US20030211927A1 - Blood processing chamber counter-balanced with blood-free liquid - Google Patents
Blood processing chamber counter-balanced with blood-free liquid Download PDFInfo
- Publication number
- US20030211927A1 US20030211927A1 US10/462,320 US46232003A US2003211927A1 US 20030211927 A1 US20030211927 A1 US 20030211927A1 US 46232003 A US46232003 A US 46232003A US 2003211927 A1 US2003211927 A1 US 2003211927A1
- Authority
- US
- United States
- Prior art keywords
- compartment
- mnc
- tubing
- prbc
- pump
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3693—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits using separation based on different densities of components, e.g. centrifuging
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3621—Extra-corporeal blood circuits
- A61M1/3622—Extra-corporeal blood circuits with a cassette forming partially or totally the blood circuit
- A61M1/36222—Details related to the interface between cassette and machine
- A61M1/362227—Details related to the interface between cassette and machine the interface providing means for actuating on functional elements of the cassette, e.g. plungers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3621—Extra-corporeal blood circuits
- A61M1/3622—Extra-corporeal blood circuits with a cassette forming partially or totally the blood circuit
- A61M1/36225—Extra-corporeal blood circuits with a cassette forming partially or totally the blood circuit with blood pumping means or components thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3621—Extra-corporeal blood circuits
- A61M1/3622—Extra-corporeal blood circuits with a cassette forming partially or totally the blood circuit
- A61M1/36226—Constructional details of cassettes, e.g. specific details on material or shape
- A61M1/362261—Constructional details of cassettes, e.g. specific details on material or shape at least one cassette surface or portion thereof being flexible, e.g. the cassette having a rigid base portion with preformed channels and being covered with a foil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3621—Extra-corporeal blood circuits
- A61M1/3622—Extra-corporeal blood circuits with a cassette forming partially or totally the blood circuit
- A61M1/36226—Constructional details of cassettes, e.g. specific details on material or shape
- A61M1/362265—Details of valves
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3621—Extra-corporeal blood circuits
- A61M1/3622—Extra-corporeal blood circuits with a cassette forming partially or totally the blood circuit
- A61M1/36226—Constructional details of cassettes, e.g. specific details on material or shape
- A61M1/362266—Means for adding solutions or substances to the blood
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3693—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits using separation based on different densities of components, e.g. centrifuging
- A61M1/3696—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits using separation based on different densities of components, e.g. centrifuging with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D21/00—Separation of suspended solid particles from liquids by sedimentation
- B01D21/26—Separation of sediment aided by centrifugal force or centripetal force
- B01D21/262—Separation of sediment aided by centrifugal force or centripetal force by using a centrifuge
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D21/00—Separation of suspended solid particles from liquids by sedimentation
- B01D21/30—Control equipment
- B01D21/32—Density control of clear liquid or sediment, e.g. optical control ; Control of physical properties
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D21/00—Separation of suspended solid particles from liquids by sedimentation
- B01D21/30—Control equipment
- B01D21/34—Controlling the feed distribution; Controlling the liquid level ; Control of process parameters
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
- B04B—CENTRIFUGES
- B04B9/00—Drives specially designed for centrifuges; Arrangement or disposition of transmission gearing; Suspending or balancing rotary bowls
- B04B9/14—Balancing rotary bowls ; Schrappers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D2221/00—Applications of separation devices
- B01D2221/10—Separation devices for use in medical, pharmaceutical or laboratory applications, e.g. separating amalgam from dental treatment residues
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
- B04B—CENTRIFUGES
- B04B5/00—Other centrifuges
- B04B5/04—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
- B04B5/0442—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation
- B04B2005/045—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation having annular separation channels
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
- B04B—CENTRIFUGES
- B04B9/00—Drives specially designed for centrifuges; Arrangement or disposition of transmission gearing; Suspending or balancing rotary bowls
- B04B9/14—Balancing rotary bowls ; Schrappers
- B04B2009/143—Balancing rotary bowls ; Schrappers by weight compensation with liquids
Definitions
- the invention relates to centrifugal processing systems and apparatus.
- One aspect of the invention provides blood processing systems and methods comprising a processing chamber carried on a rotating element.
- the processing chamber includes a first compartment containing blood for centrifugal separation into components.
- the processing chamber also includes a second compartment containing a liquid free of blood. The liquid in the second compartment counter-balances the first compartment during rotation on the rotating element.
- the second compartment is substantially free of air, and the liquid in the second compartment is subject to a positive pressure.
- the second compartment has a single access, e.g., a single access port or multiple ports served by a single access path, such that two way fluid flow simultaneously into and out of the compartment is not possible.
- Another aspect of the invention provides systems and methods to prime the single access compartment, or any like chamber serviced by a single access.
- the systems and methods operate a pump element to draw a vacuum in the chamber through the single access. While the vacuum exists, the systems and methods open communication between the chamber and a source of liquid. The vacuum draws the liquid into the chamber through the single access to prime the chamber.
- the systems and methods command a pump element to convey the liquid into the chamber while the vacuum also draws the liquid into the chamber. A positive pressure condition is thereby established in the primed chamber.
- FIG. 1 is a side section view of a blood centrifuge having a separation chamber that embodies features of the invention
- FIG. 2 shows the spool element associated with the centrifuge shown in FIG. 1, with an associated processing container wrapped about it for use;
- FIG. 3A is a perspective view of the centrifuge shown in FIG. 1, with the bowl and spool elements pivoted into their access position;
- FIG. 3B is a perspective view of the bowl and spool elements in their mutually separation condition to allow securing the processing container shown in FIG. 2 about the spool element;
- FIG. 4 is a plan view of the processing container shown in FIG. 2;
- FIG. 5 is a perspective view of a fluid circuit associated with the processing container, which comprises cassettes mounted in association with pump stations on the centrifuge;
- FIG. 6 is a schematic view of the fluid circuit shown in FIG. 5;
- FIG. 7 is a perspective view of the back side of a cassette that forms a part of the fluid circuit shown in FIG. 6;
- FIG. 8 is a perspective view of the front side of the cassette shown in FIG. 7;
- FIG. 9 is a schematic view of the flow channels and valve stations formed within the cassette shown in FIG. 7;
- FIG. 10 is a schematic view of a pump station intended to receive a cassette of the type shown in FIG. 7;
- FIG. 11 is a schematic view of the cassette shown in FIG. 9 mounted on the pump station shown in FIG. 10;
- FIG. 12 is a perspective view of a cassette and a pump station which form a part of the fluid circuit shown in FIG. 6;
- FIG. 13 is a top view of a peristaltic pump that forms a part of the fluid circuit shown in FIG. 6, with the pump rotor in a retracted position;
- FIG. 14 is a top view of a peristaltic pump that forms a part of the fluid circuit shown in FIG. 6, with the pump rotor in an extended position engaging pump tubing;
- FIG. 15 is a diagrammatic top view of the separation chamber of the centrifuge shown in FIG. 1, laid out to show the radial contours of the high-G and low-G walls;
- FIGS. 16A and 16B somewhat diagrammatically show a portion of the platelet-rich plasma collection zone in the separation chamber, in which the high-G wall surface forms a tapered wedge for containing and controlling the position of the interface between the red blood cells and platelet-rich plasma;
- FIG. 17 is a somewhat diagrammatic view of the interior of the processing chamber, looking from the low-G wall toward the high-G wall in the region where whole blood enters the processing chamber for separation into red blood cells and platelet-rich plasma, and where platelet-rich plasma is collected in the processing chamber;
- FIG. 18 is a diagrammatic view showing the dynamic flow conditions established that confine and “park” MNC within the blood separation chamber shown in FIG. 17;
- FIG. 19 is a schematic view of the process controller which configures the fluid circuit shown in FIG. 6 to conduct a prescribed MNC collection procedure
- FIG. 20 is a flow chart showing the various cycles and phases of the MNC collection procedure that the controller shown in FIG. 19 governs;
- FIG. 21 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 during the preliminary processing cycle of the procedure shown in FIG. 20;
- FIG. 22 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 during the MNC accumulation phase of the procedure shown in FIG. 20;
- FIG. 23 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 during the PRBC collection phase of the procedure shown in FIG. 20;
- FIG. 24A is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 at the beginning of the MNC removal phase of the procedure shown in FIG. 20;
- FIG. 24B is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 during the MNC removal phase of the procedure shown in FIG. 20;
- FIG. 24C is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 at the end of the MNC removal phase of the procedure shown in FIG. 20;
- FIG. 25 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 during the PRP flush phase of the procedure shown in FIG. 20;
- FIG. 26 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 during the MNC suspension phase of the procedure shown in FIG. 20;
- FIG. 27 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 during the clean up phase of the procedure shown in FIG. 20;
- FIG. 28 is a schematic view of the optical sensor used in association with the circuit shown in FIG. 6 to sense and quantify the MNC region for harvesting;
- FIG. 29 is an alternative embodiment of a fluid circuit suited for collecting and harvesting MNC
- FIG. 30 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 29 during the PRBC collection phase of the procedure shown in FIG. 20;
- FIG. 31 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 29 during the MNC removal phase of the procedure shown in FIG. 20.
- FIG. 1 shows a blood centrifuge 10 having a blood processing chamber 12 suitable for harvesting mononuclear cells (MNC) from whole blood.
- the boundaries of the chamber 12 are formed by a flexible processing container 14 carried within an annular gap 16 between a rotating spool element 18 and bowl element 20 .
- the processing container 14 takes the form of an elongated tube (see FIG. 2), which is wrapped about the spool element 18 before use.
- the bowl and spool elements 18 and 20 are pivoted on a yoke 22 between an upright position, as FIGS. 3A and 3B show, and a suspended position, as FIG. 1 shows.
- the bowl and spool elements 18 and 20 When upright, the bowl and spool elements 18 and 20 are presented for access by the user. A mechanism permits the spool and bowl elements 18 and 20 to be opened, as FIG. 3B shows, so that the operator can wrap the container 14 about the spool element 20 , as FIG. 2 shows. Pins 150 on the spool element 20 engage cutouts on the container 14 to secure the container 14 on the spool element 20 .
- the spool and bowl elements 18 and 20 can be pivoted into the suspended position shown in FIG. 1.
- the centrifuge 10 rotates the suspended bowl and spool elements 18 and 20 about an axis 28 , creating a centrifugal field within the processing chamber 12 .
- the radial boundaries of the centrifugal field are formed by the interior wall 24 of the bowl element 18 and the exterior wall 26 of the spool element 20 .
- the interior bowl wall 24 defines the high-G wall.
- the exterior spool wall 26 defines the low-G wall.
- a first peripheral seal 42 forms the outer edge of the container 14 .
- a second interior seal 44 extends generally parallel to the rotational axis 28 , dividing the container 14 into two compartments 38 and 40 .
- the compartment 38 In use, whole blood is centrifugally separated in the compartment 38 .
- the compartment 40 carries a liquid, such as saline, to counter-balance the compartment 38 .
- the compartment 38 In the embodiment shown in FIG. 4, the compartment 38 is larger than the compartment 40 by a volumetric ratio of about 1 to 1.2.
- Three ports 46 , 48 , and 50 communicate with the processing compartment 38 , to convey whole blood and its components.
- Two additional ports 52 and 54 communicate with the ballast compartment 40 to convey the counter-balancing fluid.
- a fluid circuit 200 (see FIG. 4) is coupled to the container 14 .
- FIG. 5 shows the general layout of the fluid circuit 200 , in terms of an array of flexible tubing, liquid source and collection containers, in-line pumps, and clamps, all of which will be described in greater detail later.
- FIG. 6 shows the details of the fluid circuit 200 in schematic form.
- left, middle, and right cassettes respectively 23 L, 23 M, and 23 R, centralize many of the valving and pumping functions of the fluid circuit 200 .
- the left, middle, and right cassettes 23 L, 23 M, and 23 R mate with left, middle, and right pump stations on the centrifuge 10 , which are designated, respectively, PSL, PSM, and PSR.
- Each cassette 23 L, 23 M, and 23 R is constructed the same, so a description of one cassette 23 L is applicable to all cassettes.
- FIGS. 7 and 8 show the structural details of the cassette 23 L.
- the cassette 23 L comprises a molded plastic body 202 .
- Liquid flow channels 208 are integrally molded into on the front side 204 of the body 202 .
- a rigid panel 214 covers and seals the front body side 204 .
- Valve stations 210 are molded into the back side 206 of the cassette body 202 .
- a flexible diaphragm 212 covers and seals the back side 206 of the body 202 .
- FIG. 9 schematically shows a representative array of flow channels 208 and valve stations 210 for each cassette.
- channels C 1 to C 6 intersect to form a star array, radiating from a central hub H.
- Channel C 7 intersects channel C 5 ;
- channel C 8 intersects channel C 6 ;
- channel C 9 intersects channel C 3 ;
- channel C 10 intersects channel C 2 .
- other channel patterns can be used.
- valve stations VS 1 , VS 2 , VS 9 , and VS 10 are located in, respectively, channels C 2 , C 3 , C 5 , and C 6 immediately next to their common intersection at the hub H.
- Valve stations VS 3 , VS 4 , VS 5 , VS 6 , VS 7 , and VS 8 are located at the outer extremities of channels C 8 , C 1 , C 2 , C 5 , C 4 , and C 3 , respectively.
- Each cassette 23 L carries an upper flexible tubing loop UL, which extends outside the cassette 23 L between channels C 7 and C 6 , and a lower tubing loop LL, which extends outside the cassette between channels C 3 and C 10 .
- the tube loops UL and LL engage the peristaltic pump rotors of the pumps on the associated pump station.
- the pump stations PSL, PSM, and PSR are, like the cassettes 23 L, 23 M, and 23 R, identically constructed, so a description of one station PSL is applicable to all.
- FIG. 12 shows the structural details of the left pump station PSL.
- FIG. 10 shows the left pump station PSL in a more schematic form.
- the station PSL includes two peristaltic pumps, for a total of six pumps in the circuit 200 , which are designated P 1 to P 6 (see FIG. 6).
- the station PSL also includes an array of ten valve actuators (which FIG. 10 shows), for a total of thirty valve actuators in the circuit 200 , which designated VA 1 to VA 30 (see FIG. 6).
- the tube loops UL and LL of cassette 23 L engage pumps P 1 and P 2 of the left pump station PSL.
- the tube loops UL and LL of the middle cassette 23 M engage pumps P 3 and P 4 .
- the tube loops UL and LL of the right cassette 23 L engage pumps P 5 and P 6 .
- valve stations VS 1 to VS 10 of the cassette 23 L align with the valve actuators V 1 to V 10 of the left pump station PSL.
- valve stations of the middle and right cassettes 23 M and 23 R likewise align with the valve actuators of the respective middle and right pump stations PSM and PSR.
- the cassettes 23 L, 23 M, and 23 R are mounted on their respective pump stations PSL, PSM, PSR with their back sides 206 down, so that the diaphragms 212 face and engage the valve actuators.
- the valve actuators Vn are solenoid-actuated rams 215 (see FIG. 12), which are biased toward a valve closing position.
- the valve actuators Vn are patterned to align with the cassette valve stations VSn in the manner set forth in Table 1.
- the ram 215 When a given ram 215 is energized, the associated cassette valve station is opened, allowing through-passage of liquid.
- the ram 215 When the ram 215 is not energized, it displaces the diaphragm 212 into the associated valve station, blocking passage of liquid through the associated valve station.
- the pumps P 1 to P 6 on each pump station PSL, PSM, and PSR include rotating peristaltic pump rotors 216 .
- the rotors 216 can be moved between a retracted condition (shown in FIG. 13), out of engagement with the respective tube loop, and an operating condition (shown in FIG. 14), in which the rotors 216 engage the respective tube loop against a pump race 218 .
- the pumps P 1 and P 6 can thereby be operated in three conditions:
- the fluid circuit 200 further includes lengths of flexible plastic tubing, designated T 1 to T 20 in FIG. 6.
- the flexible tubing T 1 to T 20 couple the cassettes 23 L, 23 M, and 23 R to the processing container 14 , to external source and collection bags or containers, and to the blood donor/patient.
- Tubing T 1 extends from the donor/patient (via a conventional phlebotomy needle, not shown) through an external clamp C 2 to channel C 4 of the left cassette 23 L.
- Tubing T 2 extends from tube T 1 through an external clamp C 4 to channel C 5 of the middle cassette 23 M.
- Tubing T 3 extends from an air detection chamber D 1 to channel C 9 of the left cassette 23 L.
- Tubing T 4 extends from the drip chamber D 1 to port 48 of the processing container 14 .
- Tubing T 5 extends from port 50 of the processing container 14 to channel C 4 of the middle cassette 23 M.
- Tubing T 6 extends from channel C 9 of the middle cassette 23 M to join tubing T 4 downstream of the chamber D 1 .
- Tubing T 7 extends from channel C 8 of the right cassette 23 M to channel C 8 of the left cassette 23 L.
- Tubing T 8 extends from channel C 1 of the middle cassette 23 M to join tubing T 7 .
- Tubing T 9 extends from channel C 5 of the left cassette 23 L through an air detection chamber D 2 and an external clamp C 3 to the donor/patient (via a conventional phlebotomy needle, not shown).
- Tubing T 10 extends from port 46 of the processing container 14 , through an in line optical sensor OS to channel C 4 of the right cassette 23 R.
- Tubing T 11 extends from channel C 9 of the right cassette 23 R to the chamber D 1 .
- Tubing T 12 extends from channel C 2 of the right cassette 23 R to a container intended to receive platelet-poor plasma, designated PPP.
- a weight scale (not shown) senses weight of the container PPP for the purpose of deriving fluid volume changes.
- Tubing T 13 extends from channel C 1 of the right cassette 23 R to a container intended to receive mono-nuclear cells, designated MNC.
- Tubing T 14 extends from channel C 2 of the middle cassette 23 M to a container intended to receive packed red blood cells, designated PRBC.
- a weight scale WS senses weight of the container PRBC for the purpose of deriving fluid volume changes.
- Tubing T 15 extends from a container of anticoagulant, designated ACD, to channel C 8 of the middle cassette 23 M.
- a weight scale (not shown) senses weight of the container ACD for the purpose of deriving fluid volume changes.
- Tubing T 16 and T 17 extend from a container of priming liquid, such as saline, designated PRIME, bypassing all cassettes 23 L, 23 M, and 23 R, through an external clamp C 1 , and intersecting, respectively, tubing T 9 (between the air detection chamber D 2 and the clamp C 3 ) and tubing T 1 (upstream of clamp C 3 ).
- a weight scale (not shown) senses weight of the container PRIME for the purpose of deriving fluid volume changes.
- Tubing T 18 extends from the port 52 of the processing container 14 to channel C 5 of the right cassette 23 R.
- Tubing T 19 extends from the port 54 of the processing container 14 to intersect tubing T 18 .
- Tubing T 20 extends from channel C 2 of the left cassette 23 L to a container intended to receive waste priming fluid, designated WASTE.
- a weight scale (not shown) senses weight of the container WASTE for the purpose of deriving fluid volume changes.
- umbilicus 30 Portions of the tubing are joined in umbilicus 30 (see FIG. 1).
- the umbilicus 30 provides fluid flow communication between the interior of the processing container 14 within the centrifugal field and other stationary components of the circuit 200 located outside the centrifugal field.
- a non-rotating (zero omega) holder 32 holds the upper portion of the umbilicus 30 in a non-rotating position above the suspended spool and bowl elements 18 and 20 .
- a holder 34 on the yoke 22 rotates the mid-portion of the umbilicus 30 at a first (one omega) speed about the suspended spool and bowl elements 18 and 20 .
- Another holder 36 rotates the lower end of the umbilicus 30 at a second speed twice the one omega speed (the two omega speed), at which the suspended spool and bowl elements 18 and 20 also rotate. This known relative rotation of the umbilicus 30 keeps it untwisted, in this way avoiding the need for rotating seals.
- anticoagulated whole blood is drawn from the donor/patient and conveyed into the processing compartment through the port 48 .
- the blood processing compartment 38 includes a interior seals 60 and 66 , which form a WB inlet passage 72 that leads into a WB entry region 74 .
- WB separates in the centrifugal field within the blood processing compartment 38 into packed red blood cells (PRBC, designated by numeral 96 ), which move toward the high-G wall 24 , and platelet-rich plasma (PRP, designated by numeral 98 ), which are displaced by movement of the PRBC 96 toward the low-G wall 26 .
- PRBC packed red blood cells
- PRP platelet-rich plasma
- the interior seal 60 also creates a PRP collection region 76 within the blood processing compartment 38 .
