EP0165254A1 - Systeme de centrifuge flexible jetable - Google Patents

Systeme de centrifuge flexible jetable

Info

Publication number
EP0165254A1
EP0165254A1 EP84904063A EP84904063A EP0165254A1 EP 0165254 A1 EP0165254 A1 EP 0165254A1 EP 84904063 A EP84904063 A EP 84904063A EP 84904063 A EP84904063 A EP 84904063A EP 0165254 A1 EP0165254 A1 EP 0165254A1
Authority
EP
European Patent Office
Prior art keywords
bowl
chamber
volume
processing
port
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.)
Withdrawn
Application number
EP84904063A
Other languages
German (de)
English (en)
Inventor
Richard I. Brown
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Baxter International Inc
Original Assignee
Baxter Travenol Laboratories Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Baxter Travenol Laboratories Inc filed Critical Baxter Travenol Laboratories Inc
Publication of EP0165254A1 publication Critical patent/EP0165254A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • B04B5/0407—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles
    • B04B5/0428—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles with flexible receptacles

Definitions

  • This invention relates to a centrifugal liquid processing apparatus, and more particularly, to a novel processing or separation chamber and system for use in centrifugal apheresis (e.g., plasmapheresis or plateletapheresis).
  • centrifugal apheresis e.g., plasmapheresis or plateletapheresis
  • the separation of the blood into constituent components is typically performed using a centrifuge or centrifugal liquid processing apparatus.
  • a centrifuge or centrifugal liquid processing apparatus Such systems are disclosed in U.S. Patents 3,987,961; 4,132,349; and 4,285,464.
  • the processing chamber into which the whole blood is delivered for separation has in general been bowl-shaped, rigid and usually disposable.
  • a number of different fluid connection systems are known for connecting the rotating processing chamber to external stationary blood sources or
  • OMPI component collection containers Some of these systems use stationary rather than rotating seals. See, for example, U.S. Patent 4,151,844; 4,285,464; and 4,389,207.
  • centrifuge In addition to central processing laboratories, newer systems are being developed in which the centrifuge is located at the collection center and the donor is connected to the processing apparatus during the donation, separation and collection operations. A number of advantages are recognized from such systems, such as speed of collection, increased component yield, reduced cost, and the like.
  • the volume of the separation chamber be variable so as to accommodate those volume changes occurring during the separation and collection procedures.
  • the chamber should be one-piece and removable from the centrifugal processing apparatus for transporting of blood or components within the chamber.
  • the chamber should be sterilely sealed to external sites such as component collection bags and catheters. Desirably, the entire system should be integral and disposable. It is also desirable to provide a processing chamber which is less expensive to manufacture than the ex sting bowl systems.
  • red blood cells In the processing of blood, it is generally desirable to first separate red blood cells from the whole blood and thereafter separate and collect platelets from the remaining plasma. It is also desirable to maximize platelet collection in general and, more specifically, to maximize collection of platelets which may be associated with the red blood cells.
  • the " red blood cells separate or sediment against the bowl wall.
  • the plasma forms a layer inwardly of and adjacent the red blood cell layer with an interface of "buffy layer” of platelets forming therebetween. In such a situation three adjacent layers are formed: the red blood cell layer, the platelet or buffy layer, and the plasma layer.
  • the discreteness ⁇ f the layers may not be as precise as desired.
  • a fl exibl e, one-pi ece, variabl e-vol ume processi ng chamber for use in centri fugal apheresi s (e.g. , pl asmapheresis or pl atel etapheresi s) which can be easily and economical ly manufactured.
  • the chamber is useful in receivi ng whol e bl ood, separating the bl ood i nto therapeutic components, and the sel ective coll ection of such components .
  • the chamber includes a flexible, bladder-l ke casing which is formable to a bowl-like shape having an outer wall and an inner wall which when spaced from each other define the blood-receiving and processing cavity.
  • a flexible rim area connects the inner and outer walls and defines a flexible rim edge.
  • the resulting bowl is substantially symmetric about a central spin axis, is flexible, and the rim area is constructed to fold or lay against itself and to roll in an axial direction or advance and retract as the chamber is filled and emptied.
  • At least one port provides fluid communication between the flood-receiving cavity and external sites.
  • the chamber may be one component of an integral sterile and disposable separation and collection system which also includes fluid-carrying tubing, collection bags, and a catheter.
