Patent Publication Number: US-6706008-B2

Title: Automated system and method for withdrawing compounds from blood

Description:
The present invention relates, in general, to a highly versatile, automated system for processing blood, blood components, and other fluids included in such processing. More particularly, the present invention relates to an automated system that can separate blood into two or more blood components (“apheresis”), and then perform a further procedure involving one or more of the separated components. 
     The term “apheresis” means removing whole blood from a patient or donor and separating the blood into two or more components. A separated component can be collected from a healthy donor, and later transfused to a patient in need of the component. Apheresis is also used in therapeutic applications to treat illness by removing diseased or otherwise undesirable components from a patient. 
     In a basic apheresis procedure, blood is withdrawn from a donor through a needle inserted into the vein of a donor. The needle is attached to one end of a plastic tube which provides a flow path for the blood. The other end of the tube terminates in a container for collecting the blood. The collected blood is then separated in a separator, such as a centrifuge, into its components. The desired blood component which, depending on the procedure, can be red blood cells, platelets, plasma, white blood cells or stem cells may be collected and stored for later transfusion to a patient in need of the blood component. 
     More recently, “automated” apheresis systems have come into widespread use. These automated systems utilize disposable, pre-sterilized fluid circuits (i.e., tubing sets) through which the blood flows. The fluid circuits are mounted on re-usable hardware devices or modules that have pumps, valves, sensors and the like. These automated systems further include an internal computer and associated software programs (controller) which control many of the processing functions. 
     For example, in an automated system, blood flow through the fluid circuit, the operation of valves and pumps, may be monitored and regulated by the system. An automated system can be programmed to initiate, terminate or otherwise control certain functions based on patient or donor data (e.g., height, weight, sex, hematocrit). Likewise, an automated system may monitor certain functions with the aid of sensors which can, for example, sense the amount of the collected or withdrawn component. Optical sensors are used to measure the clarity or content of a fluid, or sense the presence or absence of certain components. 
     Automated apheresis systems are available from several different manufacturers. Examples of commercially available apheresis systems include the AUTOPHERESIS C® Cell Separator and the ANICUS® Cell Separator, sold by Baxter Healthcare Corporation of Deerfield, Ill. The AUTOPHERESIS C® utilizes a separator that includes a chamber and rotating membrane. Blood is introduced into the chamber and the membrane separates the blood into (at least) plasma and red blood cells, or other plasma-depleted blood. 
     The AMICUS® Cell Separator utilizes a centrifugal separation principle. In the AMICUS® Separator, whole blood is introduced into a dual-chambered or single-chambered container mounted on a rotatable centrifuge. Whole blood is introduced into the first chamber where red blood cells are separated from platelet-rich plasma (PRP). The PRP flows into a second chamber where it is further separated into platelets and platelet-poor plasma. The disposable fluid circuit of AMICUS® uses preformed cassettes with flow paths defined therein, which is mounted on the AMICUS® device. Flow through the flow path is assisted by peristaltic pumps. A more detailed description of the AMICUS®Separator is provided in U.S. Pat. No. 5,868,696, which is incorporated herein by reference. 
     Recently, a more, portable automated apheresis system has been developed by Baxter Healthcare Corporation. As described in U.S. Pat. No. 6,325,775 entitled “Self-Contained Transportable Blood Processing Device,” which is incorporated herein by reference, the portable apheresis system is also based on the principle of centrifugal separation. It includes a re-usable hardware module and a disposable fluid circuit. The fluid circuit includes a cassette with pre-formed flow paths, valving stations and pumping stations. 
     Other manufacturers such as Gambro BCT, Haemonetics, Dideco and Fresenius also provide automated apheresis systems based on centrifugal or other separation principles. 
     While efforts continue to develop and provide more efficient, economical and easy-to-use apheresis systems, concerns about the availability and safety of the blood supply, as well as an increased understanding of the role of certain blood components and blood related diseases, have led to the development of additional blood related procedures. These additional procedures often include treatment of the blood component so as to provide a safer or more viable component. Some of the additional procedures may involve eradication or removal of undesired compounds or other substances from blood. Some of these additional procedures may involve replacement of component with another solution. In any case, these procedures often involve many manual steps, several different pieces of equipment or complex fluid circuits. Thus, there exists a need for an automated system that, in addition to separating blood into its components, can carry out one or more other procedures involving the separated components and/or the treatment thereof. 
     Thus, it would be desirable to provide an automated system that can perform additional procedures using a single piece of re-usable hardware and an easy-to-load, easy-to-use disposable that eliminates the need for many tubing connections and complex routing of tubing. It would also be desirable to provide a single system that does not require regular operator intervention to perform the selected separation and other treatment or processing steps. It would also be desirable to provide a system where all desired separation and processing steps are performed within a single integrated system, and “off-line” treatment using separate devices is not required. It would also be desirable to provide a system that can perform multiple fluid separation, processing and/or treatment steps through automated control of flow through the fluid circuit. 
     One application where automated separating and processing of blood may be desirable is in the automated pre-surgical donation of blood and administration of a replacement fluid such as a blood substitute and/or oxygen carrier. A manual version of this process is described in U.S. Pat. No. 5,865,784, incorporated herein by reference. 
     Another application where automated separating and processing blood may be desirable is in the salvaging of red blood cells during surgery on a patient. In cell salvage, blood from a wound area or from the body cavity (i.e., extra-vascular or “shed” blood) that would otherwise be lost, is collected, processed (or cleaned), and the cleaned blood is returned to the donor. Examples of systems and apparatus used for cell salvage are described in U.S. Pat. No. 5,976,388, which is incorporated herein by reference. 
     Another application where separating and processing blood may be desirable is in the removal of unwanted substances from blood or a separated blood component such as plasma. For example, the role of cholesterol and low density lipids (LDL) in cardiovascular disease has been well documented. Methods for lipid removal from the plasma of a patient have been developed and are disclosed in U.S. Pat. Nos. 4,895,558, 5,744,038 and 5,911,698, which are incorporated herein by reference. 
     Still another application where separating and processing blood may be desirable is in the treatment of blood cells. In a particular application, it may be desirable to treat separated red blood cells with enzymes to, for example, convert Type A, B and AB blood cells to the universally acceptable Type O blood cells. Examples of such methods are described in U.S. Pat. Nos. 6,175,420 and 5,671,135, which are incorporated by reference herein. 
