procedure described above with respect to fluid flow circuit 12E of FIG. 6, fluid flow circuit 12F of FIG. 7 allows for a single stage in which blood is simultaneously drawn and processed, and at least one portion of the separated components is delivered to a recipient (FIG. 43). Blood is drawn from a blood source (e.g., using a needle) into fluid flow circuit 12F via line L101. Line L101 may include a manual clamp 56 that may be initially in a closed position to prevent fluid flow through line L101. When initiating processing, an operator moves manual clamp 56 from its closed position to an open position to allow fluid to flow through line L101.

[0219] Blood is drawn into line L101 by spinner pump P4, not donor pump P2 (which is inactive in this procedure). Anticoagulant from anticoagulant bag F1 may be added to the blood via line L102 by the action of anticoagulant pump P1. Valve V10 associated with valve station C10 is opened to allow flow through line L101, while valve V4 associated with valve station C4 is closed to prevent flow through line L103, thereby directing blood via line L104 to spinning membrane separator 26. Before reaching spinning membrane separator 26, blood may pass through sensor station S2 associated with pressure sensor A2 (which may be upstream of spinner pump P4 and may monitor venous pressure if the blood source is a live donor), inlet sensor M1, and sensor station S4 associated with pressure sensor A4. Spinner inlet sensor M1 can detect the hematocrit of blood entering spinning membrane separator 26 (which can be used to set the flow rate of red blood cell pump P5 to achieve a desired concentrated red blood cell hematocrit), and pressure sensor A4 can monitor the pressure of spinning membrane separator 26.

[0220] The spinning membrane separator drive unit 14 of the blood separation device 10 operates the spinning membrane separator 26 to separate plasma from cellular blood components (i.e., red blood cells, platelets, and white blood cells). The spinning membrane separator 26 can be a smaller or larger spinning membrane separator, as described above. In one embodiment, the spinning membrane separator 26 has a stationary housing 70 and a rotatable rotor 72 to which a membrane 76 is attached. In such an embodiment, the spinning membrane separator drive unit 14 spins the rotor 72 at approximately 2,500-3,000 rpm to separate blood entering the bottom of the spinning membrane separator 26 (as described above) into plasma and cellular components.

[0221] Cellular blood components are pumped from spinning membrane separator 26 via line L105 by red blood cell pump P5. Valve V2 associated with valve station C2 is closed to prevent fluid flow through line L100 to waste bag F8, thereby directing the cellular blood components along line L105 through sensor station S1 associated with pressure sensor A1 (which may monitor intravenous pressure if the fluid recipient is a live donor), return line filter 58, air detector M3, valve station C11 associated with open valve V11, line L106 on the way to the recipient (which may be the same as the blood source) via a second needle or blood access device. Saline or other substitution fluid is drawn from saline bag F2 through sensor station S3 associated with pressure sensor A3 via line L107 to the junction by saline pump P3 where it mixes with the fluid delivered to the recipient, but more typically the substitution fluid is not delivered to the recipient until plasma collection is complete.

[0222] The cell-free plasma exits the spinning membrane separator 26 via line L108 and proceeds through valve station C8 associated with spinner outlet sensor M2, open valve V8, and into plasma bag F9. The spinner outlet sensor M2, in cooperation with the controller 18, determines one or more characteristics of the plasma, such as the amount of cellular blood components in the plasma and / or whether the plasma is hemolytic and / or lipemic. There is no pump associated with line L108, so instead, the flow rate at which the plasma exits the spinning membrane separator 26 is equal to the difference between the flow rates of the spinner pump P4 and the red blood cell pump P5. In one embodiment, the spinner pump P4 is set to a constant flow rate and the red blood cell pump P5 is set to a flow rate that produces a desired hematocrit for the separated cellular blood components, which may be in the range of about 75-85%. The flow rate of the red blood cell pump P5 may be determined using Equation 2 above.

[0223] This single-step procedure continues until the target amount of plasma is collected.

[0224] D. Platelet, Plasma, and Red Blood Cell Collection Fluid Flow Circuits and Procedures 1.Fluid circuit According to one aspect of the present disclosure, a blood separation device 10 may be used to separate and collect platelets, plasma, and red blood cells from blood. A blood separation device 10 according to the present disclosure may be used in combination with a fluid flow circuit 12 having a single blood access device (e.g., a single needle that withdraws blood and returns separated blood components to the same location). FIG. 8 is a schematic diagram of an exemplary fluid flow circuit 12G that may be used to separate and collect platelets, plasma, and red blood cells. The fluid flow circuit 12G includes a cassette 48 of the type described above and shown in FIG. 13 that connects the various components of the fluid flow circuit 12G. The various connections between the components of the fluid flow circuit 12G are shown in FIG. 8, which also shows the fluid flow circuit 12G installed on the blood separation device 10.

[0225] All of the various valves V1-V11 and pressure sensors A1-A4 of the blood separation device 10, except for pressure sensor A3, are used for the collection of platelets, plasma, and red blood cells. As described below, fluid may flow through a sensor station S3 associated with pressure sensor A3, but pressure sensor A3 does not communicate with the controller 18 to monitor pressure at any location in the fluid flow circuit 12G. In addition, valve V3 is typically only opened during a pre-treatment priming phase, during which saline from a saline bag F2 is pumped through the flow circuit 12G for priming. As described below, both the centrifuge 16 and the spinning membrane separator drive unit 14 are used to separate the blood into platelets, plasma, and red blood cells for collection.

[0226] 2. Entrainment Phase In the first stage (FIG. 44), blood is drawn from a blood source into fluid flow circuit 12G. If the blood source is a donor, blood may be drawn into fluid flow circuit 12G through a single needle connected to cassette 48 by line L110. Line L110 may include a manual clamp 56 that may be initially in a closed position to prevent fluid flow through line L110. When beginning processing, an operator moves manual clamp 56 from its closed position to an open position to allow fluid to flow through line L110.

[0227] Blood is drawn into line L110 by donor pump P2 of blood separation device 10. Anticoagulant from anticoagulant bag F1 may be drawn through line L111 under the action of anticoagulant pump P1 and added to the blood at the junction of lines L110 and L111.

[0228] In the illustrated embodiment, valve V11 associated with valve station C10 is open to allow blood to flow through lines L110 and L112, sensor station S1 associated with pressure sensor A1, and line L113, while valve V11 associated with valve station C11 is closed to prevent fluid flow through line L114. If the blood source is a living organism (e.g., a donor), pressure sensor A1 can communicate with controller 18 to monitor pressure within the veins of the blood source.

[0229] The cassette 48 includes three valve stations C1, C2, and C4 downstream of the donor pump P2, where the valves V2 and V4 associated with the valve stations C2 and C4 are closed, and the valve V1 associated with the other valve station C1 is open. The blood flows through the line L115 associated with the open valve V1 to the junction, where a part of the blood is directed through the line L116 and the sensor station S3 associated with the inactive pressure sensor A3 to the in-process bag F3, and the rest flows through the line L117 to the centrifugal pump P3. Through the line L117 it is directed to the centrifugal pump P3 (which is the same pump as the saline pump described above), which controls the amount of blood that is directed to the centrifuge chamber 36 instead of the in-process bag F3. In particular, the flow rate of the donor pump P2 is greater than the flow rate of the centrifugal pump P3, and the difference between them is equal to the flow rate of blood to the in-process bag F3. The flow rates may be selected such that the in-process bag F3 is partially or totally filled with blood at the end of the drawing phase.

[0230] Blood pumped through line L117 by centrifugal pump P3 passes through line L118, air trap 62, and sensor station S2 associated with pressure sensor A2 (which operates in conjunction with control unit 18 of blood separation device 10 to monitor the pressure within centrifuge chamber 36).

[0231] The centrifuge 16 of the blood separation device 10 operates the centrifuge chamber 36 of the fluid flow circuit 12G to separate the blood within the centrifuge chamber 36 into platelet-rich plasma and concentrated red blood cells, as described above. In one embodiment, the centrifuge chamber 36 rotates at a nominal speed of 4,500 rpm, although the particular rotational speed may vary depending on the flow rate of fluid entering and leaving the centrifuge chamber 36.

[0232] The concentrated red blood cells exit the centrifuge chamber 36 via line L119 and flow directly to the red blood cell bag F5. The white blood cells may be retained in the centrifuge chamber 36 or may be discharged along with the red blood cells.

[0233] Platelet-rich plasma is drawn from the centrifuge chamber 36 via line L120 by the combined action of two pumps P4 and P5 of the blood separation device 10. The platelet-rich plasma travels through line L120 until it reaches a junction where it splits into lines L121 and L122. One of the pumps, P5 (which can be referred to as a recirculation pump and is the same pump referred to above as the red blood cell pump), is associated with line L121 and redirects a portion of the platelet-rich plasma to the junction where it mixes in line L118 with the blood being conveyed into the centrifuge chamber 36 by the centrifugal pump P3. Recirculating a portion of the platelet-rich plasma into the centrifuge chamber 36 along with the incoming blood reduces the hematocrit of the blood entering the centrifuge chamber 36, which may improve separation efficiency. With such an arrangement, the flow rate of the fluid entering the centrifuge chamber 36 is equal to the sum of the flow rates of the centrifugal pump P3 and the recirculation pump P5.

[0234] When the platelet-rich plasma drawn from the centrifuge chamber 36 into line L121 by the recirculation pump P5 is immediately returned to the centrifuge chamber 36, a bulk or net flow rate of platelet-rich plasma leaving the centrifuge chamber 36 is obtained, which is equal to the flow rate of the other pump P4 (sometimes called a PRP pump, which is the same pump called the spinner pump mentioned above). Before reaching the spinning membrane separator 26, the portion of the platelet-rich plasma conveyed by the PRP pump P4 through line L122 passes through a sensor station S4 associated with a spinner inlet sensor M1 and a pressure sensor A4. The spinner inlet sensor M1 can detect the concentration of platelets in the platelet-rich plasma entering the spinning membrane separator 26, while the pressure sensor A4 can monitor the pressure of the spinning membrane separator 26.

[0235] Line L122 has a junction where it joins with line L123. Valve V6 associated with valve station C6 is closed to prevent fluid from flowing through line L123, thereby directing the separated platelet-rich plasma to the spinning membrane separator 26. If necessary, valve V6 can be selectively opened to divert all or a portion of the platelet-rich plasma via line L123 to plasma bag F9. One example is at the start of a procedure when separation is being initialized and platelets have not yet left the centrifuge chamber 36, in which case fluid conveyed through line L122 by PRP pump P4 can be directed to plasma bag F9.

[0236] The spinning membrane separator drive unit 14 of the blood separation apparatus 10 operates the spinning membrane separator 26 to separate the platelet-rich plasma into two subcomponents (i.e., platelet-poor plasma and platelet concentrate). As used herein, the term "platelet concentrate" is not limited to a platelet-rich containing fluid separated from the plasma of a volume of platelet-rich plasma, but may include any platelet-enriched fluid (e.g., a fluid containing platelets from the buffy coat fluid separated from the platelet-poor plasma and red blood cells in the centrifuge chamber 36).

[0237] In one embodiment, the spinning membrane separator 26 is a smaller spinning membrane separator (as described above) having a stationary housing 70 and a rotatable rotor 72 to which a membrane 76 is attached. In such an embodiment, the spinning membrane separator drive unit 14 can rotate the rotor 72 at approximately 1,500 rpm (or a different speed depending on the flow rates of fluids entering and leaving the spinning membrane separator 26 and / or the material composition of the membrane 76) to separate the platelet-rich plasma entering the bottom of the spinning membrane separator 26 into plasma and platelets according to the principles described above.

[0238] Plasma is pumped from spinning membrane separator 26 via line L124 by a sixth pump P6 of blood separation apparatus 10 (which may be referred to as a plasma pump and is the same pump as the additive pump described above). Valves V9, V8, V6, and V4 associated with valve stations C9, C8, C6, and C4 (respectively) are closed to prevent fluid flow through lines L125, L126, L123, and L127, thereby directing the separated plasma along lines L124 and L128 into plasma bag F9. On the way to plasma bag F9, the plasma passes spinner outlet sensor M2, which cooperates with controller 18 to determine one or more characteristics of the plasma, such as the amount of cellular blood components in the plasma and / or whether the plasma is hemolytic and / or lipemic.

[0239] The platelet concentrate is exported from the spinning membrane separator 26 via line L129. There is no pump associated with line L129, instead the flow rate at which the platelets exit the spinning membrane separator 26 is equal to the difference between the flow rates of the PRP pump P4 and the plasma pump P6. The platelet concentration in the platelet concentrate can be calculated as follows: Platelet concentration in platelet concentrate = (Platelet concentration in platelet-rich plasma entering the rotating membrane separator × PRP pump flow rate) / (PRP pump flow rate - plasma pump flow rate) [Equation 4]

[0240] Valve V8 associated with valve station C8 is closed to prevent fluid flow through line L126, thereby directing fluid flow along lines L129 and L130 through valve station C7 associated with open valve V7 and into fluid container F10 (which may also be referred to as a platelet concentrate bag). Valve V8 associated with valve station C8 may be selectively opened to allow fluid to flow through line L126 to a junction where it joins plasma flowing through line L124 with plasma bag F9, if desired.

[0241] The draw phase may continue until the amount of blood drawn from the blood source reaches a target volume, or until the in-process bag F3 is filled to a particular level (as determined by a weigh scale from which the in-process bag F3 can be suspended during the procedure), or until some other condition is met.

[0242] 3. Red blood cell return phase Once the draw phase is complete, the system transitions to one of two return phases (FIGS. 45 and 46), during which at least a portion of one of the separated blood components is delivered to a recipient (which may be the blood source). In particular, red blood cells (FIG. 45) and plasma (FIG. 46) may be delivered to the recipient throughout the procedure until the amount of collected platelets reaches a target volume, at which point red blood cells and plasma will no longer be removed from their respective collection containers.