  • an enclosed processing bowl for use in centrifugal apheresis which minimizes platelet separation during red blood cell separation and collection and which maximizes platelet collection by maximizing the blood sedimentation surface area and minimizing the buffy layer interface area.
  • the bowl has inner and outer walls which define bottom and side wall sections, a blood receiving cavity between said walls, and at least one port for fluid communication with said cavity.
  • the bowl bottom section defines a cylindrically-shaped plasma processing volume
  • the side wall section defines an annularly-shaped red blood cell processing volume. The red blood cell processing volume and the plasma processing volume are approximately equal.
  • the plasma processing volume and red blood cell processing volume form a generally cylindrical interface at the transition from the bottom section to the side wall section.
  • the buffy layer forms at this interface.
  • the outer wall of the side wall section forms a red blood sedimentation surface and the area of the sedimentation surface is greater than the surface area of the blood cell/plasma interface.
  • FIGURE 1 is a perspective view showing the flexible, variable-volume, bowl-shaped chamber with mating parts of a centrifugal processing apparatus;
  • FIGURE 2 shows the bowl-shaped chamber distended to show the bladder-l ke casing shape and show how the bowl-shaped chamber s formed;
  • FIGURE 3 shows a rim edge and a portion of the rim area rolled back upon itself in advanced and retracted positions;
  • FIGURE 4 shows another version of the chamber with the rim edge;
  • FIGURE 5 through FIGURE 12 show the operation of a centrifuge system using the bowl-shaped chamber
  • FIGURE 13 shows a integral sterile and disposable separation and collection system.
  • FIGURE 14 is a perspective view showing a processing apparatus and variable volume bowl
  • FIGURE 15 is a sectional and perspective view showing a fully filled bowl and the red blood cell and the plasma volumes
  • FIGURE 16 is a sectional and perspective view showing a partially filled bowl and the red blood cell and the plasma volumes;
  • FIGURE 17 is a perspective view, partially in section, showing a fixed volume and the red blood cell and the plasma volumes.
  • a flexible, variable-volume, bowl-shaped processing chamber 10 generally is shown positioned between a bowl-shaped rotor 12 and a conformingly-shaped and movable mandrel 14.
  • centrifugal liquid processing apparatus of the type used in centrifugal apheresis are known in the art.
  • Drive systems for spinning the separation chambers, speed control systems, and the like, are also known in the art. Those systems are not shown herein as they are known in the art, and as this invention is directed to the flexible, variable- olume chamber and the system of which it may be a part.
  • the rotor bowl 12 includes a bottom wall portion 16, upwardly-extending side wall 18, an upper lip or edge 20, a tube-receiving slot 21, and is generally symmetric about a vertical spin axis 22-22.
  • the rotor bowl also includes at least one port or passageway 24, which is located in the bottom wall 16 at the spin axis 22-22.
  • the flexible chamber 10 is constructed to fit within the rotor bowl 12 for rotation therewith, and the chamber may have a shape which is generally complementary to that of the rotor bowl.
  • the mandrel 14 is a cup-shaped member, similar in shape to the rotor bowl 12, and is adapted to nest therein.
  • the mandrel 14 includes a bottom wall 26, an upwardly-extending side wall 28, and skirt 30.
  • the mandrel is axially movable toward and away from the chamber 10 so that the chamber's volume may be controlled by the cooperation of the mandrel 14 and rotor bowl 12.
  • the mandrel is mounted to the processing apparatus so as to spin with the rotor bowl 12 and the chamber 10 about axis 22-22.
  • the flexible chamber 10 includes an outer wall 32 and an inner wall 34 which are joined along a flange or shoulder-like seal 36 to form an enclosed casing.
  • the space between the walls defines a blood-receiving cavity 37.
  • the inner and outer walls are formed of a flexible, medical-grade, polymeric material, such as polyvinylchloride. In the preferred embodiment, the walls are sealed, flexible and pliable.
  • the outerwall 32 includes a fluid port 38 and integral conduit 39, which provides fluid communication between the cavity 37 and external blood sources or therapeutic component collection sites.
  • the port 38 is shown as aligned with
  • OMPi v_ _TM ⁇ _ the spin axis and forms what is known as the low-gravity or low-G port.
  • the inner wall 34 is shown as depressed inwardly toward the outer wall 32 and forming a rim area 40 generally adjacent- the flange 36.
  • the flexible processing chamber 10 fits within the rotor bowl 12, and since it is flexible, the outerwall 32 will conform to the shape of. the rotor wall when the chamber is filled and spinning.
  • the conduit 39 and port 38 are positioned in the cover 12 through the slot 21.
  • the mandrel 14 fits within the depression or space formed in the inner wall 34, and the inner wall 34 will conform to the mandrel. Axial movement of the mandrel 14 cooperates in controlling the volume of the cavity 37 as well as the pressure within the chamber.