     As described below, there may be additional applications where it may be desired to separate blood into its components for further treatment and/or processing. 
     Thus, it would be desirable to provide a single system that, in addition to having the ability of withdrawing whole blood and separating it into two or more components, is programmed for, adaptable for, and capable of carrying out at least two or more applications. 
     SUMMARY OF THE INVENTION 
     In one aspect, the present invention is directed to an automated system for withdrawing a selected compound from the blood of a patient. The automated system includes a sterile, preassembled, disposable fluid circuit that includes means for withdrawing blood from a patient. The fluid circuit further includes a separation chamber that includes a first sub-chamber for separating a blood component from blood and a second sub-chamber for separating a combination of the blood component and a solvent into a first phase which substantially includes a compound-depleted blood component and a second phase that substantially includes the solvent and the compound. 
     The fluid circuit further includes a container containing a solvent where the solvent is adapted for extracting a selected compound from the blood component, and means for combining the solvent with the blood. Solvent removal means and means for returning the compound-depleted blood component to the patient are provided. 
     The fluid circuit further includes a flow control cassette having preformed flow path segments formed therein and separated by valve stations for controlling communication between the segments. 
     The automated system also includes a re-usable device that includes a means for receiving the chamber and for separating the blood component from the remainder of the blood. The re-usable module also includes means for cooperating with the valve stations to control the flow of the fluid through the preformed flow paths. 
     In a further, more particular aspect, the fluid circuit may include a first separation means based on a first separation principle for separating (from blood) a blood component including a compound, and a second separation means based on a second separation principle for separating the combination of the blood component and solvent into first and second phases. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a diagram showing the re-usable hardware component or module of the present invention and some of the available disposable fluid circuits for use therewith. 
     FIG. 2 is a perspective view of a automated system that may be employed with the present invention, including the re-usable component and the disposable fluid circuit. 
     FIG. 2A is an enlarged, perspective view of the separation chamber of the fluid circuit of FIG. 2 which can be employed in the automated system of the present invention. 
     FIG. 3 is a perspective view of an automated system that may be employed with the present invention with a disposable fluid circuit mounted on the re-usable device. 
     FIG. 4 is a plane view of the front side of a cassette of the fluid circuit of FIG.  2 . 
     FIG. 5 is a plane view of the back side of the cassette shown in FIG.  4 . 
     FIG. 6 is a flow diagram showing the steps performed in the operation of the automated system of the present invention. 
     FIG. 7 depicts the fluid circuit for a system and procedure embodying the present invention. 
     FIG. 8 depicts the fluid circuit for an automated hemodilution system and procedure embodying the present invention. 
     FIG. 9 depicts the fluid circuit for an automated plasma treatment system and procedure embodying the present invention. 
     FIG. 10 depicts the fluid circuit for an automated cell treatment system and procedure embodying the present invention. 
     FIG. 11 depicts the fluid circuit for an automated cell salvage system and procedure embodying the present invention cell salvage procedure. 
     FIG. 12 depicts the fluid circuit for an alternative automated plasma treatment system and procedure embodying the present invention. 
     FIG. 12A is a perspective view of an automated system that may be employed with the present invention with a disposable fluid circuit including a separation column mounted on the re-usable component. 
     FIG. 13 is a perspective view of the re-usable component of an alternative automated system that may be employed with the present invention. 
     FIG. 14 is a perspective view of a fluid circuit for use with the re-usable device of FIG.  13 . 
     FIG. 15 is a perspective view of the fluid circuit shown in FIG. 14 mounted on the re-usable component. 
     FIG. 16 is an enlarged perspective view of a separation chamber of the fluid circuit of FIG.  14 . 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Turning now to the drawings, FIG. 1 diagrammatically shows a multi-purpose blood and fluid processing system  10  embodying the present invention. 
     As generally shown in FIG. 1, automated system  10  includes a re-usable hardware component or module  12 . The re-usable hardware component  12  is particularly versatile and may be used with a variety of disposable fluid circuits. Thus, for example, hardware component  12  can be used with fluid circuits for red blood cell collection, plasma collection, platelet collection, white blood cell (leukocyte) collection, stem cell collection, hemodilution, cell salvage, lipid removal from plasma, conversion of red blood cells, cell washing, red blood cell exchange, leukoreduction, other therapeutic plasma treatments and, as will be seen, combinations of such procedures. 
     One embodiment of the automated, multi-purpose blood and fluid processing system that may incorporate the present invention is shown in FIG.  2 . As shown in FIG. 2, automated system  10  includes a re-usable module  12  and a disposable fluid circuit  50  for use in association with re-usable component  12 . 
     Fluid circuit  50  includes an array of tubing and interconnected containers typically made of a sterilizable, plastic material. Fluid circuit  50  is intended for a single use (i.e., disposable, not re-usable). As shown in FIG. 2, fluid circuit  50  includes a venipuncture needle  54  for insertion into the vein of the donor or patient. This needle  54  is attached to tubing, which provides a flow path for the blood withdrawn from the donor or patient. Needle  54  can also be used to return selected components to a donor or patient in a so-called “single-needle procedure. Alternatively, circuit  50  may use a “double-needle” configuration, known to those of skill in the art, where separate needles are used for withdrawal and return. 
     As shown in FIG. 2, fluid circuit  50  includes several containers for temporary and/or longer-term storage of the separated components, and for holding fluids used during the procedure, such as an anticoagulant, saline, and any other treatment or replacement fluids required for the procedure. Containers  56 ,  57 ,  58 ,  60 ,  62 ,  64 , and  66  are also typically made of a sterilizable, plastic material. 
     Fluid circuit  50  further includes separation chamber  68 . Separation chamber  68  is intended for mounting on the separator of the re-usable device  12 . As shown generally in FIG. 2, and in more detail in FIG. 2A, in one embodiment, separation chamber  68  may be pre-formed by injection molding from a rigid, biocompatible plastic material, such as a non-plasticized medical grade acrilonitrite-butadiene-styrene (ABS). 
     As further shown in FIG. 2A, separation chamber  68  includes a base  388  with a center hub  120 . Hub  120  is surrounded radially by inside and outside annular walls  122  and  134 , which define a circumferential blood separation channel  126 . Alternatively, chamber  68  may include first and second sub-chambers. The bottom of channel  126  is closed by a molded annular wall. The top of channel  126  is closed by a separately molded flat lid (not shown), which can be secured to the top of chamber  68  by welding or other securing means. 