- the PRP collection region 76 is adjacent to the WB entry region 74 .
- the velocity at which the PRBC 96 settle toward the high-G wall 24 in response to centrifugal force is greatest in the WB entry region 74 than elsewhere in the blood processing compartment 38 .
- relatively large radial plasma velocities toward the low-G wall 26 occur in the WB entry region 74 .
- These large radial velocities toward the low-G wall 26 elute large numbers of platelets from the PRBC 96 into the close-by PRP collection region 76 .
- the interior seal 66 also forms a dog-leg 70 that defines a PRBC collection passage 78 .
- a stepped-up barrier 115 extends into the PRBC mass along the high-G wall 24 , creating a restricted passage 114 between it and the facing, iso-radial high-G wall 24 .
- the restricted passage 114 allows PRBC 96 present along the high-G wall 24 to move beyond the barrier 115 into the PRBC collection region 50 , for conveyance by the PRBC collection passage 78 to the PRBC port 50 .
- the stepped-up barrier 115 blocks the passage of the PRP 98 beyond it.
- the high-G wall 24 also projects toward the low-G wall 26 to form a tapered ramp 84 in the PRP collection region 76 .
- the ramp 84 forms a constricted passage 90 along the low-G wall 26 , along which the PRP 98 layer extends.
- the ramp 84 keeps the interface 58 and PRBC 96 away from the PRP collection port 46 , while allowing PRP 98 to reach the PRP collection port 46 .
- the ramp 84 is oriented at a non-parallel angle ⁇ of less than 45° (and preferably about 30°) with respect to the axis of the PRP port 46 .
- the angle ⁇ mediates spill-over of the interface and PRBC through the constricted passage 90 .
- the ramp 84 also displays the interface 26 for viewing through a side wall of the container 14 by an associated interface controller 220 (see FIG. 19).
- the interface controller 220 controls the relative flow rates of WB, the PRBC, and the PRP through their respective ports 48 , 50 , and 46 . In this way, the controller 220 can maintain the interface 58 at prescribed locations on ramp, either close to the constricted passage 90 (as FIG. 16A shows) or spaced away from the constricted passage 90 (as FIG. 16B shows).
- the controller 220 can also control the platelet content of the plasma collected through the port 46 .
- the concentration of platelets in the plasma increases with proximity to the interface 58 .
- the controller 220 can also control the platelet content of the plasma collected through the port 46 .
- the concentration of platelets in the plasma increases with proximity to the interface 58 .
- the controller 220 can also control the platelet content of the plasma collected through the port 46 .
- the concentration of platelets in the plasma increases with proximity to the interface 58 .
- the controller 220 can also control the platelet content of the plasma collected through the port 46 .
- the concentration of platelets in the plasma increases with proximity to the interface 58 .
- the controller could control the location of the interface 58 by varying the rate at which WB is introduced into the blood processing compartment 38 , or the rate at which PRBC are conveyed from the blood processing compartment 134 , or both.
- radially opposed surfaces 88 and 104 form a flow-restricting region 108 along the high-G wall 24 of the WB entry region 74 .
- the region 108 restricts WB flow in the WB entry region 74 to a reduced passage, thereby causing more uniform perfusion of WB into the blood processing compartment 38 along the low-G wall 26 .
- This uniform perfusion of WB occurs adjacent to the PRP collection region 76 and in a plane that is approximately the same as the plane in which the preferred, controlled position of the interface 58 lies.
- the constricted region 108 brings WB into the entry region 74 at approximately the preferred, controlled height of the interface 58 .
- WB brought into the entry region 74 below or above the controlled height of the interface 58 will immediately seek the interface height and, in so doing, oscillate about it, causing unwanted secondary flows and perturbations along the interface 58 .
- the region 108 reduces the incidence of secondary flows and perturbations along the interface 58 .
- the low-G wall 26 tapers outward away from the axis of rotation 28 toward the high-G wall 24 in the direction of WB flow, while the facing high-G wall 24 retains a constant radius.
- the taper can be continuous (as FIG. 15 shows) or can occur in step fashion.
- the circumferential plasma flow condition in this direction continuously drags the interface 58 back toward the PRP collection region 76 , where the higher radial plasma flow conditions already described exist to sweep even more platelets off the interface 58 .
- the counterflow patterns serve to circulate the other heavier components of the interface 58 (the lymphocytes, monocytes, and granulocytes) back into the PRBC mass, away from the PRP stream.
- MNC (designated as such in FIG. 18) initially settle along the high-G wall 24 , but eventually float up to the surface of the interface 58 near the high-hematocrit PRBC collection region 50 .
- the tapering low-G wall creates the plasma counterflow patterns, shown by arrows 214 in FIG. 18. These counterflow patterns 214 draw the MNC back toward the low-hematocrit PRP collection region 76 .
- MNC again resettle near the low-hematocrit PRP collection region 76 toward the high-G wall 24 .
- the MNC circulate in this path, designated 216 in FIG. 18, while WB is separated into PRBC and PRP.
- the MNC are thus collected and “parked” in this confined path 216 within the compartment 38 away from both the PRBC collection region 50 and the PRP collection region 76 .
- the centrifuge 10 includes a process controller 222 (see FIG. 19), which commands operation of the fluid circuit 200 to carry out a prescribed MNC collection and harvesting procedure 224 using the container 14 .
- the procedure 224 comprises a pre-processing priming cycle 226 , which primes the fluid circuit 200 .
- the procedure 224 next includes a preliminary processing cycle 228 , which processes PPP from whole blood obtained from the donor/patient for use later in the procedure 224 as a suspension medium for the harvested MNC.
- the procedure 224 next includes at least one main processing cycle 230 .
- the main processing cycle 230 comprises a collection stage 232 , followed by a harvesting stage 234 .
- the collection stage 232 includes a series of collection phases 236 and 238 , during which whole blood is processed to accumulate mononuclear cells in the first compartment 38 , in the manner previously described.
- the harvesting stage likewise includes a series of harvesting phases 240 , 242 , 244 , and 246 , during which the accumulation of mononuclear cells are transferred from the first compartment 38 into a collection container MNC coupled to the circuit 200 . Suspension medium, collected during the preliminary processing cycle 228 , is added to the MNC.
- the main processing cycle 230 will be carried out more than once during a given procedure 224 .
- the number of processing cycles 230 conducted in a given procedure 224 will depend upon the total volume of MNC sought to be collected.
- a representative procedure 224 five main processing cycles 230 are repeated, one after the other.
- each main processing cycle 230 from about 1500 to about 3000 ml of whole blood can be processed, to obtain a MNC volume per cycle of about 3 ml.
- a MNC volume of about 15 ml can be collected, which is suspended in a final dilution PPP of about 200 ml.
- the controller 222 Before a donor/patient is coupled to the fluid circuit 200 (via tubing T 1 and T 9 ), the controller 222 conducts a priming cycle 228 .
- the controller 222 commands the centrifuge 10 to rotate the spool and bowl elements 18 and 20 about the axis 28 , while commanding the pumps P 1 to P 6 to convey a sterile priming liquid, such as saline, from the container PRIME and anticoagulant from the container ACD throughout the entire fluid circuit 15 and container 14 .
- the priming liquid displaces air from the circuit 15 and container 14 .
- the second compartment 40 is served by single tubing T 18 and therefore has, in effect, a single access port.
- the compartment 40 is isolated from flow communication with the priming liquid, while pump P 5 is operated to draw air from the compartment 40 , thereby creating a negative pressure (vacuum) condition in the compartment 40 .
- pump P 5 is operated to draw air from the compartment 40 , thereby creating a negative pressure (vacuum) condition in the compartment 40 .
- communication is then opened to the flow of priming liquid, which is drawn into the compartment 40 by the vacuum.
- Pump P 5 is also operated to aid in the conveyance of liquid into the compartment 40 and to create a positive pressure condition in the compartment 40 .
- the controller 222 retains priming liquid in the second compartment 40 , to counter-balance the first compartment 38 during blood processing.
- MNC that is harvested in container MNC is preferably suspended in a platelet-poor plasma (PPP) media obtained from the MNC donor/patient.
- PPP platelet-poor plasma
- the controller 222 configures the fluid circuit 222 to collect a preestablished volume of PPP from the donor/patient for retention in the container PPP. This volume is later used as a suspension medium for the MNC during processing, as well as added to the MNC after processing to achieve the desired final dilution volume.
- the controller 222 configures the pump stations PSL, PSM, and PSR to begin the preliminary processing cycle 228 .
- whole blood is centrifugally separated in the compartment 38 into packed red blood cells (PRBC) and platelet-rich plasma (PRP), as before described.
- PRBC are returned to the donor/patient, while mononuclear cells accumulate in the compartment 38 .
- pump P 2 draws whole blood (WB) from the donor/patient through tubing T 1 into the left cassette 23 L, into tubing T 3 , through the chamber D 1 , and into the blood processing compartment 38 through tubing T 4 .
- Pump P 3 draws anticoagulant ACD through tubing T 15 , into the middle cassette 23 M and into tubing T 2 , for mixing with the whole blood.
- the anticoagulated whole blood is conveyed into the compartment 38 through port 48 .
- the whole blood is separated into PRP, PRBC, and the interface (including MNC), as previously described.
- the port 50 conveys PRBC 96 from the blood processing compartment 38 , through tubing T 5 into the middle cassette 23 M.
- the PRBC enters tubing T 7 through tubing T 8 , for return to the donor/patient via the left cassette 23 L and tubing T 9 .
- the port 46 conveys PPP from the blood processing compartment 38 .
- the PPP follows tubing T 10 into the right cassette 23 R.
- Pump P 5 conveys a portion of the PPP into tubing T 7 for return with PRBC to the donor/patient.
- the interface controller 220 sets the flow rate of pump P 5 to maintain the interface at a low position on the ramp 84 (as shown in FIG. 16B), to thereby minimize the concentration of platelets conveyed from the compartment 38 during this cycle.
- Pump P 6 conveys a portion of the PPP through tubing T 12 into container PPP, until the volume prescribed for MNC suspension and final dilution is collected. This volume is designated VOL sus .
- the controller 222 now switches to the MNC collect stage 232 of the main processing cycle 230 .
- the controller 222 configures the fluid circuit 200 for the MNC accumulation phase 236 .
- the controller 222 changes the configuration of the pump station PSR to stop collection of PPP.
- the controller 222 also commands the interface controller 220 to maintain a flow rate for pump P 5 to maintain the interface at a higher location on the ramp 84 (such as shown in FIG. 16A), thereby enabling the separation of PRP.
- the pump P 6 Due to the changed configuration, the pump P 6 also recirculates a portion of the PRP to the blood processing chamber 38 to enhance platelet separation efficiencies, as will be described in greater detail later.
- MPV mean platelet volume
- femtoliters, fl, or cubic microns mean platelet volume
- MPV can be measured by conventional techniques from a PRP sample. Larger platelets (i.e., larger than about 20 femtoliters) are most likely to become entrapped in the interface 58 and not enter the PRP for return to the donor/patient. This results in a reduced population of larger platelets in the PRP, and therefore a lower MPV, for return to the donor/patient.
- the controller sets a PRP recirculation flow rate Q Recirc for pump P 6 to achieve a desired inlet hematocrit H i .
- H i is no greater that about 40%, and, most preferably, is about 32%, which will achieve a high MPV.
- Inlet hematocrit H i can be conventionally measured by an in-line sensor in tubing T 4 (not shown). Inlet hematocrit H i can also be determined empirically based upon sensed flow conditions, as disclosed in copending U.S. patent application Ser. No. 08/471,883, which is incorporated herein by reference.
- the counter flow of plasma (arrows 214 ) in the compartment 38 drags the interface 58 back toward the PRP collection region 76 , where the enhanced radial plasma flow conditions sweep platelets off the interface 58 for return to the donor/patient.
- the counterflow patterns 214 also circulate other heavier components of the interface 58 , such as lymphocytes, monocytes, and granulocytes, back for circulation into the PRBC mass.
- MNC float near the region 80 to the surface of the interface 58 .
- the MNC are drawn by the plasma counter-flow 214 toward the low-hematocrit PRP collection region 76 .
- MNC resettle again toward the high-G wall 24 .
- Arrow 216 in FIG. 18 shows the desired circulating flow of MNC as it accumulates in the compartment 38.
- Maintaining a desired PRBC outlet hematocrit H o in the PRBC collection region 50 is important. If the outlet hematocrit H o , of the PRBC falls below a given low threshold value (e.g., below about 60%), the majority of MNC will not circulate as a cellular mass, as shown by the arrow 216 in FIG. 18. Exposed to a low H o all or some of the MNC will fail to float toward the interface 58 . Instead, the MNC will remain congregated along the high-G wall and will be carried out of the compartment 38 with the PRBC. An insufficient MNC yield results.
- a given low threshold value e.g., below about 60%
- H o exceeds a given high threshold value (e.g., about 85%)
- a given high threshold value e.g., about 85%
- larger numbers of the heavier granulocytes will float on the interface 58 .
- fewer granulocytes will be carried away from the interface 58 for return with the PRBC to the donor/patient. Instead, more granulocytes will occupy the interface 58 and contaminate the MNC.
- the process controller 222 commands the pump P 4 to recirculate a portion of the PRBC flowing in tubing T 5 back into the WB inlet port 48 .
- FIGS. 21 and 22 show, recirculating PRBC flows through the middle cassette 23 M into tubing T 6 , which joins tubing T 4 coupled to the inlet port 48 .
- the recirculating PRBC mixes with WB entering the blood processing compartment 38 .
- the magnitude of the outlet hematocrit H o varies conversely as a function of PRBC recirculation flow rate Q r , which is governed by the pump P 4 (PRBC) and the pump P 2 (WB). Given a flow rate for WB set by pump P 2 , the outlet hematocrit H o can be increased by lowering Q r , and, conversely, outlet hematocrit H o can be decreased by raising Q r .
- Q r and H o takes into account the centrifugal acceleration of fluid in the compartment 38 (governed by the magnitude of centrifugal forces in the compartment 38 ), the area of the compartment 38 , as well as the inlet flow rate whole blood (Q b ) into the compartment 38 (governed by pump P 2 ) and the outlet flow rate PRP (Q p ) from the compartment 38 (governed by the interface control pump P 5 ).
- the controller 222 periodically samples Q b , Q p , and Q r . Further taking into account the centrifugal force factors active in the compartment 38 , the controller derives a new PRBC recirculation pump rate Q r (NEW) for the pump P 4 , based upon a targeted H o , as follows:
- H o is the targeted exit hematocrit value, expressed as a decimal (e.g., 0.75 for 75%).
- ⁇ is the rate of rotation of the compartment 38 , expressed in radians per second.
- r is the radius of rotation.
- g is unit gravity, equal to 981 cm/sec 2 .
- A is the area of the compartment 38 .
- k is hematocrit constant and m is a separation performance constant, which are derived based upon empirical data and/or theoretical modeling.
- S r is an empirically derived red blood cell sedimentation factor, which, upon empirical data, can be set at 95 ⁇ 10 ⁇ 9 s.
- Q o is the flow rate of PRBC through outlet tubing T 5 , which can be expressed as:
- ⁇ /S r can, based upon empirical data, be expressed as a constant value of 1.57/ ⁇ s.
- m has a value of 531.13.
- a range of values for m between about 500 and about 600 is believed to be applicable to centrifugal, continuous flow whole blood separation procedures, in general.
- the y-intercept value for (k) equals 0.9489.
- a range of values for k between about 0.85 and about 1.0 is believed to be applicable to centrifugal, continuous flow whole blood separation procedures, in general.
- Q r is measured at selected intervals, and these instantaneous measurements are averaged over the processing period, as follows:
- F can comprise a constant or, alternatively, it can vary as a function of processing time, e.g., starting at a first value at the outset of a given procedure and changing to a second or more values as the procedure progresses.
- the controller 222 simultaneously sets and maintains multiple pump flow rates to achieve processing conditions in the compartment 38 optimal for the accumulation of a high yield of MNC of high purity.
- the controller sets and maintains WB inlet flow rate Q b (via the pump P 2 ), PRP outlet flow rate Q p (via the pump PS), PRP recirculation flow rate Q Recirc (via the pump P 6 ), and PRBC recirculation flow rate Q r (via the pump P 4 ).
- WB inlet flow rate Q b which is typically set for donor/patient comfort and the achievement of an acceptable processing time
- the controller 222 Given a WB inlet flow rate Q b , which is typically set for donor/patient comfort and the achievement of an acceptable processing time, the controller 222 :
- (ii) commands the pump P 6 to maintain a Q Recirc set to hold the desired inlet hematocrit H i (e.g., between about 32% and 34%), and thereby achieve high platelet separation efficiencies; and
- (iii) commands the pump P 4 to maintain a Q r set to hold a desired outlet hematocrit H o (e.g., between about 75% to 85%), and thereby prevent granulocyte contamination and maximize MNC yields.
- a desired outlet hematocrit H o e.g., between about 75% to 85%
- the controller 222 terminates the MNC accumulation phase 236 when a preestablished volume of whole blood (e.g., 1500 ml to 3000 ml) is processed. Alternatively, the MNC accumulation phase can be terminated when a targeted volume of MNC is collected.
- a preestablished volume of whole blood e.g., 1500 ml to 3000 ml
- the MNC accumulation phase can be terminated when a targeted volume of MNC is collected.
- the controller 22 then enters the PRBC collection phase 238 of the MNC collection stage 232 .
- the configuration of the pump station PSM is altered to stop the return of PRBC to the donor/patient (by closing V 14 ), stop the recirculation of PRBC (by closing valve V 18 and placing pump P 4 into a closed, pump off condition, and instead conveying PRBC to the container PRBC (by opening V 15 ).
- PRBC in line TS is conveyed through the middle cassette 23 M, into line T 14 , and into the container PRBC.
- the controller 222 operates in this phase 238 until a desired volume of PRBC (e.g., 35 ml to 50 ml) collects in the container PRBC.
- This PRBC volume is later used in the MNC removal phase 240 of the MNC harvesting stage 234 , as will be described in greater detail later.
- the controller 222 ends the PRBC collection phase 238 upon sensing (gravimetrically, using the weight scale WS) that the container PRBC holds the desired volume of PRBC.
- the controller 222 enters the MNC harvesting stage 234 of the main processing cycle 230 .
- whole blood is drawn and recirculated back to the donor/patient without passage through the blood processing compartment 38 .
- PRBC collected in the container PRBC in the preceding PRBC collection phase 238 is returned to the processing compartment 38 through WB inlet tubing T 4 , while rotation of the compartment 38 continues.
- the MNC accumulated in the compartment 38 during the MNC collection stage 232 is conveyed with PRP through tubing T 10 out of the compartment 38 .
- the controller 222 closes PRBC outlet tubing T 5 while PRBC is conveyed by pump P 4 from the container PRBC through tubing T 14 and T 6 into tubing T 4 , for introduction into compartment 38 through the WB inlet port 48 .
- the controller 222 starts a cycle time counter at TCYC START .
- the inflow of PRBC from the container PRBC through the WB inlet port 48 increases the hematocrit in the PRP collection region 76 .
- the concentrated region of MNC accumulated in the compartment 38 (as shown in FIG. 18), float to the surface of the interface 58 .
- the incoming PRBC volume displaces PRP through the PRP outlet port 46 .
- the interface 58 , and with it, the concentrated MNC region (designated MNC Region in FIG. 24A) are also displaced out of the compartment 38 through the PRP outlet port 46 .
- the MNC Region moves along the PRP tubing T 10 toward the optical sensor OS.
- a region 112 of PRP precedes the concentrated MNC Region.
- the PRP in this region 112 is conveyed into the container PPP through the right cassette 23 R and tubing T 12 (as FIG. 24A shows).
- a region 114 of PRBC also follows the concentrated MNC Region within the tubing T 10 .
- a first transition region 116 exists between the PRP region 112 and concentrated MNC Region.
- the first transition region 116 consists of a steadily decreasing concentration of platelets (shown by a square pattern in FIG. 28) and a steadily increasing number of MNC's (shown by a textured pattern in FIG. 28).
- a second transition region 118 exists between the concentrated MNC Region and the PRBC region 114 .
- the second transition region 118 consists of a steadily decreasing concentration of MNC's (shown by the textured pattern in FIG. 28) and a steadily increasing number of PRBC's (shown by a wave pattern in FIG. 28).
- the regions 112 and 116 preceding the MNC Region and the regions 118 and 114 trailing the MNC Region present a transition optical densities in which the MNC Region can be discerned.