  • the chamber 10 is vacuum formed by separately vacuum forming each of two polyvinyl sheets over a male die, and thereafter, nesting the formed sheets and RF (radio frequency) sealing the sheets along the peripheral edge or flange line.
  • RF radio frequency
  • the casing When the chamber is distended, as suggested in Figure 2, the casing assumes a bladder-like configuration which may be referred to as a prolate ellipsoid. From the d stended position, the top end of the inner wall 34 is depressed inwardly so as to form the depression which receives the mandrel 14.
  • the chamber walls be capable of being flattened against themselves and that the only space provided between the rotor bowl 12 and mandrel 14 will be about the thickness of the chamber's inner and outer walls.
  • the chamber material is sufficiently flexible at the rim area 40 that it can be folded back upon itself.
  • the inner wall 34 is folded back so that wall portions, such as 34a_ and 34b_, contact each other and there is no space therebetween.
  • the folded wall portions form the rim edge 34c_.
  • the rim edge 34£ advances and retracts, and in a sense rolls, while retaining an edge.
  • the bowl is shown in an expanded position by the dashed lines with the inner wall 34 flattened against itself as it rolls axially upwardly and downwardly.
  • the inner wall 34 flattened against itself as it rolls axially upwardly and downwardly.
  • one of the inherent character stics of the material selected for the inner wall is that it be capable of being folded flat against itself so as to define a rim area and rim edge and roll upwardly and downwardly without tearing or leaking.
  • FIG 4 there are situations in which it is desirable to begin processing with an initial liquid volume in the chamber and/or to leave some liquid in the chamber at the end of the processing cycle.
  • the mandrel and rotor are arranged to permit the inner wall portions 34_a and 34 ⁇ to be spaced from each other in the rim area while still forming the rim edge 34c_.
  • the rim edge 34 advances upwardly and downwardly, but with the inner and outer walls spaced from each other. Again, the rim edge will not tear or leak.
  • a single fluid port 38 is provided. Depending upon how the system is used, all fluid flow and separation can be accomplished through the port 38. Since the port is located on the spin axis, the port is referred to as the low-G (low-gravity) port. Alternatively, a single port could be provided at the greatest radial distance from the spin axis and this would be referred to as the high-G
  • the high-G port is formed by bonding tubing between the inner and outer wal l s at the fl ange 36.
  • the tubi ng connects the port to a Y-connector 43 or to a harness which hol ds the tubing connecting the low-G port 38.
  • the connection between the rotating parts and stationary parts external of the rotor and. chamber may be made in the manner disclosed in U.S. Patents Re. 29,738; 3,986 ,442; and 4,108,353.
  • a number of different processing techniques can be used for separating the therapeutic components using the rate of the spin, the mandrel and either one or two ports.
  • a three-port system may be desirable.
  • a third port 44 is provided through the outer wal l 32 at a position intermediate the low-G port 38 and high-G 42.
  • the third port coul d be used as a blood inl et, so that bl ood entering at port 44 woul d immediately begin to separate with high density components (such as red bl ood cel l s) moving toward the hi gh-G port 42 and the low density components (such as plasma) separating toward the low-G port 38.
  • Thi s is but one technique to be used, and it is important to note that bl ood inlet port 44 can be provided through the side wal l 32. If such a port were added, it coul d be connected via tubing to the Y-connector 43 adjacent port 38 in the same manner as the tubing from the high-G port 42.
  • the embodiment previously described is fabricated by the vacuum forming of two sheets and incl usion of mol ded ports and tubing.
  • Another technique by which such a system can be prepared is by blow-mol ding in which, for exampl e, the high-G port and return tubing are mol ded into the si de wal l .
  • OMPI One mode for operating the flexible volume reservoir is shown in diagrammatic form in Figures 5-12. Here for ease of consideration the variable-volume chamber is shown without the mandrel and rotor. It is understood that the chamber is held against the rotor wall and has assumed the shape of the rotor wall and mandrel.
  • the chamber 50 includes a low-G port 52 and line 53, and a high-G port 54 and line 56.
  • the lines 53 and 58 are shown connected to a multiple-lumen umbilicus, which connects the low-G and high-G ports to external points.
  • Various valves, clamps and pumps can be provided external of the chamber for controlling flow through the ports 52 and 54.
  • One such system is described hereinafter.
  • the mandrel has compressed the chamber so that the chamber's inner and outer walls are compressed together.
  • a small amount of anticoagulant is metered into the processing chamber (or is provided at the time of manufactured), and. as shown in Figure 6, whole blood is delivered to the chamber and enters via low-G port 52.