     Chamber  68  also includes passageways  142 ,  144  and  146 , which extend from hub  120  and communicate with channel  126 . During processing, blood is introduced into passageway  146  at the underside of base  388  via an attached multi-lumened tube or umbilicus  69  (shown as in FIG.  2 ). Blood enters the channel  126  where it is separated into heavier and lighter components. The heavier components occupy the outer periphery of the channel, while the lighter component occupies the channel interior. The separated components are withdrawn through passageways  142  and  144 . Introduction and separation of blood using chamber  68  is described in more detail in U.S. Pat. No. 6,325,775, previously incorporated by reference. 
     Fluid circuit  50  further includes a cassette  70  which provides a network of flow path segments in fluid communication with and in association with numerous valving and pumping stations. Cassette  70  provides a centralized, programmable, integrated platform for all the pumping and valving functions required for a given blood processing procedure. A more detailed view of cassette  70  is provided in FIGS. 4 and 5. Cassette  70  interacts with the pneumatically actuated pump and valve station  30  on re-usable module  12  described below. 
     As shown in FIGS. 4 and 5, cassette  70  has an array of interior cavities formed on both the front and back sides. The interior cavities define the valve stations and flow paths. Pump stations PP 1  to PP 4  are formed as wells that are open on the front side of the cassette  70 . The valves V 1  to V 23  are likewise formed as wells that are open on the front side of cassette  70 . The liquid flow paths F 1  to F 38  are formed as elongated channels that are open on the back side of cassette  70 , except for liquid paths at F 15 , F 23 , and F 24 , which are formed as elongated channels that are open on the front side of the cassette  70 . The pre-molded ports P 1  to P 13  extend out along two side edges of the cassette  70 . As shown in FIG. 3, the cassette  70  is vertically mounted for use in the pump and valve station  30  described below. In this orientation, ports P 8  to P 13  face downward, and the ports P 1  to P 7  are vertically stacked one above the other and face inward. 
     Cassette  70  is preferably made of a rigid, medical grade plastic material. Flexible diaphragms overlay both of the front side and back side of cassette  70 . The diaphragms are preferably made of flexible sheets of medical grade plastic. The diaphragms are sealed about their peripheries to the peripheral edges of the front and back sides of cassette  70 . Interior regions of the diaphragms can also be sealed to interior regions of the cassette body. 
     The action of the pump and valve stations is controlled by a pneumatic pressure source which supplies negative and positive air pressure. As shown generally in FIG.  2  and described in more detailed in U.S. Pat. No. 6,325,775, under the control of the controller  11 , a pneumatic pressure source selectively distributes the different pressure and vacuum levels to the pump and valve stations. These levels of pressure and vacuum are systematically applied to the cassette  70  to route blood and processing fluids. The details of the cassette, the pump and valve station  30 , and the transport of blood and processing fluids through the cassette are set forth and described in U.S. Pat. No. 6,325,775, previously incorporated by reference. 
     Turning now to the re-usable hardware component or module, re-usable component  12  includes (at least one) means for effecting separation of blood components or “separator”  20 . In one embodiment, separator  20  is cooperatively associated with the chamber  68  of the fluid circuit. In a more particular embodiment, separator  20  is adapted to receive the separation chamber of the fluid circuit (described above) and effects separation of whole blood or a blood fraction into two or more components. In a preferred embodiment, separator  20  may be a rotatable centrifuge. However, it will be understood that separator  20  is not limited to a separator that utilizes a centrifugal separation principle. Accordingly, separator  20  may employ a different separation principle, such as a magnetic drive for receiving a spinning membrane as described, for example, in U.S. Pat. No. 5,194,145. In another embodiment, separator  20  may also be a separation column with its own integral chamber or passageway. Separator  20  may also be a filter. In the preferred embodiment, where separator  20  is a centrifuge, the spinning action of the centrifuge separates the blood components (within separation chamber  68 ) by density. For example, the spinning action of the centrifuge can separate whole blood into the more dense red cell component and a less dense plasma component. 
     Re-usable component  12  also houses the internal computer or controller  11 . The programmable controller includes pre-programmed instructions for carrying out several different blood and fluid processing procedures, allowing the operator to select from a menu, the particular procedure or procedures desired. The controller also includes pre-programmed instructions which selectively activate pumping of fluid and the opening and closing of valves in the fluid circuit described above. The controller may also include data storage capability for storing donor/patient information, processing or collection information and other data for later downloading or compilation. 
     As further shown in FIG. 2, re-usable device  12  includes a control panel such as flat screen display  24  for displaying the status of the procedure as well as providing a touch panel screen to allow for operator interface with the system. Data output capability may also include standard parallel or serial ports or other network connection capability, as desired, for communication with other computers or networks. 
     Device  12  further includes pump and valve station  30 . As indicated above, pump and valve station  30  is designed to mate with corresponding structures of cassette  70 . Pump and valve station  30  contains four pump actuators PA 1  to PA 4  and twenty-three valve actuators VA 1  to VA 23 . The pump and valve actuators are oriented to form a mirror image of the pump stations PP 1  to PP 4  and valve stations V 1  to V 23  of cassette  70 . During operation, pump and valve station  30  (and, more specifically, pump and valve actuators PA(N) and VA(N)), apply positive and negative pressure upon cassette  70  and the corresponding pump and valve stations therein, to direct liquid flow through the flow path segments defined therein. Access to pump and valve station  30  is obtained through door  34 . 
     All of the above-described parts of re-usable device  12 , such as separator  20 , controller  11 , pump and valve station  30 , and display screen  24  are mounted inside a portable housing or case  38 . Case  38  is suited for set-up and operation upon a table top or other smooth and flat surface. Case  38  includes a base  39  and hinged lid  40  which opens and closes. Lid  40  includes latch  42  for releasably locking the lid. Lid  40  further includes a handle  44 , which the operator can grasp for easy transport of case  38  to a collection site, hospital, etc. Case  38  is made by molding and, preferably, of a light-weight, durable plastic material. 