- the optical sensor OS senses changes in optical density in the liquid conveyed by the tubing T 10 between the PRP outlet port 46 and the right cassette 23 R. As FIG. 28 shows, the optical density will change from a low value, indicating highly light transmissive (i.e., in the PRP region 112 ), to a high value, indicating highly light absorbent (i.e., in the PRBC region 114 ), as the MNC Region progresses past the optical sensor OS.
- the optical sensor OS is a conventional hemoglobin detector, used, e.g., on the Autopheresis-C® blood processing device sold by the Fenwal Division of Baxter Healthcare Corporation.
- the sensor OS comprises a red light emitting diode 102 , which emits light through the tubing T 10 .
- red light emitting diode 102 which emits light through the tubing T 10 .
- other wavelengths like green or infrared, could be used.
- the sensor OS also includes a PIN diode detector 106 on the opposite side of the tubing T 10 .
- the controller 222 includes a processing element 100 , which analyzes voltage signals received from the emitter 102 and detector 106 to compute the optical transmission of the liquid in the tubing T 10 , which is called OPTTRANS.
- OPTRANS can equal the output of the diode detector 106 when the red light emitting diode 102 is on and the liquid flows through the tubing T 10 (RED).
- OPTTRANS COR ⁇ ⁇ ( RED ⁇ ⁇ SPILL ) CORRREF
- RED is the output of the diode detector 106 when the red light emitting diode 102 is on and the liquid flows through the tubing T 10 ;
- REDBKGRD is the output of the diode detector 106 when the red light emitting diode 102 is off and the liquid flows through the tubing T 10 ;
- REF is the output of the red light emitting diode 102 when the diode is on.
- REFBKGRD is the output of the red light emitting diode 102 when the diode is off.
- the processing element 100 normalizes the sensor OS to the optical density of the donor/patient's PRP, by obtaining data from the sensor OS during the preceding MNC collection stage 232 , as the donor/patient's PRP conveys through the tubing T 10 .
- This data establishes a baseline optical transmission value for the tubing and the donor/patient's PRP (OPTTRANS BASE ).
- OPTTRANS BASE can be measured at a selected time during the collection stage 232 , e.g., half way through the stage 232 , using either a filtered or non-filtered detection scheme, as described above.
- a set of optical transmission values are calculated during the MNC collection stage 232 using either a filtered or non-filtered detection scheme. The set of values are averaged over the entire collection stage to derive OPTTRANS BASE .
- the processing element 100 continues during the subsequent MNC removal phase 240 to sense one or more optical transmission values for the tubing T 10 and the liquid flowing in it (OPTTRANS HARVEST ) during the MNC removal phase 240 .
- OPTTRANS HARVEST can comprise a single reading sensed at a selected time of the MNC removal phase 240 (e.g., midway through the phase 240 ), or it can comprise an average of multiple readings taken during the MNC removal phase 240 .
- the processing element 100 derives a normalized value DENSITY by establishing OPTTRANS BASE as 0.0, establishing the optical saturation value as 1.0, and fitting the value of OPTTRANS HARVEST proportionally into the normalized 0 . 0 to 1 . 0 value range.
- the processing element 100 retains two predetermined threshold values THRESH(1) and THRESH(2).
- the value of THRESH(1) corresponds to a selected nominal value for DENSITY (e.g., 0.45 in a normalized scale of 0.0 to 1.0), which has been empirically determined to occur when the concentration of MNC's in the first transition region 116 meets a preselected processing goal.
- the value of THRESH(2) corresponds to another selected nominal value for DENSITY (e.g., 0.85 in a normalized scale of 0.0 to 1.0), which has been empirically determined to occur when the concentration of PRBC in the second transition region 118 exceeds the preselected processing goal.
- the liquid volume of the tubing T 10 between the optical sensor OS and the valve station V 24 in the right cassette 23 R constitutes a known value, which is inputted to the controller 222 as a first offset volume VOL OFF(1)
- the operator can specify and input to the controller 222 a second offset volume VOL OFF(2) , which represents a nominal additional volume (shown in FIG. 28) to increase the total MNC harvested volume VOL MNC .
- the quantity VOL OFF(2) takes into account system and processing variances, as well as variances among donors/patients in MNC purity.
- the interface 58 and MNC Region advance through the PRP tubing T 10 toward the optical sensor OS.
- PRP preceding the MNC Region advances beyond the optical sensor OD, through the tubing T 12 , and into the container PPP.
- the volume of MNC sensed can be derived based upon the interval between TC 1 and TC 2 for a given QP 4 .
- the controller 222 compares the magnitudes of TC 1 to the first control time T 1 , as well as compares TC 2 to the second control time T 2 .
- the controller 222 commands valve station V 24 to open, and commands valve station V 25 to close.
- the controller 222 marks this event on the cycle time counter as TCYC SWITCH .
- the targeted MNC Region is conveyed into the tubing T 13 that leads to the container MNC.
- VOL MNC The total MNC volume selected for harvesting (VOL MNC ) for the given cycle is thereby present in the tubing T 13 .
- the controller 222 commands the pump P 4 to stop. Further advancement of VOL MNC in the tubing T 13 therefore ceases.
- the controller 222 ends the MNC removal phase, independent of TC 1 and TC 2 when the pump P 4 conveys more than a specified fluid volume of PRBC after TCYC START (e.g., more than 60 ml).
- This time-out circum-stance could occur, e.g., if the optical sensor OS fails to detect THRESH(1).
- VOL PRP 60 ⁇ VOL OFF(1) .
- the controller 222 can end the MNC removal phase independent of TC 1 and TC 2 when the weight scale WS for the container PRBC senses a weight less than a prescribed value (e.g., less than 4 grams, or the weight equivalent of a fluid volume less than 4 ml).
- a prescribed value e.g., less than 4 grams, or the weight equivalent of a fluid volume less than 4 ml.
- the controller 222 enters the PRP flush phase 242 of the MNC harvesting stage 234 . During this phase 242 , the controller 222 configures the circuit 200 to move VOL PRP out of the container PPP and tubing T 12 and into the blood processing compartment 38 .
- the controller 222 configures the pump stations PSL, PSM, and PSR to stop whole blood recirculation, and, while continuing rotation of the compartment 38 , to pump VOL PRP to the processing compartment 38 through tubing T 11 .
- VOL PRP is conveyed by the pump P 6 through tubing T 12 into the right cassette 23 R, and thence to tubing T 11 , for entry into the processing compartment 38 through tubing T 4 and port 48 .
- PRBC are conveyed from the processing compartment 38 through port 50 and tubing T 5 into the middle cassette 23 M, and thence into tubings T 8 and T 7 into the left cassette 23 L.
- the PRBC is conveyed into tubing T 9 for return to the donor/patient. No other fluid is conveyed in the fluid circuit 15 during this phase 242 .
- VOL PRP restores the volume of liquid in container PPP to VOL SUS as collected during the preliminary processing cycle 228 previously described.
- the return of VOL PRP also preserves a low platelet population in the VOL SUS in the container PPP slated for suspension of MNC.
- the controller 222 With the return of VOL PRP to the compartment 38 , the controller 222 enters the MNC suspension phase 244 of the MNC harvesting stage 234 . During this phase 244 , a portion of the VOL SUS in the container PPP is conveyed with VOL MNC into the container MNC.
- the controller closes C 3 to stop the return to PRBC to the donor/patient.
- a predetermined aliquot of VOL SUS e.g., 5 ml to 10 ml
- the pump P 6 is conveyed by the pump P 6 through tubing T 12 into the right cassette 23 R and then into tubing T 13 .
- the aliquot of VOL SUS further advances VOL MNC through the tubing T 13 into the container MNC.
- the controller 222 enters the final, clean up phase 246 of the MNC harvesting stage 234 . During this phase 246 , the controller 222 returns PRBC resident in the tubing T 10 to the processing compartment 38 .
- the controller 222 closes all valve stations in the left and middle cassettes 23 L and 23 M and configures the right pump station PSR to circulated PRBC from tubing T 10 back into the processing compartment 38 through tubings T 11 and T 4 . During this period, no components are being drawn from or returned to the donor/patient.
- the controller 222 commences a new main processing cycle 230 .
- the controller 222 repeats a series of main processing cycles 230 until the desired volume of MNC targeted for the entire procedure is reached.
- the operator may desire additional VOL SUS to further dilute the MNC collected during the procedure.
- the controller 222 can be commanded to configure the fluid circuit 200 to carry out a preliminary processing cycle 228 , as above described, to collect additional VOL SUS in the container PPP.
- the controller 222 then configures the fluid circuit 200 to carry out an MNC suspension phase 244 , to convey additional VOL SUS into the container MNC to achieve the desired dilution of VOL MNC .
- FIG. 29 shows an alternative embodiment of a fluid circuit 300 , which is suited for collecting and harvesting MNC.
- the circuit 300 is in most respects the same as the circuit 200 , shown in FIG. 6, and common components are given the same reference numbers.
- the circuit 300 differs from the circuit 200 in that the second compartment 310 of the container 14 is identical to the compartment 38 , and thereby itself comprises a second blood processing compartment with the same features as compartment 38 .
- the compartment 310 includes interior seals, as shown for compartment 38 in FIG. 4, creating the same blood collection regions for PRP and PRBC, the details of which are not shown in FIG. 29.
- the compartment 310 includes a port 304 for conveying whole blood into the compartment 310 , a port 306 for conveying PRP from the compartment 310 , and a port 302 for conveying PRBC from the compartment 310 .
- Compartment 310 also includes a tapered ramp 84 , as shown in FIGS. 16A and 16B and as earlier described in connection with the compartment 38 .
- the fluid circuit 300 also differs from the fluid circuit 200 in that tubings T 14 , T 18 , and T 19 are not included. In addition, the container PRBC is not included. Instead, fluid circuit 300 includes several new tubing paths and clamps, as follows:
- Tubing path T 21 leads from the PRP outlet port 306 of the compartment 310 through a new clamp C 5 to join tubing path T 10 .
- Tubing path T 22 leads from the WB inlet port 306 of the compartment 310 through a new air detector D 3 and a new clamp C 6 to join tubing path T 3 .
- Tubing path T 33 leads from the PRBC outlet port 302 of the compartment 310 through a new clamp C 8 to join tubing T 4 .
- New clamp C 7 is also provided in tubing T 3 upstream of the air detector D 1 .
- New clamp C 9 is also provided in tubing T 10 between the optical sensor OS and the junction of new tubing T 21 .
- the controller 222 proceeds through the previous described priming cycle 226 , preliminary processing cycle 228 , and main processing cycle 230 as previously described for circuit 200 , up through the MNC accumulation phase 236 .
- the PRBC collect phase 238 differs when using the circuit 300 , in that PRBC used for subsequent removal of MNC from the compartment 38 are processed and collected in the second compartment 310 .
- the controller 222 conveys a volume of whole blood from the donor/patient into the second compartment 310 .
- the whole blood volume is drawn by pump P 2 through tubing T 1 into tubing T 3 and thence through open clamp C 6 into tubing T 22 , which leads to the compartment 310 .
- Clamp C 7 is closed, to block conveyance of whole blood into the compartment 38 , where the MNC have been accumulated for harvesting.
- Clamp C 9 is also closed to block conveyance of PRP from the compartment 38 , thereby keeping the accumulation of MNC undisturbed in the compartment 38 .
- the whole blood volume is separated into PRBC and PRP, in the same fashion that these components are separated in the compartment 38 .
- PRP is conveyed from the compartment 310 through tubing T 23 and open clamp C 5 by operation of the pump P 5 , for return to the donor/patient.
- the clamp C 8 is closed, to retain PRBC in the compartment 310 .
- the controller 222 also conducts a different MNC removal phase 240 using circuit 300 . As shown in FIG. 31, during the MNC removal phase 240 , the controller 222 recirculates a portion of the drawn whole blood back to the donor/patient, while directing another portion of the whole blood into the compartment 310 , following the same path as previously described in connection with FIG. 30.
- the controller 222 opens clamps C 8 and C 9 , while closing clamp CS.
- the whole blood entering the compartment 310 displaces PRBC through the PRBC outlet port 302 into tubing T 23 .
- the PRBC from the compartment 310 enters the WB inlet port 48 of the compartment 38 .
- the incoming flow of PRBC from outside the compartment 38 increases the hematocrit of PRBC within the compartment 38 , causing the accumulated MNC to float to the interface 58 .
- the incoming PRBC from outside the compartment 38 displaces PRP through the PRP port 46 , together with the MNC Region, shown in FIG. 31. This MNC Region is detected by the optical sensor OS and harvested in subsequent processing 242 , 244 , and 246 in the same fashion as described for circuit 200 .
Abstract
Blood processing systems and methods rotate a processing chamber on a rotating element. The processing chamber includes a first compartment and a second compartment. Blood is conveyed into the first compartment for centrifugal separation into components. A liquid free of blood occupies the second compartment to counter-balance the first compartment during rotation on the rotating element. In one embodiment, the second compartment is served by a single fluid flow access. Prior to use, the single access is coupled to tubing, through which a vacuum is drawn to remove air from the second compartment. While the vacuum exists, communication is opened between the tubing and a source of liquid. The vacuum draws the liquid into the second compartment through the single access, thereby priming the second compartment for use.
Description
- This application is a divisional of copending U.S. patent application Ser. No. 09/669,752 filed Sep. 26, 2000, which is a divisional of application Ser. No. 09/377,339 filed Aug. 19, 1999 (now U.S. Pat. No. 6,168,561), which is a divisional of application Ser. No. 08/886,179 filed Jul. 1, 1997 (now U.S. Pat. No. 6,027,441).
- The invention relates to centrifugal processing systems and apparatus.
- Today blood collection organizations routinely separate whole blood by centrifugation into its various therapeutic components, such as red blood cells, platelets, and plasma.
- Conventional blood processing systems and methods use durable centrifuge equipment in association with single use, sterile processing chambers, typically made of plastic. The centrifuge equipment introduces whole blood into these chambers while rotating them to create a centrifugal field.
- Whole blood separates within the rotating chamber under the influence of the centrifugal field into higher density red blood cells and platelet-rich plasma. An intermediate layer of leukocytes forms the interface between the red blood cells and platelet-rich plasma.
- One aspect of the invention provides blood processing systems and methods comprising a processing chamber carried on a rotating element. The processing chamber includes a first compartment containing blood for centrifugal separation into components. The processing chamber also includes a second compartment containing a liquid free of blood. The liquid in the second compartment counter-balances the first compartment during rotation on the rotating element.
- In a preferred embodiment, the second compartment is substantially free of air, and the liquid in the second compartment is subject to a positive pressure.
- In one embodiment, the second compartment has a single access, e.g., a single access port or multiple ports served by a single access path, such that two way fluid flow simultaneously into and out of the compartment is not possible. Another aspect of the invention provides systems and methods to prime the single access compartment, or any like chamber serviced by a single access. The systems and methods operate a pump element to draw a vacuum in the chamber through the single access. While the vacuum exists, the systems and methods open communication between the chamber and a source of liquid. The vacuum draws the liquid into the chamber through the single access to prime the chamber.
- In a preferred embodiment, the systems and methods command a pump element to convey the liquid into the chamber while the vacuum also draws the liquid into the chamber. A positive pressure condition is thereby established in the primed chamber.
- Other features and advantages of the invention will become apparent upon reviewing the following specification, drawings, and appended claims.
- FIG. 1 is a side section view of a blood centrifuge having a separation chamber that embodies features of the invention;
- FIG. 2 shows the spool element associated with the centrifuge shown in FIG. 1, with an associated processing container wrapped about it for use;
- FIG. 3A is a perspective view of the centrifuge shown in FIG. 1, with the bowl and spool elements pivoted into their access position;
- FIG. 3B is a perspective view of the bowl and spool elements in their mutually separation condition to allow securing the processing container shown in FIG. 2 about the spool element;
- FIG. 4 is a plan view of the processing container shown in FIG. 2;
- FIG. 5 is a perspective view of a fluid circuit associated with the processing container, which comprises cassettes mounted in association with pump stations on the centrifuge;
- FIG. 6 is a schematic view of the fluid circuit shown in FIG. 5;
- FIG. 7 is a perspective view of the back side of a cassette that forms a part of the fluid circuit shown in FIG. 6;
- FIG. 8 is a perspective view of the front side of the cassette shown in FIG. 7;
- FIG. 9 is a schematic view of the flow channels and valve stations formed within the cassette shown in FIG. 7;
- FIG. 10 is a schematic view of a pump station intended to receive a cassette of the type shown in FIG. 7;
- FIG. 11 is a schematic view of the cassette shown in FIG. 9 mounted on the pump station shown in FIG. 10;
- FIG. 12 is a perspective view of a cassette and a pump station which form a part of the fluid circuit shown in FIG. 6;
- FIG. 13 is a top view of a peristaltic pump that forms a part of the fluid circuit shown in FIG. 6, with the pump rotor in a retracted position;
- FIG. 14 is a top view of a peristaltic pump that forms a part of the fluid circuit shown in FIG. 6, with the pump rotor in an extended position engaging pump tubing;
- FIG. 15 is a diagrammatic top view of the separation chamber of the centrifuge shown in FIG. 1, laid out to show the radial contours of the high-G and low-G walls;
- FIGS. 16A and 16B somewhat diagrammatically show a portion of the platelet-rich plasma collection zone in the separation chamber, in which the high-G wall surface forms a tapered wedge for containing and controlling the position of the interface between the red blood cells and platelet-rich plasma;
- FIG. 17 is a somewhat diagrammatic view of the interior of the processing chamber, looking from the low-G wall toward the high-G wall in the region where whole blood enters the processing chamber for separation into red blood cells and platelet-rich plasma, and where platelet-rich plasma is collected in the processing chamber;
- FIG. 18 is a diagrammatic view showing the dynamic flow conditions established that confine and “park” MNC within the blood separation chamber shown in FIG. 17;
- FIG. 19 is a schematic view of the process controller which configures the fluid circuit shown in FIG. 6 to conduct a prescribed MNC collection procedure;
- FIG. 20 is a flow chart showing the various cycles and phases of the MNC collection procedure that the controller shown in FIG. 19 governs;
- FIG. 21 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 during the preliminary processing cycle of the procedure shown in FIG. 20;
- FIG. 22 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 during the MNC accumulation phase of the procedure shown in FIG. 20;
- FIG. 23 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 during the PRBC collection phase of the procedure shown in FIG. 20;
- FIG. 24A is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 at the beginning of the MNC removal phase of the procedure shown in FIG. 20;
- FIG. 24B is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 during the MNC removal phase of the procedure shown in FIG. 20;
- FIG. 24C is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 at the end of the MNC removal phase of the procedure shown in FIG. 20;
- FIG. 25 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 during the PRP flush phase of the procedure shown in FIG. 20;
- FIG. 26 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 during the MNC suspension phase of the procedure shown in FIG. 20;
- FIG. 27 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 6 during the clean up phase of the procedure shown in FIG. 20;
- FIG. 28 is a schematic view of the optical sensor used in association with the circuit shown in FIG. 6 to sense and quantify the MNC region for harvesting;
- FIG. 29 is an alternative embodiment of a fluid circuit suited for collecting and harvesting MNC;
- FIG. 30 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 29 during the PRBC collection phase of the procedure shown in FIG. 20; and
- FIG. 31 is a schematic view showing the conveyance of blood components and fluids in the circuit shown in FIG. 29 during the MNC removal phase of the procedure shown in FIG. 20.
- The invention may be embodied in several forms without departing from its spirit or essential characteristics. The scope of the invention is defined in the appended claims, rather than in the specific description preceding them. All embodiments that fall within the meaning and range of equivalency of the claims are therefore intended to be embraced by the claims.