  • the blood fills the chamber and mixes with the anticoagulant.
  • the rotor rotates slowly and the mandrel retracts so as to fill the chamber with about 525 illil ters of whole blood.
  • the processing apparatus spins the rotor, chamber and mandrel in a first spin so as to separate the blood into red blood cells (RBC) and platelet-rich plasma (PRP).
  • RBC red blood cells
  • PRP platelet-rich plasma
  • This spin is sometimes referred to as a soft spin and the specific spin conditions, as is known in the art, depend on factors such as rotational velocity, bowl surface area, time, initial blood he atocrit, and the like.
  • the red blood cel l s (RBC) move radial ly outwardly along the sides of the chamber, and the pl atel et-rich pl asma coll ects in the center portion of the chamber and is identified as PRP.
  • Red blood cell s may be col lected by cl osing the l ow-G port 52, opening the high-G port 54, and moving the mandrel downwardly so that the vol ume of the processing chamber is reduced, and red blood cel l s are forced from the chamber through the high-G port 54 and l ine 58 for harvesting and col l ection-.
  • This l eaves the pl atelet-rich pl asma (PRP) in the fl exible bowl as shown in Figure 8.
  • PRP pl atelet-rich pl asma
  • the bowl is than subjected to a second spin which separates the platelets from the platelet- ich plasma by driving the platelets along the outer wall, which leaves the platelet-free plasma at the center.
  • This is sometimes known as a hard spin.
  • the high-G port 54 is closed, the low-G port 52 is opened, the mandrel is moved downwardly, and the platelet-free plasma (PRP) is expressed from the chamber, as shown in Figure 10.
  • PRP platelet-free plasma
  • the mandrel is then retracted, which draws a small amount of air into the system from an empty but sterile and closed transfer pack or collection bag. Agitation resuspends the platelets into a small volume of carrier plasma. Under a third spin,, or soft spin, as shown in Figure 12, the mandrel expresses the platelet concentrate out of the chamber and into a collection bag for transporting.. Alternatively, the platelets can be transported in the processing bowl rather than being collected and transported in a separate bag.
  • the volume of the chamber varies as blood is introduced into the chamber and in accordance with the separation procedure which is being used.
  • the rim edge 34c moves upwardly and downwardly, and thus that area must be flexible as previously described.
  • the outer wall of the chamber may be rigid and a predetermined portion of the inner wall may be rigid. But the rim area and the rim edge must remain flexible.
  • FIG. 13 A complete, integral, disposable, sterile and sealed collection and separation system is shown in Figure 13. This entire system is sterilely sealed upon manufacture and, as such, can be used to store and transport whole blood and components for times greater than those permitted by regulation when the system is open or pierced in the field.
  • the flexible, variable-volume processing chamber 60 includes a high-G port 62 and tubing 64 and a low-G port 66 and tubing 68.
  • the tubing may be threaded through peristaltic roller pumps 70 and 72 and then connected at a Y-junction 74. It will be recalled that the chamber 60 is rotating while the pumps 70 and 72 are fixed in place.
  • the rotating chamber and stationary pumps are connected via tubing 64 and 68.
  • This connection is made in accordance with the teaching of U.S. Patents Re. 29,738; 3,986,442; and 4,108,353, which permit a seal!ess connection between rotary and stationary members. This fluid communication is established without rotary seals or the like.
  • the tubing 76 leading from junction 74 connects to a standard red blood cell collection bag 78, a standard plasma collection bag 80, a special breathable platelet collection bag 82, a saline-containing bag 84, an anticoagulant bag 85, and a catheter 86.
  • Anticoagulant can be provided from a separate bag as shown or may be initially provided in the processing chamber 60 in which case an anticoagulant bag, such as 85, is not included the system.
  • the saline solution may be drawn from bag 84- and anticoagulant from bag 85, through line 76, and into the chamber 60 for priming. Thereafter, blood is taken from the patient via catheter 86 and delivered via line 76 to chamber 60, preferably through low-G port 62. During this phase, the collection bags may be clamped using external clamping means, such as forceps or nemostats.
  • red blood cells for example, may be drawn from the high-G port 62 utilizing roller pump 70 and delivered to the red blood cell collection bag 78.
  • platelet-free plasma may be . drawn from the low-G port 66 using pump 72 and delivered to the plasma collection bag 80. Then platelet concentrate may be collected via high-G port 62, pump 70 and delivered to the special platelet collection bag 82.
  • the entire system is disposable and sterilely sealed at the plant. Thus, it may be removed from the centrifuge, from the roller pumps 70 and 72, from the patient 86 and delivered to the processing site.