     For supporting containers in a hanging position, lid  40  includes hooks (not shown) for hanging containers of saline, anticoagulant or other treatment or processing fluid. Similarly, a retractable hanger  45  is provided for supporting one or more collection containers in which whole blood and/or separated blood components are (at least temporarily) stored. Hanger  45  and hooks are preferably mounted on a scale  47  within lid  40  to allow automated measurement of the amount of whole blood or blood component collected. 
     Inclined container support surface  48  provides additional areas within the case for supporting containers associated with the disposable circuit  50 . One or more areas of the support surface  48  may be heated, if desired, to warm the solution of the container prior to infusion to the donor or patient. 
     As discussed above, controller  11  includes a micro-processor and pre-programmed software. Although some interface and involvement by the operator is required, many of the functions of the automated system  10  are automatically controlled by controller  11 . 
     For example, as shown in FIG. 6 after the operator turns on the power to the re-usable device  12 , the system automatically undergoes a system check procedure to confirm that all electrical and mechanical components of the device  12  are functioning properly and within preset parameters. If during the system check the controller detects a problem, the system may generate an audible alarm which prompts the operator to intervene. If the system successfully completes the system check, the system may prompt the operator to select the desired procedure. 
     As shown in FIG. 6, the automated system allows the operator to select from a variety of procedures. For example, the operator may select a red cell collection (apheresis) procedure, a plasma collection procedure a platelet collection procedure, a white blood cell collection procedure, a stem cell collection procedure. 
     In addition, the operator may select from a one or more other additional procedures. Thus, the operator can select a first procedure to separate whole blood into two or more components, and also instruct the system to perform another additional treatment or other processing procedure including the separated component(s). Alternatively, the operator may directly select one of the additional procedures, which already combines aspects of the above-mentioned apheresis procedures with additional “downstream” blood processing and/or treatment protocols. 
     As shown in FIG. 6, these additional procedures include procedures for hemodilution, plasma treatment, such as lipid removal, the conversion of cells, cell salvage and other procedures including, but not limited to, therapeutic plasma treatments, removal of certain compounds from plasma using monoclonal antibodies, magnetic, para-magnetic, and other beads. Additional supplemental procedures involving the separated components of blood may also be performed. 
     In any event, once the operator has selected the desired procedure, under the control of the controller  11 , the system prompts the operator to load the appropriate fluid circuit. Referring back to FIG. 1, it is shown that re-usable device  12  is adapted to receive any one of a variety of disposable fluid circuits. Each of the enumerated procedures may require its own unique disposable fluid circuit or, more preferably, a disposable fluid circuit will be suitable for two or more procedures. 
     Most of the disposable fluid circuits will have many common elements such as a venipuncture needle, anticoagulant container, saline container, storage containers for red blood cells, plasma or whole blood, a separation chamber and the cassette  70 . As mentioned above, each procedure may have its own unique disposable fluid circuit. However, it is also possible that a universal fluid processing circuit can be used and any additional required containers of fluid (e.g., treating agents), additional separators or other components can be easily attached at the time of use. These additional fluid circuit components can be connected to the universal set in a sterile manner in ways that are well known to those of skill in the art. Any additional tubes or flow paths can be attached to existing ports (e.g., P 13 ) on the cassette and the system programmed to perform the additional procedures. 
     The versatility of the cassette, with its flow path segments that can be interconnected in a variety of ways through selective opening and closing of valves coupled with the programmable microprocessor in the controller lends itself particularly well to the automated system of the present invention. It allows the system to be used with different fluid circuits, to perform a variety of different procedures or protocols, and allows the system to combine aspects of apheresis with additional downstream treatment or processing of blood components. 
     Once the fluid circuit  50  has been mounted on the re-usable device  12 , the system, under the control of the controller  11 , will verify that the correct disposable has been loaded and/or that it has been loaded properly. Once proper loading of the disposable processing circuit has been confirmed, the system will automatically initiate a priming sequence based on the selected protocol. Typically, the priming sequence will include priming the fluid circuit with anticoagulant and/or saline. In addition, if a particular treatment or replacement fluid is intended for use in a particular procedure, the system may also prime the disposable fluid circuit with such fluid or the patient&#39;s or donor&#39;s blood. 
     The system may allow the operator to enter desired patient or donor data, such as height, weight, gender, hematocrit, or any other donor or patient characteristic that the controller may utilize during the course of the procedure. Entry of donor data may occur before or after prime. For example, the system may use the above-described donor data to determine flow rates, and/or duration of a particular step. After prime and entry of any required donor data, the system prompts the operator to begin the procedure. 
     FIG. 7 shows an automated system embodying the present invention including a typical fluid circuit. As shown in FIG. 7, whole blood is withdrawn from donor  100  and introduced into cassette  70  via line (tubing)  74 . Anticoagulant from container  56  is likewise drawn into cassette  70 . Anticoagulant enters through one of the ports (e.g., P 10 ) of cassette  70 . Controller opens the selected valve(s) to allow anticoagulant flow through the fluid segment, and establishes flow communication between the anticoagulant line  75  and line  74  to combine anticoagulant with the whole blood being withdrawn from the patient. 
     Anticoagulated whole blood is introduced into container  58 , which serves as an interim whole blood source. As described above, the hardware component  12  can include weight scales. Thus, container  58  is suspended from a weight scale so that when the required amount of whole blood is collected a sensor attached to the weight scale prompts the controller and the draw cycle is terminated. The controller then initiates pumping (by controlling the pump and valve station) of whole blood from container  58  into the separator. 
     The separator separates whole blood into two or more components. (It will be understood that the separator may be cooperatively associated with separator chamber  68  of the fluid circuit, either physically or as described in, for example, U.S. Pat. No. 5,194,145, incorporated herein by reference.) In one embodiment, separation of whole blood results in a plasma component and a red blood cell component. The separated plasma and red cell components may be withdrawn from separation chamber  68  and collected in separate containers  60  and  62  for temporary storage. 
     At this point, depending on the procedure or protocol selected (see FIG.  6 ), further processing of one or both of the separated components may be initiated by the system. Thus, for example, if the additional procedure involves treatment of the separated component, fluid circuit  50  may include a treatment fluid container  64 . In another embodiment, if the additional procedure requires administration of a replacement fluid (to, for example, provide the biological function of the withdrawn component), container  64  may include a replacement fluid. 