- I. The Centrifuge
- FIG. 1 shows a
blood centrifuge 10 having ablood processing chamber 12 suitable for harvesting mononuclear cells (MNC) from whole blood. The boundaries of thechamber 12 are formed by aflexible processing container 14 carried within anannular gap 16 between arotating spool element 18 andbowl element 20. In the illustrated and preferred embodiment, theprocessing container 14 takes the form of an elongated tube (see FIG. 2), which is wrapped about thespool element 18 before use. - Further details of the
centrifuge 10 are set forth in U.S. Pat. No. 5,370,802, entitled “Enhanced Yield Platelet Systems and Methods,” which is incorporated herein by reference. - The bowl and
spool elements yoke 22 between an upright position, as FIGS. 3A and 3B show, and a suspended position, as FIG. 1 shows. - When upright, the bowl and
spool elements bowl elements container 14 about thespool element 20, as FIG. 2 shows.Pins 150 on thespool element 20 engage cutouts on thecontainer 14 to secure thecontainer 14 on thespool element 20. - When closed, the spool and
bowl elements centrifuge 10 rotates the suspended bowl andspool elements axis 28, creating a centrifugal field within theprocessing chamber 12. - Further details of the mechanism for causing relative movement of the spool and
bowl elements - The radial boundaries of the centrifugal field (see FIG. 1) are formed by the
interior wall 24 of thebowl element 18 and theexterior wall 26 of thespool element 20. Theinterior bowl wall 24 defines the high-G wall. Theexterior spool wall 26 defines the low-G wall. - II. The Processing Container
- In the illustrated embodiment (see FIG. 4), a first
peripheral seal 42 forms the outer edge of thecontainer 14. A secondinterior seal 44 extends generally parallel to therotational axis 28, dividing thecontainer 14 into twocompartments - In use, whole blood is centrifugally separated in the
compartment 38. In use, thecompartment 40 carries a liquid, such as saline, to counter-balance thecompartment 38. In the embodiment shown in FIG. 4, thecompartment 38 is larger than thecompartment 40 by a volumetric ratio of about 1 to 1.2. - Three
ports processing compartment 38, to convey whole blood and its components. Twoadditional ports ballast compartment 40 to convey the counter-balancing fluid. - III. The Fluid Processing Circuit
- A fluid circuit200 (see FIG. 4) is coupled to the
container 14. FIG. 5 shows the general layout of thefluid circuit 200, in terms of an array of flexible tubing, liquid source and collection containers, in-line pumps, and clamps, all of which will be described in greater detail later. FIG. 6 shows the details of thefluid circuit 200 in schematic form. - In the illustrated embodiment, left, middle, and right cassettes, respectively23L, 23M, and 23R, centralize many of the valving and pumping functions of the
fluid circuit 200. The left, middle, andright cassettes centrifuge 10, which are designated, respectively, PSL, PSM, and PSR. - A. The Cassettes
- Each
cassette cassette 23L is applicable to all cassettes. FIGS. 7 and 8 show the structural details of thecassette 23L. - The
cassette 23L comprises a moldedplastic body 202.Liquid flow channels 208 are integrally molded into on thefront side 204 of thebody 202. Arigid panel 214 covers and seals thefront body side 204. -
Valve stations 210 are molded into theback side 206 of thecassette body 202. Aflexible diaphragm 212 covers and seals theback side 206 of thebody 202. - FIG. 9 schematically shows a representative array of
flow channels 208 andvalve stations 210 for each cassette. As shown, channels C1 to C6 intersect to form a star array, radiating from a central hub H. Channel C7 intersects channel C5; channel C8 intersects channel C6; channel C9 intersects channel C3; and channel C10 intersects channel C2. Of course, other channel patterns can be used. - In this arrangement, valve stations VS1, VS2, VS9, and VS10 are located in, respectively, channels C2, C3, C5, and C6 immediately next to their common intersection at the hub H. Valve stations VS3, VS4, VS5, VS6, VS7, and VS8 are located at the outer extremities of channels C8, C1, C2, C5, C4, and C3, respectively.
- Each
cassette 23L carries an upper flexible tubing loop UL, which extends outside thecassette 23L between channels C7 and C6, and a lower tubing loop LL, which extends outside the cassette between channels C3 and C10. In use, the tube loops UL and LL engage the peristaltic pump rotors of the pumps on the associated pump station. - B. The Pumping Stations
- The pump stations PSL, PSM, and PSR are, like the
cassettes - The station PSL includes two peristaltic pumps, for a total of six pumps in the
circuit 200, which are designated P1 to P6 (see FIG. 6). The station PSL also includes an array of ten valve actuators (which FIG. 10 shows), for a total of thirty valve actuators in thecircuit 200, which designated VA1 to VA30 (see FIG. 6). - In use (see FIG. 11), the tube loops UL and LL of
cassette 23L engage pumps P1 and P2 of the left pump station PSL. In like fashion (as FIG. 6 shows), the tube loops UL and LL of themiddle cassette 23M engage pumps P3 and P4. The tube loops UL and LL of theright cassette 23L engage pumps P5 and P6. - As FIG. 11 shows, the valve stations VS1 to VS10 of the
cassette 23L align with the valve actuators V1 to V10 of the left pump station PSL. As FIG. 6 shows, the valve stations of the middle andright cassettes - The following Table 1 summarizes the operative association of the pump station valve actuators V1 to V30 to the cassette valve stations S1 to VS10 shown in FIG. 6.
TABLE 1 Alignment of Cassette Valve Stations to Valve Actuators Left Cassette Middle Cassette Right Cassette Valve Chambers 23L 23M 23R VS1 Valve Actuator Valve Actuator Valve Actuator V1 V11 V21 VS2 Valve Actuator Valve Actuator Valve Actuator V2 V12 V22 VS3 Valve Actuator Valve Actuator Valve Actuator V3 V13 V23 VS4 Valve Actuator Valve Actuator Valve Actuator V4 V14 V24 VS5 Valve Actuator Valve Actuator Valve Actuator V5 V15 V25 VS6 Valve Actuator Valve Actuator Valve Actuator V6 V16 V26 VS7 Valve Actuator Valve Actuator Valve Actuator V7 V17 V27 VS8 Valve Actuator Valve Actuator Valve Actuator V8 V18 V28 VS9 Valve Actuator Valve Actuator Valve Actuator V9 V19 V29 VS10 Valve Actuator Valve Actuator Valve Actuator V10 V20 V30 - The
cassettes back sides 206 down, so that thediaphragms 212 face and engage the valve actuators. The valve actuators Vn are solenoid-actuated rams 215 (see FIG. 12), which are biased toward a valve closing position. The valve actuators Vn are patterned to align with the cassette valve stations VSn in the manner set forth in Table 1. When a givenram 215 is energized, the associated cassette valve station is opened, allowing through-passage of liquid. When theram 215 is not energized, it displaces thediaphragm 212 into the associated valve station, blocking passage of liquid through the associated valve station. - In the illustrated embodiment, as FIG. 12 shows, the pumps P1 to P6 on each pump station PSL, PSM, and PSR include rotating
peristaltic pump rotors 216. Therotors 216 can be moved between a retracted condition (shown in FIG. 13), out of engagement with the respective tube loop, and an operating condition (shown in FIG. 14), in which therotors 216 engage the respective tube loop against apump race 218. - The pumps P1 and P6 can thereby be operated in three conditions:
- (i) in a pump on condition, during which the
pump rotors 216 rotate and are in their operating position to engage the pump tubing against the pump race 218 (as FIG. 14 shows). Therotating pump rotors 216 therefore convey fluid in a peristaltic fashion through the tubing loop. - (ii) in an opened, pump off condition, during which the
pump rotors 216 are not rotated and are in their retracted position, so as not to engage the pump tubing loop (as FIG. 13 shows). The opened, pump off condition therefore permits fluid flow through the pump tube loop in the absence of pump rotor rotation. - (iii) in a closed, pump off condition, during which the
pump rotors 216 are not rotated, and the pump rotors are in the operating condition. Thestationary pump rotors 216 thereby engage the pump tubing loop, and serve as a clamp to block fluid flow through the pump tubing loop. - Of course, equivalent combinations of pump conditions can be achieved using peristaltic pump rotors that do not retract, by suitable placement of clamps and tubing paths upstream and downstream of the pump rotors.
- Further structural details of the
cassettes - C. The Fluid Flow Tubing
- The
fluid circuit 200 further includes lengths of flexible plastic tubing, designated T1 to T20 in FIG. 6. The flexible tubing T1 to T20 couple thecassettes processing container 14, to external source and collection bags or containers, and to the blood donor/patient. - The fluid flow function of the tubing T1 to T20 in connection with collecting and harvesting MNC will be described later. The following summarizes, from a structural standpoint, the attachment of the tubing T1 to T20, as shown in FIG. 6:
- Tubing T1 extends from the donor/patient (via a conventional phlebotomy needle, not shown) through an external clamp C2 to channel C4 of the
left cassette 23L. - Tubing T2 extends from tube T1 through an external clamp C4 to channel C5 of the
middle cassette 23M. - Tubing T3 extends from an air detection chamber D1 to channel C9 of the
left cassette 23L. - Tubing T4 extends from the drip chamber D1 to
port 48 of theprocessing container 14. - Tubing T5 extends from
port 50 of theprocessing container 14 to channel C4 of themiddle cassette 23M. - Tubing T6 extends from channel C9 of the
middle cassette 23M to join tubing T4 downstream of the chamber D1. - Tubing T7 extends from channel C8 of the
right cassette 23M to channel C8 of theleft cassette 23L. - Tubing T8 extends from channel C1 of the
middle cassette 23M to join tubing T7. - Tubing T9 extends from channel C5 of the
left cassette 23L through an air detection chamber D2 and an external clamp C3 to the donor/patient (via a conventional phlebotomy needle, not shown). - Tubing T10 extends from
port 46 of theprocessing container 14, through an in line optical sensor OS to channel C4 of theright cassette 23R. - Tubing T11 extends from channel C9 of the
right cassette 23R to the chamber D1. - Tubing T12 extends from channel C2 of the
right cassette 23R to a container intended to receive platelet-poor plasma, designated PPP. A weight scale (not shown) senses weight of the container PPP for the purpose of deriving fluid volume changes. - Tubing T13 extends from channel C1 of the
right cassette 23R to a container intended to receive mono-nuclear cells, designated MNC. - Tubing T14 extends from channel C2 of the
middle cassette 23M to a container intended to receive packed red blood cells, designated PRBC. A weight scale WS senses weight of the container PRBC for the purpose of deriving fluid volume changes. - Tubing T15 extends from a container of anticoagulant, designated ACD, to channel C8 of the
middle cassette 23M. A weight scale (not shown) senses weight of the container ACD for the purpose of deriving fluid volume changes. - Tubing T16 and T17 extend from a container of priming liquid, such as saline, designated PRIME, bypassing all
cassettes - Tubing T18 extends from the
port 52 of theprocessing container 14 to channel C5 of theright cassette 23R. - Tubing T19 extends from the
port 54 of theprocessing container 14 to intersect tubing T18. - Tubing T20 extends from channel C2 of the
left cassette 23L to a container intended to receive waste priming fluid, designated WASTE. A weight scale (not shown) senses weight of the container WASTE for the purpose of deriving fluid volume changes. - Portions of the tubing are joined in umbilicus30 (see FIG. 1). The
umbilicus 30 provides fluid flow communication between the interior of theprocessing container 14 within the centrifugal field and other stationary components of thecircuit 200 located outside the centrifugal field. A non-rotating (zero omega)holder 32 holds the upper portion of the umbilicus 30 in a non-rotating position above the suspended spool andbowl elements holder 34 on theyoke 22 rotates the mid-portion of the umbilicus 30 at a first (one omega) speed about the suspended spool andbowl elements holder 36 rotates the lower end of the umbilicus 30 at a second speed twice the one omega speed (the two omega speed), at which the suspended spool andbowl elements umbilicus 30 keeps it untwisted, in this way avoiding the need for rotating seals. - IV. Separation in the Blood Processing Chamber (An Overview)
- Before explaining the details of the procedure by which MNC are collected using the
container 14 and thefluid circuit 200, the fluid dynamics of whole blood separation in theprocessing compartment 38 will first be generally described, with reference principally to FIGS. 4 and 15 to 17. - Referring first to FIG. 4, anticoagulated whole blood (WB) is drawn from the donor/patient and conveyed into the processing compartment through the
port 48. Theblood processing compartment 38 includes a interior seals 60 and 66, which form aWB inlet passage 72 that leads into aWB entry region 74. - As WB follows a circumferential flow path in the
compartment 38 about therotational axis 28. The sidewalls of thecontainer 14 expand to conform to the profiles of the exterior (low-G)wall 26 of thespool element 18 and the interior (high-G)wall 24 of thebowl element 20. - As FIG. 17 shows, WB separates in the centrifugal field within the
blood processing compartment 38 into packed red blood cells (PRBC, designated by numeral 96), which move toward the high-G wall 24, and platelet-rich plasma (PRP, designated by numeral 98), which are displaced by movement of thePRBC 96 toward the low-G wall 26. An intermediate layer, called the interface (designed by numeral 58), forms between thePRBC 96 andPRP 98. - Referring back to FIG. 4, the
interior seal 60 also creates aPRP collection region 76 within theblood processing compartment 38. As FIG. 17 further shows, thePRP collection region 76 is adjacent to theWB entry region 74. The velocity at which thePRBC 96 settle toward the high-G wall 24 in response to centrifugal force is greatest in theWB entry region 74 than elsewhere in theblood processing compartment 38. There is also relatively more plasma volume to displace toward the low-G wall 26 in theWB entry region 74. As a result, relatively large radial plasma velocities toward the low-G wall 26 occur in theWB entry region 74. These large radial velocities toward the low-G wall 26 elute large numbers of platelets from thePRBC 96 into the close-byPRP collection region 76. - As FIG. 4 shows, the
interior seal 66 also forms a dog-leg 70 that defines aPRBC collection passage 78. A stepped-up barrier 115 (see FIG. 15) extends into the PRBC mass along the high-G wall 24, creating arestricted passage 114 between it and the facing, iso-radial high-G wall 24. Therestricted passage 114 allowsPRBC 96 present along the high-G wall 24 to move beyond thebarrier 115 into thePRBC collection region 50, for conveyance by thePRBC collection passage 78 to thePRBC port 50. Simultaneously, the stepped-upbarrier 115 blocks the passage of thePRP 98 beyond it. - As FIGS. 15, 16A and16B show, the high-
G wall 24 also projects toward the low-G wall 26 to form a taperedramp 84 in thePRP collection region 76. Theramp 84 forms aconstricted passage 90 along the low-G wall 26, along which thePRP 98 layer extends. Theramp 84 keeps theinterface 58 andPRBC 96 away from thePRP collection port 46, while allowingPRP 98 to reach thePRP collection port 46. - In the illustrated and preferred embodiment (see FIG. 16A), the
ramp 84 is oriented at a non-parallel angle α of less than 45° (and preferably about 30°) with respect to the axis of thePRP port 46. The angle α mediates spill-over of the interface and PRBC through the constrictedpassage 90. - As FIGS. 16A and 16B show, the
ramp 84 also displays theinterface 26 for viewing through a side wall of thecontainer 14 by an associated interface controller 220 (see FIG. 19). Theinterface controller 220 controls the relative flow rates of WB, the PRBC, and the PRP through theirrespective ports controller 220 can maintain theinterface 58 at prescribed locations on ramp, either close to the constricted passage 90 (as FIG. 16A shows) or spaced away from the constricted passage 90 (as FIG. 16B shows). - By controlling the position of the
interface 58 on theramp 84 relative to the constrictedpassage 90, thecontroller 220 can also control the platelet content of the plasma collected through theport 46. The concentration of platelets in the plasma increases with proximity to theinterface 58. By maintaining theinterface 58 at a relatively low position on the ramp 84 (as FIG. 16B shows), the platelet-rich region is kept away from theport 46, and the plasma conveyed by theport 46 has a relatively low platelet content. By maintaining theinterface 58 at a high position on the ramp 84 (as FIG. 16A shows), closer to theport 46, the plasma conveyed by theport 46 is platelet-rich. - Alternatively, or in combination, the controller could control the location of the
interface 58 by varying the rate at which WB is introduced into theblood processing compartment 38, or the rate at which PRBC are conveyed from the blood processing compartment 134, or both. - Further details of a preferred embodiment for the interface controller are described in U.S. Pat. No. 5,316,667, which is incorporated herein by reference.
- As FIG. 15 shows, radially opposed
surfaces region 108 along the high-G wall 24 of theWB entry region 74. As FIG. 17 also shows, theregion 108 restricts WB flow in theWB entry region 74 to a reduced passage, thereby causing more uniform perfusion of WB into theblood processing compartment 38 along the low-G wall 26. This uniform perfusion of WB occurs adjacent to thePRP collection region 76 and in a plane that is approximately the same as the plane in which the preferred, controlled position of theinterface 58 lies. Once beyond the constrictedregion 108 of thezone dam 104, thePRBC 96 rapidly move toward the high-G wall 24 in response to centrifugal force. - The constricted
region 108 brings WB into theentry region 74 at approximately the preferred, controlled height of theinterface 58. WB brought into theentry region 74 below or above the controlled height of theinterface 58 will immediately seek the interface height and, in so doing, oscillate about it, causing unwanted secondary flows and perturbations along theinterface 58. By bringing the WB into theentry region 74 approximately at interface level, theregion 108 reduces the incidence of secondary flows and perturbations along theinterface 58. - As FIG. 15 shows, the low-
G wall 26 tapers outward away from the axis ofrotation 28 toward the high-G wall 24 in the direction of WB flow, while the facing high-G wall 24 retains a constant radius. The taper can be continuous (as FIG. 15 shows) or can occur in step fashion. These contours along the high-G and low-G walls PRP collection region 76. As depicted schematically in FIG. 18, the circumferential plasma flow condition in this direction (arrow 214) continuously drags theinterface 58 back toward thePRP collection region 76, where the higher radial plasma flow conditions already described exist to sweep even more platelets off theinterface 58. Simultaneously, the counterflow patterns serve to circulate the other heavier components of the interface 58 (the lymphocytes, monocytes, and granulocytes) back into the PRBC mass, away from the PRP stream. - Within this dynamic circumferential plasma flow condition, MNC (designated as such in FIG. 18) initially settle along the high-
G wall 24, but eventually float up to the surface of theinterface 58 near the high-hematocritPRBC collection region 50. The tapering low-G wall creates the plasma counterflow patterns, shown byarrows 214 in FIG. 18. Thesecounterflow patterns 214 draw the MNC back toward the low-hematocritPRP collection region 76. MNC again resettle near the low-hematocritPRP collection region 76 toward the high-G wall 24. - The MNC circulate in this path, designated216 in FIG. 18, while WB is separated into PRBC and PRP. The MNC are thus collected and “parked” in this confined
path 216 within thecompartment 38 away from both thePRBC collection region 50 and thePRP collection region 76. - Further details of the dynamics of separation in the
processing compartment 38 are found in U.S. Pat. No. 5,573,678, which is incorporated herein by reference. - V. Mononuclear Cell Processing Procedure
- The
centrifuge 10 includes a process controller 222 (see FIG. 19), which commands operation of thefluid circuit 200 to carry out a prescribed MNC collection andharvesting procedure 224 using thecontainer 14. - As FIG. 20 shows, the
procedure 224 comprises apre-processing priming cycle 226, which primes thefluid circuit 200. Theprocedure 224 next includes apreliminary processing cycle 228, which processes PPP from whole blood obtained from the donor/patient for use later in theprocedure 224 as a suspension medium for the harvested MNC. Theprocedure 224 next includes at least onemain processing cycle 230. Themain processing cycle 230 comprises acollection stage 232, followed by aharvesting stage 234. - The
collection stage 232 includes a series of collection phases 236 and 238, during which whole blood is processed to accumulate mononuclear cells in thefirst compartment 38, in the manner previously described. - The harvesting stage likewise includes a series of harvesting phases240, 242, 244, and 246, during which the accumulation of mononuclear cells are transferred from the
first compartment 38 into a collection container MNC coupled to thecircuit 200. Suspension medium, collected during thepreliminary processing cycle 228, is added to the MNC. - Usually, the
main processing cycle 230 will be carried out more than once during a givenprocedure 224. The number ofprocessing cycles 230 conducted in a givenprocedure 224 will depend upon the total volume of MNC sought to be collected. - For example, in a
representative procedure 224, five main processing cycles 230 are repeated, one after the other. During eachmain processing cycle 230, from about 1500 to about 3000 ml of whole blood can be processed, to obtain a MNC volume per cycle of about 3 ml. At the end of the fiveprocessing cycles 230, a MNC volume of about 15 ml can be collected, which is suspended in a final dilution PPP of about 200 ml. - A. Pre-Processing Priming/Ballast Sequence
- Before a donor/patient is coupled to the fluid circuit200 (via tubing T1 and T9), the
controller 222 conducts apriming cycle 228. During thepriming cycle 228, thecontroller 222 commands thecentrifuge 10 to rotate the spool andbowl elements axis 28, while commanding the pumps P1 to P6 to convey a sterile priming liquid, such as saline, from the container PRIME and anticoagulant from the container ACD throughout the entire fluid circuit 15 andcontainer 14. The priming liquid displaces air from the circuit 15 andcontainer 14. - The
second compartment 40 is served by single tubing T18 and therefore has, in effect, a single access port. To accomplish priming, thecompartment 40 is isolated from flow communication with the priming liquid, while pump P5 is operated to draw air from thecompartment 40, thereby creating a negative pressure (vacuum) condition in thecompartment 40. Upon removal of air from thecompartment 40, communication is then opened to the flow of priming liquid, which is drawn into thecompartment 40 by the vacuum. Pump P5 is also operated to aid in the conveyance of liquid into thecompartment 40 and to create a positive pressure condition in thecompartment 40. Thecontroller 222 retains priming liquid in thesecond compartment 40, to counter-balance thefirst compartment 38 during blood processing. - It should, of course, be appreciated that this vacuum priming procedure is applicable to the priming of virtually any container serviced by a single access port or its equivalent.