  • FIG. 14 through 17 A preferred embodiment of the processing chamber is shown in Figures 14 through 17, being therein identified by reference numeral 112.
  • the chamber 112 includes an inner wall 116 and an outer wall 118. These walls form a bowl-shaped chamber having a generally cylindrical bottom section 120 and a generally annular upstanding side wall section 122.
  • the bottom section 120 is formed by the transverse bottom wall portions of the inner wall 116a_ and of the outer wall 118a_.
  • the side wall portions are formed by the upstanding side wall 116_b of inner wall and upstanding side wall 118J? of the outer wall.
  • the inner wall 116 and outer wall 118 form a flexible rim area 124 which flexes and appears to roll as the chamber volume increases and decreases, thereby permitting changes without tearing or rupturing.
  • the walls are each formed from a flexible polyvinylchloride sheet which is vacuum formed and the sheets are then heat sealed along a peripheral flange 126 so as to form the sealed chamber.
  • a high-gravity port 128 is formed in the flange at the radially outermost point and a low-gravity port 130 is formed in the bottom wall at the intersection of the spin axis A-A.
  • Conduits 132 and 134 connect the ports 128 and 130 to external blood sources and collection containers.
  • the chamber 112 is fitted into the bowl cover 110 and tubing from the chamber ports its within slot 129.
  • a chamber engaging mandrel 114 is also provided as heretofore described. Stationary seal connections are made to the external blood sources and collection points as shown in U.S. Patents 4,151,844; 4,285,464; and 4,389,207.
  • Vp cylindrical or disc-like plasma processing volume
  • Vbc red blood cell processing volume
  • the interface between the blood volume and plasma volume is along the cylindrical surface 138, which forms at the transition from the bottom to the side wall.
  • the bowl is shaped so that when blood having a he atocrit between 40-60 (ie., volume percent red blood cells) is processed, the red blood cell volume 40 and plasma volume 36 are approximately equal whether the bowl is fully filled as in Figure 15 or partially filled as in Figure 16.
  • the bowl is also constructed such that the red blood cell sedimentation surface area (S,) 118 is greater than the interface surface area (S ⁇ ) 132.
  • the red blood cell sedimentation surface area -118J3 may be about four times that of the interface 138.
  • whole blood is introduced into the chamber through the low-G port 130, for example, and the apparatus is spun about the axis A-A in a first or hard spin.
  • the heavier red blood cells are driven toward or sediment against the outer wall 118b_ and red blood cells fill the blood cell volume 40.
  • Platelet-rich plasma in the volume 40 is displaced inwardly toward the plasma volume 36.
  • the red blood cells which are experiencing high gravity forces, sediment or "pack out", thus filling the volume 40.
  • platelet separation from the red blood cells is maximized as is red blood cell purity.
  • the plasma volume 36 fills with the platelet-rich plasma initially in the volume and with the platelet-rich plasma displaced into the volume.
  • the platelet-rich plasma in the plasma volume 36 experiences low-G forces as compared to the forces experienced by the red blood cells.
  • the amount of platelet separation and buffy layer formation is minimized and is related to the spin rate, plasma viscosity, interface position, and the like. The intent is to minimize platelet separation and buffy layer formation during red blood cell separation.
  • the chamber was fully filled with about 500 milliliters of whole blood which has a hematocrit of about 40 (ie., 40 volume per cent red blood cells).
  • the red blood cells formed a bed of packed cells in the volume 40, platelet-rich plasma collected in volume 36, and a thin buffy layer formed at interface 138.
  • the packed cell volume was about 250 milliliters and the plasma volume v/as about 250 milliliters.
  • the red blood cells can be collected through the high-G port 128 with minimal platelet contamination. Thereafter, the chamber can be utilized for platelet/plasma separation.
  • Figure 16 shows the variable volume chamber set to process less than 525 milliliters of whole blood. As in Figure 15, the volumes are about equal and the red blood cell surface area is greater than the interface area. Processing is performed in substantially the same manner and the same type of separation is effected.
  • an enclosed, rigid, fixed volume processing bowl 150 is shown.
  • the housings, drives and controls for operating a rigid bowl system are known in the art.
  • the bowl 150 may be blow-molded or fabricated from plastic members and includes rigid inner and outer walls 152 and 154 which define a fixed internal volume that includes a red blood cell volume 56 in the side wall and a plasma volume 58 in the bottom wall.
  • the howl includes a red blood cell sedimentation surface 160 and is structured- to permit a buffy layer or interface 162 to form and be defined.
  • High-G and low-G ports 164 and 166 and related conduits are also provided. Separation of therapeutic components using this bowl is similar to separation using the variable volume bowl except that no volume variation occurs.