     In any event, further processing or treatment of the separated component may take place in separation chamber  68 , one of the containers  60  or  62 , or, if required, a second and separate separator (shown in dashed lines in FIG.  7  and labeled “Separator  2 ”). The second separator may utilize the same separation principle as Separator  1 . Thus, in one embodiment, both Separators  1  and  2  may be centrifuges. In another embodiment, one of the separators may be a centrifuge while the other separator may be a drive mechanism for cooperation with a rotating member and separation membrane of the type described in U.S. Pat. No. 5,194,145. In another embodiment, one of the separators may be a centrifuge or a drive for a rotating membrane and the other separator can be a filter medium or a separation column. 
     The blood component separated in Separator  1  can be directly introduced into Separator  2  for further treatment and/or processing. Alternatively, blood component can be introduced into cassette  70  from where it can be directed and/or pumped into Separator  2 . Likewise, upon exiting Separator  2 , the separated (and/or treated) component can be directly reinfused back to the donor, as shown by dashed line  87 , or through cassette  70  and return line  84 . 
     Although FIG. 7 shows a single vein access point (i.e., single needle) for withdrawal of blood and return of blood component, it will be understood that the fluid circuit shown in FIG. 7 (or any one of the other FIGS. 8-12) may also utilize a so-called “double-needle” configuration described above. 
     Once treatment is complete, the desired component (red blood cells or plasma) can be returned to the donor or patient via line  84 . As will be described below, depending on the procedure, there may be variations to the general separation and processing sequence described above. 
     A more particular example of a system embodying the present invention is shown in FIG.  8 . FIG. 8 shows an automated system and procedure for the automated pre-surgical withdrawal of blood, separation into plasma and red blood cells, followed by the return of plasma and infusion of one or more replacement fluids (i.e., “hemodilution”). 
     A system of the type shown in FIG. 8 is particularly useful in the collection of autologous blood from a patient just prior to a surgical procedure. The plasma component is returned and is supplemented with a volume replacement fluid (such as saline) and a blood substitute which can provide the same biological function (i.e., oxygen transport) as the collected red blood cells. 
     As shown in FIG. 8, whole blood is withdrawn from a patient just prior to the surgical procedure. The whole blood is withdrawn through line  74  and introduced into cassette  70  in the manner generally described above. 
     Whole blood is combined with anticoagulant and the anticoagulated whole blood may be introduced into container  58  or immediately introduced into the separator. Once inside the separator and, more particularly, the separation chamber  68  associated with the separator, whole blood is separated into a red blood cell component and a plasma component. The red cell component is removed from the separator (by pumping of the pump stations in the cassette  70 ) and collected in container  60  where it is stored until needed (if needed) during or after surgery. If long-term storage of red cells is required, the collected red cells may be combined with a red blood cell preservative solution such as ADSOL® or Erythro-Sol, available from Baxter Healthcare Corporation of Deerfield Ill. Administration of a preservative (stored, for example, in container  57  (FIG. 2) can also be controlled by controller  11 . 
     The separated plasma can be introduced into container  62  from where it can be metered back to the patient during surgery or, in the alternative, immediately returned to the patient. In another alternative, plasma (with platelets) may be returned to the patient after surgery, at or around the time that the red blood cells are returned. 
     In order to compensate for the lost volume of red blood cells, a volume replacement fluid such as saline may also be administered to the patient. In addition, because red blood cells include hemoglobin, an oxygen carrying compound in blood, a blood substitute or other synthetic oxygen carrying compound that can perform the same oxygen transport function as the red blood cells may also be administered to the patient. Such blood substitutes and/or oxygen carrying compounds are known and are available from Alliance Pharmaceutical Corporation of San Diego, Calif., and are described in U.S. Pat. No. 5,865,784. Other blood substitutes known to those of skill may also be used. 
     The blood substitute may be combined with the saline or administered separately either before or after administration of the saline. In addition, other volume replacement fluids in lieu of saline (which is a crystalline solution) may also be used as the volume replacement fluid. This includes colloidal solutions, such as dextran and albumin. 
     In accordance with a present invention, the system  10  can automatically determine the amount and flow rate of the fluids, i.e., saline and a blood substitute required. In one embodiment, the controller can be pre-programmed to administer the selected amount of saline or other fluid and a replacement fluid having a known biological function, such as a blood substitute, based on the amount of the red blood cells collected as measured by the weight scale  47  in hardware component  12 . Alternatively, the system can determine the amount (and flow rate) of the replacement fluid to be administered based on the amount of whole blood withdrawn. In still another alternative, the system can determine the amount of replacement fluid and blood substitute to be administered based on donor data entered at the beginning of the procedure. In any event, the automated system of the present invention provides benefits that manual hemodilution cannot achieve. 
     For example, by separating whole blood into red cells and plasma, and returning the plasma to the patient, the extra-corporeal volume of blood is reduced as compared with the manual systems where whole blood is withdrawn. This results in several benefits not available in “manual” hemodilution. 
     In the manual hemodilution procedure, the homoglobin concentration of the blood is reduced from approximately 12 mg/dl to 9 mg/dl by withdrawing blood and administering support fluid (3 times the saline or albumin). This represents a total whole blood volume removed of approximately 1L. To replace this lost volume either 1L of albumin or 3L of saline would have to be administered. Three times the volume of saline is necessary due to salinels limited ability to stay within the vascular space. Albumin, being a molecule of larger size, can stay within the vascular space and will not be as quickly excreted as saline. 
     In accordance with the present invention, because the plasma component is returned to the patient, the volume of fluid removed would be limited to the red blood cell volume which would be approximately 400 ml (based on an average, hematocrit of 40%). When 1L of whole blood is removed with a 40% hematocrit, the total volume of red blood cells removed is 400 ml, with the remaining 600 ml consisting of plasma. To remove an equal amount of red blood cells using the automated system and procedure would require the removal of only 400 ml of concentrated red blood cells with all of the plasma processed by the system being returned to the patient. This reduces the volume removed by 60%. To replace this, only 400 ml of albumin or 1,200 ml of saline would be necessary. This is substantially less than the typical manual hemodilution procedure. 
     By reducing the volume of saline administered, any potential fluid complication caused by saline can be reduced. Saline can cause fluid overload and tissue edema in patients with renal insufficiency. A large volume saline infusion and associated increase in tissue fluid can necessitate the need for diuretic administration to assist in fluid removal after the surgical procedure. 