- B. Preliminary Processing Cycle
- MNC that is harvested in container MNC is preferably suspended in a platelet-poor plasma (PPP) media obtained from the MNC donor/patient. During the
preliminary processing cycle 228, thecontroller 222 configures thefluid circuit 222 to collect a preestablished volume of PPP from the donor/patient for retention in the container PPP. This volume is later used as a suspension medium for the MNC during processing, as well as added to the MNC after processing to achieve the desired final dilution volume. - Once the donor/patient has been phlebotomized, the
controller 222 configures the pump stations PSL, PSM, and PSR to begin thepreliminary processing cycle 228. During thiscycle 228, whole blood is centrifugally separated in thecompartment 38 into packed red blood cells (PRBC) and platelet-rich plasma (PRP), as before described. PRBC are returned to the donor/patient, while mononuclear cells accumulate in thecompartment 38. - As MNC accumulate in the
compartment 38, a portion of the separated plasma component is removed and collected for use as a MNC suspension medium. During thiscycle 228, thecontroller 222 maintains theinterface 58 at a relatively low position on the ramp 84 (as depicted in FIG. 16B). As a result, plasma that is conveyed from thecompartment 38 and stored in the container PPP is relatively poor in platelets, and can thus be characterized as PPP. The remainder of the PPP conveyed from thecompartment 38 is returned to the donor/patient during thiscycle 228. - The configuration of the
fluid circuit 200 during thepreliminary processing cycle 228 is shown in FIG. 21, and is further summarized in Table 2.TABLE 2 Preliminary Processing Cycle V1 V9 V17 ◯ V25 ◯ C1 P1 ◯ V2 V10 ◯ V18 V26 C2 ◯ P2 V3 ◯ V11 V19 V27 ◯ C3 ◯ P3 V4 V12 V20 V28 C4 ◯ P4 V5 V13 ◯ V21 ◯ V29 ◯ P5 V6 ◯ V14 ◯ V22 V30 P6 V7 ◯ V15 V23 ◯ V8 ◯ V16 ◯ V24 - During the
preliminary cycle 228, pump P2 draws whole blood (WB) from the donor/patient through tubing T1 into theleft cassette 23L, into tubing T3, through the chamber D1, and into theblood processing compartment 38 through tubing T4. Pump P3 draws anticoagulant ACD through tubing T15, into themiddle cassette 23M and into tubing T2, for mixing with the whole blood. - The anticoagulated whole blood is conveyed into the
compartment 38 throughport 48. The whole blood is separated into PRP, PRBC, and the interface (including MNC), as previously described. - The
port 50 conveysPRBC 96 from theblood processing compartment 38, through tubing T5 into themiddle cassette 23M. The PRBC enters tubing T7 through tubing T8, for return to the donor/patient via theleft cassette 23L and tubing T9. - The
port 46 conveys PPP from theblood processing compartment 38. The PPP follows tubing T10 into theright cassette 23R. Pump P5 conveys a portion of the PPP into tubing T7 for return with PRBC to the donor/patient. Theinterface controller 220 sets the flow rate of pump P5 to maintain the interface at a low position on the ramp 84 (as shown in FIG. 16B), to thereby minimize the concentration of platelets conveyed from thecompartment 38 during this cycle. Pump P6 conveys a portion of the PPP through tubing T12 into container PPP, until the volume prescribed for MNC suspension and final dilution is collected. This volume is designated VOLsus. - C. Main Processing Cycle
-
- a. MNC Accumulation Phase
- The
controller 222 now switches to the MNC collectstage 232 of themain processing cycle 230. First, thecontroller 222 configures thefluid circuit 200 for theMNC accumulation phase 236. - For the
phase 236, thecontroller 222 changes the configuration of the pump station PSR to stop collection of PPP. Thecontroller 222 also commands theinterface controller 220 to maintain a flow rate for pump P5 to maintain the interface at a higher location on the ramp 84 (such as shown in FIG. 16A), thereby enabling the separation of PRP. - Due to the changed configuration, the pump P6 also recirculates a portion of the PRP to the
blood processing chamber 38 to enhance platelet separation efficiencies, as will be described in greater detail later. - The configuration for the
MNC accumulation phase 236 of the MNC collectstage 232 is shown in FIG. 22, and is further summarized in Table 3.TABLE 3 Mononuclear Cell Collect Condition (MNC Accumulation Phase) V1 V9 V17 ◯ V25 C1 P1 ◯ V2 V10 ◯ V18 ◯ V26 C2 ◯ P2 V3 ◯ V11 V19 V27 ◯ C3 ◯ P3 V4 V12 V20 ◯ V28 ◯ C4 ◯ P4 V5 V13 ◯ V21 ◯ V29 P5 V6 ◯ V14 ◯ V22 V30 ◯ P6 V7 ◯ V15 V23 ◯ V8 ◯ V16 ◯ V24 - b. Promoting High Platelet Separation Efficiencies By Recirculation of PRP
- Normally, platelets are not collected during a MNC procedure. Instead, it is believed desirable to return them to the donor/patient. A high mean platelet volume MPV (expressed in femtoliters, fl, or cubic microns) for separated platelets is desirable, as it denotes a high platelet separation efficiency. MPV can be measured by conventional techniques from a PRP sample. Larger platelets (i.e., larger than about 20 femtoliters) are most likely to become entrapped in the
interface 58 and not enter the PRP for return to the donor/patient. This results in a reduced population of larger platelets in the PRP, and therefore a lower MPV, for return to the donor/patient. - The establishment of radial plasma flow conditions sufficient to lift larger platelets from the
interface 58, as previously described, is highly dependent upon the inlet hematocrit Hi of WB entering theblood processing compartment 38. For this reason, the pump 6 recirculates a portion of the PRP flowing in tubing T10 back into theWB inlet port 48. The recirculating PRP flows through theright cassette 23R into tubing T11, which joins tubing T4 coupled to theinlet port 48. The recirculating PRP mixes with WB entering theblood processing compartment 38, thereby lowering inlet hematocrit Hi. - The controller sets a PRP recirculation flow rate QRecirc for pump P6 to achieve a desired inlet hematocrit Hi. In a preferred implementation, Hi is no greater that about 40%, and, most preferably, is about 32%, which will achieve a high MPV.
- Inlet hematocrit Hi can be conventionally measured by an in-line sensor in tubing T4 (not shown). Inlet hematocrit Hi can also be determined empirically based upon sensed flow conditions, as disclosed in copending U.S. patent application Ser. No. 08/471,883, which is incorporated herein by reference.
- 2. Promoting High MNC Concentration and Purity By Recirculation of PRBC
- As depicted schematically in FIG. 18, the counter flow of plasma (arrows214) in the
compartment 38 drags theinterface 58 back toward thePRP collection region 76, where the enhanced radial plasma flow conditions sweep platelets off theinterface 58 for return to the donor/patient. Thecounterflow patterns 214 also circulate other heavier components of theinterface 58, such as lymphocytes, monocytes, and granulocytes, back for circulation into the PRBC mass. - Meanwhile, due to the relatively high hematocrit in the PRBC collection region80, MNC float near the region 80 to the surface of the
interface 58. There, the MNC are drawn by theplasma counter-flow 214 toward the low-hematocritPRP collection region 76. Due to the lower hematocrit in thisregion 76, MNC resettle again toward the high-G wall 24.Arrow 216 in FIG. 18 shows the desired circulating flow of MNC as it accumulates in thecompartment 38. - Maintaining a desired PRBC outlet hematocrit Ho in the
PRBC collection region 50 is important. If the outlet hematocrit Ho, of the PRBC falls below a given low threshold value (e.g., below about 60%), the majority of MNC will not circulate as a cellular mass, as shown by thearrow 216 in FIG. 18. Exposed to a low Ho all or some of the MNC will fail to float toward theinterface 58. Instead, the MNC will remain congregated along the high-G wall and will be carried out of thecompartment 38 with the PRBC. An insufficient MNC yield results. - On the other hand, if Ho exceeds a given high threshold value (e.g., about 85%), larger numbers of the heavier granulocytes will float on the
interface 58. As a result, fewer granulocytes will be carried away from theinterface 58 for return with the PRBC to the donor/patient. Instead, more granulocytes will occupy theinterface 58 and contaminate the MNC. - For this reason, during the
MNC collection stage 232, theprocess controller 222 commands the pump P4 to recirculate a portion of the PRBC flowing in tubing T5 back into theWB inlet port 48. As FIGS. 21 and 22 show, recirculating PRBC flows through themiddle cassette 23M into tubing T6, which joins tubing T4 coupled to theinlet port 48. The recirculating PRBC mixes with WB entering theblood processing compartment 38. - Generally speaking, the magnitude of the outlet hematocrit Ho varies conversely as a function of PRBC recirculation flow rate Qr, which is governed by the pump P4 (PRBC) and the pump P2 (WB). Given a flow rate for WB set by pump P2, the outlet hematocrit Ho can be increased by lowering Qr, and, conversely, outlet hematocrit Ho can be decreased by raising Qr. The exact relationship between Qr and Ho takes into account the centrifugal acceleration of fluid in the compartment 38 (governed by the magnitude of centrifugal forces in the compartment 38), the area of the
compartment 38, as well as the inlet flow rate whole blood (Qb) into the compartment 38 (governed by pump P2) and the outlet flow rate PRP (Qp) from the compartment 38 (governed by the interface control pump P5). - There are various ways of expressing this relationship and thereby quantifying Qr based upon a desired Ho. In the illustrated embodiment, the
controller 222 periodically samples Qb, Qp, and Qr. Further taking into account the centrifugal force factors active in thecompartment 38, the controller derives a new PRBC recirculation pump rate Qr (NEW) for the pump P4, based upon a targeted Ho, as follows: - (i) Start at sample time n=0
-
- where:
- Ho is the targeted exit hematocrit value, expressed as a decimal (e.g., 0.75 for 75%).
-
- where:
- Ω is the rate of rotation of the
compartment 38, expressed in radians per second. - r is the radius of rotation.
- g is unit gravity, equal to 981 cm/sec2.
- A is the area of the
compartment 38. -
- where:
- C R=1.08 S I
- and where:
-
- and where:
- based upon empirical data, b=6.0 s−n and n=0.75, and shear rate is defined as:
- τ=du/dy
- in which (u) is the fluid velocity and (y) is a spatial dimension.
- and where:
- Sr is an empirically derived red blood cell sedimentation factor, which, upon empirical data, can be set at 95×10−9 s.
- This model is based upon Equation (19) of Brown, “The Physics of Continuous Flow Centrifugal Cell Separation,”Artificial Organs; 13(1):4-20, Raven Press, Ltd., New York (1989) (the “Brown Article”), which is incorporated herein by reference. The plot of the model appears in FIG. 9 of the Brown Article.
- The above model is linearized using simple linear regression over an expected, practical operating range of blood processing conditions. Algebraic substitutions are made based upon the following expressions:
- HiQb=HoQo
- where:
- Qo is the flow rate of PRBC through outlet tubing T5, which can be expressed as:
- Qo=Qb−Qp
- This linearization yields a simplified curve in which the value of (m) constitutes the slope and the value of (k) constitutes the y-intercept.
-
- where:
- β/Sr can, based upon empirical data, be expressed as a constant value of 1.57/μs.
- Therefore, in the simplified curve, m has a value of 531.13. A range of values for m between about 500 and about 600 is believed to be applicable to centrifugal, continuous flow whole blood separation procedures, in general.
- For the simplified curve, the y-intercept value for (k) equals 0.9489. A range of values for k between about 0.85 and about 1.0 is believed to be applicable to centrifugal, continuous flow whole blood separation procedures, in general.
- (iii) Calculate Average Qr
- Qr is measured at selected intervals, and these instantaneous measurements are averaged over the processing period, as follows:
- Q r(AVG)=[0.95(Q r(AVG LAST)]+[0.05 *Q r]
- (iv) Calculate New Qr, as Follows:
- Q r(NEW)=Q r(AVG)*F
- where:
- F is an optional control factor, which enables the control of Qr (when F=1), or disables the control of Qr (when F=0), or enables a scaling of Qr based upon system variances (when F is expressed as a fraction between 0 and 1). F can comprise a constant or, alternatively, it can vary as a function of processing time, e.g., starting at a first value at the outset of a given procedure and changing to a second or more values as the procedure progresses.
- (v) Keep Qr within prescribed limits (e.g., between 0 ml/min and 20 ml/min)
- IF
- Qr(NEW)>20 ml/min THEN
- Q r(NEW)=20 ml/min
- ENDIF
- IF
- Q r(NEW)<0 ml/min THEN
- Q r(NEW)=0ml/min
- ENDIF
- n=n+1
- During the MNC collect stage232 (FIG. 22), the
controller 222 simultaneously sets and maintains multiple pump flow rates to achieve processing conditions in thecompartment 38 optimal for the accumulation of a high yield of MNC of high purity. The controller sets and maintains WB inlet flow rate Qb (via the pump P2), PRP outlet flow rate Qp (via the pump PS), PRP recirculation flow rate QRecirc (via the pump P6), and PRBC recirculation flow rate Qr (via the pump P4). Given a WB inlet flow rate Qb, which is typically set for donor/patient comfort and the achievement of an acceptable processing time, the controller 222: - (i) commands pump PS to maintain a Qp set to hold a desired interface position on the
ramp 84, and thereby achieve the desired platelet concentrations in the plasma (PPP or PRP); - (ii) commands the pump P6 to maintain a QRecirc set to hold the desired inlet hematocrit Hi (e.g., between about 32% and 34%), and thereby achieve high platelet separation efficiencies; and
- (iii) commands the pump P4 to maintain a Qr set to hold a desired outlet hematocrit Ho (e.g., between about 75% to 85%), and thereby prevent granulocyte contamination and maximize MNC yields.
- 3. Second Phase (PRBC Collect)
- The
controller 222 terminates theMNC accumulation phase 236 when a preestablished volume of whole blood (e.g., 1500 ml to 3000 ml) is processed. Alternatively, the MNC accumulation phase can be terminated when a targeted volume of MNC is collected. - The
controller 22 then enters thePRBC collection phase 238 of theMNC collection stage 232. In thisphase 238, the configuration of the pump station PSM is altered to stop the return of PRBC to the donor/patient (by closing V14), stop the recirculation of PRBC (by closing valve V18 and placing pump P4 into a closed, pump off condition, and instead conveying PRBC to the container PRBC (by opening V15). - This new configuration is shown in FIG. 23, and is further summarized in Table 4.