[0243] During the red blood cell return phase (FIG. 45), anticoagulant pump P1 stops drawing anticoagulant from anticoagulant bag F1. Valve V10 associated with valve station C10 closes to prevent fluid flow through line L112, and valve V11 associated with valve station C11 opens to allow fluid flow through line L114. Valve V2 associated with valve station C2 opens to allow flow through line L131, while valve V1 associated with valve station C1 closes and valve V3 associated with valve station C3 remains closed to prevent flow through lines L115 and L109, respectively.

[0244] With the valves so positioned, donor pump P2 reverses direction to allow the contents of red blood cell bag F5 to be delivered to the recipient through the same needle used to draw blood into fluid flow circuit 12G. On its way to the recipient, the return fluid (red blood cells) is pumped through line L131, valve station C2 associated with open valve V2, line L113, sensor station S1 associated with pressure sensor A1, line L132, return line filter 58, air detector M3, valve station C11 associated with open valve V11, lines L114 and L110.

[0245] While the fluid is being delivered to the recipient, the blood in the in-process bag F3 acts as a blood supply for the centrifuge 16. As the system transitions to this return phase, the centrifugal pump P3 remains unchanged and separation continues in the same manner as described for the draw phase (i.e., blood is separated into red blood cells and platelet-rich plasma in the centrifuge chamber 36, the red blood cells flow out of the centrifuge chamber 36 into the red blood cell bag F5, the platelet-rich plasma flows to the spinning membrane separator 26 for separation, and the separated platelets and plasma are collected in their respective containers) until the in-process bag F3 is emptied. Thus, system components downstream of centrifugal pump P3 are "blind" as to whether the system is in the draw or return phase. The method described herein is preferable to batch processes (which separate blood only during the collection phase and not during the return phase) because separation and collection are continuous, thereby reducing the time required to complete the procedure. Furthermore, by continuously processing blood within the centrifuge chamber 36, the interface between the separated red blood cells and the platelet-rich plasma is maintained, whereas in the return phase of batch processing the location of the interface is lost, which requires the interface to be re-established between every draw / separation phase and further increases the duration of the procedure.

[0246] It will be seen that the separated red blood cells are delivered to the red blood cell bag F5 at the same time that the contents of the red blood cell bag F5 are delivered to the recipient. The speed at which the donor pump P2 operates may be greater than the speed at which the red blood cells leave the centrifuge chamber 36 and allow the red blood cell bag F5 to empty during this return phase, even if separation continues. Once the red blood cell bag F5 is empty, the system can return to the draw phase or the plasma return phase or a different phase.

[0247] 4. Plasma return phase Similar to the red blood cell return phase (FIG. 45), the anticoagulant pump P1 stops drawing anticoagulant from the anticoagulant bag F1 during the plasma return phase (FIG. 46). Depending on whether the plasma return phase is initiated from the draw phase or the red blood cell return phase, selected valve stations may need to move between their open and closed states to allow plasma to be delivered to the recipient. In particular, valves V10 and V3 associated with valve stations C10 and C3 (respectively) are closed to prevent fluid flow through lines L112 and L109, while valve V11 associated with valve station C11 allows fluid flow through line L114. Valves V1 and V2 associated with valve stations C1 and C2 (respectively) are closed to prevent flow through lines L115 and L131, while valve V4 associated with valve station C4 is opened to allow flow through line L127.

[0248] With the valves so positioned, donor pump P2 operates in the same direction as the red blood cell return phase (or in the opposite direction of its operation in the draw phase) to allow the contents of plasma bag F9 to be transported to the recipient through the same needle used to draw blood into fluid flow circuit 12G. On its way to the recipient, the return fluid (cell-free plasma) is pumped through lines L128 and L127, valve station C4 associated with open valve V4, line L113, sensor station S1 associated with pressure sensor A1, line L132, return line filter 58, air detector M3, valve station C11 associated with open valve V11, lines L114 and L110.

[0249] While the fluid is being delivered to the recipient, the blood in the in-process bag F3 acts as a blood supply for the centrifuge 16. As the system transitions to this return phase, the centrifugal pump P3 does not change and continues the separation in the same manner as described for the draw phase and red blood cell return phase (i.e., blood is separated into red blood cells and platelet-rich plasma in the centrifuge chamber 36, the red blood cells flow from the centrifuge chamber 36 to the red blood cell bag F5, the platelet-rich plasma flows to the spinning membrane separator 26 for separation, and the separated platelets and plasma are collected in their respective containers) until the in-process bag F3 is empty. Thus, the system components downstream of the centrifugal pump P3 are "blind" as to whether the system is in the draw or return phase. The method described here is preferable to a batch process (which separates blood only during the draw phase and not during the return phase) because the separation and collection are continuous, thereby reducing the time required to complete the procedure. Furthermore, by continuously processing blood within the centrifuge chamber 36, the interface between the separated red blood cells and the platelet-rich plasma is maintained, whereas the interface is lost during the return phase of batch processing, which requires the interface to be established at every draw / separation phase, further increasing processing time.

[0250] It will be seen that the separated plasma is delivered to plasma bag F9 at the same time that the contents of plasma bag F9 are delivered to the recipient. The rate at which donor pump P2 operates to draw plasma from plasma bag F9 may be greater than the rate at which plasma pump P6 operates to deliver plasma into plasma bag F9, allowing plasma bag F9 to empty during this return, even as separation continues. Once plasma bag F9 is empty, the system can return to the draw phase or red blood cell return phase or a different phase.

[0251] 5. Final Stage When the target amount of platelets, plasma, and red blood cells has been collected, the blood source / recipient is disconnected from the fluid flow circuit 12G and the system may proceed to the final stage, which is shown in Figures 47-49.

[0252] During the final phase, an additive solution (such as Adsol) may be added to the collected red blood cells, as shown in Figure 47. This may be performed by operating valves V5 and V2 associated with valve stations C5 and C2 (respectively) to open to allow flow through line L133 and line L131, while closing valves V11, V3, V10, V1, and V4 associated with valve stations C11, C3, C10, C1, and C4 (respectively) to prevent flow through lines L114, L109, L112, L115, and L127. Donor pump P2 operates in the same direction as the draw phase to draw additive solution from additive bag F7 through line L133, leukoreduction filter 60, valve station C5 associated with open valve V5, line L132, sensor station S1, lines L113 and L131, valve station C2 associated with open valve V2, line L119, and into red blood cell bag F5.

[0253] The mixture of red blood cells and additive solution may then be leukoreduced, as shown in Figure 48. This may be done by maintaining the valves as in Figure 47 but reversing the direction in which donor pump P2 operates. Thus, the mixture of red blood cells and additive solution reverses the path traversed by the additive solution in the course of Figure 47, thereby transporting the mixture through leukoreduction filter 60 as a leukoreduced red blood cell product to additive bag F7 (which may alternatively be referred to as a red blood cell product bag). During this phase, pressure sensor A1 associated with sensor station S1 may be used to monitor the pressure of leukoreduction filter 60 instead of the donor venous pressure (as in the draw phase).

[0254] Finally, as shown in FIG. 49, platelet additive solution ("PAS") may be added to the collected platelets. This may be done with valves V9 and V7 (respectively) associated with valve stations C9 and C7 open to allow flow through lines L125 and L130, and with valves V4, V8, V6 (respectively) associated with valve stations C4, C8, C6 closed to prevent flow through lines L127, L126, and L123. With the valves so positioned, plasma pump P6 may operate to draw platelet additive solution from fluid container F11 (which may be referred to as a PAS bag) via line L125, through valve station C9 associated with valve V9, line L124, spinner outlet sensor M2, spinning membrane separator 26, lines L129 and L130, valve station C7 associated with open valve V7, and into platelet concentrate bag F10.

[0255] E. Collection of Platelets or Platelets and Plasma According to one aspect of the present disclosure, blood separation device 10 may be used to separate and collect platelets, or both platelets and substantially cell-free plasma, from blood. Blood separation device 10 according to the present disclosure may be used in combination with a fluid flow circuit 12 having a single blood access device (e.g., a single needle that withdraws blood and returns separated blood components to the same location) or two blood access devices (e.g., one needle that withdraws blood from a source and a second needle that flows separated blood components to the same source or to a different recipient). Exemplary fluid flow circuits 12H, 12I and procedures are described for each configuration.

[0256] 1. Single-Needle Fluid Flow Circuit and Procedure a. Fluid flow circuit 9 is a schematic diagram of an exemplary fluid flow circuit 12H having a single blood access device (e.g., a single needle that draws blood and returns separated blood components to the same location) that may be used to separate and collect platelets, or both platelets and plasma. Fluid flow circuit 12H includes a cassette 48 of the type described above and shown in FIG. 13 that connects the various components of fluid flow circuit 12H. The various connections between the components of fluid flow circuit 12H are shown in FIG. 9, which also shows fluid flow circuit 12H installed on blood separation device 10.

[0257] All of the various valves V1-V11 and pressure sensors A1-A4 of blood separation device 10, except for pressure sensor A3, are used in combination with fluid flow circuit 12H of FIG. 9 to separate and collect platelets, or platelets and plasma. As will be described below, fluid may flow through sensor station S3 associated with pressure sensor A3, but pressure sensor A3 does not communicate with controller 18 to monitor pressure at any location in fluid flow circuit 12G. Additionally, as will be described below, both centrifuge 16 and spinning membrane separator drive unit 14 are used to separate blood into platelets, or platelets and plasma for collection.

[0258] B. Retraction phase In the first stage (FIG. 50), blood is drawn from the blood source into fluid flow circuit 12H. If the blood source is a donor, blood may be drawn into fluid flow circuit 12H through a single needle connected to cassette 48 by line L140. Line L140 may include a manual clamp 56 that may be initially in a closed position to prevent fluid flow through line L140. When beginning processing, an operator moves manual clamp 56 from its closed position to an open position to allow fluid to flow through line L140.

[0259] Blood is drawn into line L140 by donor pump P2 of blood separation device 10. Anticoagulant from anticoagulant bag F1 is drawn through line L141 under the action of anticoagulant pump P1 and is added to the blood at the junction of lines L140 and L141.

[0260] In the illustrated embodiment, valve V10 associated with valve station C10 of fluid flow circuit 12H is open to allow blood to flow through lines L140 and L142 and sensor station S1 associated with pressure sensor A1, while valve V11 associated with valve station C11 is closed to prevent fluid flow through line L143. If the blood source is a living organism (e.g., a donor), pressure sensor A1 can communicate with controller 18 to monitor the pressure in the veins of the blood source.

[0261] The cassette 48 includes two valve stations C1 and C2 downstream of the donor pump P2 and the line L144, with the valve V2 associated with the valve station C2 closed to prevent flow through the line L145 and the valve V1 associated with the valve station C1 open to allow flow through the line L146. The blood flows through the line L146 associated with the open valve V1 to the junction, where a part of the blood is directed through the line L147 and the sensor station S3 associated with the inactive pressure sensor A3 to the in-process bag F3, and the rest is directed through the line L148 to the centrifugal pump P3, which controls the amount of blood that is directed to the centrifuge chamber 36 instead of the in-process bag F3. In particular, the flow rate of the donor pump P2 is greater than the flow rate of the centrifugal pump P3, and the difference between them is equal to the flow rate of blood to the in-process bag F3. The flow rates may be selected such that the in-process bag F3 is partially or totally filled with blood at the end of the drawing phase.

[0262] Blood pumped by centrifugal pump P3 through line L148 passes through line L149, air trap 62, and sensor station S2 associated with pressure sensor A2 (which operates in conjunction with control unit 18 of blood separation device 10 to monitor the pressure within centrifuge chamber 36) before reaching centrifuge chamber 36 of fluid separation circuit 12H. As described above, centrifuge 16 of blood separation device 10 operates centrifuge chamber 36 to separate blood within centrifuge chamber 36 into platelet-rich plasma and concentrated red blood cells. In one embodiment, centrifuge chamber 36 rotates at a nominal speed of 4,500 rpm, although the particular rotational speed may vary depending on the flow rate of fluid entering and leaving centrifuge chamber 36.

[0263] The concentrated red blood cells exit the centrifuge chamber 36 via line L150 and flow through line L151 into return bag F4. The white blood cells may be retained in the centrifuge chamber 36 or may be discharged along with the red blood cells.

[0264] Platelet-rich plasma is withdrawn from the centrifuge chamber 36 via line L152 by the combined action of the recirculation pump P5 and the PRP pump P4 of the blood separation device 10. The platelet-rich plasma proceeds through line L152 until it reaches a junction where it splits into lines L153 and L154. The recirculation pump P5 is associated with line L153 and redirects a portion of the platelet-rich plasma to the junction where it mixes with the blood being conveyed into the centrifuge chamber 36 by the centrifugal pump P3 in line L148. Recirculating a portion of the platelet-rich plasma into the centrifuge chamber 36 along with the incoming blood reduces the hematocrit of the blood entering the centrifuge chamber 36, which may improve separation efficiency. With this configuration, the flow rate of the fluid entering the centrifuge chamber 36 is equal to the sum of the flow rates of the centrifugal pump P3 and the recirculation pump P5.

[0265] Because the platelet-rich plasma drawn from the centrifuge chamber 36 into line L153 by the recirculation pump P5 is immediately returned to the centrifuge chamber 36, the bulk or net platelet-rich plasma flow rate out of the centrifuge chamber 36 is equal to the flow rate of the PRP pump P4. Before reaching the spinning membrane separator 26, a portion of the platelet-rich plasma conveyed by the PRP pump P4 through line L154 passes through a sensor station S4 associated with a spinner inlet sensor M1 and a pressure sensor A4. The spinner inlet sensor M1 may detect the concentration of platelets in the platelet-rich plasma entering the spinning membrane separator 26, while the pressure sensor A4 may monitor the pressure of the spinning membrane separator 26.