     Another advantage of the automated system of the present invention is that the system can be programmed by the anesthesiologist and the procedure accomplished automatically. The system can add the appropriate amount of anticoagulant to the blood to prevent clotting in the blood storage container and red cell additive solutions can be used as necessary. 
     Citrate anticoagulation can cause some citrate reactions in patients during apheresis procedures. Citrate reactions are usually controlled by infusion of calcium containing solutions. Using the automated system of the present invention, when the collected blood products are transfused back to the patient, the minimum amount of anticoagulant will be present in the collected blood which, upon transfusion, should cause fewer complications due to citrate transfusion compared to the manual method. 
     By reducing the volume of fluid removed, the time until blood is to be administered may be prolonged. More importantly, this automated system and procedure can reduce or eliminate the need for non-autologous blood. By eliminating or reducing the need for non-autologous blood, the patient can have limited exposure to non-autologous homologous blood. This can reduce the possibility of post transfusion immunosuppression or inflammatory response due to transfusion of stored blood (cytokine generation during storage). 
     The automated system of the present invention will allow for the plasma (and platelets) to be returned to the patient. By returning the plasma (and platelets), the patient can more easily maintain normal hemostasis. (In the standard manual hemodilution procedure, severe dilution can cause hemostasis problems which may require infusion of cryoprecipitated clotting proteins (cryoprecipitate) or fresh frozen plasma (FFP). This also occurs during the manual procedure because whole blood is removed which removes platelets and plasma as well as RBC&#39;s.) 
     FIG. 9 shows another application of the automated system of the present invention. In particular, FIG. 9 shows a procedure that results in removal of undesired compounds from blood plasma. More particularly, the fluid circuit and flow system shown in FIG. 9 can be used for removal of lipids from the plasma of the patient. 
     As shown in FIG. 9, whole blood is withdrawn from a patient  100  via venipuncture and allowed to flow through line  74  into cassette  70 , and combined with anticoagulant as previously described. The anticoagulated whole blood may be collected in container  58  until a selected weight is attained. Once the desired amount of whole blood has been collected, under control of the controller  11 , the system introduces whole blood into the separator, which can include or is otherwise cooperatively associated with separation chamber  68 , where it is separated into red blood cells and plasma. The separated red blood cells may then be returned to the patient immediately, or temporarily stored in container  60  for later return. 
     The separated plasma may then be further treated to remove lipids (or any other undesirable compounds). In one embodiment, plasma may be combined with a solvent contained in container  64 . The solvent is capable of extracting lipids from the plasma. Such solvents are described in, for example, U.S. Pat. Nos. 4,895,558, 5,744,558 and 5,911,698, which are incorporated herein by reference. Examples of solvents are DIPE (di-isopropylether). of course, other solvents capable of extracting lipids from plasma and known to those of skill in the art may likewise be used. 
     Plasma and the solvent may be combined in, for example, container  62  or inside separator  68 . If combined outside of the separator, the plasma and solvent may then be reintroduced into the separator to further separate plasma from the lipid containing solvent. In a preferred embodiment, the separator is a centrifugal separator of the type shown in FIGS. 2-3 and/or FIGS. 13-16. Centrifugal action results in the separation into a two-phase solution, an upper organic phase that includes the solvent and extracted lipid, and a lower lipid-depleted plasma phase. Under control of the controller, the lipid containing solvent may then be pumped to a separate waste container. The lipid-depleted plasma may be returned to the patient. 
     Because some of the solvents that may be useful in removing lipids from the plasma may (in certain concentrations) be harmful to the patient, a further processing step that involves purging or otherwise removing any residual solvent from the plasma may be preferred. Thus, after removal of the organic phase, the plasma may be treated with a further washing solution from container  69 . Treatment in the washing solution can take place in the separation chamber before return of the plasma to the patient. 
     Alternatively, as shown in FIG. 9, system  10  may include a second separator (Separator  2 ) for the cleansing and/or washing step. As set forth above, Separator  2  may employ the same separation principle (e.g., centrifugation) as Separator  1 , or more preferably, may employ a different separation principle. 
     In one embodiment, Separator  2  may be a column packed with coated beads that have an affinity for the solvent. Thus, plasma may be removed from Separator  1  and introduced into column Separator  2  (either directly or via cassette  70 ) to remove any residual solvent. Plasma that has been passed through Separator  2  may then be suitable for return to the patient. In another alternative, Separator  2  may be filter medium. The system can include an optical detector  83 , which is capable of detecting lipids in the plasma being returned. Such detectors are described in U.S. Pat. No. 5,958,250, incorporated herein by reference. 
     In still another embodiment of the automated system of the present invention, removal of undesired compounds from plasma may be achieved without resort to a solvent-based system. Instead, plasma that has been separated in the separator may be treated or contacted with another material for removing lipids from plasma. For example, in one embodiment, a blood component that has been separated from whole blood can be further treated with particles or beads that have a specific affinity for the compound to be removed. As shown in FIG. 10, container  64  may include the beads or particles. In a preferred embodiment, the beads may be lightweight, simple, hollow (or solid) sphere-like structures. The beads are coated with an affinity material, such as monoclonal antibodies. The beads may have a specific affinity for lipids, sickled cells, immunoglobulins, Factor VIII or other proteins. The beads, preferably, have a density less than the density of plasma. Alternatively, the beads may be of the type described in U.S. Pat. Nos. 5,916,743 and 5,641,622, which are incorporated herein by reference. 
     In any event, as shown in FIG. 10, whole blood is withdrawn from the donor (or patient) through line  74  and combined with anticoagulant as previously described. Anticoagulated whole blood is collected and temporarily stored in container  58 . When a predetermined amount of whole blood has been collected, under the control of the controller, whole blood is introduced in the separator where it is separated into a cellular component and a plasma component. The cellular component can be removed from the separator and collected in, for example, container  60 . The plasma component can be combined with beads in container  60  or, to ensure greater contact between the beads and the compound to be removed, in the separator. The controller will cause beads to be pumped into either container  62  or the separator. The bound particle can then be collected in container  62  and the plasma returned to the donor. Alternatively, in another embodiment, plasma may be passed through a filter or other type of medium that has attached to its surface monoclonal antibodies that have a specific affinity for lipids. The filter medium may be a flat sheet or a packed column of the type described above. In addition, the separation medium (e.g., separator  80 ) may be used to extract or remove lipids or other compounds (through affinity separation) such as IgG, IgM, Factor VIII, and the like from plasma. 