TABLE 4 Mononuclear Cell Collect Stage (Collect PRBC Phase) V1 V9 V17 ◯ V25 C1 P1 ◯ V2 V10 ◯ V18 V26 C2 ◯ P2 V3 ◯ V11 V19 V27 ◯ C3 ◯ P3 V4 V12 V20 ◯ V28 ◯ C4 ◯ P4 V5 V13 ◯ V21 ◯ V29 P5 V6 ◯ V14 V22 V30 P6 V7 ◯ V15 ◯ V23 ◯ V8 ◯ V16 ◯ V24 - In this
phase 238, PRBC in line TS is conveyed through themiddle cassette 23M, into line T14, and into the container PRBC. Thecontroller 222 operates in thisphase 238 until a desired volume of PRBC (e.g., 35 ml to 50 ml) collects in the container PRBC. This PRBC volume is later used in theMNC removal phase 240 of theMNC harvesting stage 234, as will be described in greater detail later. - The
controller 222 ends thePRBC collection phase 238 upon sensing (gravimetrically, using the weight scale WS) that the container PRBC holds the desired volume of PRBC. - The ends the
MNC collection stage 232 of themain processing cycle 230. - 4. Mononuclear Cell Harvesting Stage
- a. First Phase (MNC Removal)
- The
controller 222 enters theMNC harvesting stage 234 of themain processing cycle 230. In thefirst phase 240 of thisstage 234, whole blood is drawn and recirculated back to the donor/patient without passage through theblood processing compartment 38. PRBC collected in the container PRBC in the precedingPRBC collection phase 238 is returned to theprocessing compartment 38 through WB inlet tubing T4, while rotation of thecompartment 38 continues. The MNC accumulated in thecompartment 38 during theMNC collection stage 232 is conveyed with PRP through tubing T10 out of thecompartment 38. - The configuration of the fluid circuit15 during the
MNC removal phase 240 of theMNC harvesting stage 234 is shown in FIG. 24A, and is further summarized in Table 5:TABLE 5 Mononuclear Cell Harvesting Stage (MNC Removal Phase) V1 V9 ◯ V17 ◯ V25 ◯ C1 P1 or V2 ◯ V10 ◯ V18 ◯ V26 C2 ◯ P2 V3 V11 V19 V27 ◯ C3 ◯ P3 V4 V12 V20 V28 ◯ C4 ◯ P4 V5 V13 ◯ V21 ◯ V29 P5 V6 ◯ V14 V22 V30 ◯ P6 V7 ◯ V15 ◯ V23 ◯ V8 ◯ V16 ◯ V24 - As FIG. 24A shows, the
controller 222 closes PRBC outlet tubing T5 while PRBC is conveyed by pump P4 from the container PRBC through tubing T14 and T6 into tubing T4, for introduction intocompartment 38 through theWB inlet port 48. Thecontroller 222 starts a cycle time counter at TCYCSTART. - The inflow of PRBC from the container PRBC through the
WB inlet port 48 increases the hematocrit in thePRP collection region 76. In response, the concentrated region of MNC accumulated in the compartment 38 (as shown in FIG. 18), float to the surface of theinterface 58. The incoming PRBC volume displaces PRP through thePRP outlet port 46. Theinterface 58, and with it, the concentrated MNC region (designated MNC Region in FIG. 24A) are also displaced out of thecompartment 38 through thePRP outlet port 46. The MNC Region moves along the PRP tubing T10 toward the optical sensor OS. - As FIG. 28 shows, within the tubing T10, a
region 112 of PRP precedes the concentrated MNC Region. The PRP in thisregion 112 is conveyed into the container PPP through theright cassette 23R and tubing T12 (as FIG. 24A shows). Aregion 114 of PRBC also follows the concentrated MNC Region within the tubing T10. - A
first transition region 116 exists between thePRP region 112 and concentrated MNC Region. Thefirst transition region 116 consists of a steadily decreasing concentration of platelets (shown by a square pattern in FIG. 28) and a steadily increasing number of MNC's (shown by a textured pattern in FIG. 28). - A
second transition region 118 exists between the concentrated MNC Region and thePRBC region 114. Thesecond transition region 118 consists of a steadily decreasing concentration of MNC's (shown by the textured pattern in FIG. 28) and a steadily increasing number of PRBC's (shown by a wave pattern in FIG. 28). - Viewed by the optical sensor OS, the
regions regions PRP outlet port 46 and theright cassette 23R. As FIG. 28 shows, the optical density will change from a low value, indicating highly light transmissive (i.e., in the PRP region 112), to a high value, indicating highly light absorbent (i.e., in the PRBC region 114), as the MNC Region progresses past the optical sensor OS. - In the illustrated embodiment shown in FIG. 28, the optical sensor OS is a conventional hemoglobin detector, used, e.g., on the Autopheresis-C® blood processing device sold by the Fenwal Division of Baxter Healthcare Corporation. The sensor OS comprises a red
light emitting diode 102, which emits light through the tubing T10. Of course, other wavelengths, like green or infrared, could be used. The sensor OS also includes a PIN diode detector 106 on the opposite side of the tubing T10. - The
controller 222 includes aprocessing element 100, which analyzes voltage signals received from theemitter 102 and detector 106 to compute the optical transmission of the liquid in the tubing T10, which is called OPTTRANS. - Various algorithms can be used by the
processing element 100 to compute OPTTRANS. - For example, OPTRANS can equal the output of the diode detector106 when the red
light emitting diode 102 is on and the liquid flows through the tubing T10 (RED). -
- where COR(RED SPILL) is calculated as follows: COR(RED SPILL)=RED-REDBKGRD
- where:
- RED is the output of the diode detector106 when the red
light emitting diode 102 is on and the liquid flows through the tubing T10; - REDBKGRD is the output of the diode detector106 when the red
light emitting diode 102 is off and the liquid flows through the tubing T10; - and where CORREF is calculated as follows:
- CORREF=REF−REFBKGRD
- where:
- REF is the output of the red
light emitting diode 102 when the diode is on; and - REFBKGRD is the output of the red
light emitting diode 102 when the diode is off. - The
processing element 100 normalizes the sensor OS to the optical density of the donor/patient's PRP, by obtaining data from the sensor OS during the precedingMNC collection stage 232, as the donor/patient's PRP conveys through the tubing T10. This data establishes a baseline optical transmission value for the tubing and the donor/patient's PRP (OPTTRANSBASE). For example, OPTTRANSBASE can be measured at a selected time during thecollection stage 232, e.g., half way through thestage 232, using either a filtered or non-filtered detection scheme, as described above. Alternatively, a set of optical transmission values are calculated during theMNC collection stage 232 using either a filtered or non-filtered detection scheme. The set of values are averaged over the entire collection stage to derive OPTTRANSBASE. - The
processing element 100 continues during the subsequentMNC removal phase 240 to sense one or more optical transmission values for the tubing T10 and the liquid flowing in it (OPTTRANSHARVEST) during theMNC removal phase 240. OPTTRANSHARVEST can comprise a single reading sensed at a selected time of the MNC removal phase 240 (e.g., midway through the phase 240), or it can comprise an average of multiple readings taken during theMNC removal phase 240. - The
processing element 100 derives a normalized value DENSITY by establishing OPTTRANSBASE as 0.0, establishing the optical saturation value as 1.0, and fitting the value of OPTTRANSHARVEST proportionally into the normalized 0.0 to 1.0 value range. - As FIG. 28 shows, the
processing element 100 retains two predetermined threshold values THRESH(1) and THRESH(2). The value of THRESH(1) corresponds to a selected nominal value for DENSITY (e.g., 0.45 in a normalized scale of 0.0 to 1.0), which has been empirically determined to occur when the concentration of MNC's in thefirst transition region 116 meets a preselected processing goal. The value of THRESH(2) corresponds to another selected nominal value for DENSITY (e.g., 0.85 in a normalized scale of 0.0 to 1.0), which has been empirically determined to occur when the concentration of PRBC in thesecond transition region 118 exceeds the preselected processing goal. -
-
- As operation of the pump P4 conveys PRBC through the
WB inlet port 48, theinterface 58 and MNC Region advance through the PRP tubing T10 toward the optical sensor OS. PRP preceding the MNC Region advances beyond the optical sensor OD, through the tubing T12, and into the container PPP. - When the MNC Region reaches the optical sensor OS, the sensor OS will sense DENSITY=THRESH(1). Upon this event, the
controller 222 starts a first time counter TC1. When the optical sensor OS senses DENSITY=THRESH(2) thecontroller 222 starts a second time counter TC2. The volume of MNC sensed can be derived based upon the interval between TC1 and TC2 for a given QP4. - As time advances, the
controller 222 compares the magnitudes of TC1 to the first control time T1, as well as compares TC2 to the second control time T2. When TC1=T1, the leading edge of the targeted MNC Region has arrived at the valve station V24, as FIG. 24B shows. Thecontroller 222 commands valve station V24 to open, and commands valve station V25 to close. Thecontroller 222 marks this event on the cycle time counter as TCYCSWITCH. The targeted MNC Region is conveyed into the tubing T13 that leads to the container MNC. When TC2=T2, the second offset volume VOLOFF(2) has also been conveyed into the tubing T13, as FIG. 24C shows. The total MNC volume selected for harvesting (VOLMNC) for the given cycle is thereby present in the tubing T13. When TC2=T2, thecontroller 222 commands the pump P4 to stop. Further advancement of VOLMNC in the tubing T13 therefore ceases. -
- In a preferred embodiment, the
controller 222 ends the MNC removal phase, independent of TC1 and TC2 when the pump P4 conveys more than a specified fluid volume of PRBC after TCYCSTART (e.g., more than 60 ml). This time-out circum-stance could occur, e.g., if the optical sensor OS fails to detect THRESH(1). In this volumetric time-out circumstance, VOLPRP=60−VOLOFF(1). - Alternatively, or in combination with a volumetric time-out, the
controller 222 can end the MNC removal phase independent of TC1 and TC2 when the weight scale WS for the container PRBC senses a weight less than a prescribed value (e.g., less than 4 grams, or the weight equivalent of a fluid volume less than 4 ml). - b. Second Phase (PRP Flush)
- Once the MNC Region is positioned as shown in FIG. 24C, the
controller 222 enters the PRPflush phase 242 of theMNC harvesting stage 234. During thisphase 242, thecontroller 222 configures thecircuit 200 to move VOLPRP out of the container PPP and tubing T12 and into theblood processing compartment 38. - The configuration of the
fluid circuit 200 during the PRPflush phase 242 is shown in FIG. 25, and is further summarized in Table 6.TABLE 6 Mononuclear Cell Harvesting Stage (PRP Flush Phase) V1 V9 V17 ◯ V25 ◯ C1 P1 ◯ V2 V10 ◯ V18 ◯ V26 C2 P2 V3 ◯ V11 V19 V27 C3 ◯ P3 V4 V12 V20 ◯ V28 ◯ C4 P4 V5 V13 ◯ V21 ◯ V29 P5 V6 ◯ V14 ◯ V22 V30 P6 V7 ◯ V15 V23 ◯ V8 ◯ V16 ◯ V24 ◯ - During the PRP
flush stage 242, thecontroller 222 configures the pump stations PSL, PSM, and PSR to stop whole blood recirculation, and, while continuing rotation of thecompartment 38, to pump VOLPRP to theprocessing compartment 38 through tubing T11. VOLPRP is conveyed by the pump P6 through tubing T12 into theright cassette 23R, and thence to tubing T11, for entry into theprocessing compartment 38 through tubing T4 andport 48. PRBC are conveyed from theprocessing compartment 38 throughport 50 and tubing T5 into themiddle cassette 23M, and thence into tubings T8 and T7 into theleft cassette 23L. The PRBC is conveyed into tubing T9 for return to the donor/patient. No other fluid is conveyed in the fluid circuit 15 during thisphase 242. - The return of VOLPRP restores the volume of liquid in container PPP to VOLSUS as collected during the
preliminary processing cycle 228 previously described. The return of VOLPRP also preserves a low platelet population in the VOLSUS in the container PPP slated for suspension of MNC. The return of VOLPRP also conveys residual MNC present in thefirst transition region 116 before TC1=T1 (and therefore not part of VOLMNC), back to theprocessing compartment 38 for further collection in a subsequentmain processing cycle 230. - C. Third Phase (MNC Suspension)
- With the return of VOLPRP to the
compartment 38, thecontroller 222 enters theMNC suspension phase 244 of theMNC harvesting stage 234. During thisphase 244, a portion of the VOLSUS in the container PPP is conveyed with VOLMNC into the container MNC. - The configuration of the
fluid circuit 200 during theMNC suspension phase 244 is shown in FIG. 26, and is further summarized in Table 7.TABLE 7 Mononuclear Cell Harvesting Stage (MNC Suspension Phase) V1 V9 V17 ◯ V25 ◯ C1 P1 ◯ V2 V10 ◯ V18 ◯ V26 C2 P2 V3 ◯ V11 V19 V27 C3 P3 V4 V12 V20 ◯ V28 C4 P4 V5 V13 ◯ V21 ◯ V29 ◯ P5 V6 ◯ V14 ◯ V22 V30 P6 V7 ◯ V15 V23 ◯ V8 ◯ V16 ◯ V24 ◯ - In the
MNC suspension phase 244, the controller closes C3 to stop the return to PRBC to the donor/patient. A predetermined aliquot of VOLSUS (e.g., 5 ml to 10 ml) is conveyed by the pump P6 through tubing T12 into theright cassette 23R and then into tubing T13. As FIG. 26 shows, the aliquot of VOLSUS further advances VOLMNC through the tubing T13 into the container MNC. - d. Fourth Phase (Clean Up)
- At this time, the
controller 222 enters the final, clean upphase 246 of theMNC harvesting stage 234. During thisphase 246, thecontroller 222 returns PRBC resident in the tubing T10 to theprocessing compartment 38. - The configuration of the
fluid circuit 200 during the clean upphase 246 is shown in FIG. 27, and is further summarized in Table 7.TABLE 7 Mononuclear Cell Harvesting Stage (Clean Up Phase) V1 V9 V17 V25 C1 P1 V2 V10 V18 V26 C2 P2 V3 V11 V19 V27 ◯ C3 P3 V4 V12 V20 V28 ◯ C4 P4 V5 V13 V21 ◯ V29 P5 V6 V14 V22 V30 ◯ P6 V7 V15 V23 ◯ V8 V16 V24 - The clean up
phase 246 returns any residual MNC present in the second transition region 118 (see FIG. 28) after TC2=T2 (and therefore not part of VOLSEN), back to theprocessing compartment 38 for further collection in a subsequent processing cycle. - In the clean up
phase 246, thecontroller 222 closes all valve stations in the left andmiddle cassettes processing compartment 38 through tubings T11 and T4. During this period, no components are being drawn from or returned to the donor/patient. - At the end of the clean up
phase 246, thecontroller 222 commences a newmain processing cycle 230. Thecontroller 222 repeats a series of main processing cycles 230 until the desired volume of MNC targeted for the entire procedure is reached. - At the end of the last
main processing cycle 230, the operator may desire additional VOLSUS to further dilute the MNC collected during the procedure. In this circumstance, thecontroller 222 can be commanded to configure thefluid circuit 200 to carry out apreliminary processing cycle 228, as above described, to collect additional VOLSUS in the container PPP. Thecontroller 222 then configures thefluid circuit 200 to carry out anMNC suspension phase 244, to convey additional VOLSUS into the container MNC to achieve the desired dilution of VOLMNC. - IV. Alternative Mononuclear Cell Processing Procedure
- FIG. 29 shows an alternative embodiment of a
fluid circuit 300, which is suited for collecting and harvesting MNC. Thecircuit 300 is in most respects the same as thecircuit 200, shown in FIG. 6, and common components are given the same reference numbers. - The
circuit 300 differs from thecircuit 200 in that thesecond compartment 310 of thecontainer 14 is identical to thecompartment 38, and thereby itself comprises a second blood processing compartment with the same features ascompartment 38. Thecompartment 310 includes interior seals, as shown forcompartment 38 in FIG. 4, creating the same blood collection regions for PRP and PRBC, the details of which are not shown in FIG. 29. Thecompartment 310 includes aport 304 for conveying whole blood into thecompartment 310, aport 306 for conveying PRP from thecompartment 310, and aport 302 for conveying PRBC from thecompartment 310.Compartment 310 also includes a taperedramp 84, as shown in FIGS. 16A and 16B and as earlier described in connection with thecompartment 38. - The
fluid circuit 300 also differs from thefluid circuit 200 in that tubings T14, T18, and T19 are not included. In addition, the container PRBC is not included. Instead,fluid circuit 300 includes several new tubing paths and clamps, as follows: - Tubing path T21 leads from the
PRP outlet port 306 of thecompartment 310 through a new clamp C5 to join tubing path T10. - Tubing path T22 leads from the
WB inlet port 306 of thecompartment 310 through a new air detector D3 and a new clamp C6 to join tubing path T3. - Tubing path T33 leads from the
PRBC outlet port 302 of thecompartment 310 through a new clamp C8 to join tubing T4. - New clamp C7 is also provided in tubing T3 upstream of the air detector D1.
- New clamp C9 is also provided in tubing T10 between the optical sensor OS and the junction of new tubing T21.
- Using
circuit 300, thecontroller 222 proceeds through the previous described primingcycle 226,preliminary processing cycle 228, andmain processing cycle 230 as previously described forcircuit 200, up through theMNC accumulation phase 236. The PRBC collectphase 238 differs when using thecircuit 300, in that PRBC used for subsequent removal of MNC from thecompartment 38 are processed and collected in thesecond compartment 310. - More particularly, as shown in FIG. 30, during the
PRBC collection phase 238, thecontroller 222 conveys a volume of whole blood from the donor/patient into thesecond compartment 310. The whole blood volume is drawn by pump P2 through tubing T1 into tubing T3 and thence through open clamp C6 into tubing T22, which leads to thecompartment 310. Clamp C7 is closed, to block conveyance of whole blood into thecompartment 38, where the MNC have been accumulated for harvesting. Clamp C9 is also closed to block conveyance of PRP from thecompartment 38, thereby keeping the accumulation of MNC undisturbed in thecompartment 38. - In the
compartment 310, the whole blood volume is separated into PRBC and PRP, in the same fashion that these components are separated in thecompartment 38. PRP is conveyed from thecompartment 310 through tubing T23 and open clamp C5 by operation of the pump P5, for return to the donor/patient. The clamp C8 is closed, to retain PRBC in thecompartment 310. - The
controller 222 also conducts a differentMNC removal phase 240 usingcircuit 300. As shown in FIG. 31, during theMNC removal phase 240, thecontroller 222 recirculates a portion of the drawn whole blood back to the donor/patient, while directing another portion of the whole blood into thecompartment 310, following the same path as previously described in connection with FIG. 30. Thecontroller 222 opens clamps C8 and C9, while closing clamp CS. The whole blood entering thecompartment 310 displaces PRBC through thePRBC outlet port 302 into tubing T23. The PRBC from thecompartment 310 enters theWB inlet port 48 of thecompartment 38. As before described, the incoming flow of PRBC from outside thecompartment 38 increases the hematocrit of PRBC within thecompartment 38, causing the accumulated MNC to float to theinterface 58. As before described, the incoming PRBC from outside thecompartment 38 displaces PRP through thePRP port 46, together with the MNC Region, shown in FIG. 31. This MNC Region is detected by the optical sensor OS and harvested insubsequent processing circuit 200. - Various features of the inventions are set forth in the following claims.
Claims (3)
1. A blood processing system comprising
a rotating element,
a processing chamber on the rotating element for common rotation with the rotating element, the processing chamber including a separation compartment for receiving whole blood for centrifugal separation into components, the separation compartment including an inlet region where whole blood enters for separation into packed red blood cells, a plasma constituent, and an interface carrying platelets between the packed red blood cells and the plasma constituent, and
a controller for the rotating element operable in a control mode to convey whole blood into the separation compartment for centrifugal separation into components, the controller including an interface control unit operative (i) in a first condition to retain platelets in the processing chamber to enable removal of platelet-poor plasma and packed red blood cells from the processing chamber, and (ii) in a second condition to enable removal of platelets from the processing chamber enabling removal of platelet-rich plasma and packed red blood cells from the processing chamber.
2. A system according to claim 1
wherein the interface control unit includes a sensing element to locate the interface in the separation compartment and provide a sensed output.