Landscapes

  • External Artificial Organs (AREA)

Abstract

Chambre en forme de cuvette destinée à être utilisée dans l'aphérèse centrifuge. La chambre est utilisée pour recevoir le sang total, le séparer en ses composants thérapeutiques et recueillir sélectivement les composants thérapeutiques. Dans un mode de réalisation, la chambre (10) comprend une enceinte en forme de vessie, composée d'un chambre en forme de cuvette possédant une paroi externe en forme de cuvette (32) et une paroi interne en forme de cuvette (34). Les parois interne et externe (32, 34) définissent entre elles une cavité de traitement du sang (37) et une zone flexible de bordure (40) relie les parois interne et externe. La zone de bordure (40) définit un bord (34c) et la cuvette est sensiblement symétrique autour d'un axe central de révolution. La zone de bordure (40) peut se replier sur elle-même de manière à fermer le bord (34) qui peut avancer ou reculer en fonction des changements de volume de la chambre. Dans un autre mode de réalisation, la cuvette (112) possède des parois interne et externe (116 et 118) qui définissent des sections de fond et de parois latérales (120 et 122), une cavité recevant le sang entre les parois, et au moins un port (128, 130) en communication de fluide avec la cavité. La section de fond de la cuvette (120) définit un volume cylindrique de traitement de plasma (136) et la section de paroi latérale définit un volume annulaire de traitement d'érythrocytes (140). Le volume de traitement d'érythrocytes (140) et le volume de traitement de plasma (136) sont approximativement identiques.
EP84904063A 1983-12-13 1984-11-05 Systeme de centrifuge flexible jetable Withdrawn EP0165254A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US56098783A 1983-12-13 1983-12-13
US56094683A 1983-12-13 1983-12-13
US560946 1983-12-13
US560987 1983-12-13

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EP0165254A1 true EP0165254A1 (fr) 1985-12-27

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EP (1) EP0165254A1 (fr)
IT (1) IT1181911B (fr)
WO (1) WO1985002561A1 (fr)

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IT1181911B (it) 1987-09-30
IT8423978A1 (it) 1986-06-11
IT8423978A0 (it) 1984-12-11
WO1985002561A1 (fr) 1985-06-20

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