     Another application for the automated system of the present invention is in the treatment of blood cells, such as red cells, white cells or platelets. In one specific embodiment, the automated system can be used to treat red blood cells with an enzyme to convert, for example, Type-A, Type-B, or Type-AB red blood cells to Type-O red blood cells. Accordingly, as shown in FIG. 10, whole blood is withdrawn from a patient  100 , anticoagulated in the manner described above, and separated in separator  68  to provide a red blood cell component and a plasma component. The plasma component can be collected in container  60  or can be returned to the donor immediately. The red blood cell component can be temporarily collected in container  60 . Under the control of controller  11 , the red blood cell component can be combined with a solution (stored in container  64 ) that includes a particular enzyme suitable for the red blood cell conversion. Examples of such enzymes are included in U.S. Pat. Nos. 6,175,420 and 5,671,135, which are incorporated by reference herein. The treated red blood component may then be collected and stored in container  62 . In addition, if Type-O blood cells are to be stored long term (e.g., up to 42 days), a preservative solution of the type described above can be added to the red blood cells. In another treatment-type application, red blood cells, platelets or even plasma may be treated to eradicate or inactivate pathogens present in these components. 
     Another application of the automated system of the present invention can be the salvage of blood during a surgical procedure. As shown, for example, in FIG. 11, whole blood can be collected from the body cavity of a patient  100  undergoing surgery. In this embodiment, fluid circuit will include a suction device  120  instead of a venipuncture needle. Suction device  120  maybe of the type shown in, for example, U.S. Pat. No. 5,976,388, which is incorporated herein by reference. Blood that is removed by suction device  120  is introduced into the separator where it is separated into a red blood cell component and supernatant. The red cell product may then the returned to patient. 
     Turning briefly to FIG. 12, an alternative, automated system for treating separated plasma is shown. The system includes a first separator and a second separator. As shown in FIG. 12A, the second separator is a separation column  80  that can be used to remove the above-described compounds from plasma. Columns that can be used for such separation are generally disclosed in U.S. Pat. Nos. 5,733,254 and 5,782,792, which are incorporated herein by reference. 
     As shown in FIG. 12, separation of plasma from whole blood proceeds as generally described above, i.e., in the separator. The separated plasma may be introduced into column  80 . It should be noted that plasma can be directly introduced into column  80  via line  81 , or can be conveyed by the pumps and valves of cassette  70  (under the direction of the controller) to column  80 . Likewise, plasma that has passed through column  80  can be returned via cassette  70 , can be directly introduced into line  74  for direct return to the donor, or can be introduced into container  62  from where it is pumped (through cassette  70 ) back to the donor. Red cells in container  60  may be returned to the donor during processing of plasma. 
     Column  80  may be provided as part of the fluid circuit  50 . In one embodiment, re-usable component  12  can be equipped with clips  13  and  15  for holding column  80 , as generally shown in FIG.  12 A. 
     FIGS. 13-16 show an alternative embodiment of another reusable hardware device and fluid circuit that can be used in the automated system and procedure of the present invention. The embodiment shown in FIGS. 13-16 include a centrifuge assembly  200  and a fluid processing circuit  50  for use in association with the centrifuge assembly. The centrifuge assembly includes a reusable hardware device capable of long-term use. The disposable fluid circuits, like the fluid circuits described above, are intended to be a single-use, disposable item. 
     Like the disposable fluid circuits described above, the fluid circuits shown in FIGS. 13-16 include a processing chamber, shown in FIG. 16, that can be loaded onto a separator of the re-usable device, to centrifugally separate blood components. The separator may separate whole blood into a red blood cell component, a plasma component, a white blood cell component, stem cells or a platelet component. The disposable fluid circuit also includes an array of flexible tubing to convey liquid to and from the processing chamber, described in more detail below. 
     Fluid circuit  50  includes one or more cassettes  222 A, B and C, generally of the type described above. The cassettes shown in FIGS. 14-15 include inter-connectable flow segments and valving stations. In contrast to cassettes  70  described above in connection with other embodiments, the cassettes of this embodiment do not include internal pumping stations. Instead, the cassettes of this embodiment include external tubing loops  223  which engage peristaltic pump rotors  250 , which effect movement of fluid through the tubing and the fluid circuit. The details of this embodiment of the automated system are described in U.S. Pat. No. 5,868,696, which is incorporated herein by reference. 
     As shown in FIG. 16, in the embodiment of FIGS. 13-16, fluid circuit  50  includes a “two-staged” separation chamber  68 . Thus, the first sub-chamber  226  can be used to perform a first separation step and the second sub-chamber  224  can be used to perform a second separation step. For example, where a blood component such as plasma or red blood cell is to be treated with a treating agent or described above, plasma can be separated from red cells in the first “sub-chamber”  226  and the treatment carried out in the second “sub-chamber”  224 . A treating agent can be directly introduced into the second subchamber or can be combined with the component elsewhere, such as in one of the containers. 
     The second subchamber can also be used to remove undesirable solvents, compounds, treating agents from the separated component. In most other respects, the blood and fluid processing procedures described above are applicable to the automated system described and shown in FIGS. 13-16. Of course, the chamber  68  may have only a single chamber. 
     More particularly, disposable circuit  50  shown in FIG. 14 is adapted for single needle platelet collection. Circuit  50  includes processing chamber  68  having separation and collection chambers  34  and  36 . The ports of processing chamber  68  communicate with multi-lumen umbilicus  240  which, in turn, communicates with donor needle  14  and containers  220   a-g , either directly or through cassettes  222   a-c.    
     In a typical apheresis procedure, processing circuit  50  is initially primed with saline withdrawn from container  220   a . During the draw cycle, the donor&#39;s blood is mixed with anticoagulant from container  220   e . A portion stored in reservoir container  220   b  and the remainder is conveyed through umbilicus  240  to separation chamber  68  where it is separated into red cells and platelet rich plasma. The red blood cells are conveyed through umbilicus  240  to red cell storage container  220   d . The platelet rich plasma is conveyed through umbilicus  240  to cassette  222   c  and then back through umbilicus  240  to collection chamber  68  where the platelets are sedimented onto the hi-g wall for subsequent processing. The platelet poor plasma is conveyed through umbilicus  240  to plasma reservoir container  220   c . During the return cycle, plasma from container  220   c  and red cells from container  220   d  are returned to the donor, while blood held in reserve in container  220   b  is being processed. After the donation is completed, processing chamber  68  is removed from the centrifuge, the platelets are resuspended and conveyed to platelet storage containers  220   f  and  220   g  along with sufficient plasma to provide adequate storage for up to five days. 