[0266] Line L154 has a junction where it joins with line L155. Valve V6 associated with valve station C6 is closed to prevent fluid flow through line L155, thereby directing the separated platelet-rich plasma to the spinning membrane separator 26. If necessary, valve V6 can be selectively opened to direct all or a portion of the platelet-rich plasma through line L155 to return bag F4. One example is at the start of the procedure when separation is initialized and platelets have not yet left the centrifuge chamber 36, in which case the fluid conveyed through line L154 by PRP pump P4 can be directed to return bag F4.

[0267] The spinning membrane separator drive unit 14 of the blood separation device 10 operates the spinning membrane separator 26 to separate the platelet-rich plasma into two subcomponents (i.e., platelet-poor plasma and platelet concentrate). In one embodiment, the spinning membrane separator 26 is a smaller spinning membrane separator (as described above) having a stationary housing 70 and a rotatable rotor 72 to which a membrane 76 is attached. In such an embodiment, the spinning membrane separator drive unit 14 can rotate the rotor 72 at approximately 1,500 rpm (or a different speed depending on the flow rate of fluids entering and leaving the spinning membrane separator 26) in accordance with the principles described above to separate the platelet-rich plasma entering the bottom of the spinning membrane separator 26 into plasma and platelets.

[0268] Plasma is pumped from spinning membrane separator 26 via line L156 by plasma pump P6 of blood separation apparatus 10. Valves V9, V8, V6, and V5 associated with valve stations C9, C8, C6, and C5 (respectively) are closed to prevent flow through lines L157, L158, L155, and L159, thereby directing the separated plasma along lines L156 and L160, through valve station C4 associated with open valve V4, and into return bag F4 (along with separated red blood cells). On the way to return bag F4, the plasma passes spinner outlet sensor M2, which cooperates with controller 18 to determine the amount of cellular blood components in the plasma and / or one or more characteristics of the plasma, such as the amount of cellular blood components in the plasma and / or whether the plasma is hemolytic and / or lipemic.

[0269] The platelet concentrate is conveyed out of the spinning membrane separator 26 via line L161. There is no pump associated with line L161; instead, the flow rate at which the platelets exit the spinning membrane separator 26 is equal to the difference between the flow rates of the PRP pump P4 and the plasma pump P6. The concentration of platelets in the platelet concentrate can be calculated according to Equation 4 above.

[0270] Valve V8 associated with valve station C8 is closed to prevent fluid flow through line L158, thereby directing platelet flow along lines L161 and L162 through valve station C7 associated with open valve V7 to platelet concentrate bag F10. Valve V8 associated with valve station C8 may be selectively opened to allow fluid to flow through line L158 to a junction where it joins plasma flowing through line L156 to return bag F4, if desired.

[0271] The draw phase may continue until the amount of blood drawn from the blood source reaches a target volume, or until in-process bag F3 is filled to a particular level (as determined by a weighing scale from which in-process bag F3 is suspended during the procedure), or until some other condition is met.

[0272] c. Return phase - platelet collection only Once the draw phase is complete, the system transitions to one of two return phases (FIGS. 51 and 52), depending on whether only platelets are being collected (FIG. 51) or both platelets and plasma are being collected (FIG. 52). While the collection of platelets (FIG. 51) or both platelets and plasma (FIG. 52) is ongoing, at least a portion of one of the separated blood components is delivered to a recipient (which may be the blood source).

[0273] During the return phase of the procedure (FIG. 51), when only platelets are being collected, anticoagulant pump P1 stops drawing anticoagulant from anticoagulant bag F1. Valve V10 associated with valve station C10 closes to prevent fluid flow through line L142, and valve V11 associated with valve station C11 opens to allow fluid flow through line L143. Valve V2 associated with valve station C2 also opens to allow flow through line L145, while valve V1 associated with valve station C1 closes to prevent flow through line L146.

[0274] With the valves so positioned, donor pump P2 reverses direction to allow the contents of return bag F4 to be delivered to the recipient through the same needle used to draw blood into fluid flow circuit 12H. The return fluid (red blood cells and plasma) is pumped through lines L151 and L145, valve station C2 associated with open valve V2, line L144, sensor station S1 associated with pressure sensor A1, and into line L163. The return fluid travels along line L163 through return line filter 58 and air detector M3 until it reaches the junction connecting lines L163 and L164 (leading to saline bag F2). Valve V3 associated with valve station C3 is closed, thereby preventing fluid flow through line L164 and directing the return fluid further along line L163, through valve station C11 associated with open valve V11, along lines L143 and L140 to the recipient.

[0275] While the fluid is being delivered to the recipient, the blood in the in-process bag F3 acts as a blood supply for the centrifuge 16. As the system transitions to this return phase, the centrifugal pump P3 remains unchanged and separation continues in the same manner as described for the draw phase (i.e., blood is separated into red blood cells and platelet-rich plasma in the centrifuge chamber 36, red blood cells flow out of the centrifuge chamber 36 into the return bag F4, platelet-rich plasma flows to the spinning membrane separator 26 for separation, and separated platelets are collected, while plasma is directed to the return bag F4) until the in-process bag F3 is emptied. Thus, the system components downstream of the centrifugal pump P3 are "blind" as to whether the system is in the draw phase or this return phase. The method described here is preferable to a batch process (which separates blood only during the draw phase and not during the return phase) because separation and collection are continuous, thereby reducing the time required to complete the procedure. Furthermore, by continuously processing blood within the centrifuge chamber 36, the interface between the separated red blood cells and the platelet-rich plasma is maintained, whereas the location of the interface is lost during the return phase of batch processing, which requires the interface to be re-established between every draw / separation phase, further increasing the duration of the procedure.

[0276] It will be seen that the separated plasma and red blood cells are delivered to the return bag F4 at the same time that the contents of the return bag F4 are delivered to the recipient. The rate at which the donor pump P2 operates may be greater than the rate at which the plasma and red blood cells are delivered to the return bag F4 to allow the return bag F4 to empty during this return phase, even if separation continues. Once the processing bag and / or the return bag F3, F4 are empty, the system can return to the draw phase (Figure 50) or the final phase (Figure 53).

[0277] d. Return Phase - Platelet and Plasma Collection The return stage when collecting platelets and plasma (FIG. 52) is similar to the return stage when collecting platelets only (FIG. 51). The main difference is that when collecting platelets and plasma, valve V5 associated with valve station C5 opens to allow flow through line L159, while valve V4 associated with valve station C4 closes to prevent flow through line L160, so that the separated plasma leaving the spinning membrane separator 26 through line L159 associated with open valve V5 is sent to plasma bag F9 instead of return bag F4. Depending on the amount of plasma to be collected, the valves may be so arranged for the entire return stage, or the conditions of valves V4 and V5 may be reversed for part of the stage (thereby directing the separated plasma to return bag F4 instead of plasma bag F9).

[0278] Once the in-process bag and / or return bag F3, F4 are empty, the system can return to the retraction stage (FIG. 50) or to the final stage (FIG. 53).

[0279] e. Final stage Once the target amount of platelets or the target amount of platelets and plasma has been collected, the blood source / recipient may be disconnected from fluid flow circuit 12H and the system may transition to the final stage where a platelet additive solution is added to the collected platelets as shown in Figure 53. This may be accomplished with valves V9, V7 associated with valve stations C9, C7 (respectively) in an open state to allow flow through lines L157 and L162, while valves V8, V6, V5, and V4 associated with valve stations C8, C6, C5, and C4 (respectively) in a closed state to prevent flow through lines L158, L155, L159, and L160. With the valves so positioned, plasma pump P6 can be operated to draw platelet additive solution from PAS bag F11 through valve station C9 associated with open valve V9, line L156, spinner outlet sensor M2, spinning membrane separator 26, lines L161 and L162, and valve station C7 associated with open valve V7 and into platelet concentrate bag F10.

[0280] 2. Dual-Needle Fluid Flow Circuit and Procedure a. Fluid flow circuit FIGURE 10 is a schematic diagram of an exemplary fluid flow circuit 12I having a pair of blood access devices (e.g., needles) for separating and collecting platelets, or both platelets and plasma, from blood. Fluid flow circuit 12I includes a cassette 48 of the type described above and shown in FIGURE 13 that connects the various components of fluid flow circuit 12I. The various connections between the components of fluid flow circuit 12I are shown in FIGURE 10, which also shows fluid flow circuit 12I installed on blood separation device 10.

[0281] With the exception of donor pump P2, all of the various valves V1-V11 and pressure sensors A1-A4 of fluid flow circuit 12I of FIG. 10 are used in the collection of platelets or platelets and plasma, along with all of the pumps P1-P6. Additionally, as described below, both the centrifuge 16 and spinning membrane separator drive unit 14 are used to separate the blood into platelets, or platelets and plasma for collection. Fluid flow circuit 12I includes waste bag F8, which in the procedure shown in FIGS. 54 and 56 is used only in the priming stage prior to processing; saline from saline bag F2 is pumped through fluid flow circuit 12I for priming before being conveyed to waste bag F8 for disposal at the end of the procedure.

[0282] b. Separation and collection - platelets only In contrast to the separation procedure described above with respect to fluid flow circuit 12H of Figure 9, fluid flow circuit 12I of Figure 10 allows for a single stage in which blood is simultaneously drawn from a blood source and processed, and at least a portion of one of the separated components is delivered to a recipient (Figures 54 and 55). Valves V1-V11 of blood separation device 10 are placed in different states depending on whether only platelets (Figure 54) or both platelets and plasma (Figure 55) are being collected.

[0283] When only platelets are being collected (FIG. 54), blood is drawn from a blood source (e.g., using a needle) through line L170 into fluid flow circuit 12I. Line L170 may include a manual clamp 56 that may be initially in a closed position to prevent fluid flow through line L170. When starting processing, an operator moves manual clamp 56 from its closed position to an open position to allow fluid to flow through line L170.

[0284] Blood is drawn into line L170 by centrifugal pump P3 rather than donor pump P2 (which is inactive in this procedure). Anticoagulant from anticoagulant bag F1 may be drawn through line L171 under the action of anticoagulant pump P1 and added to the blood at the junction of lines L170 and L171.

[0285] In the illustrated embodiment, valve V10 associated with valve station C10 is open to allow blood to flow through line L170 and sensor station S3 associated with pressure sensor A3, while valve V3 associated with valve station C3 is closed to prevent flow through line L172. If the blood source is a living organism (e.g., a donor), pressure sensor A3 can be in communication with controller 18 to monitor pressure within the veins of the blood source.

[0286] Continued operation of centrifugal pump P3 transports blood through line L173, air trap 62, and sensor station S2 associated with pressure sensor A2 (which serves to monitor the pressure within centrifuge chamber 36) before the blood reaches centrifuge chamber 36 of fluid flow circuit 12I. As described above, the centrifuge 16 of blood separation device 10 operates centrifuge chamber 36 to separate the blood within centrifuge chamber 36 into platelet-rich plasma and concentrated red blood cells. In one embodiment, centrifuge chamber 36 rotates at a nominal 4,500 rpm, although the particular rotational speed may vary depending on the flow rate of fluid entering and leaving centrifuge chamber 36.

[0287] The concentrated red blood cells (along with the white blood cells, if not retained within the centrifuge chamber 36) exit the centrifuge chamber 36 through line L174 and flow through line L175 to the junction of lines L175 and L176. Valve V2 associated with valve station C2 is closed to prevent flow through line L176, while valve V1 associated with valve station C1 is opened to allow flow through line L177, thereby directing the red blood cells through line L177. On their way to the recipient, the red blood cells pass through valve station C11 associated with return line filter 58, air detector M3, and open valve V11. If the fluid recipient is a living organism, pressure sensor A1 associated with sensor station S1 may monitor the donor's venous pressure.

[0288] Platelet-rich plasma is drawn from the centrifuge chamber 36 via line L178 by the combined action of the recirculation pump P5 and the PRP pump P4 of the blood separation device 10. The platelet-rich plasma travels through line L178 until it reaches a junction, where it splits into lines L179 and L180. The recirculation pump P5 is associated with line L179 and redirects a portion of the platelet-rich plasma to the junction, where it mixes in line L170 with the blood conveyed to the centrifuge chamber 36 by the centrifugal pump P3 via line L173. Recirculating a portion of the platelet-rich plasma into the centrifuge chamber 36 along with the incoming blood reduces the hematocrit of the blood entering the centrifuge chamber 36, which may improve separation efficiency. With such an arrangement, the flow rate of the fluid entering the centrifuge chamber 36 is equal to the sum of the flow rates of the centrifugal pump P3 and the recirculation pump P5.

[0289] Because the platelet-rich plasma drawn from the centrifuge chamber 36 into line L179 by the recirculation pump P5 is immediately returned to the centrifuge chamber 36, the bulk or net platelet-rich plasma flow rate out of the centrifuge chamber 36 is equal to the flow rate of the PRP pump P4. Before reaching the spinning membrane separator 26, the portion of the platelet-rich plasma conveyed by the PRP pump P4 through line L180 passes through a sensor station S4 associated with a spinner inlet sensor M1 and a pressure sensor A4. The spinner inlet sensor M1 can detect the concentration of platelets in the platelet-rich plasma entering the spinning membrane separator 26, while the pressure sensor A4 can monitor the pressure of the spinning membrane separator 26.