3. A system according to claim 2
wherein the sensing element optically locates the interface in the separation compartment.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/462,320 US20030211927A1 (en) | 1997-07-01 | 2003-06-16 | Blood processing chamber counter-balanced with blood-free liquid |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/886,179 US6027441A (en) | 1997-07-01 | 1997-07-01 | Systems and methods providing a liquid-primed, single flow access chamber |
US09/377,339 US6168561B1 (en) | 1997-07-01 | 1999-08-19 | Blood processing chamber counter-balanced with blood-free liquid |
US09/669,752 US6582349B1 (en) | 1997-07-01 | 2000-09-26 | Blood processing system |
US10/462,320 US20030211927A1 (en) | 1997-07-01 | 2003-06-16 | Blood processing chamber counter-balanced with blood-free liquid |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/669,752 Division US6582349B1 (en) | 1997-07-01 | 2000-09-26 | Blood processing system |
Publications (1)
Publication Number | Publication Date |
---|---|
US20030211927A1 true US20030211927A1 (en) | 2003-11-13 |
Family
ID=25388544
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/886,179 Expired - Lifetime US6027441A (en) | 1997-07-01 | 1997-07-01 | Systems and methods providing a liquid-primed, single flow access chamber |
US09/377,339 Expired - Fee Related US6168561B1 (en) | 1997-07-01 | 1999-08-19 | Blood processing chamber counter-balanced with blood-free liquid |
US09/669,752 Expired - Lifetime US6582349B1 (en) | 1997-07-01 | 2000-09-26 | Blood processing system |
US10/462,320 Abandoned US20030211927A1 (en) | 1997-07-01 | 2003-06-16 | Blood processing chamber counter-balanced with blood-free liquid |
Family Applications Before (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/886,179 Expired - Lifetime US6027441A (en) | 1997-07-01 | 1997-07-01 | Systems and methods providing a liquid-primed, single flow access chamber |
US09/377,339 Expired - Fee Related US6168561B1 (en) | 1997-07-01 | 1999-08-19 | Blood processing chamber counter-balanced with blood-free liquid |
US09/669,752 Expired - Lifetime US6582349B1 (en) | 1997-07-01 | 2000-09-26 | Blood processing system |
Country Status (7)
Country | Link |
---|---|
US (4) | US6027441A (en) |
EP (1) | EP1007183A4 (en) |
JP (1) | JP2002509535A (en) |
CN (1) | CN1268069A (en) |
BR (1) | BR9810653A (en) |
CA (1) | CA2294307A1 (en) |
WO (1) | WO1999001198A1 (en) |
Cited By (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080087613A1 (en) * | 2005-06-22 | 2008-04-17 | Gambro Bct, Inc. | Apparatus and Method for Separating Discrete Volumes of A Composite Liquid |
US20080096750A1 (en) * | 2006-10-20 | 2008-04-24 | Navigant Biotechnologies, Llc | Methods for Washing a Red Blood Cell Component and for Removing Prions Therefrom |
US20090166298A1 (en) * | 2007-12-26 | 2009-07-02 | Caridianbct, Inc. | Methods And Apparatus For Controlled Addition Of Solutions To Blood Components |
US20100217174A1 (en) * | 2008-02-26 | 2010-08-26 | Kyungyoon Min | Blood processing system for single or double access draw and return |
US7789245B2 (en) | 1999-09-03 | 2010-09-07 | Fenwal, Inc. | Blood separation chamber |
US20100234788A1 (en) * | 2009-03-12 | 2010-09-16 | Haemonetics Corporation | System and Method for the Re-Anticoagulation of Platelet Rich Plasma |
US20110003675A1 (en) * | 2009-07-06 | 2011-01-06 | Caridianbct, Inc. | Apparatus and Method for Automatically Loading Washing Solution In A Multi-Unit Blood Processor |
US7918350B2 (en) | 2002-10-24 | 2011-04-05 | Fenwal, Inc. | Separation apparatus and method |
US8075468B2 (en) | 2008-02-27 | 2011-12-13 | Fenwal, Inc. | Systems and methods for mid-processing calculation of blood composition |
CN103191015A (en) * | 2012-01-09 | 2013-07-10 | 金卫医疗科技(上海)有限公司 | Separation soft bag for improving separating efficiency during plasma continuous separation |
US20130334420A1 (en) * | 2012-06-15 | 2013-12-19 | Fenwal, Inc. | Process for Predicting Hematocrit of Whole Blood Using IR Light |
US8685258B2 (en) | 2008-02-27 | 2014-04-01 | Fenwal, Inc. | Systems and methods for conveying multiple blood components to a recipient |
US8840535B2 (en) | 2010-05-27 | 2014-09-23 | Terumo Bct, Inc. | Multi-unit blood processor with temperature sensing |
US9173990B2 (en) | 2011-08-12 | 2015-11-03 | Terumo Bct, Inc. | System for blood separation with replacement fluid apparatus and method |
US9302042B2 (en) | 2010-12-30 | 2016-04-05 | Haemonetics Corporation | System and method for collecting platelets and anticipating plasma return |
US9733805B2 (en) | 2012-06-26 | 2017-08-15 | Terumo Bct, Inc. | Generating procedures for entering data prior to separating a liquid into components |
US10004841B2 (en) | 2013-12-09 | 2018-06-26 | Michael C. Larson | Blood purifier device and method |
Families Citing this family (58)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6466879B1 (en) * | 2000-07-13 | 2002-10-15 | Baxter International Inc. | Systems and methods for monitoring introduction of a processing fluid during a fluid processing procedure |
US6835316B2 (en) | 2001-04-09 | 2004-12-28 | Medtronic, Inc. | Clam shell blood reservoir holder with index line |
WO2002087662A1 (en) * | 2001-04-27 | 2002-11-07 | Nexell Therapeutics Inc. | Cell processing and fluid transfer apparatus and method of use |
US6589153B2 (en) * | 2001-09-24 | 2003-07-08 | Medtronic, Inc. | Blood centrifuge with exterior mounted, self-balancing collection chambers |
US7479123B2 (en) | 2002-03-04 | 2009-01-20 | Therakos, Inc. | Method for collecting a desired blood component and performing a photopheresis treatment |
US7211037B2 (en) * | 2002-03-04 | 2007-05-01 | Therakos, Inc. | Apparatus for the continuous separation of biological fluids into components and method of using same |
AU2003226398A1 (en) * | 2002-04-12 | 2003-10-27 | Gambro, Inc. | Fluid separation using a centrifuge and roller pump |
US6982038B2 (en) * | 2002-06-14 | 2006-01-03 | Medtronic, Inc. | Centrifuge system utilizing disposable components and automated processing of blood to collect platelet rich plasma |
US20050049539A1 (en) * | 2003-09-03 | 2005-03-03 | O'hara Gerald P. | Control system for driving fluids through an extracorporeal blood circuit |
US7381187B2 (en) * | 2003-09-12 | 2008-06-03 | Textronics, Inc. | Blood pressure monitoring system and method of having an extended optical range |
US7837167B2 (en) * | 2003-09-25 | 2010-11-23 | Baxter International Inc. | Container support device |
AU2004237844B2 (en) | 2003-12-23 | 2011-01-27 | Therakos, Inc. | Extracorporeal photopheresis in combination with anti-TNF treatment |
US7476209B2 (en) * | 2004-12-21 | 2009-01-13 | Therakos, Inc. | Method and apparatus for collecting a blood component and performing a photopheresis treatment |
US20100210441A1 (en) * | 2005-06-22 | 2010-08-19 | Caridianbct, Inc. | Apparatus And Method For Separating Discrete Volumes Of A Composite Liquid |
CN101351118B (en) * | 2005-11-02 | 2015-05-27 | 特拉科斯有限公司 | Use of apoptotic cells ex vivo to generate regulatory t cells |
US7559914B2 (en) * | 2005-12-14 | 2009-07-14 | Alcon, Inc. | Priming a microsurgical system |
US7981082B2 (en) * | 2007-08-21 | 2011-07-19 | Hospira, Inc. | System and method for reducing air bubbles in a fluid delivery line |
US9026370B2 (en) | 2007-12-18 | 2015-05-05 | Hospira, Inc. | User interface improvements for medical devices |
US20110086752A1 (en) * | 2009-10-08 | 2011-04-14 | Brierton Mark J | Dynamically balanced chamber for centrifugal separation of blood |
EP2576073B1 (en) | 2010-06-07 | 2018-06-13 | Terumo BCT, Inc. | Multi-unit blood processor with volume prediction |
US9555171B2 (en) | 2010-09-30 | 2017-01-31 | Depuy Mitek, Llc | Methods and devices for collecting separate components of whole blood |
US8808978B2 (en) | 2010-11-05 | 2014-08-19 | Haemonetics Corporation | System and method for automated platelet wash |
EP2694131B1 (en) | 2011-04-07 | 2019-08-28 | Fenwal, Inc. | Automated methods and systems for providing platelet concentrates with reduced residual plasma volumes and storage media for such platelet concentrates |
WO2012151243A2 (en) | 2011-05-03 | 2012-11-08 | Fenwal, Inc. | Platelet resuspension method and apparatus |
AU2012299169B2 (en) | 2011-08-19 | 2017-08-24 | Icu Medical, Inc. | Systems and methods for a graphical interface including a graphical representation of medical data |
EP2731725B1 (en) * | 2011-09-22 | 2015-01-14 | Fenwal, Inc. | Drive system for centrifuge |
WO2013043315A1 (en) | 2011-09-22 | 2013-03-28 | Fenwal, Inc. | Drive system for centrifuge |
WO2013090709A1 (en) | 2011-12-16 | 2013-06-20 | Hospira, Inc. | System for monitoring and delivering medication to a patient and method of using the same to minimize the risks associated with automated therapy |
US9101944B2 (en) * | 2012-01-04 | 2015-08-11 | Fenwal, Inc. | Drive system for centrifuge |
US9327296B2 (en) | 2012-01-27 | 2016-05-03 | Fenwal, Inc. | Fluid separation chambers for fluid processing systems |
ES2741725T3 (en) | 2012-03-30 | 2020-02-12 | Icu Medical Inc | Air detection system and method to detect air in a pump of an infusion system |
US10463788B2 (en) | 2012-07-31 | 2019-11-05 | Icu Medical, Inc. | Patient care system for critical medications |
US8803090B2 (en) | 2012-11-09 | 2014-08-12 | Fenwal, Inc. | Citrate detector for blood processing system |
EP2956187B1 (en) | 2013-02-18 | 2017-11-01 | Terumo BCT, Inc. | System for blood separation with a separation chamber having an internal gravity valve |
WO2014190264A1 (en) | 2013-05-24 | 2014-11-27 | Hospira, Inc. | Multi-sensor infusion system for detecting air or an occlusion in the infusion system |
EP3003442B1 (en) | 2013-05-29 | 2020-12-30 | ICU Medical, Inc. | Infusion system and method of use which prevents over-saturation of an analog-to-digital converter |
CA2913915C (en) | 2013-05-29 | 2022-03-29 | Hospira, Inc. | Infusion system which utilizes one or more sensors and additional information to make an air determination regarding the infusion system |
US9861736B2 (en) | 2013-05-31 | 2018-01-09 | Fenwal, Inc. | Methods for extracting platelet-rich plasma for therapeutic injection |
US10039877B2 (en) | 2013-08-23 | 2018-08-07 | Fenwal, Inc. | Apheresis platelets with fixed residual plasma volume |
EP3110474B1 (en) | 2014-02-28 | 2019-12-18 | ICU Medical, Inc. | Infusion system and method which utilizes dual wavelength optical air-in-line detection |
JP2017517302A (en) | 2014-05-29 | 2017-06-29 | ホスピーラ インコーポレイテッド | Infusion system and pump with configurable closed loop delivery rate catchup |
US11344668B2 (en) | 2014-12-19 | 2022-05-31 | Icu Medical, Inc. | Infusion system with concurrent TPN/insulin infusion |
US10850024B2 (en) | 2015-03-02 | 2020-12-01 | Icu Medical, Inc. | Infusion system, device, and method having advanced infusion features |
JP7175609B2 (en) | 2015-04-05 | 2022-11-21 | アーテリオサイト・メディカル・システムズ・インコーポレイテッド | Centrifuge balance weight with adjustable center of gravity and method of use thereof |
EP3124063B1 (en) | 2015-07-29 | 2019-04-10 | Fenwal, Inc. | Five-port blood separation chamber and methods of using the same |
US10329530B2 (en) | 2016-01-18 | 2019-06-25 | Fenwal, Inc. | Cell washing system and methods for washing small volumes of cells |
WO2017197024A1 (en) | 2016-05-13 | 2017-11-16 | Icu Medical, Inc. | Infusion pump system and method with common line auto flush |
CA3027176A1 (en) | 2016-06-10 | 2017-12-14 | Icu Medical, Inc. | Acoustic flow sensor for continuous medication flow measurements and feedback control of infusion |
US20200030503A1 (en) | 2017-04-20 | 2020-01-30 | Fenwal, Inc. | Systems And Methods For Platelet Filtration Using An Additive |
EP3441094A1 (en) | 2017-08-11 | 2019-02-13 | Fenwal, Inc. | Systems and methods for monitoring a fluid procedure using hydrostatic pressure |
US11338076B2 (en) | 2017-09-07 | 2022-05-24 | Fenwal, Inc. | System and method of using frequency analysis to monitor flow rates |
EP3466449B1 (en) | 2017-10-06 | 2022-08-03 | Fenwal, Inc. | Integrated platelet collection and pathogen inactivation processing systems and fluid circuits |
US10089055B1 (en) | 2017-12-27 | 2018-10-02 | Icu Medical, Inc. | Synchronized display of screen content on networked devices |
EP3669904A1 (en) | 2018-12-21 | 2020-06-24 | Fenwal, Inc. | Methods and systems for platelet cryopreservation |
US11801334B2 (en) * | 2019-09-24 | 2023-10-31 | Enso Discoveries, Llc | Platelet rich plasma separation kit |
US11278671B2 (en) | 2019-12-04 | 2022-03-22 | Icu Medical, Inc. | Infusion pump with safety sequence keypad |
WO2022020184A1 (en) | 2020-07-21 | 2022-01-27 | Icu Medical, Inc. | Fluid transfer devices and methods of use |
US11135360B1 (en) | 2020-12-07 | 2021-10-05 | Icu Medical, Inc. | Concurrent infusion with common line auto flush |
Citations (79)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3145713A (en) * | 1963-09-12 | 1964-08-25 | Protein Foundation Inc | Method and apparatus for processing blood |
US3297244A (en) * | 1959-06-24 | 1967-01-10 | George N Hein | Centrifuge and receptacle assembly therefor |
US3456875A (en) * | 1966-08-18 | 1969-07-22 | George N Hein | Air driven centrifuge |
US3519201A (en) * | 1968-05-07 | 1970-07-07 | Us Health Education & Welfare | Seal means for blood separator and the like |
US3655123A (en) * | 1966-08-08 | 1972-04-11 | Us Health Education & Welfare | Continuous flow blood separator |
US3737096A (en) * | 1971-12-23 | 1973-06-05 | Ibm | Blood processing control apparatus |
US3748101A (en) * | 1972-01-28 | 1973-07-24 | Ibm | Centrifuge fluid container |
US3957197A (en) * | 1975-04-25 | 1976-05-18 | The United States Of America As Represented By The United States Energy Research And Development Administration | Centrifuge apparatus |
US3987961A (en) * | 1974-01-29 | 1976-10-26 | Heraeus-Christ Gmbh | Centrifuge bag for treatment of biological liquids |
US4007871A (en) * | 1975-11-13 | 1977-02-15 | International Business Machines Corporation | Centrifuge fluid container |
US4010894A (en) * | 1975-11-21 | 1977-03-08 | International Business Machines Corporation | Centrifuge fluid container |
US4094461A (en) * | 1977-06-27 | 1978-06-13 | International Business Machines Corporation | Centrifuge collecting chamber |
US4113173A (en) * | 1975-03-27 | 1978-09-12 | Baxter Travenol Laboratories, Inc. | Centrifugal liquid processing apparatus |
US4114802A (en) * | 1977-08-29 | 1978-09-19 | Baxter Travenol Laboratories, Inc. | Centrifugal apparatus with biaxial connector |
US4133281A (en) * | 1977-07-20 | 1979-01-09 | Albro Fillers And Engineering Company Ltd. | Vacuum charging of containers from bulk supply |
US4146172A (en) * | 1977-10-18 | 1979-03-27 | Baxter Travenol Laboratories, Inc. | Centrifugal liquid processing system |
US4164318A (en) * | 1977-10-12 | 1979-08-14 | Baxter Travenol Laboratories, Inc. | Centrifugal processing apparatus with reduced-load tubing |
US4191182A (en) * | 1977-09-23 | 1980-03-04 | Hemotherapy Inc. | Method and apparatus for continuous plasmaphersis |
US4245383A (en) * | 1978-11-08 | 1981-01-20 | Baxter Travenol Laboratories, Inc. | Centrifugal processing apparatus with reduced-load tubing |
US4278202A (en) * | 1978-07-25 | 1981-07-14 | Separek Teknik Ab | Centrifuge rotor and collapsible separation container for use therewith |
US4283004A (en) * | 1979-08-15 | 1981-08-11 | Baxter Travenol Laboratories, Inc. | Vibration attenuation support assembly for a centrifugal liquid processing apparatus |
US4285464A (en) * | 1979-01-22 | 1981-08-25 | Haemonetics Corporation | Apparatus for separation of blood into components thereof |
US4386730A (en) * | 1978-07-21 | 1983-06-07 | International Business Machines Corporation | Centrifuge assembly |
US4387848A (en) * | 1977-10-03 | 1983-06-14 | International Business Machines Corporation | Centrifuge assembly |
US4405079A (en) * | 1980-11-10 | 1983-09-20 | Haemonetics Corporation | Centrifugal displacer pump |
US4419089A (en) * | 1977-07-19 | 1983-12-06 | The United States Of America As Represented By The Department Of Health And Human Services | Blood cell separator |
US4425112A (en) * | 1976-02-25 | 1984-01-10 | The United States Of America As Represented By The Department Of Health And Human Services | Flow-through centrifuge |
US4430072A (en) * | 1977-06-03 | 1984-02-07 | International Business Machines Corporation | Centrifuge assembly |
US4445883A (en) * | 1982-01-18 | 1984-05-01 | Haemonetics Corporation | Deformable support for fluid processing centrifuge |
US4447220A (en) * | 1979-09-22 | 1984-05-08 | Eberle Guenter | Method and apparatus for separating blood components |
US4447221A (en) * | 1982-06-15 | 1984-05-08 | International Business Machines Corporation | Continuous flow centrifuge assembly |
US4464167A (en) * | 1981-09-03 | 1984-08-07 | Haemonetics Corporation | Pheresis apparatus |
US4525155A (en) * | 1983-04-20 | 1985-06-25 | Alfa-Laval Marine And Powering Engineering Ab | Centrifugal separator and method of operating the same |
US4530691A (en) * | 1983-12-13 | 1985-07-23 | Baxter Travenol Laboratories, Inc. | Centrifuge with movable mandrel |
US4557717A (en) * | 1982-09-20 | 1985-12-10 | American National Red Cross | Cup insert for balancing |
US4605503A (en) * | 1983-05-26 | 1986-08-12 | Baxter Travenol Laboratories, Inc. | Single needle blood fractionation system having adjustable recirculation through filter |
US4636193A (en) * | 1976-05-14 | 1987-01-13 | Baxter Travenol Laboratories, Inc. | Disposable centrifugal blood processing system |
US4647279A (en) * | 1985-10-18 | 1987-03-03 | Cobe Laboratories, Inc. | Centrifugal separator |
US4648866A (en) * | 1983-07-07 | 1987-03-10 | Rhone-Poulenc S.A. | Process/apparatus for the withdrawal/return of body fluids |
US4655742A (en) * | 1983-07-13 | 1987-04-07 | Rhone-Poulenc S.A. | Process/apparatus for the withdrawal/return of body fluids |
US4670002A (en) * | 1985-12-09 | 1987-06-02 | Hitachi Koki Company, Ltd. | Centrifugal elutriator rotor |
US4675117A (en) * | 1984-03-21 | 1987-06-23 | Fresenius Ag | Method of separating blood and apparatus for carrying out the method |
US4708712A (en) * | 1986-03-28 | 1987-11-24 | Cobe Laboratories, Inc. | Continuous-loop centrifugal separator |
US4710161A (en) * | 1985-04-22 | 1987-12-01 | The Green Cross Corporation | Continuous type centrifugal separator |
US4714457A (en) * | 1986-09-15 | 1987-12-22 | Robert Alterbaum | Method and apparatus for use in preparation of fibrinogen from a patient's blood |
US4724317A (en) * | 1985-12-05 | 1988-02-09 | Baxter Travenol Laboratories, Inc. | Optical data collection apparatus and method used with moving members |
US4767397A (en) * | 1987-03-09 | 1988-08-30 | Damon Corporation | Apparatus for liquid separation |
US4772262A (en) * | 1985-04-16 | 1988-09-20 | Natural Technologies, Inc. | Portable electric breast pump |
US4806252A (en) * | 1987-01-30 | 1989-02-21 | Baxter International Inc. | Plasma collection set and method |
US4834890A (en) * | 1987-01-30 | 1989-05-30 | Baxter International Inc. | Centrifugation pheresis system |
US4911833A (en) * | 1984-08-24 | 1990-03-27 | William F. McLaughlin | Closed hemapheresis system and method |
US4923612A (en) * | 1988-07-26 | 1990-05-08 | Trivett Gordon S | Fluid recovery and transfer system |
US4934995A (en) * | 1977-08-12 | 1990-06-19 | Baxter International Inc. | Blood component centrifuge having collapsible inner liner |
US4936820A (en) * | 1988-10-07 | 1990-06-26 | Baxter International Inc. | High volume centrifugal fluid processing system and method for cultured cell suspensions and the like |
US4990132A (en) * | 1986-05-16 | 1991-02-05 | Omega Medicinteknik Ab | Method and apparatus for plasmapheresis |
US5006103A (en) * | 1977-08-12 | 1991-04-09 | Baxter International Inc. | Disposable container for a centrifuge |
US5076911A (en) * | 1987-01-30 | 1991-12-31 | Baxter International Inc. | Centrifugation chamber having an interface detection surface |
US5078671A (en) * | 1988-10-07 | 1992-01-07 | Baxter International Inc. | Centrifugal fluid processing system and method |
US5104526A (en) * | 1987-01-30 | 1992-04-14 | Baxter International Inc. | Centrifugation system having an interface detection system |
US5114396A (en) * | 1987-09-15 | 1992-05-19 | Omega Medicinteknik Ab | Method of washing blood cells and container assembly thereof |
US5190515A (en) * | 1992-01-13 | 1993-03-02 | Eastman Kodak Company | Vacuum degassing apparatus |
US5269924A (en) * | 1991-07-26 | 1993-12-14 | Elp Rochat | Blood collecting and filtering apparatus |
US5279550A (en) * | 1991-12-19 | 1994-01-18 | Gish Biomedical, Inc. | Orthopedic autotransfusion system |