     In accordance with the present invention, many different and additional procedures can be performed with the system shown in FIGS. 13-16, by reconfiguring the interconnections of disposable circuit  50  and providing different containers  220   a-g  and processing chamber  68 . One such reconfiguration provides for the collection of mono-nuclear cells and is described in U.S. Pat. No. 5,980,760, which is incorporated herein by reference. The flexibility to reconfigure the functions and characteristics of disposable circuit  50  is provided, in large part, by the versatility of cassettes  222   a-c . Several such different procedures are described below. 
     For example, when the system of FIGS. 13-16 is used for hemodilution, some red cells are stored for subsequent transfusion, a replacement solution is provided and a supplemental oxygen carrier may be also supplied. As in the mono-nuclear cell procedure of U.S. Pat. No. 5,980,760, only a single separation chamber is required. Thus, the system can be supplied with a single chamber, or the dual chambered embodiment may be used, but only utilizing sub-chamber  226 . 
     The circuit is again primed with saline withdrawn from container  220   a . During the draw cycle, blood is again mixed with anticoagulant from container  220   e  with a portion stored in container  220   b  and the remainder supplied to separation chamber  68 . Separated, packed red blood cells are again stored in container  220   d  with separated plasma stored in container  220   c . During return, sequestered blood from container  220   b  is conveyed to separation chamber  68 , the separated red blood cells collected, while instantaneously separated plasma, along with that plasma previously sequestered in container  220   c  are returned to the patient along with replacement solution from saline container  220   a . Supplemental oxygen carrier held in containers  220   f  and  220   g  can also be administered to the patient during the return cycle in a predetermined quantity based upon the amount of red cells collected. An additional tubing section can be provided between saline container  220   a  and an unused port on cassette  222   a  to facilitate metered control of saline administration during the return cycle. 
     During the cell salvaging procedure, a patient&#39;s extra-vascular (“shed”) blood is withdrawn from the surgical field, washed, and returned to the patient. Disposable circuit  50  can again be reconfigured to accomplish cell salvaging. A reconfigured circuit  50  would again be primed with saline from container  220   a . Needle  14  would be replaced by a suction wand, not shown and of known construction, and the extra-vascular or shed blood mixed with anticoagulant from container  220   e  and stored in blood reservoir  220   b  until a sufficient quantity is obtained. Upon processing, the stored blood is mixed with saline from container  220   a , conveyed to separation chamber  68  and separated into now washed, packed red blood cells and a supernatant fluid containing blood plasma and washing solution saline. The packed red blood cells are stored in container  220   d  until required, while the supernatant fluid is collected in waste container  220   c.    
     An administration set can be provided to return the packed cells stored in container  220   d  to the patient by known gravity means or a separate return line (not shown) could be provided so that the washed red blood cells could be pumped directly to the patient. Alternatively, extra-vascular or shed blood could be drawn into a stand-alone vacuum cannister (not shown, but of known construction) and withdrawn through needle  14  when processing is desired. As with the hemodilution application above, an addition tubing segment can be supplied between saline container  220   a  and cassette  222   a  to provide metered control of saline during the washing process. 
     During lipid removal, lipid are removed from a patient&#39;s blood. Circuit  50  can again be reconfigured to effect such a removal. The circuit can again be primed with saline from container  220   a . During the draw cycle, blood is again mixed with anticoagulant from container  220   e  with a portion stored in container  220   b  and the remainder supplied to separation chamber  68 . Separated, packed red blood cells are again stored in container  220   d . The separated plasma is mixed with a solvent held in containers  220   f  and  220   g  and conveyed to secondary separation stage  224  where lipid reduced plasma is produced and conveyed to plasma container  220   c . The solvent agglutinated lipids can be sequestered in secondary separation chamber  221 , or, alternatively, an additional lumen can be provided in umbilicus  240  so that the lipids could be continuously pumped into a waste container connected into an unused port in cassette  222   c  (not shown). Alternatively, affinity based materials could be used in place of solvents to affect removal of lipids, as described above. 
     As previously discussed, red blood cells having Type-A, Type-B, or Type-AB antigens can be converted to Type-O red cells by certain enzymatic treatments. Disposable circuit  50  can again be reconfigured to affect such a treatment. The circuit can again be primed with saline withdrawn from container  220   a , or, if desired, primed with blood. During the draw cycle, blood is again mixed with anticoagulant from container  220   e  with a portion stored in container  220   b  and the remainder supplied to separation chamber  68 . Separated, packed red blood cells are again stored in container  220   d  and the separated plasma stored in container  220   c . The plasma is returned during the return cycle. The red cells then undergo enzymatic conversion in a post processing step. The packed red cells are transferred from container  220   d  to container  220   b  and mixed with enzymes from containers  220   f  and  220   g . The treated red cells are then admixed with saline from container  220   a  and conveyed to separation chamber  68 . The washed and treated red cells are again stored in container  220   d , while the separated supernatant is conveyed to the now unused plasma container  220   c  for subsequent disposal. The process of transferring the red cells from container  220   d  to container  220   b , admixing the saline from container  220   a  and separated into washed, packed cells and supernatant solution in separation chamber  68  can be repeated as many times as desired. 
     Alternatively, a normal platelet collection procedure could be performed using disposable circuit  50  with the collected platelets stored in containers  220   f  and  220   g , as described above. A concurrent red cell product can be collected and stored in container  220   d . A new container holding the enzymes would be provided and connected into the unused port on cassette  222   c , so that the collected red cells could be converted to Type-O, as discussed above. As with the hemodilution application above, an additional tubing segment can be supplied between saline container  220   a  and cassette  222   a  to provide metered control of saline during the washing process. 
     The many procedures discussed above have been based upon the single needle disposable circuit  50  of FIG. 13, but it should be appreciated by those skilled in the art that a two-needle circuit can also be modified to accomplish the desired procedures as well. 
     The various features of the present invention are set forth in the attached claims.