[0290] Line L180 has a junction where it joins with line L181. Valve V6 associated with valve station C6 is closed to prevent fluid from flowing through line L181, thereby directing the separated platelet-rich plasma to the spinning membrane separator 26. If necessary, valve V6 is selectively opened to divert all or a portion of the platelet-rich plasma to line L182 and through line L183 and valve station C4 associated with open valve V4 where the platelet-rich plasma reaches the junction where lines L174 and L175 join to join the separated red blood cells to be delivered to the recipient.

[0291] The spinning membrane separator drive unit 14 of the blood separation device 10 operates the spinning membrane separator 26 to separate the platelet-rich plasma into two subcomponents (i.e., platelet-poor plasma and platelet concentrate). In one embodiment, the spinning membrane separator 26 is a smaller spinning membrane separator (as described above) having a stationary housing 70 and a rotatable rotor 72 to which a membrane 76 is attached. In such an embodiment, the spinning membrane separator drive unit 14 can rotate the rotor 72 at approximately 1,500 rpm (or a different speed depending on the flow rate of fluids entering and leaving the spinning membrane separator 26) in accordance with the principles described above to separate the platelet-rich plasma entering the bottom of the spinning membrane separator 26 into plasma and platelets.

[0292] Plasma is pumped from spinning membrane separator 26 via line L182 by plasma pump P6 of blood separation apparatus 10. Valves V9, V8, V6, and V5 associated with valve stations C9, C8, C6, and C5 (respectively) are closed to prevent flow through lines L184, L185, L181, and L186, thereby directing the separated plasma along lines L182 and L183 to the junction of lines L174 and L175 where red blood cells are joined for delivery to the recipient. On its way to the fluid recipient, the plasma passes spinner outlet sensor M2, which cooperates with control unit 18 to determine one or more characteristics of the plasma, such as the amount of cellular blood components in the plasma and / or whether the plasma is hemolytic and / or lipemic.

[0293] The platelet concentrate is conveyed out of the spinning membrane separator 26 via line L187. There is no pump associated with line L187, instead the flow rate at which the platelets exit the spinning membrane separator 26 is equal to the difference between the flow rates of the PRP pump P4 and the plasma pump P6. The concentration of platelets in the platelet concentrate can be calculated according to Equation 4 above.

[0294] As explained, valve V8 associated with valve station C8 is closed to prevent fluid flow through line L185, thereby directing the flow of platelets through valve station C7 associated with lines L187 and L188 and open valve V7 and into platelet concentrate bag F10. Valve V8 may be selectively opened to allow fluid flow through line L185 to its junction with line L182, where it optionally joins with the plasma flowing to the fluid recipient.

[0295] This stage can continue until the amount of platelets collected equals the target volume (as determined by a weigh scale on which the platelet concentrate bag F10 can be suspended during the procedure), at which point the system transitions to the final stage (FIG. 56).

[0296] C. Separation and collection – platelets and plasma The procedure when collecting platelets and plasma (FIG. 55) is similar to the procedure when collecting platelets only (FIG. 54). The main difference is that when collecting platelets and plasma, valve V5 associated with valve station C5 is opened while valve V4 associated with valve station C5 is closed, so that the separated plasma exits the spinning membrane separator 26 through line L186 and is collected in plasma bag F9 instead of being delivered to the fluid recipient with the separated red blood cells. If the target amount of one component is collected before the target amount of the other component, the component that is already completely collected is diverted to line L183 and delivered to the fluid recipient with the separated red blood cells during collection of the other targeted component.

[0297] This stage may continue until the amount of platelets and plasma collected equals the target volume, at which point the system may transition to the final stage (Figure 56).

[0298] d. Final stage Once the target amount of platelets or the target amount of platelets and plasma has been collected, the blood source / recipient is disconnected from the fluid flow circuit 12I and the system may transition to the final stage where platelet additive solution is added to the collected platelets as shown in Figure 56. This may be accomplished with valves V9, V7 associated with valve stations C9, C7 (respectively) in an open state and valves V8, V6, V5, V4 associated with valve stations C8, C6, C5, C4 (respectively) in a closed state. With the valves so positioned, plasma pump P6 draws platelet additive solution from PAS bag F11 through valve station C9 associated with open valve V9, line L182, spinner outlet sensor M2, spinning membrane separator 26, lines L187 and L188, valve station C7 associated with valve V7 and into platelet concentrate bag F10.

[0299] 3. Low-treatment Volume Circuit and Procedure According to one aspect of the disclosure, the blood cell separator 10 may be used (e.g., in combination with a fluid flow circuit 12J of the type shown in FIG. 11) to separate and collect platelets, or platelets and substantially cell-free plasma, from a low processing volume of blood. This may be considered a variation of the single needle process of FIGS. 50-53, in which a portion of the blood drawn from a source is treated while another portion of the blood is drawn into an in-process bag F3 so that the separated components are treated while being transported to a fluid recipient. If an equal volume of blood is processed and accumulated in the in-process bag F3, an extracorporeal volume of about 200-300 ml of blood may be typical to ensure that an adequate amount of blood is available for processing during both the draw and return phases. The procedure of Figures 50-53 may not be preferred for sources having relatively small amounts of blood available for processing (e.g., smaller human donors) and it may be preferable to use a fluid flow circuit 12J of the type shown in Figure 11 and a procedure of the type shown in Figures 57-60 when collecting platelets, or platelets and plasma, from such blood sources.

[0300] As will be explained in more detail, the procedure of Figures 57-60 can collect the same amount of platelets, or platelets and plasma, as the procedure of Figures 50-53, with a smaller processing volume of blood. Rather than temporarily holding the blood in bag F3 during processing, all of the blood is drawn into the centrifuge chamber 36 and separated into red blood cells and platelet-rich plasma during the draw phase (Figure 57). The separated red blood cells are delivered to a fluid container F12 (sometimes referred to herein as a reprocessing bag), while the platelet-rich plasma is separated into a platelet concentrate and substantially cell-free plasma in the spinning membrane separator 26. The platelets are collected in the platelet concentrate bag F10, while the plasma is delivered to the reprocessing bag F12. During the return phase (FIG. 58 or FIG. 59), the contents of the reprocessing bag F12 (mainly red blood cells and plasma) are processed using the centrifuge chamber 36 and the spinning membrane separator 26 to extract further platelets from the fluid in the reprocessing bag F12, while the separated red blood cells (FIG. 59) or separated red blood cells and plasma (FIG. 58) are transported to a fluid recipient (e.g., the same blood source). By such a procedure, the interface is maintained within the centrifuge chamber 36, while requiring a lower processing / extracorporeal volume of blood (e.g., about 100 ml instead of about 200-300 ml), improving platelet collection efficiency for each blood volume drawn.

[0301] a, fluid flow circuit FIGURE 11 is a schematic diagram of an exemplary fluid flow circuit 12J having a single blood access device (e.g., a single needle that draws blood and returns separated blood components to the same location) that may be used to separate and collect platelets only, or platelets and plasma, from a smaller processing volume of blood. Fluid flow circuit 12J includes a cassette 48 of the type described above and shown in FIGURE 13 that connects the various components of fluid flow circuit 12J. The various connections between the components of fluid flow circuit 12J are shown in FIGURE 11, which also shows fluid flow circuit 12J installed on blood separation device 10.

[0302] All of the various valves V1-V11 and pressure sensors A1-A4 of blood separation device 10, except for donor pump P2, are used in combination with fluid flow circuit 12J of Figure 11 to separate and collect platelets, or platelets and plasma. Additionally, as described below, both the centrifuge 16 and spinning membrane separator drive unit 14 are used to separate the blood into platelets, or platelets and plasma for collection.

[0303] B. Retraction phase In the first stage (FIG. 57), blood is drawn from the blood source into fluid flow circuit 12J. If the blood source is a donor, blood may be drawn into fluid flow circuit 12J through a single needle connected to cassette 48 by line L190. Line L190 may include a manual clamp 56 that may be initially in a closed position to prevent fluid flow through line L190. When beginning processing, an operator moves manual clamp 56 from its closed position to an open position to allow fluid to flow through line L190.

[0304] Blood is drawn into line L190 by centrifugal pump P3 of blood separation device 10. Anticoagulant from anticoagulant bag F1 may be drawn through line L191 under the action of anticoagulant pump P1 and added to the blood at the junction of lines L190 and L191.

[0305] In the illustrated embodiment, valve V10 associated with valve station C10 of fluid flow circuit 12J is open, while valves V11 and V3 associated with valve stations C11 and C3 are closed to prevent fluid flow through lines L192 and L193, thereby allowing blood to flow through lines L190 and L194 and sensor station S3 associated with pressure sensor A3. If the blood source is a living organism (e.g., a donor), pressure sensor A3 can be in communication with controller 18 to monitor pressure within the veins of the blood source.

[0306] The cassette 48 includes a junction downstream of the sensor station S3 where the line L194 meets the lines L195 and L196. Prior to reaching the centrifuge chamber 36 of the fluid separation circuit 12J, the valve V1 associated with the valve station C1 is closed to prevent flow through the line L195, which directs all of the blood through the lines L196 and L197, the air trap 62, and the sensor station S2 associated with the pressure sensor A2 (which functions in conjunction with the control unit 18 of the blood separation device 10 to monitor the pressure within the centrifuge chamber 36). As described above, the centrifuge 16 of the blood separation device 10 operates the centrifuge chamber 36 to separate the blood within the centrifuge chamber 36 into platelet-rich plasma and concentrated red blood cells. In one embodiment, the centrifuge chamber 36 rotates at a nominal speed of 4,500 rpm, although the particular rotational speed may vary depending on the flow rate of fluid entering and leaving the centrifuge chamber 36.

[0307] The concentrated red blood cells exit the centrifuge chamber 36 through line L198 and flow through line L199 to the junction where line L199 meets lines L200 and L192. Valve V11 associated with valve station C11 (along with valve V3 associated with valve station C3) is closed to prevent flow through line L192, thereby directing the separated red blood cells through line L200 and valve station C2 associated with open valve V2 into reprocessing bag F12. The white blood cells may be retained in the centrifuge chamber 36 or may be discharged along with the red blood cells.

[0308] Platelet-rich plasma is drawn from the centrifuge chamber 36 via line L201 by the combined action of the recirculation pump P5 and the PRP pump P4 of the blood separation device 10. The platelet-rich plasma travels through line L201 until it reaches a junction, where it is split into lines L202 and L203. The recirculation pump P5 is associated with line L202 and redirects a portion of the platelet-rich plasma to the junction, where it mixes in line L197 with the blood being conveyed into the centrifuge chamber 36 by the centrifugal pump P3. Recirculating a portion of the platelet-rich plasma into the centrifuge chamber 36 along with the incoming blood reduces the hematocrit of the blood entering the centrifuge chamber 36, which may improve separation efficiency. With this configuration, the flow rate of the fluid entering the centrifuge chamber 36 is equal to the sum of the flow rates of the centrifugal pump P3 and the recirculation pump P5.

[0309] Since the platelet-rich plasma drawn from the centrifuge chamber 36 into line L202 by the recirculation pump P5 is immediately returned to the centrifuge chamber 36, the bulk or net platelet-rich plasma flow rate out of the centrifuge chamber 36 is equal to the flow rate of the PRP pump P4. Before reaching the spinning membrane separator 26, a portion of the platelet-rich plasma conveyed by the PRP pump P4 through line L203 passes through a sensor station S4 associated with a spinner inlet sensor M1 and a pressure sensor A4. The spinner inlet sensor M1 can detect the concentration of platelets in the platelet-rich plasma entering the spinning membrane separator 26, while the pressure sensor A4 can monitor the pressure of the spinning membrane separator 26.

[0310] Line L203 has a junction where it joins with line L204. Valve V6 associated with valve station C6 is closed to prevent fluid flow through line L204, thereby directing the separated platelet-rich plasma to the spinning membrane separator 26. If necessary, valve V6 is selectively opened to direct all or a portion of the platelet-rich plasma through lines L204, L205, and L206 and valve station C4 associated with open valve V4 to the junction where it joins the separated red blood cells flowing through line L198 to the reprocessing bag F12. One example is at the start of the procedure when the separation is being initialized and the platelets have not yet left the centrifuge chamber 36, in which case the fluid conveyed through line L203 by PRP pump P4 can be directed to the reprocessing bag F12.

[0311] The spinning membrane separator drive unit 14 of the blood separation device 10 operates the spinning membrane separator 26 to separate the platelet-rich plasma into two subcomponents (i.e., platelet-poor plasma and platelet concentrate). In one embodiment, the spinning membrane separator 26 is a smaller spinning membrane separator (as described above) having a stationary housing 70 and a rotatable rotor 72 to which a membrane 76 is attached. In such an embodiment, the spinning membrane separator drive unit 14 can rotate the rotor 72 between about 1,000-3,000 rpm (or different speeds depending on the flow rates of fluids entering and leaving the spinning membrane separator 26 and / or the material composition of the membrane 76) to separate the platelet-rich plasma entering the bottom of the spinning membrane separator 26 into plasma and platelets according to the principles described above.

[0312] Plasma is pumped from spinning membrane separator 26 via line L205 by plasma pump P6 of blood separation apparatus 10. Valves V9, V8, V6, and V5 associated with valve stations C9, C8, C6, and C5 (respectively) are closed to prevent flow through lines L207, L208, L204, and L209, thereby directing the separated plasma along lines L205 and L206 through valve station C4 associated with open valve V4 to a junction where the plasma joins with red blood cells flowing through line L198 toward reprocessing bag F12. On the way to reprocessing bag F12, the plasma passes spinner outlet sensor M2, which cooperates with controller 18 to determine one or more characteristics of the plasma, such as the amount of cellular blood components in the plasma and / or whether the plasma is hemolytic and / or lipemic.