US5316667A (en) * | 1989-05-26 | 1994-05-31 | Baxter International Inc. | Time based interface detection systems for blood processing apparatus |
US5356365A (en) * | 1992-04-15 | 1994-10-18 | Cobe Laboratories, Inc. | Temperature controlled centrifuge |
US5360542A (en) * | 1991-12-23 | 1994-11-01 | Baxter International Inc. | Centrifuge with separable bowl and spool elements providing access to the separation chamber |
US5368542A (en) * | 1993-01-13 | 1994-11-29 | Cobe Laboratories, Inc. | Apparatus and method for separating microscopic units in a substantially continuous density gradient solution |
US5370802A (en) * | 1987-01-30 | 1994-12-06 | Baxter International Inc. | Enhanced yield platelet collection systems and methods |
US5437624A (en) * | 1993-08-23 | 1995-08-01 | Cobe Laboratories, Inc. | Single needle recirculation system for harvesting blood components |
US5549458A (en) * | 1994-07-01 | 1996-08-27 | Baxter International Inc. | Peristaltic pump with quick release rotor head assembly |
US5551942A (en) * | 1993-12-22 | 1996-09-03 | Baxter International Inc. | Centrifuge with pivot-out, easy-load processing chamber |
US5573678A (en) * | 1987-01-30 | 1996-11-12 | Baxter International Inc. | Blood processing systems and methods for collecting mono nuclear cells |
US5651766A (en) * | 1995-06-07 | 1997-07-29 | Transfusion Technologies Corporation | Blood collection and separation system |
US5690815A (en) * | 1992-07-13 | 1997-11-25 | Pall Corporation | Automated system for processing biological fluid |
US5704889A (en) * | 1995-04-14 | 1998-01-06 | Cobe Laboratories, Inc. | Spillover collection of sparse components such as mononuclear cells in a centrifuge apparatus |
US5733253A (en) * | 1994-10-13 | 1998-03-31 | Transfusion Technologies Corporation | Fluid separation system |
US6053856A (en) * | 1995-04-18 | 2000-04-25 | Cobe Laboratories | Tubing set apparatus and method for separation of fluid components |
US6228017B1 (en) * | 1987-01-30 | 2001-05-08 | Baxter International Inc. | Compact enhanced yield blood processing systems |
US6451203B2 (en) * | 1995-06-07 | 2002-09-17 | Baxter International Inc. | Blood processing systems and methods using apparent hematocrit as a process of control parameter |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2020256A (en) * | 1978-03-08 | 1979-11-14 | Biggleswade Developments Ltd | Suction Filling Apparatus |
SE459791B (en) * | 1986-05-16 | 1989-08-07 | Omega Medicinteknik Ab | centrifuge |
SE9302369D0 (en) | 1993-07-08 | 1993-07-08 | Omega Medicinteknik Ab | PASS SYSTEM PROVIDED FOR CENTRIFUGAL SEPARATION WITH USE OF THIS PASS SYSTEM |
US5704888A (en) | 1995-04-14 | 1998-01-06 | Cobe Laboratories, Inc. | Intermittent collection of mononuclear cells in a centrifuge apparatus |
-
1997
- 1997-07-01 US US08/886,179 patent/US6027441A/en not_active Expired - Lifetime
-
1998
- 1998-06-22 BR BR9810653-8A patent/BR9810653A/en not_active IP Right Cessation
- 1998-06-22 CA CA002294307A patent/CA2294307A1/en not_active Abandoned
- 1998-06-22 CN CN98806731A patent/CN1268069A/en active Pending
- 1998-06-22 JP JP50721499A patent/JP2002509535A/en active Pending
- 1998-06-22 EP EP98931452A patent/EP1007183A4/en not_active Withdrawn
- 1998-06-22 WO PCT/US1998/012925 patent/WO1999001198A1/en not_active Application Discontinuation
-
1999
- 1999-08-19 US US09/377,339 patent/US6168561B1/en not_active Expired - Fee Related
-
2000
- 2000-09-26 US US09/669,752 patent/US6582349B1/en not_active Expired - Lifetime
-
2003
- 2003-06-16 US US10/462,320 patent/US20030211927A1/en not_active Abandoned
Patent Citations (81)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3297244A (en) * | 1959-06-24 | 1967-01-10 | George N Hein | Centrifuge and receptacle assembly therefor |
US3145713A (en) * | 1963-09-12 | 1964-08-25 | Protein Foundation Inc | Method and apparatus for processing blood |
US3655123A (en) * | 1966-08-08 | 1972-04-11 | Us Health Education & Welfare | Continuous flow blood separator |
US3456875A (en) * | 1966-08-18 | 1969-07-22 | George N Hein | Air driven centrifuge |
US3519201A (en) * | 1968-05-07 | 1970-07-07 | Us Health Education & Welfare | Seal means for blood separator and the like |
US3737096A (en) * | 1971-12-23 | 1973-06-05 | Ibm | Blood processing control apparatus |
US3748101A (en) * | 1972-01-28 | 1973-07-24 | Ibm | Centrifuge fluid container |
US3987961A (en) * | 1974-01-29 | 1976-10-26 | Heraeus-Christ Gmbh | Centrifuge bag for treatment of biological liquids |
US4113173A (en) * | 1975-03-27 | 1978-09-12 | Baxter Travenol Laboratories, Inc. | Centrifugal liquid processing apparatus |
US3957197A (en) * | 1975-04-25 | 1976-05-18 | The United States Of America As Represented By The United States Energy Research And Development Administration | Centrifuge apparatus |
US4007871A (en) * | 1975-11-13 | 1977-02-15 | International Business Machines Corporation | Centrifuge fluid container |
US4010894A (en) * | 1975-11-21 | 1977-03-08 | International Business Machines Corporation | Centrifuge fluid container |
US4425112A (en) * | 1976-02-25 | 1984-01-10 | The United States Of America As Represented By The Department Of Health And Human Services | Flow-through centrifuge |
US4636193A (en) * | 1976-05-14 | 1987-01-13 | Baxter Travenol Laboratories, Inc. | Disposable centrifugal blood processing system |
US4430072A (en) * | 1977-06-03 | 1984-02-07 | International Business Machines Corporation | Centrifuge assembly |
US4094461A (en) * | 1977-06-27 | 1978-06-13 | International Business Machines Corporation | Centrifuge collecting chamber |
US4419089A (en) * | 1977-07-19 | 1983-12-06 | The United States Of America As Represented By The Department Of Health And Human Services | Blood cell separator |
US4133281A (en) * | 1977-07-20 | 1979-01-09 | Albro Fillers And Engineering Company Ltd. | Vacuum charging of containers from bulk supply |
US4934995A (en) * | 1977-08-12 | 1990-06-19 | Baxter International Inc. | Blood component centrifuge having collapsible inner liner |
US5006103A (en) * | 1977-08-12 | 1991-04-09 | Baxter International Inc. | Disposable container for a centrifuge |
US4114802A (en) * | 1977-08-29 | 1978-09-19 | Baxter Travenol Laboratories, Inc. | Centrifugal apparatus with biaxial connector |
US4191182A (en) * | 1977-09-23 | 1980-03-04 | Hemotherapy Inc. | Method and apparatus for continuous plasmaphersis |
US4387848A (en) * | 1977-10-03 | 1983-06-14 | International Business Machines Corporation | Centrifuge assembly |
US4164318A (en) * | 1977-10-12 | 1979-08-14 | Baxter Travenol Laboratories, Inc. | Centrifugal processing apparatus with reduced-load tubing |
US4146172A (en) * | 1977-10-18 | 1979-03-27 | Baxter Travenol Laboratories, Inc. | Centrifugal liquid processing system |
US4386730A (en) * | 1978-07-21 | 1983-06-07 | International Business Machines Corporation | Centrifuge assembly |
US4278202A (en) * | 1978-07-25 | 1981-07-14 | Separek Teknik Ab | Centrifuge rotor and collapsible separation container for use therewith |
US4245383A (en) * | 1978-11-08 | 1981-01-20 | Baxter Travenol Laboratories, Inc. | Centrifugal processing apparatus with reduced-load tubing |
US4285464A (en) * | 1979-01-22 | 1981-08-25 | Haemonetics Corporation | Apparatus for separation of blood into components thereof |
US4283004A (en) * | 1979-08-15 | 1981-08-11 | Baxter Travenol Laboratories, Inc. | Vibration attenuation support assembly for a centrifugal liquid processing apparatus |
US4447220A (en) * | 1979-09-22 | 1984-05-08 | Eberle Guenter | Method and apparatus for separating blood components |
US4405079A (en) * | 1980-11-10 | 1983-09-20 | Haemonetics Corporation | Centrifugal displacer pump |
US4464167A (en) * | 1981-09-03 | 1984-08-07 | Haemonetics Corporation | Pheresis apparatus |
US4445883A (en) * | 1982-01-18 | 1984-05-01 | Haemonetics Corporation | Deformable support for fluid processing centrifuge |
US4447221A (en) * | 1982-06-15 | 1984-05-08 | International Business Machines Corporation | Continuous flow centrifuge assembly |
US4557717A (en) * | 1982-09-20 | 1985-12-10 | American National Red Cross | Cup insert for balancing |
US4525155A (en) * | 1983-04-20 | 1985-06-25 | Alfa-Laval Marine And Powering Engineering Ab | Centrifugal separator and method of operating the same |
US4605503A (en) * | 1983-05-26 | 1986-08-12 | Baxter Travenol Laboratories, Inc. | Single needle blood fractionation system having adjustable recirculation through filter |
US4648866A (en) * | 1983-07-07 | 1987-03-10 | Rhone-Poulenc S.A. | Process/apparatus for the withdrawal/return of body fluids |
US4655742A (en) * | 1983-07-13 | 1987-04-07 | Rhone-Poulenc S.A. | Process/apparatus for the withdrawal/return of body fluids |
US4530691A (en) * | 1983-12-13 | 1985-07-23 | Baxter Travenol Laboratories, Inc. | Centrifuge with movable mandrel |
US4675117A (en) * | 1984-03-21 | 1987-06-23 | Fresenius Ag | Method of separating blood and apparatus for carrying out the method |
US4911833A (en) * | 1984-08-24 | 1990-03-27 | William F. McLaughlin | Closed hemapheresis system and method |
US4772262A (en) * | 1985-04-16 | 1988-09-20 | Natural Technologies, Inc. | Portable electric breast pump |
US4710161A (en) * | 1985-04-22 | 1987-12-01 | The Green Cross Corporation | Continuous type centrifugal separator |
US4647279A (en) * | 1985-10-18 | 1987-03-03 | Cobe Laboratories, Inc. | Centrifugal separator |
US4724317A (en) * | 1985-12-05 | 1988-02-09 | Baxter Travenol Laboratories, Inc. | Optical data collection apparatus and method used with moving members |
US4670002A (en) * | 1985-12-09 | 1987-06-02 | Hitachi Koki Company, Ltd. | Centrifugal elutriator rotor |
US4708712A (en) * | 1986-03-28 | 1987-11-24 | Cobe Laboratories, Inc. | Continuous-loop centrifugal separator |
US4990132A (en) * | 1986-05-16 | 1991-02-05 | Omega Medicinteknik Ab | Method and apparatus for plasmapheresis |
US4714457A (en) * | 1986-09-15 | 1987-12-22 | Robert Alterbaum | Method and apparatus for use in preparation of fibrinogen from a patient's blood |
US5104526A (en) * | 1987-01-30 | 1992-04-14 | Baxter International Inc. | Centrifugation system having an interface detection system |
US5322620A (en) * | 1987-01-30 | 1994-06-21 | Baxter International Inc. | Centrifugation system having an interface detection surface |
US5573678A (en) * | 1987-01-30 | 1996-11-12 | Baxter International Inc. | Blood processing systems and methods for collecting mono nuclear cells |
US5370802A (en) * | 1987-01-30 | 1994-12-06 | Baxter International Inc. | Enhanced yield platelet collection systems and methods |
US6228017B1 (en) * | 1987-01-30 | 2001-05-08 | Baxter International Inc. | Compact enhanced yield blood processing systems |
US5076911A (en) * | 1987-01-30 | 1991-12-31 | Baxter International Inc. | Centrifugation chamber having an interface detection surface |
US4806252A (en) * | 1987-01-30 | 1989-02-21 | Baxter International Inc. | Plasma collection set and method |
US4834890A (en) * | 1987-01-30 | 1989-05-30 | Baxter International Inc. | Centrifugation pheresis system |
US4767397A (en) * | 1987-03-09 | 1988-08-30 | Damon Corporation | Apparatus for liquid separation |
US5114396A (en) * | 1987-09-15 | 1992-05-19 | Omega Medicinteknik Ab | Method of washing blood cells and container assembly thereof |
US4923612A (en) * | 1988-07-26 | 1990-05-08 | Trivett Gordon S | Fluid recovery and transfer system |
US4936820A (en) * | 1988-10-07 | 1990-06-26 | Baxter International Inc. | High volume centrifugal fluid processing system and method for cultured cell suspensions and the like |
US5078671A (en) * | 1988-10-07 | 1992-01-07 | Baxter International Inc. | Centrifugal fluid processing system and method |
US5316667A (en) * | 1989-05-26 | 1994-05-31 | Baxter International Inc. | Time based interface detection systems for blood processing apparatus |
US5269924A (en) * | 1991-07-26 | 1993-12-14 | Elp Rochat | Blood collecting and filtering apparatus |
US5279550A (en) * | 1991-12-19 | 1994-01-18 | Gish Biomedical, Inc. | Orthopedic autotransfusion system |
US5360542A (en) * | 1991-12-23 | 1994-11-01 | Baxter International Inc. | Centrifuge with separable bowl and spool elements providing access to the separation chamber |
US5190515A (en) * | 1992-01-13 | 1993-03-02 | Eastman Kodak Company | Vacuum degassing apparatus |
US5356365A (en) * | 1992-04-15 | 1994-10-18 | Cobe Laboratories, Inc. | Temperature controlled centrifuge |
US5690815A (en) * | 1992-07-13 | 1997-11-25 | Pall Corporation | Automated system for processing biological fluid |
US5368542A (en) * | 1993-01-13 | 1994-11-29 | Cobe Laboratories, Inc. | Apparatus and method for separating microscopic units in a substantially continuous density gradient solution |
US5437624A (en) * | 1993-08-23 | 1995-08-01 | Cobe Laboratories, Inc. | Single needle recirculation system for harvesting blood components |
US5551942A (en) * | 1993-12-22 | 1996-09-03 | Baxter International Inc. | Centrifuge with pivot-out, easy-load processing chamber |
US5549458A (en) * | 1994-07-01 | 1996-08-27 | Baxter International Inc. | Peristaltic pump with quick release rotor head assembly |
US5733253A (en) * | 1994-10-13 | 1998-03-31 | Transfusion Technologies Corporation | Fluid separation system |
US5885239A (en) * | 1994-10-13 | 1999-03-23 | Transfusion Technologies Corporation | Method for collecting red blood cells |
US5704889A (en) * | 1995-04-14 | 1998-01-06 | Cobe Laboratories, Inc. | Spillover collection of sparse components such as mononuclear cells in a centrifuge apparatus |
US6053856A (en) * | 1995-04-18 | 2000-04-25 | Cobe Laboratories | Tubing set apparatus and method for separation of fluid components |
US5651766A (en) * | 1995-06-07 | 1997-07-29 | Transfusion Technologies Corporation | Blood collection and separation system |
US6451203B2 (en) * | 1995-06-07 | 2002-09-17 | Baxter International Inc. | Blood processing systems and methods using apparent hematocrit as a process of control parameter |
Cited By (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7789245B2 (en) | 1999-09-03 | 2010-09-07 | Fenwal, Inc. | Blood separation chamber |
US7918350B2 (en) | 2002-10-24 | 2011-04-05 | Fenwal, Inc. | Separation apparatus and method |
US7438679B2 (en) | 2005-06-22 | 2008-10-21 | Caridianbct Biotechnologies, Llc | Apparatus and method for separating volumes of a composite liquid with a balancing assembly |
US20090317305A1 (en) * | 2005-06-22 | 2009-12-24 | Caridianbct, Inc. | Bag Set for Separating Discrete Volumes of A Composite Liquid |
US7674221B2 (en) | 2005-06-22 | 2010-03-09 | Caridianbct, Inc. | Apparatus for separating discrete volumes of a composite liquid with balancing elements |
US7766809B2 (en) | 2005-06-22 | 2010-08-03 | Caridianbct, Inc. | Apparatus for separating discrete volumes of a composite liquid |
US20080087613A1 (en) * | 2005-06-22 | 2008-04-17 | Gambro Bct, Inc. | Apparatus and Method for Separating Discrete Volumes of A Composite Liquid |
US20080096749A1 (en) * | 2005-06-22 | 2008-04-24 | Navigant Biotechnologies, Llc | Apparatus and Method for Separating Discrete Volumes of A Composite Liquid |
US8070665B2 (en) | 2005-06-22 | 2011-12-06 | CaridianBCT, Inc | Method for separating discrete volumes of a composite liquid |
US20100273627A1 (en) * | 2005-06-22 | 2010-10-28 | Caridianbct, Inc. | Method for Separating Discrete Volumes of A Composite Liquid |
US8016736B2 (en) | 2006-10-20 | 2011-09-13 | Caridianbct Biotechnologies, Llc | Methods for washing a red blood cell component and for removing prions therefrom |
US20080096750A1 (en) * | 2006-10-20 | 2008-04-24 | Navigant Biotechnologies, Llc | Methods for Washing a Red Blood Cell Component and for Removing Prions Therefrom |
US7935043B2 (en) * | 2007-12-26 | 2011-05-03 | Caridianbct, Inc. | Methods and apparatus for controlled addition of solutions to blood components |
US20090166298A1 (en) * | 2007-12-26 | 2009-07-02 | Caridianbct, Inc. | Methods And Apparatus For Controlled Addition Of Solutions To Blood Components |
US20100217174A1 (en) * | 2008-02-26 | 2010-08-26 | Kyungyoon Min | Blood processing system for single or double access draw and return |
US8211049B2 (en) * | 2008-02-26 | 2012-07-03 | Fenwal, Inc. | Blood processing system for single or double access draw and return |
US8685258B2 (en) | 2008-02-27 | 2014-04-01 | Fenwal, Inc. | Systems and methods for conveying multiple blood components to a recipient |
US8075468B2 (en) | 2008-02-27 | 2011-12-13 | Fenwal, Inc. | Systems and methods for mid-processing calculation of blood composition |
US20100234788A1 (en) * | 2009-03-12 | 2010-09-16 | Haemonetics Corporation | System and Method for the Re-Anticoagulation of Platelet Rich Plasma |
US8834402B2 (en) * | 2009-03-12 | 2014-09-16 | Haemonetics Corporation | System and method for the re-anticoagulation of platelet rich plasma |
US9789243B2 (en) | 2009-03-12 | 2017-10-17 | Haemonetics Corporation | System and method for the re-anticoagulation of platelet rich plasma |
US9248227B2 (en) | 2009-03-12 | 2016-02-02 | Haemonetics Corporation | System and method for the re-anticoagulation of platelet rich plasma |
US20110003675A1 (en) * | 2009-07-06 | 2011-01-06 | Caridianbct, Inc. | Apparatus and Method for Automatically Loading Washing Solution In A Multi-Unit Blood Processor |
US10226567B2 (en) | 2010-05-27 | 2019-03-12 | Terumo Bct, Inc. | Multi-unit blood processor with temperature sensing |
US9687598B2 (en) | 2010-05-27 | 2017-06-27 | Terumo Bct, Inc. | Multi-unit blood processor with temperature sensing |
US8840535B2 (en) | 2010-05-27 | 2014-09-23 | Terumo Bct, Inc. | Multi-unit blood processor with temperature sensing |
US10806847B2 (en) | 2010-12-30 | 2020-10-20 | Haemonetics Corporation | System and method for collecting platelets and anticipating plasma return |
US9302042B2 (en) | 2010-12-30 | 2016-04-05 | Haemonetics Corporation | System and method for collecting platelets and anticipating plasma return |
US9173990B2 (en) | 2011-08-12 | 2015-11-03 | Terumo Bct, Inc. | System for blood separation with replacement fluid apparatus and method |
US10112002B2 (en) | 2011-08-12 | 2018-10-30 | Terumo Bct, Inc. | System for blood separation with replacement fluid apparatus and method |
CN103191015A (en) * | 2012-01-09 | 2013-07-10 | 金卫医疗科技(上海)有限公司 | Separation soft bag for improving separating efficiency during plasma continuous separation |
US9164078B2 (en) * | 2012-06-15 | 2015-10-20 | Fenwal, Inc. | Process for predicting hematocrit of whole blood using IR light |
US20130334420A1 (en) * | 2012-06-15 | 2013-12-19 | Fenwal, Inc. | Process for Predicting Hematocrit of Whole Blood Using IR Light |
US9733805B2 (en) | 2012-06-26 | 2017-08-15 | Terumo Bct, Inc. | Generating procedures for entering data prior to separating a liquid into components |
US10004841B2 (en) | 2013-12-09 | 2018-06-26 | Michael C. Larson | Blood purifier device and method |
Also Published As
Publication number | Publication date |
---|---|
WO1999001198A1 (en) | 1999-01-14 |
US6168561B1 (en) | 2001-01-02 |
CA2294307A1 (en) | 1999-01-14 |
US6582349B1 (en) | 2003-06-24 |
EP1007183A4 (en) | 2001-11-28 |
EP1007183A1 (en) | 2000-06-14 |
BR9810653A (en) | 2000-08-08 |
JP2002509535A (en) | 2002-03-26 |
US6027441A (en) | 2000-02-22 |
CN1268069A (en) | 2000-09-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6168561B1 (en) | Blood processing chamber counter-balanced with blood-free liquid | |
US5980760A (en) | System and methods for harvesting mononuclear cells by recirculation of packed red blood cells | |
US6027657A (en) | Systems and methods for collecting diluted mononuclear cells | |
US5961842A (en) | Systems and methods for collecting mononuclear cells employing control of packed red blood cell hematocrit | |
US6354986B1 (en) | Reverse-flow chamber purging during centrifugal separation | |
US6228017B1 (en) | Compact enhanced yield blood processing systems | |
EP0618831B1 (en) | Enhanced yield platelet collection systems and methods | |
EP0936932B1 (en) | Extracorporeal blood processing method and apparatus | |
US6514189B1 (en) | Centrifugal separation method for separating fluid components | |
US7396452B2 (en) | Apparatus for determining flow rates of biological fluids | |
EP0619752B1 (en) | Compact enhanced yield blood processing systems | |
MXPA99011979A (en) | Systems and methods for collecting diluted mononuclear cells | |
MXPA99011977A (en) | Systems and methods for harvesting mononuclear cells by recirculation of packed red blood cells | |
MXPA99011985A (en) | Blood processing chamber counter-balanced with blood-free liquid | |
MXPA99001874A (en) | Systems and methods for collecting mononuclear cells employing control of packed red blood cell hematocrit |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |