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

• Tubing T3 extends from an air detection chamber Dl to channel C9 of the left cassette 23L.
• Tubing T4 extends from the drip chamber
• Tubing T10 extends from port 46 of the processing container 14, through an in line optical sensor OS to channel C4 of the right cassette 23R.
• 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
• 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 23L,
• 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.
• 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
• An intermediate layer, called the interface (designed by numeral 58) forms between the PRBC 96 and PRP 98.
• 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 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 452 (and preferably about 30s) 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) .
• 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 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.
• These contours along the high-G and low-G walls 24 and 26 produces a dynamic circumferential plasma flow condition generally transverse the centrifugal force field in the direction of the PRP collection region 76.
• the circumferential plasma flow condition in this direction (arrow 214) 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 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 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.
• the second compartment 40 is served by single tubing T18 and therefore has, in effect, a single access port.
• the compartment 40 is isolated from flow communication with the priming liquid, while pump P5 is operated to draw air from the compartment 40, thereby creating a negative pressure (vacuum) condition in the compartment 40.
• pump P5 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 P5 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.
• a portion of the separated plasma component is removed and collected for use as a MNC suspension medium.
• the controller 222 maintains the interface 58 at a relatively low position on the ramp 84 (as depicted in Fig. 16B) .
• plasma that is conveyed from the compartment 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 the compartment 38 is returned to the donor/patient during this cycle 228.
• the configuration of the fluid circuit 200 during the preliminary processing cycle 228 is shown in Fig. 21, and is further summarized in Table 2.
• ⁇ o indicates an opened, pump off condition, during which the pump rotors are not rotating and in which the pump rotors do not engage the pump tubing loop, and therefore permit fluid flow through the pump tubing loop.
• pump P2 draws whole blood (WB) from the donor/patient through tubing Tl into the left cassette 23L, into tubing T3, through the chamber Dl, and into the blood processing compartment 38 through tubing T4.
• Pump P3 draws anticoagulant ACD through tubing T15, into the middle cassette 23M and into tubing T2 , 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 T5 into the middle cassette 23M.
• the PRBC enters tubing T7 through tubing T8 , for return to the donor/patient via the left cassette 23L and tubing T9.
• the port 46 conveys PPP from the blood processing compartment 38.
• the PPP follows tubing T10 into the right cassette 23R.
• Pump P5 conveys a portion of the PPP into tubing T7 for return with PRBC to the donor/patient.
• the interface 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 the compartment 38 during this cycle.
• 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 VOL sus .
• 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 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.
• E indicates a pump on condition, during which the pump rotors rotate and engage the pump tubing to convey fluid in a peristaltic fashion.
• H o indicates an opened, pump off condition, during which the pump rotors are not rotating and in which the pump rotors do not engage the pump tubing loop, and therefore permit fluid flow through the pump tubing loop.
• ⁇ • indicates a closed, pump off condition, during which the pump rotors are not rotating, and in which the pump rotors do engage with pump tubing loop, and therefore do not permit fluid flow through the pump tubing loop.
• 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 controller sets a PRP recirculation flow rate Q Recjrc for pump P6 to achieve a desired inlet hematocrit H f
• H j is no greater that about 40%, and, most preferably, is about 32%, which will achieve a high MPV.
• Inlet hematocrit H can be conventionally measured by an in-line sensor in tubing T4 (not shown) .
• Inlet hematocrit H i can also be determined empirically based upon sensed flow conditions, as disclosed in copending United States Patent Application Serial No. 08/471,883, which is incorporated herein by reference.
• MNC float near the region 80 to the surface of the interface 58. There, the MNC are drawn by the plasma counter-flow 214 toward the low-hematocrit PRP collection region 76. Due to the lower hematocrit in this 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 0 in the PRBC collection region 50 is important. If the outlet hematocrit H 0 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 0 , 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 0 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 P4 to recirculate a portion of the PRBC flowing in tubing T5 back into the WB inlet port 48.
• Figs. 21 and 22 show, recirculating PRBC flows through the middle cassette 23M into tubing T6, which joins tubing T4 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 Q varies conversely as a function of PRBC recirculation flow rate Q r , which is governed by the pump P4 (PRBC) and the pump P2 (WB) .
• PRBC PRBC recirculation flow rate
• WB pump P2
• the outlet hematocrit H 0 can be increased by lowering Q r
• outlet hematocrit H 0 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 P2) and the outlet flow rate PRP (Q_) from the compartment 38 (governed by the interface control pump P5) .
• the controller 222 periodically samples Q h , Q , 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 P4 , based upon a targeted H o , as follows:
• H 0 is the targeted exit hematocrit value, expressed as a decimal (e.g., 0.75 for 75%)
• a is the acceleration of fluid, governed by centrifugal forces, calculated at follows: r ⁇ 2
• ⁇ 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. In the preferred embodiment, the following theoretical model is used:
• ⁇ /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, (iii) Calculate Average Q r 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 P2) , PRP outlet flow rate Q (via the pump P5) , PRP recirculation flow rate Q Recirc (via the pump P6) , and PRBC recirculation flow rate Q r (via the pump P4) .
• the controller 222 (i) commands pump P5 to maintain a Q set to hold a desired interface position on the ramp 84, and thereby achieve the desired platelet concentrations in the plasma (PPP or PRP) ;
• Second Phase 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.
• 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 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) .
• E o indicates an opened, pump off condition, during which the pump rotors are not rotating and in which the pump rotors do not engage the pump tubing loop, and therefore permit fluid flow through the pump tubing loop.
• H • indicates a closed, pump off condition, during which the pump rotors are not rotating, and in which the pump rotors do engage with pump tubing loop, and therefore do not permit fluid flow through the pump tubing loop.
• PRBC in line T5 is conveyed through the middle cassette 23M, into line T14, and into the container PRBC.
• the controller 222 operates in this phase 238 until a desired volume of PRBC (e.g., 35 ml to 50ml) 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
• the controller 222 enters the MNC harvesting stage 234 of the main processing cycle 230.
• first phase 240 of this stage 234 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 T4 , 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 T10 out of the compartment 38.
• E indicates a pump on condition, during which the pump rotors rotate and engage the pump tubing to convey fluid in a peristaltic fashion.
• E o indicates an opened, pump off condition, during which the pump rotors are not rotating and in which the pump rotors do not engage the pump tubing loop, and therefore permit fluid flow through the pump tubing loop.
• E • indicates a closed, pump off condition, during which the pump rotors are not rotating, and in which the pump rotors do engage with pump tubing loop, and therefore do not permit fluid flow through the pump tubing loop.
• 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 into compartment 38 through the WB inlet port 48.
• the controller 222 starts a cycle time counter at TCYC START .
• 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 T10 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 23R and tubing T12 (as Fig. 24A shows) .
• a region 114 of PRBC also follows the concentrated MNC Region within the tubing T10.
• 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 T10 between the PRP outlet port 46 and the right 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
• the optical sensor OS is a conventional hemoglobin detector, used, e.g., on the
• 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 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 T10, 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 T10 (RED) .
• Background optical "noise" can be filtered from RED to obtain OPTTRANS, as follows:
• 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 T10;
• 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 T10; and where CORREF is calculated as follows:
• 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 preceding MNC 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 (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 ⁇ ASE .
• the processing element 100 continues during the subsequent MNC removal phase 240 to sense one or more optical transmission values for the tubing T10 and the liquid flowing in it (0PTTRANS 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 T10 between the optical sensor OS and the valve station V24 in the right cassette 23R constitutes a known value, which is inputted to the controller 222 as a first offset volume VOL 0FF(1) .
• the controller 222 calculates a first control time value Time 1 based upon VOL 0FF(1) and the pump rate of pump P4 (Q P ) , as follows:
• the operator can specify and input to the controller 222 a second offset volume VOL 0FF(2) , which represents a nominal additional volume (shown in Fig. 28) to increase the total MNC harvested volume VOL ⁇ .
• VOL 0FF(2) represents a nominal additional volume (shown in Fig. 28) to increase the total MNC harvested volume VOL ⁇ .
• the quantity V0L 0FF(2) takes into account system and processing variances, as well as variances among donors/patients in MNC purity.
• the controller 222 calculates a second control time value Time 2 based upon VOL 0FF(2) and the pump rate of pump P4 (Q p4 ) , as follows:
• Tine VOL ° F 2 > * 60 Q P4
• the interface 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.
• the volume of MNC sensed can be derived based upon the interval between TC, and TC 2 for a given Q pl> .
• the controller 222 compares the magnitudes of TC, to the first control time T,, as well as compares TC 2 to the second control time T 2 .
• the controller 222 commands valve station V24 to open, and commands valve station V25 to close.
• the controller 222 marks this event on the cycle time counter as TCYC SU]TCH .
• the targeted MNC Region is conveyed into the tubing T13 that leads to the container MNC.
• the total MNC volume selected for harvesting (VOL ⁇ ) for the given cycle is thereby present in the tubing T13.
• the controller 222 commands the pump P4 to stop. Further advancement of VOL ⁇ in the tubing T13 therefore ceases.
• the controller 222 derives the volume of PRP that was conveyed into the container PPP during the preceding MNC removal phase.
• This PRP volume (which is designated VOL pRp ) is derived, as follows:
• the controller 222 ends the MNC removal phase, independent of TC, and TC 2 when the pump P4 conveys more than a specified fluid volume of PRBC after TCYC START (e.g., more than 60 ml).
• a specified fluid volume of PRBC after TCYC START e.g., more than 60 ml.
• This time-out circumstance could occur, e.g., if the optica.1 sensor OS fails to detect THRESH (1) .
• VOL pRp 60 -
• the controller 222 can end the MNC removal phase independent of TC, 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 T12 and into the blood processing compartment 38.
• E indicates a pump on condition, during which the pump rotors rotate and engage the pump tubing to convey fluid in a peristaltic fashion .
• E o indicates an opened, pump off condition, during which the pump rotors are not rotating and in which the pump rotors do not engage the pump tubing loop, and therefore permit fluid flow through the pump tubing loop.
• ⁇ • indicates a closed, pump off condition, during which the pump rotors are not rotating, and in which the pump rotors do engage with pump tubing loop, and therefore do not permit fluid flow through the pump tubing loop.
• 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 Til.
• VOL pRp is conveyed by the pump P6 through tubing T12 into the right cassette 23R, and thence to tubing Til, for entry into the processing compartment 38 through tubing T4 and port 48.
• PRBC are conveyed from the processing compartment 38 through port 50 and tubing T5 into the middle cassette 23M, and thence into tubings T8 and T7 into the left 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 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.
• E indicates a pump on condition, during which the pump rotors rotate and engage the pump tubing to convey fluid in a peristaltic fashion.
• E o indicates an opened, pump off condition, during which the pump rotors are not rotating and in which the pump rotors do not engage the pump tubing loop, and therefore permit fluid flow through the pump tubing loop.
• B • indicates a closed, pump off condition, during which the pump rotors are not rotating, and in which the pump rotors do engage with pump tubing loop, and therefore do not permit fluid flow through the pump tubing loop.
• the controller closes C3 to stop the return to PRBC to the donor/patient.
• a predetermined aliquot of VOL sus e.g., 5ml to 10ml
• the pump P6 through tubing T12 into the right cassette 23R and then into tubing T13.
• the aliquot of V0L sus further advances VOL MNC through the tubing T13 into the container MNC.
• B indicates a pump on condition, during which the pump rotors rotate and engage the pump tubing to convey fluid in a peristaltic fashion.
• E o indicates an opened, pump off condition, during which the pump rotors are not rotating and in which the pump rotors do not engage the pump tubing loop, and therefore permit fluid flow through the pump tubing loop.
• B • indicates a closed, pump off condition, during which the pump rotors are not rotating, and in which the pump rotors do engage with pump tubing loop, and therefore do not permit fluid flow through the pump tubing loop.
• the controller 222 closes all valve stations in the left and middle cassettes 23L and 23M and configures the right pump station PSR to circulated PRBC from tubing T10 back into the processing compartment 38 through tubings Til and T4. 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 V0L 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 V0L 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 V0L sus into the container MNC to achieve the desired dilution of VOL ⁇ .
• 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
• 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 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 the compartment 310 through a new clamp C5 to join tubing path T10.
• Tubing path T22 leads from the WB inlet port 306 of the compartment 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 the compartment 310 through a new clamp C8 to join tubing T4.
• New clamp C7 is also provided in tubing T3 upstream of the air detector Dl.
• New clamp C9 is also provided in tubing T10 between the optical sensor OS and the junction of new tubing T21.
• 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 P2 through tubing Tl into tubing T3 and thence through open clamp C6 into tubing T22, which leads to the compartment 310.
• Clamp C7 is closed, to block conveyance of whole blood into the compartment 38, where the MNC have been accumulated for harvesting.
• Clamp C9 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 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 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 C8 and C9, while closing clamp C5.
• the whole blood entering the compartment 310 displaces PRBC through the PRBC outlet port 302 into tubing T23.
• 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.

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• 1997
  • 1997-07-01 US US08/886,179 patent/US6027441A/en not_active Expired - Lifetime
• 1998
  • 1998-06-22 JP JP50721499A patent/JP2002509535A/ja active Pending
  • 1998-06-22 CN CN98806731A patent/CN1268069A/zh active Pending
  • 1998-06-22 BR BR9810653-8A patent/BR9810653A/pt not_active IP Right Cessation
  • 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
  • 1998-06-22 CA CA002294307A patent/CA2294307A1/en not_active Abandoned
• 1999
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• 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

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