[0313] The platelet concentrate is conveyed out of the spinning membrane separator 26 via line L210. There is no pump associated with line L210, instead the flow rate at which the platelets exit the spinning membrane separator 26 is equal to the difference between the flow rates of the PRP pump P4 and the plasma pump P6. The concentration of platelets in the platelet concentrate can be calculated according to Equation 4 above.

[0314] Valve V8 associated with valve station C8 is closed to prevent fluid flow through line L208, thereby directing the flow of platelets along lines L210 and L211 through valve station C7 associated with open valve V7 to platelet concentrate bag F10. Valve V8 associated with valve station C8 may be selectively opened to allow fluid to flow through line L208 to a junction where it joins with plasma flowing through line L205 to reprocessing bag F12, if necessary.

[0315] The draw phase continues until the amount of blood drawn from the blood source reaches a target volume (e.g., about 100 ml), or until the reprocessing bag F12 is filled to a certain level (determined by a weighing scale on which the reprocessing bag F12 is hung during the procedure), or until some other condition is met.

[0316] c. Return phase - platelet collection only Once the retraction phase is complete, the system transitions into one of two return phases (FIGS. 58 and 59) depending on whether only platelets have been collected (FIG. 58) or both platelets and plasma have been collected (FIG. 59).

[0317] During the return phase of the procedure (FIG. 58), when only platelets are being collected, anticoagulant pump P1 stops drawing anticoagulant from anticoagulant bag F1. Valve V10 associated with valve station C10 closes to prevent fluid flow through line L194, and valve V11 associated with valve station C11 is opened to allow fluid flow through line L192. Valve V1 associated with valve station C1 is also open to allow flow through line L195, while valve V2 associated with valve station C2 is closed to prevent flow therethrough.

[0318] Centrifugal pump P3 continues to operate in the same direction as in the draw phase, but draws fluid (typically a mixture of red blood cells and plasma) from the reprocessing bag F12 rather than from the blood source. The fluid in the reprocessing bag F12 thus acts as a fluid source for the centrifuge 16. Once the system has transitioned to this return phase, separation continues in the same manner as described for the draw phase (i.e., blood is separated into red blood cells and platelet-rich plasma in the centrifuge chamber 36, the red blood cells exit the centrifuge chamber 36, the platelet-rich plasma enters and is separated in the centrifuge 26, and the separated platelets are collected) until the reprocessing bag F12 is emptied.

[0319] With the valves so positioned, the separated red blood cells and plasma will be conveyed to the fluid recipient rather than flowing to reprocessing bag F12. In particular, the mixture of red blood cells and plasma flowing through line L199 is directed through line L192 instead of line L200 at the junction of lines L199, L192, and L200. The fluid flows through line L192, sensor station S1 associated with pressure sensor A1 (which can monitor venous pressure if the recipient is a living patient), return line filter 58, air detector M3, and so on until it reaches the junction joining lines L192 and L193 (which leads to saline bag F2). Valve V3 associated with valve station C3 is closed, thereby preventing fluid flow through line L193 and directing the fluid further along line L192, through valve station C11 associated with open valve V11, and back along line L190 to the recipient. It will thus be appreciated that the majority of blood drawn from the blood source is processed twice before being delivered to the fluid recipient (which may be the same blood source) as a mixture of separated red blood cells and plasma.

[0320] By continuously processing the fluid in the centrifuge chamber 36, the interface between the separated red blood cells and the platelet-rich plasma can be maintained. However, the fluid flowing toward the centrifuge chamber 36 through line L196 during this return phase (which typically contains a mixture of red blood cells and plasma) has a higher hematocrit than the blood flowing through line L196 during the draw phase due to the diversion of some plasma into the platelet concentrate bag F10. If the hematocrit of the fluid entering the centrifuge chamber 36 through line L197 during this return phase is the same as the hematocrit of the fluid entering the centrifuge chamber 36 at the same volumetric flow rate during the draw phase, the centrifuge 16 may continue to rotate the centrifuge chamber 36 at the same speed in both phases to maintain the interface in the proper position. It may therefore be advantageous for the control unit 18 to coordinate the operation of one or more components of the blood separation device 10 to cause the fluid entering the centrifuge chamber 36 during this return phase to be transported at the same volumetric flow rate and have the same hematocrit.

[0321] According to an exemplary approach for adjusting the hematocrit of the fluid entering the centrifuge chamber 36, the controller 18 can slow down the centrifugal pump P3 (compared to the operation of the draw phase) to reduce the volumetric flow rate of the fluid through line L196, while accelerating the recirculation pump P5 (compared to the operation of the draw phase) to increase the volumetric flow rate of the platelet-rich plasma through line L202. Because the platelet-rich plasma pumped into line L197 by the recirculation pump P5 has a hematocrit of zero, which is lower than the hematocrit of the fluid pumped into line L197 by the centrifugal pump P3, adjusting the operating speeds of the centrifugal pump P3 and the recirculation pump P5 in this manner will effectively reduce the hematocrit of the fluid entering the centrifuge chamber 36. Thus, the relative operating speeds of centrifugal pump P3 and recirculation pump P5 can be adjusted so that the hematocrit of the fluid entering the centrifuge chamber 36 is the same (or at least substantially or approximately the same) in this return phase, and the same volumetric flow rate (or at least substantially or approximately the same as in the draw phase), which enables the centrifuge 16 to rotate the centrifuge chamber 36 at the same speed in both phases to maintain the interface in the proper position.

[0322] More specifically, during the retraction phase (FIG. 57), the centrifugal pump P3 pumps the hematocrit H dnr Blood is pumped with a volume flow rate Q in-wb Recirculation pump P5 operates to draw the separated platelet rich plasma through line L202 at a volumetric flow rate Q recirc-wb This operates to deliver a target hematocrit (H recirc ) and can be calculated as follows: Q recirc-wb =((Q in-wb ×H dnr ) / H recirc )-Q in-wb [Formula 5]

[0323] As mentioned above, the volumetric flow rate of fluid entering the centrifuge chamber 36 (Q cent The centrifugal pump P3 (sometimes called Q in-wb ) and recirculation pump (Q recirc-wb ) is equal to the sum of the flow rates given by the operation of Q cent =Q in-wb +Q recirc-wb [Formula 6]

[0324] As explained, to help control the interface between the red blood cells and the platelet-rich plasma in the centrifuge chamber 36, a volumetric flow rate (Q cent ) and the hematocrit (H recirc It is preferred that the hematocrit (H) of blood from the source be held constant throughout the procedure. dnr ), this is easily accomplished in a typical batch platelet collection procedure (blood is processed only once), which requires a single recirculation rate Q regardless of whether the system is in the retract or return state. recirc-wb However, during the procedure of Figures 57-60, the fluid being processed during the return phase will have a higher hematocrit than the blood drawn from the source during the draw phase, due to the removal of plasma along with the platelet concentrate. Therefore, the operating speeds of the centrifuge pump P3 and the recirculation pump P5 are set to a constant volumetric flow rate (Q cent ) and hematocrit (H recirc ) can be adjusted between the retraction and return phases to maintain the inlet velocity Q in-wb The operating speed of the centrifugal pump P3 to provide the appropriate recirculation rate may be a constant set by the system, and the operating speed of the recirculation pump P5 to provide the appropriate recirculation rate Q recirc is the hematocrit (H dnr Setting the flow rates for the retraction phase is straightforward since the hematocrit (H reproc) must also be known, which requires calculations.

[0325] The determination of the hematocrit of the fluid in the reprocessing bag F12 is independent of the recirculation rate applied during the draw (Figure 57), and the system operates independently of the inlet parameters (Q in-wb and H dnr ) and the outlet parameters, i.e., the volumetric flow rate and hematocrit (Q out-reproc and H reproc ) and the volumetric flow rate of the platelet concentrate entering the platelet concentrate bag F10 during the draw phase (Q out-pc )

[0326] At steady state, the amount of red blood cells entering fluid flow circuit 12J must equal the amount of red blood cells exiting fluid flow circuit 12J. Q in-wb ×H dnr =Q out-reproc ×H reproc [Formula 7] Here, the volumetric flow rate of fluid entering reprocessing bag F12 is the difference between the volumetric flow rate of blood drawn into fluid flow circuit 12J and the volumetric flow rate of platelets entering platelet concentrate bag F10. Q out-reproc =Q in-wb -Q out-pc [Formula 8]

[0327] Substituting equation 8 into equation 7 and solving for the hematocrit of the fluid entering reprocessing bag F12 gives: H reproc =(Q in-wb ×H dnr ) / (Q in-wb -Q out-pc ) [Formula 9]

[0328] Thus, when the system transitions from the draw phase (Figure 57) to the return phase (Figure 58), the hematocrit (H reproc ) is known, and the appropriate volumetric flow rate of fluid out of the reprocessing bag F12 (Qin-reproc It can be used to set the operating speed of the centrifugal pump P3 to achieve the hematocrit value (H reproc ) is the hematocrit value (H dnr ), the volumetric flow rate of the fluid leaving the reprocessing bag F12 applied during the return phase (Q in-reproc ) is the volumetric flow rate of blood into the fluid flow circuit F12 during the intake phase (Q in-wb ), meaning that the centrifugal pump P3 operates at a slower speed during the return phase than during the draw phase.

[0329] The goal is to reduce the red blood cell fraction flow rate Q of the fluid being reprocessed. reproc-rbc is the red blood cell fraction flow rate Q drawn from the source during the draw phase. wb-rbc The volumetric flow rate (Q ) leaving the reprocessing bag F12 during return is set to be equal to in-reproc ) is adjusted. Q reproc-rbc =Q in-reproc ×H reproc [Formula 10] Q wb-rbc =Q in-wb ×H dnr [Equation 11], the purpose of which is to Q reproc-rbc =Q wb-rbc [Formula 12]

[0330] Therefore, combining equations 10, 11, and 12, we get Q in-reproc Solving this gives us the following: Q in-reproc =(Q in-wb ×H dnr ) / H reproc [Formula 13]

[0331] The same volumetric flow rate (Q cent ) and hematocrit (H recirc ), the operating speed of the recirculation pump P5 is adjusted to compensate for the reduction in volumetric flow rate (Q in-wbFrom Q in-reproc To account for the larger volume flow rate Q recirc-reproc The volumetric flow provided by the operation of the recirculation pump P5 during the return phase can be calculated as follows: Q recirc-reproc =((Q in-reproc ×H reproc ) / H recirc )-Q in-reproc [Formula 14]

[0332] The lower volumetric flow rate (Q in-reproc ) is thus higher than the higher volumetric flow rate (Q recirc-reproc ) to ensure that the volumetric flow rate of fluid into the centrifuge chamber 36 (Q cent ) remains the same during the return phase (FIG. 58) as it did during the retraction phase (FIG. 57). Q cent =Q in-reproc +Q recirc-reproc [Formula 15]

[0333] As an example, blood has a volume flow rate Q of 100 ml / min. in-wb (which can be a system-defined constant) and blood is drawn from the source at 40% hematocrit H dnr and the target hematocrit value H of the fluid entering the centrifuge chamber 36. recirc Using Equation 5 above, Q recirc-wb = (100 x 0.40) / 0.34)-100 = 17.6 ml / min. Using equation 6 above, Q cent =100+17.6=117.6 ml / min.

[0334] The volumetric flow rate of platelets into the platelet concentrate bag F10 is a constant defined by the system or can be determined by the control unit 18 (e.g., by communicating with a weighing scale that hangs the platelet concentrate bag F10 during the procedure) and can be 8 ml / min, so the parameter required to calculate the hematocrit of the fluid in the reprocessing bag F12 (Q in-wb, H dnr , and Q out-pc ) are all known. Using Equation 9 above, H reproc =(100×0.40) / (100-8)=43.5%. Using this value, Q in-reproc can be calculated using Equation 13 above: Q in-reproc = (100 x 0.40) / 0.435 = 92 ml / min. Inserting the appropriate values ​​into Equation 10 and Equation 11 above returns the red blood cell fraction flow rate (Q reproc-rbc = 92 × 0.435 = 40 ml / min) and withdrawal (Q wb-rbc = 100 × 0.40 = 40 ml / min).

[0335] The operation of the centrifugal pump P3 is in the draw phase (Q in-wb = 100 ml / min) during the return phase (Q in-reproc = 92 ml / min), resulting in a lower volumetric flow rate to the centrifuge chamber at the same volumetric flow rate (Q cent ), the speed of the recirculation pump P5 must be increased. According to Equation 14 above, Q recirc-reproc = ((92 x 0.435) / 0.34) - 92 = 25.6 ml / min. Equation 15 above can be used to ensure that the volumetric flow rate of fluid entering the centrifuge chamber 36 and the hematocrit of that fluid are the same on retraction and return (117.6 ml / min and 34%, respectively), thereby allowing the centrifuge 16 to operate the same in both stages.

[0336] In any case, once the reprocessing bag F12 is empty, the system can return to the retraction stage (Figure 57) or to the final stage (Figure 60).

[0337] d. Return Phase - Platelet and Plasma Collection The return phase when collecting platelets and plasma (FIG. 59) is similar to the return phase when collecting platelets only (FIG. 58), including the manner in which the operation of centrifugal pump P3 and recirculation pump P5 are controlled to maintain the volumetric flow rate and hematocrit of the fluid entering the centrifuge chamber 36. The main difference is that when collecting platelets and plasma, valve V5 associated with valve station C5 opens to allow flow through line L209, while valve V4 associated with valve station C4 closes to prevent flow through line L206, whereby separated plasma leaving the spinning membrane separator 26 is directed through line L209 associated with open valve V5 to plasma bag F9 instead of the fluid recipient. The valves may be so positioned for the entire return phase, or the state of valves V4 and V5 may be reversed for part of the phase (thereby directing separated plasma to the fluid recipient instead of plasma bag F9), depending on the amount of plasma to be collected.

[0338] Once the reprocessing bag F12 is empty, the system can return to the retraction stage (Figure 57) or to the final stage (Figure 60).

[0339] e. Final stage 60, when the target amount of platelets or the target amount of platelets and plasma has been collected, the blood source / recipient can be disconnected from fluid flow circuit 12J and the system can move to the final stage where a platelet additive solution is added to the collected platelets. This can be done with valves V9 and V7 associated with valve stations C9 and C7 (respectively) in an open state to allow flow through lines L207 and L211, and valves V8, V6, V5, and V4 associated with valve stations C8, C6, C5, and C4 (respectively) in a closed state to prevent flow through lines L208, L204, L209, and L206. With the valves so positioned, plasma pump P6 can be operated to draw platelet additive solution from PAS bag F11 via line L207, through valve station C9 associated with open valve V9, line L205, spinner outlet sensor M2, spinning membrane separator 26, lines L210 and L211, valve station C7 associated with open valve V7 and into platelet concentrate bag F10.

[0340] IV. Other Possible Variations Although a fluid flow circuit 12 having only a spinning membrane separator 26 (and no centrifuge chamber 36), or a fluid flow circuit 12 having both a spinning membrane separator 26 and a centrifuge chamber 36 and a method using only a spinning membrane separator drive unit 14 (and no centrifuge 16), or a method using both a spinning membrane separator drive unit 14 and a centrifuge 16 are described, it should be understood that other variations are possible. For example, it is within the scope of this disclosure for a fluid flow circuit including a centrifuge chamber and no spinning membrane separator to be used in combination with blood separation device 10 for procedures using only a centrifuge 16 and not a spinning membrane separator drive unit 14 (e.g., white blood cell collection procedures). It is also within the scope of this disclosure for a fluid flow circuit including both a spinning membrane separator 26 and a centrifuge chamber 36 to be used in procedures using only one of them to separate fluids.

[0341] Additionally, it may be advantageous to use a blood separation device 10 incorporating both the spinning membrane separator drive unit 14 and the centrifuge device 16 in a common case 20, although it should be understood that blood separation procedures for using spinning membrane separator drive units and centrifuges associated with different blood separation devices are also within the scope of the present disclosure. When two such separate blood separation devices are used to perform a multi-stage separation procedure according to the present disclosure, it may be advantageous for the system to also include a controller capable of communicating with and controlling both blood separation devices to ensure that the procedure is performed correctly. Such a controller may generally be programmed and configured according to the foregoing description of the controller 18 of the blood separation device 10, or may be programmed and configured differently. Additionally, the controller may be incorporated into the blood separation device or provided separately (e.g., incorporated into a computer or control station) and may communicate with the blood separation device via a physical connection (e.g., via a cable) or wirelessly.

[0342] V. aspect Aspect 1: A blood separation device comprising a centrifuge, a rotating membrane separation drive unit, and a control unit configured and / or programmed to control the operation of the centrifuge and the rotating membrane separation drive unit, wherein the centrifuge and the rotating membrane separation drive unit are incorporated in a case.

[0343] Aspect 2. The blood separation device of aspect 1, wherein the control unit is configured and / or programmed to control only one of the centrifuge and the spinning membrane separator drive device, or both the centrifuge and the spinning membrane separator drive device, to separate blood into two or more blood components or to separate blood components into two or more subcomponents.

[0344] Aspect 3. The blood separation device of any of Aspects 1 to 2, further comprising first and second pumps, wherein the controller is configured and / or programmed to control the centrifuge to separate the blood into two or more blood components, to control the first pump to recirculate a portion of one of the blood components to the centrifuge along with the blood entering the centrifuge, and to control the second pump to transport the other portion of the one of the blood components to the spinning membrane separator drive unit for separation of the other portion of the one of the blood components into two or more subcomponents.

[0345] Aspect 4 The blood separation device of any of Aspects 1 to 3, further comprising an interface monitoring system associated with the centrifuge and including a light source configured to emit light through separated blood components in the centrifuge, and a light detector configured to receive at least a portion of the light emitted by the light source and cooperate with the controller to determine a position of an interface between two separated blood components in the centrifuge, wherein the light source includes a laser.

[0346] Aspect 5. The blood separation device of aspect 4, wherein the centrifuge is disposed within the centrifuge compartment, and the light source and the light detector are attached to a stationary surface of the centrifuge compartment.

[0347] Aspect 6. The blood separation device of any of Aspects 4-5, wherein the photodetector is positioned and oriented to receive light traveling in a direction that is substantially perpendicular to the direction of light emitted by the light source.

[0348] Aspect 7. The blood separation device of any one of Aspects 1 to 6, wherein the spinning membrane separator drive unit comprises an upper end cap and a base, and at least one of the upper end cap and the base is movable relative to the other of the upper end cap and the base to accommodate spinning membrane separators of different sizes.

[0349] Aspect 8. The blood separation device of any of Aspects 1 to 7, further comprising at least one pump and an inlet sensor configured to optically detect a characteristic of a fluid to be separated by the spinning membrane separator drive unit, and wherein the control unit is configured and / or programmed to control operation of the at least one pump based at least in part on the characteristic of the fluid to be separated by the spinning membrane separator drive unit.

[0350] Aspect 9. The blood separation device of aspect 8, wherein the inlet sensor is configured to optically detect a hematocrit of the fluid to be separated by the spinning membrane separator drive unit.

[0351] Aspect 10. The blood separation device of aspect 8, wherein the inlet sensor is configured to optically detect a concentration of platelets in the fluid to be separated by the spinning membrane separator drive unit.

[0352] Aspect 11. The blood separation device of any one of Aspects 1 to 10, further comprising an outlet sensor configured to optically detect a property of a fluid exiting the spinning membrane separator drive unit.

[0353] Aspect 12. The blood separation device of aspect 11, wherein the outlet sensor is configured to optically detect whether the fluid exiting the spinning membrane separator drive unit is lipemic and / or hemolytic.

[0354] Aspect 13. The blood separation device of any of Aspects 1 to 12, wherein the controller is configured and / or programmed to simultaneously control both the centrifuge and the spinning membrane separator drive units to separate blood into two or more blood components or to separate blood components into two or more subcomponents.

[0355] Aspect 14. A fluid flow circuit for use in combination with a blood separation device comprising a centrifuge chamber and a spinning membrane separator in fluid communication with the centrifuge chamber.

[0356] Aspect 15. The fluid flow circuit of Aspect 14, further comprising an in-process container configured to receive a portion of the blood transported into the fluid flow circuit from the blood source, and the centrifuge chamber configured to receive another portion of the blood transported into the fluid flow circuit.

[0357] Aspect 16. The fluid flow circuit of aspect 15, including six tubing loops in fluid communication with the centrifuge chamber, the spinning membrane separator, and the in-process container, and configured to cooperate with different peristaltic pumps of the blood separation device.

[0358] Aspect 17. The fluid flow circuit of Aspect 14, further comprising a reprocessing vessel configured to receive at least a portion of the at least one blood component separated from the blood by the centrifuge chamber and / or the spinning membrane separator and to supply the at least a portion of the at least one blood component to the centrifuge chamber for separation of the at least a portion of the at least one blood component into two or more blood components.

[0359] Aspect 18. The flow path circuit of aspect 17, including five tubing loops in fluid communication with the centrifuge chamber, the spinning membrane separator, and the in-process container, and configured to cooperate with different peristaltic pumps of the blood separation device.

[0360] Aspect 19. The fluid flow circuit of any of Aspects 14-18, further comprising a single blood access device configured to allow blood to be delivered to the fluid flow circuit and to allow fluid to be transported out of the fluid flow circuit.

[0361] Aspect 20 The fluid flow circuit of Aspect 14, further comprising a first blood access device and a second blood access device, the first blood access device configured to allow blood to be delivered to the fluid flow circuit and the second blood access device configured to allow fluid to be transported out of the fluid flow circuit.

[0362] Aspect 21. The fluid flow circuit of Aspect 20, further comprising a cassette including a centrifuge chamber, a spinning membrane separator, and five tubing loops in fluid communication with the first blood access device and the second blood access device and configured to cooperate with different peristaltic pumps of the blood separation device.

[0363] Aspect 22: A blood separation system comprising a blood separation device including a centrifuge and a spinning membrane separator drive unit assembled in a case, and a centrifuge chamber configured to be attached to the centrifuge and / or a fluid flow circuit including a spinning membrane separator configured to be attached to the spinning membrane separator drive unit.

[0364] Aspect 23. The blood separation system of aspect 22, including a controller configured and / or programmed to control only one of the centrifuge and the spinning membrane separator drive unit, or both the centrifuge and the spinning membrane separator drive unit, to separate the blood into two or more blood components in a fluid flow circuit, or to separate the blood components into two or more subcomponents in a fluid flow circuit.

[0365] Aspect 24: The blood separation system of Aspects 22-23, including a first pump, a second pump, and a controller configured and / or programmed to control the centrifuge to separate the blood into two or more blood components, to control the first pump to recirculate a portion of one of the blood components through the fluid flow circuit into the centrifuge along with the blood entering the centrifuge, and to control the second pump to transport the other portion of the one of the blood components through the fluid flow circuit into a spinning membrane separator drive unit for separation of the other portion of the one of the blood components into two or more subcomponents.

[0366] Aspect 25. The blood separation device of any of Aspects 22-24, wherein the blood separation device includes an interface monitoring system associated with the centrifuge and including a light source configured to emit light through the centrifuge chamber and the separated blood components in the centrifuge chamber, and a light detector configured to receive at least a portion of the light emitted by the light source and cooperate with the controller to determine a position of an interface between two separated blood components in the centrifuge chamber.

[0367] Aspect 26. The blood separation system of aspect 25, wherein the light source comprises a laser.

[0368] Aspect 27. The blood separation system of any of Aspects 25-26, wherein the centrifuge is disposed within the centrifuge compartment, and the light source and the light detector are mounted to a stationary surface of the centrifuge compartment.

[0369] Aspect 28. The blood separation system of any of Aspects 25-27, wherein the photodetector is positioned and oriented to receive light traveling in a direction substantially perpendicular to the direction of light emitted by the light source.

[0370] Aspect 29. The blood separation system of any of Aspects 22-28, wherein the rotating membrane separator drive unit includes a top cap and a base, and at least one of the top cap and the base is movable relative to the other of the top cap and the base to accommodate different sized rotating membrane separators in the fluid flow circuit.

[0371] Aspect 30. The blood separation system of Aspect 22, wherein the blood separation apparatus includes at least one pump and an inlet sensor configured to optically detect a characteristic of a fluid in the fluid flow circuit to be separated in the spinning membrane separator, and the controller is configured and / or programmed to control operation of the at least one pump based at least in part on said characteristic of the fluid to be separated in the spinning membrane separator.

[0372] Aspect 31. The blood separation system of aspect 30, wherein the inlet sensor is configured to optically detect a hematocrit of the fluid to be separated in the spinning membrane separator.

[0373] Aspect 32. The blood separation system of aspect 30, wherein the inlet sensor is configured to optically detect a concentration of platelets in the fluid to be separated in the spinning membrane separator.

[0374] Aspect 33. The blood separation system of any one of Aspects 22-32, wherein the blood separation device includes an outlet sensor configured to optically detect a characteristic of the fluid exiting the spinning membrane separator.

[0375] Aspect 34. The blood separation system of aspect 33, wherein the outlet sensor is configured to optically detect whether the fluid exiting the spinning membrane separator is lipemic and / or hemolytic.

[0376] Aspect 35. The blood separation system of any of Aspects 22 to 34, wherein the blood separation apparatus includes a pump, the fluid flow circuit includes an in-process container, and the pump is configured to transport a portion of blood entering the fluid flow circuit from the blood source to the in-process container and to transport another portion of the transported blood entering the fluid flow circuit to the centrifuge chamber.

[0377] Aspect 36. The blood separation system of aspect 35, wherein the blood separation apparatus includes six peristaltic pumps, and the fluid flow circuit includes a centrifuge chamber, a spinning membrane separator, and a cassette including six tubing loops in fluid communication with the in-process container and configured to cooperate with the six different peristaltic pumps, respectively.

[0378] Aspect 37. The blood separation system of any of Aspects 22-34, wherein the blood separation apparatus includes a first pump and a second pump, the fluid flow circuit includes a reprocessing vessel, the first pump is configured to transport at least a portion of at least one blood component separated from the blood by the centrifuge chamber and / or the spinning membrane separator, and the second pump is configured to transport the at least a portion of the one of the blood components to the centrifuge chamber for separation of the at least a portion of the one of the blood components into two or more blood components.

[0379] Aspect 38. The blood separation system of Aspect 37, wherein the blood separation apparatus includes five peristaltic pumps, and the fluid flow circuit includes a centrifuge chamber, a spinning membrane separator, and a cassette including five tubing loops in fluid communication with the in-process container, each loop configured to cooperate with a different one of the five peristaltic pumps.

[0380] Aspect 39. The blood separation system of any of Aspects 22-37, wherein the fluid flow circuit includes a single blood access device configured to allow blood to be transported into the fluid flow circuit and to allow fluid to be transported out of the fluid flow circuit.

[0381] Aspect 40. The blood separation system of any of Aspects 22-34, wherein the fluid flow circuit includes a first blood access device and a second blood access device, the first blood access device configured to allow blood to be transported into the fluid flow circuit and the second blood access device configured to allow fluid to be transported out of the fluid flow circuit.

[0382] Aspect 41. The blood separation system of Aspect 40, wherein the blood separation device includes five peristaltic pumps and the fluid flow circuit includes a centrifuge chamber, a spinning membrane separator, and a cassette including five tubing loops in fluid communication with the first blood access device and the second blood access device, each configured to cooperate with a different one of the five peristaltic pumps.

[0383] Aspect 42 In the blood separation system of any one of Aspects 22 to 41, the centrifuge and the spinning membrane separator drive unit are configured to operate simultaneously.

[0384] Aspect 43. A method of separating blood comprising providing a blood separation apparatus including a centrifuge and a spinning membrane separator drive unit, attaching a fluid flow circuit to the blood separation apparatus, conveying blood through the fluid flow circuit, and separating at least a portion of the blood in the fluid flow circuit into two or more blood components using the centrifuge and / or the spinning membrane separator drive unit.

[0385] Aspect 44. The method of aspect 43, wherein separating at least a portion of the blood in the fluid flow circuit into two or more blood components using a centrifuge and / or a spinning membrane separator drive unit includes separating red blood cells from the blood using a spinning membrane separator drive unit.

[0386] Aspect 45. The method of aspect 44, further comprising separating and collecting red blood cells from the blood and conveying fluid out of the fluid circuit.

[0387] Aspect 46 The method of any of aspects 44-45, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at the same location.

[0388] Aspect 47. The method of any one of Aspects 44-46, further comprising simultaneously conveying a portion of the blood to an in-process container of the fluid flow circuit, conveying another portion of the blood to a spinning membrane separator drive unit for separating and collecting red blood cells from the other portion of the blood, and then conveying the portion of blood from the in-process container to the spinning membrane separator drive unit for separating and collecting red blood cells from the portion of the blood from the in-process container.

[0389] Aspect 48 The method of aspect 44, further comprising: conveying blood into the fluid flow circuit; and conveying fluid out of the fluid flow circuit.

[0390] Aspect 49. The method of any one of Aspects 44-48, further comprising delivering blood into the fluid flow circuit and delivering fluid out of the fluid flow circuit at a different location.

[0391] Aspect 50. The method of aspect 43, wherein separating at least a portion of the blood in the fluid flow circuit into two or more blood components using a centrifuge and / or a spinning membrane separator drive unit includes using a spinning membrane separator drive unit to separate and collect red blood cells and plasma from the blood.

[0392] Aspect 51. The method of aspect 50, further comprising separating and collecting plasma, or red blood cells and plasma simultaneously, from the blood and conveying the fluid out of the fluid flow circuit.

[0393] Aspect 52. The method of aspects 50-51, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at the same location.

[0394] Aspect 53 The method of any of Aspects 50-52, further comprising simultaneously conveying a portion of the blood to an in-process container of a fluid flow circuit and another portion of the blood to a spinning membrane separator drive unit for separation and collection of plasma, or red blood cells and plasma, from another portion of the blood, and then conveying the portion of the blood from the in-process container into the spinning membrane separator drive unit for separation and collection of plasma, or red blood cells and plasma, from the portion of the blood from the in-process container.

[0395] Aspect 54. The method of aspect 50, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit.

[0396] Aspect 55 The method of any of Aspects 50 and 54, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at a different location.

[0397] Aspect 56. The method of aspect 43, wherein separating at least a portion of the blood in the fluid flow circuit into two or more blood components using a centrifuge and / or a spinning membrane separator drive unit includes using a spinning membrane separator drive unit to separate and collect plasma from the blood.

[0398] Aspect 57. The method of aspect 56, comprising simultaneously separating and collecting plasma from the blood and transporting the fluid out of the fluid circuit.

[0399] Aspect 58. The method of any of Aspects 56-57, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at the same location.

[0400] Aspect 59. The method of any of Aspects 56-58, further comprising simultaneously conveying a portion of the blood into an in-process container of the fluid flow circuit, conveying another portion of the blood into a spinning membrane separator drive unit for separating and collecting plasma from another portion of the blood, and thereafter conveying the portion of the blood from the in-process container to the spinning membrane separator drive unit for separating and collecting plasma from the portion of the blood from the in-process container.

[0401] Aspect 60. The method of aspect 56, further comprising simultaneously conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit.

[0402] Aspect 61 The method of any of Aspects 56 and 60, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at a different location.

[0403] Aspect 62. The method of aspect 43, wherein separating at least a portion of the blood in the fluid flow circuit into two or more blood components using a centrifuge and / or a spinning membrane separator drive unit includes using a centrifuge and a spinning membrane separator drive unit to separate and collect red blood cells, platelets, and plasma from the blood.

[0404] Aspect 63. The method of aspect 62, further comprising simultaneously separating and collecting plasma and platelets, or red blood cells and platelets, from the blood and transporting the fluid out of the fluid circuit.

[0405] Aspect 64. The method of aspects 62-63, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at the same location.

[0406] Aspect 65. The method of any one of Aspects 62-64, further comprising simultaneously conveying a portion of the blood to an in-process container of the fluid flow circuit and another portion of the blood to a centrifuge and spinning membrane separator drive unit for separating and collecting red blood cells, platelets and plasma from another portion of the blood, and thereafter conveying another portion of the blood from the in-process container to the centrifuge and spinning membrane separator drive unit for separating and collecting plasma and platelets, or red blood cells and platelets, from said portion of the blood.

[0407] Aspect 66. The method of aspect 43, wherein separating at least a portion of the blood in the fluid flow circuit into two or more blood components using a centrifuge and / or a spinning membrane separator drive unit includes using a centrifuge and a spinning membrane separator drive unit to separate and collect platelets, or platelets and plasma, from the blood.

[0408] Aspect 67 The method of aspect 66, further comprising simultaneously separating and collecting platelets, or platelets and plasma, from the blood and transporting fluid out of the fluid flow circuit.

[0409] Aspect 68. The method of any of Aspects 66-67, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at the same location.

[0410] Aspect 69. The method of any of Aspects 66-68, further comprising simultaneously conveying a portion of the blood to an in-process container of the fluid flow circuit, conveying another portion of the blood to a centrifuge and spinning membrane separator drive unit for separating and collecting platelets, or platelets and plasma, from another portion of the blood, and thereafter conveying the portion of the blood from the in-process container to the centrifuge and spinning membrane separator drive unit for separating and collecting platelets, or platelets and plasma, from the portion of the blood from the in-process container.

[0411] Aspect 70. The method of any of Aspects 66-68, further comprising simultaneously separating and collecting the platelets and / or platelets and plasma, transporting the red blood cells and / or red blood cells and plasma separated from the blood to a reprocessing container in the fluid flow circuit, and thereafter transporting the red blood cells and / or red blood cells and plasma from the reprocessing container to a centrifuge and spinning membrane separator drive unit for separating and collecting the platelets and / or platelets and plasma from the red blood cells and / or red blood cells and plasma from the reprocessing container.

[0412] Aspect 71 The method of aspect 66, further comprising simultaneously conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit.

[0413] Aspect 72. The method of any of Aspects 66 and 71, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at a different location.

[0414] Aspect 73. The method of any of Aspects 43-72, wherein separating at least a portion of the blood in the fluid flow circuit into two or more blood components using a centrifuge and / or a spinning membrane separator drive unit includes simultaneously operating the centrifuge and the spinning membrane separator drive unit.

[0415] Aspect 74. A method of controlling a blood separation procedure comprising providing a blood separation apparatus including a pump, a centrifuge, and a spinning membrane separator drive unit, attaching a fluid flow circuit to the blood separation apparatus, controlling the pump to transport blood through the fluid flow circuit, and controlling the centrifuge and / or the spinning membrane separator drive unit to separate at least a portion of the blood in the fluid flow circuit into two or more blood components.

[0416] Aspect 75. The method of aspect 74, wherein controlling the centrifuge and / or spinning membrane separator drive unit to separate at least a portion of the blood in the fluid flow circuit into two or more blood components includes controlling the spinning membrane separator drive unit to separate red blood cells from the blood.

[0417] Aspect 76. The method of aspect 75, further comprising simultaneously separating and collecting red blood cells from the blood and conveying fluid out of the fluid circuit.

[0418] Aspect 77 The method of any of Aspects 75-76, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at the same location.

[0419] Aspect 78. The method of any of Aspects 75-77, further comprising simultaneously conveying a portion of the blood to an in-process container of the fluid flow circuit and another portion of the blood into the spinning membrane separator drive unit for separating and collecting red blood cells from the other portion of the blood, and thereafter conveying the portion of the blood from the in-process container into the spinning membrane separator drive unit for separating and collecting red blood cells from the portion of the blood from the in-process container.

[0420] Aspect 79. The method of aspect 75, further comprising simultaneously conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit.

[0421] Aspect 80 The method of any of Aspects 75 and 79, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at a different location.

[0422] Aspect 81. The method of aspect 74, wherein controlling the centrifuge to separate at least a portion of the blood in the fluid flow circuit into two or more blood components includes controlling a spinning membrane separator drive unit to separate and collect red blood cells and plasma from the blood.

[0423] Aspect 82. The method of aspect 81, further comprising simultaneously separating and collecting plasma, or red blood cells and plasma, from the blood and conveying the fluid out of the fluid flow circuit.

[0424] Aspect 83. The method of any of Aspects 81-82, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at the same location.

[0425] Aspect 84. The method of any of Aspects 81-83, further comprising simultaneously conveying a portion of the blood to an in-process container of the fluid flow circuit, conveying another portion of the blood to a spinning membrane separator drive unit for separating and collecting plasma, or red blood cells and plasma, from another portion of the blood, and thereafter conveying the portion of blood from the in-process container into the spinning membrane separator drive unit for separating and collecting plasma, or red blood cells and plasma, from the portion of the blood in the in-process container.

[0426] Aspect 85. The method of aspect 81, further comprising simultaneously conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit.

[0427] Aspect 86. The method of any of Aspects 81 and 85, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at a different location.

[0428] Aspect 87. The method of aspect 74, wherein controlling the centrifuge and / or spinning membrane separator drive unit to separate at least a portion of the blood in the fluid flow circuit into two or more blood components includes controlling the spinning membrane separator drive unit to separate and collect plasma from the blood.

[0429] Aspect 88. The method of aspect 87, further comprising simultaneously separating and collecting plasma from the blood and conveying the fluid out of the fluid flow circuit.

[0430] Aspect 89. The method of any of Aspects 87-88, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at the same location.

[0431] Aspect 90. The method of any of Aspects 87-89, further comprising simultaneously conveying a portion of the blood to an in-process container of the fluid flow circuit and another portion of the blood to a spinning membrane separator drive unit for separating and collecting plasma from another portion of the blood, and thereafter conveying the portion of the blood from the in-process container into the spinning membrane separator drive unit for separating and collecting plasma from the portion of the blood from the in-process container.

[0432] Aspect 91 The method of aspect 87, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit.

[0433] Aspect 92. The method of any of Aspects 87 and 91, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at a different location.

[0434] Aspect 93. The method of aspect 74, wherein controlling the centrifuge and / or spinning membrane separator drive unit to separate at least a portion of the blood in the fluid flow circuit into two or more blood components includes controlling the centrifuge and spinning membrane separator drive unit to separate and collect red blood cells, platelets, and plasma from the blood.

[0435] Aspect 94. The method of aspect 93, further comprising simultaneously separating and collecting plasma and platelets, or red blood cells and platelets, from the blood and conveying the fluid out of the fluid flow circuit.

[0436] Aspect 95. The method of any of Aspects 93-94, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at the same location.

[0437] Aspect 96. The method of any of Aspects 93-95, further comprising simultaneously conveying a portion of the blood to an in-process container of the fluid flow circuit, conveying another portion of the blood to a centrifuge and spinning membrane separator drive unit for separating and collecting red blood cells, platelets and plasma from another portion of the blood, and thereafter conveying the portion of the blood from the in-process container to a centrifuge and spinning membrane separator drive unit for separating and collecting plasma and platelets, or red blood cells and platelets, from the portion of the blood from the in-process container.

[0438] Aspect 97. The method of aspect 74, wherein controlling the centrifuge and / or spinning membrane separator drive unit to separate at least a portion of the blood in the fluid flow circuit into two or more blood components includes controlling the centrifuge and spinning membrane separator drive unit to separate and collect plasma platelets, or platelets and plasma, from the blood.

[0439] Aspect 98. The method of aspect 97, further comprising simultaneously separating and collecting platelets, or platelets and plasma, from the blood and conveying fluid out of the fluid flow circuit.

[0440] Aspect 99. The method of any of Aspects 97-98, further comprising conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit at the same location.

[0441] Aspect 100. The method of any of Aspects 97-99, further comprising simultaneously conveying a portion of blood to an in-process container of the fluid flow circuit, conveying another portion of the blood to a centrifuge and spinning membrane separator drive unit for separating and collecting platelets, or platelets and plasma, from another portion of the blood, and thereafter conveying the portion of blood from the in-process container to a centrifuge and spinning membrane separator drive unit for separating and collecting platelets, or platelets and plasma, from the portion of blood from the in-process container.

[0442] Aspect 101. The method of any of Aspects 97-99, further comprising simultaneously separating and collecting the platelets or the platelets and plasma, transporting the red blood cells or the red blood cells and plasma separated from the blood into a reprocessing container in the fluid flow circuit, and then transporting the red blood cells or the red blood cells and plasma from the reprocessing container to a centrifuge and spinning membrane separator drive unit for separating and collecting the platelets or the platelets and plasma from the red blood cells or the red blood cells and plasma from the reprocessing container.

[0443] Aspect 102. The method of aspect 97, comprising simultaneously conveying blood into the fluid flow circuit and conveying fluid out of the fluid flow circuit.

[0444] Aspect 103. The method of any of Aspects 97 and 102, further comprising conveying the blood into the fluid flow circuit and conveying the fluid out of the fluid flow circuit at a different location.

[0445] Aspect 104. The method of any of Aspects 74-103, wherein controlling the centrifuge and / or the spinning membrane separator drive unit to separate at least a portion of the blood in the fluid flow circuit into two or more blood components includes simultaneously controlling the centrifuge and the spinning membrane separator drive unit to separate at least a portion of the blood in the fluid flow circuit into two or more blood components.

[0446] Aspect 105. A method of separating blood, comprising conveying blood through a fluid flow circuit, separating at least a portion of the blood in the fluid flow circuit into two or more blood components using a centrifuge, and further separating at least a portion of one of the separated blood components into two or more subcomponents using a spinning membrane separator drive unit.

[0447] Aspect 106. The method of aspect 105, wherein separating at least a portion of the blood in the fluid flow circuit using a centrifuge into two or more blood components includes separating the blood into red blood cells and platelet-rich plasma, and further wherein separating at least a portion of one of the separated blood components into two or more subcomponents using a rotating membrane separator drive unit includes separating the platelet-rich plasma into plasma and a platelet concentrate.

[0448] Aspect 107. The method of any of Aspects 105-106, further comprising providing a blood separation device including a centrifuge and a spinning membrane separator drive unit.

[0449] Aspect 108. The method of any of Aspects 105-107, wherein separating at least a portion of the blood in the fluid flow circuit into two or more blood components using a centrifuge includes conveying a combination of the blood and a recirculated portion of one of the separated blood components to the centrifuge.

[0450] Aspect 109. The method of any of Aspects 105-108, wherein separating at least a portion of the blood in the fluid flow circuit into two or more blood components using a centrifuge includes separating and collecting red blood cells from said at least a portion of the blood using a centrifuge, and further wherein separating at least a portion of one of the separated blood components into two or more subcomponents using a rotating membrane separator drive unit includes separating and collecting plasma and platelet concentrate from the platelet-rich plasma using a rotating membrane separator drive unit.

[0451] Aspect 110. The method of any of Aspects 105-109, wherein conveying the blood through the fluid flow circuit includes conveying a portion of the blood into a container and another portion of the blood into a centrifuge.

[0452] Aspect 111. The method of aspect 110, further comprising conveying at least a portion of the blood in the container into a centrifuge, separating at least a portion of the blood from the container into two or more blood components using the centrifuge, and further separating at least a portion of one of the separated blood components from the container into two or more subcomponents using a spinning membrane separator drive unit.

[0453] Aspect 112. The method of aspect 111, wherein separating at least a portion of the blood from the container into two or more blood components using a centrifuge includes conveying a combination of the blood from the container and a recycled portion of one of the blood components separated from the blood from the container to the centrifuge.

[0454] Aspect 113. The method of any of Aspects 111-112, wherein separating at least a portion of the blood from the container into two or more blood components using a centrifuge includes simultaneously conveying separated red blood cells out of the fluid flow circuit, and further separating the blood components separated from the blood from the container using a spinning membrane separator drive unit into two or more subcomponents includes simultaneously collecting plasma and platelet concentrate.

[0455] Aspect 114. The method of aspects 111-112, wherein separating at least a portion of the blood from the container into two or more blood components using a centrifuge includes simultaneously collecting separated red blood cells, and further separating the separated blood components from the blood from the container using a spinning membrane separator drive unit into two or more subcomponents includes simultaneously collecting a platelet concentrate and conveying plasma out of the fluid flow circuit.

[0456] Aspect 115. The method of any of Aspects 105-114, further comprising conveying the additive solution through a leukoreduction filter, mixing the additive solution with the separated red blood cells, and passing the mixture of red blood cells and additive solution through the leukoreduction filter.

[0457] Aspect 116: The method of any of Aspects 105-108, wherein separating at least a portion of the blood from the container into two or more blood components using a centrifuge includes separating red blood cells from at least a portion of the blood and conveying at least a portion of the separated red blood cells into the container, and further separating the separated blood components from the blood from the container into two or more subcomponents using the rotating membrane separator drive unit includes separating plasma and platelet concentrate from the platelet-rich plasma using the rotating membrane separator drive unit, collecting at least a portion of the separated platelet concentrate, and conveying at least a portion of the separated plasma with the separated red blood cells into the container.

[0458] Aspect 117. The method of aspect 116, wherein conveying the blood through the fluid flow circuit includes conveying a portion of the blood to a container for processing and another portion of the blood to a centrifuge.

[0459] Aspect 118. The method of aspect 117, further comprising conveying at least a portion of the blood in the in-process container into a centrifuge, separating at least a portion of the blood from the in-process container into two or more blood components using the centrifuge, and further separating at least a portion of the blood components separated from the blood from the in-process container into two or more subcomponents using a spinning membrane separator drive unit.

[0460] Aspect 119. The method of aspect 118, wherein separating at least a portion of the blood from the in-process container into two or more blood components using a centrifuge includes conveying into the centrifuge a mixture of the blood from the in-process container and a recycled portion of one of the blood components separated from the blood from the in-process container.

[0461] Aspect 120. The method of any of Aspects 118-119, wherein separating at least a portion of the blood from the container during processing into said two or more blood components using a centrifuge includes simultaneously transporting separated red blood cells out of the fluid flow circuit, and further wherein separating at least a portion of one of the blood components separated from the blood from the container during processing using a spinning membrane separator drive unit into two or more subcomponents includes simultaneously collecting plasma and platelet concentrate.

[0462] Aspect 121 The method of any of Aspects 118-119, wherein separating at least a portion of the blood from the in-process container into two or more blood components using a centrifuge includes simultaneously conveying separated red blood cells out of the fluid flow circuit, and further separating at least a portion of one of the blood components separated from the blood from the in-process container into two or more subcomponents using a spinning membrane separator drive unit includes simultaneously collecting a platelet concentrate and conveying plasma out of the fluid flow circuit.

[0463] Aspect 122. The method of any of Aspects 105-108, wherein separating at least a portion of the blood in the fluid flow circuit into two or more blood components using a centrifuge includes simultaneously conveying separated red blood cells out of the fluid flow circuit, and further separating at least a portion of one of the separated blood components using a spinning membrane separator drive unit into two or more subcomponents includes simultaneously collecting a platelet concentrate and conveying plasma out of the fluid flow circuit.

[0464] Aspect 123. The method of any of Aspects 105-108, wherein separating at least a portion of the blood in the fluid flow circuit into two or more blood components using a centrifuge includes simultaneously transporting separated red blood cells out of the fluid flow circuit, and further separating at least a portion of one of the separated blood components into two or more subcomponents using a rotating membrane separator drive unit includes simultaneously collecting a platelet concentrate and plasma.

[0465] Aspect 124. The method of any of Aspects 105-123, further comprising transporting the at least a portion of one of the separated blood components from the centrifuge to a spinning membrane separator drive unit and optically detecting a characteristic of the at least a portion of one of the separated blood components.

[0466] Aspect 125. The method of aspect 124, wherein a concentration of platelets in at least a portion of one of the separated blood components is optically detected.

[0467] Aspect 126. The method of aspect 125, further comprising conveying the platelet concentrate from the spinning membrane separator drive unit at a volumetric flow rate based at least in part on a concentration of platelets in at least a portion of one of the separated blood components.

[0468] Aspect 127. The method of any of Aspects 105-126, wherein further separating at least a portion of one of the blood components separated using the spinning membrane separator drive unit into two or more subcomponents includes separating plasma from the at least one blood component using the spinning membrane separator drive unit, conveying at least a portion of the plasma out of the spinning membrane separator drive unit, and optically detecting a property of the plasma.

[0469] Aspect 128. The method of aspect 127, wherein optically detecting a characteristic of the plasma includes determining whether the plasma is lipemic and / or hemolytic.

[0470] Aspect 129. The method of any of Aspects 105-128, wherein further separating at least a portion of one of the separated blood components into two or more subcomponents using the spinning membrane separator drive unit includes simultaneously operating a centrifuge to separate at least a portion of the blood in the fluid flow circuit into two or more blood components, and operating the spinning membrane separator drive unit to further separate at least a portion of one of the separated blood components into two or more subcomponents.

[0471] Aspect 130. A method of controlling a blood separation procedure, comprising controlling a pump to transport blood through a fluid flow circuit, controlling a centrifuge to separate at least a portion of the blood in the fluid flow circuit into two or more blood components, and controlling a spinning membrane separator drive unit to further separate at least a portion of one of the separated blood components into two or more subcomponents.

[0472] Aspect 131. The method of aspect 130, wherein controlling the centrifuge to separate at least a portion of the blood in the fluid flow circuit into two or more blood components includes separating the blood into red blood cells and platelet-rich plasma, and controlling the spinning membrane separator drive unit to further separate at least a portion of one of the separated blood components into two or more subcomponents includes separating the platelet-rich plasma into plasma and platelet concentrate.

[0473] Aspect 132. The method of any of Aspects 130-131, further comprising providing a blood separation device including a centrifuge and a spinning membrane separator drive unit.

[0474] Aspect 133. The method of any of Aspects 130-132, wherein controlling the centrifuge to separate at least a portion of the blood in the fluid flow path into two or more blood components includes conveying a combination of the blood and a recirculated portion of one of the separated blood components into the centrifuge.

[0475] Aspect 134. The method of any of Aspects 130-133, wherein contr...

Claims

1. A centrifuge comprising a prismatic reflector, the prismatic reflector comprising: The inner and outer walls, a first end wall and a second end wall, the first end wall being inclined at approximately 45° relative to the second end wall; the prismatic reflector is formed of a light-transmitting material; the inner wall is configured to receive light traveling along an initial path and transmit the light to the first end wall; the first end wall is configured to receive light transmitted through the inner wall and direct the light toward the second end wall in a direction oblique to the initial path; The second end wall is configured to receive light from the first end wall and transmit light out of the prismatic reflector.

2. 2. The centrifuge of claim 1, wherein the first end wall, the inner wall, and the outer wall are configured to transmit light from the first end wall to the second end wall by total internal reflection.

3. 3. The centrifuge of claim 1 or claim 2, wherein at least a portion of the second end wall is roughened to diffuse light transmitted out of the prismatic reflector.

4. 1. A blood separation system comprising: a fluid flow circuit and a blood separation device; the fluid flow circuit includes a centrifuge chamber having an axis of rotation and having a defined groove between a low-g sidewall and a high-g sidewall; The blood separation device includes a centrifuge, an interface monitoring system, a light source, and a light detector; the centrifuge is configured to receive at least a portion of the centrifuge chamber and rotate the at least a portion of the centrifuge chamber about the axis of rotation; The interface monitoring system comprises: a light source configured to transmit light along an initial path toward the axis of rotation, into the centrifuge chamber, and through the groove of the centrifuge chamber; a photodetector configured to receive at least a portion of the light as it exits the centrifuge chamber; the centrifuge chamber includes a prismatic reflector associated with the low-g sidewall; the prismatic reflector is formed of a light-transmitting material and includes an inner wall, an outer wall, a first end wall, and a second end wall; the inner wall is configured to receive light traveling along an initial path and transmit the light to the first end wall; the first end wall is configured to receive light transmitted through the inner wall and direct the light toward the second end wall in a direction oblique to the initial path; The second end wall is configured to receive light from the first end wall and transmit light out of the prismatic reflector towards the light detector.

5. The blood separation system of claim 4 , wherein the first end wall is angled at about 45° relative to the second end wall.

6. 6. The blood separation system of claim 4 or claim 5, wherein the first end wall, the inner wall, and the outer wall are configured to transmit light from the first end wall to the second end wall by total internal reflection.

7. 3. The blood separation system of claim 1 or claim 2, wherein at least a portion of the second end wall is roughened to diffuse light transmitted out of the prismatic reflector.

8. 8. The blood separation system of claim 4, wherein the light detector is oriented to receive light traveling in a direction generally perpendicular to the initial path of the light.

9. At least a portion of the sidewall is formed entirely of a rigid, light-transmitting material; The blood separation system of claim 4 , wherein the light source is configured to transmit light through the sidewall.

10. 10. The blood separation system of claim 4, wherein the photodetector is oriented to receive light that has passed through the groove only once.

11. the blood separation device includes a centrifuge compartment in which at least a portion of the centrifuge is disposed; 11. The blood separation system of claim 4, wherein the light source and the light detector are mounted to a stationary surface of the centrifuge compartment.

12. 1. A method for detecting a position of an interface between separated fluid components in a groove of a centrifuge chamber having an axis of rotation, comprising: Separating a fluid within a groove of the centrifuge chamber into at least two fluid components; directing light along an initial path through the groove so as to intersect at least one of the fluid components; directing the light exiting the channel out of the centrifuge chamber; detecting at least a portion of the light exiting the centrifuge chamber; generating a signal indicative of a position of an interface of separated fluid components within the groove; A prismatic reflector is associated with the groove; the prismatic reflector is formed of a light-transmitting material and includes an inner wall, an outer wall, a first end wall, and a second end wall; the first end wall is inclined at approximately 45° relative to the second end wall; the inner wall is configured to receive light traveling along an initial path and transmit the light to the first end wall; the first end wall is configured to receive light transmitted through the inner wall and direct the light toward the second end wall in a direction oblique to the initial path; the second end wall is configured to receive light from the first end wall and transmit light out of the prismatic reflector toward the light detector and out of the centrifuge chamber.

13. The method of claim 12, wherein detecting at least a portion of the light exiting the centrifuge chamber comprises receiving light traveling in a direction generally perpendicular to the initial path of the light.

14. 14. The method of claim 12 or claim 13, wherein detecting at least a portion of the light exiting the centrifuge chamber comprises detecting light that has passed through the groove only once.

15. directing light along an initial path through the groove to intersect at least one of the fluid components includes emitting the light from a stationary position; 15. The method of claim 12, wherein detecting at least a portion of the light exiting the centrifuge chamber comprises detecting the at least a portion of the light in a stationary position.

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