WO1987006844A1 - Method and apparatus for plasmapheresis - Google Patents

Method and apparatus for plasmapheresis Download PDF

Info

Publication number
WO1987006844A1
WO1987006844A1 PCT/SE1987/000240 SE8700240W WO8706844A1 WO 1987006844 A1 WO1987006844 A1 WO 1987006844A1 SE 8700240 W SE8700240 W SE 8700240W WO 8706844 A1 WO8706844 A1 WO 8706844A1
Authority
WO
WIPO (PCT)
Prior art keywords
blood
primary container
container
rotor
processing assembly
Prior art date
Application number
PCT/SE1987/000240
Other languages
French (fr)
Inventor
Peter Unger
Eric Westberg
Original Assignee
Omega Medicinteknik Ab
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
Priority claimed from SE8602242A external-priority patent/SE459791B/en
Application filed by Omega Medicinteknik Ab filed Critical Omega Medicinteknik Ab
Priority to AT87903463T priority Critical patent/ATE90575T1/en
Publication of WO1987006844A1 publication Critical patent/WO1987006844A1/en

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
    • 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
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • A61M1/30—Single needle dialysis ; Reciprocating systems, alternately withdrawing blood from and returning it to the patient, e.g. single-lumen-needle dialysis or single needle systems for hemofiltration or pheresis
    • A61M1/301—Details
    • A61M1/304—Treatment chamber used as reservoir, e.g. centrifuge bowl or filter with movable membrane
    • 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
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3496—Plasmapheresis; Leucopheresis; Lymphopheresis
    • 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
    • A61M1/3693—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
    • 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
    • A61M1/3698—Expressing processed fluid out from the turning rotor using another fluid compressing the treatment chamber; Variable volume rotors
    • 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
    • A61M1/02—Blood transfusion apparatus
    • A61M1/025—Means for agitating or shaking blood containers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4022—Concentrating samples by thermal techniques; Phase changes
    • G01N2001/4027—Concentrating samples by thermal techniques; Phase changes evaporation leaving a concentrated sample
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00465—Separating and mixing arrangements
    • G01N2035/00495—Centrifuges

Definitions

  • This invention relates to a method and an apparatus for carrying out plasmapheresis.
  • Plasma a yellowish liquid containing various proteins.
  • the other half of the blood contains cellular material, such as red blood cells, white blood cells and platelets.
  • Plasma is used in transfu ⁇ sions and as raw material for the pharmaceutical industry in connection with the production of pharmaceuticals, such as albumin, gamma globulin and Factor VIII (haemophilia medicament) .
  • Plasma may be obtained in pure form by centrifugation, about 200 ml of red blood cells and about 250 ml of plasma being obtainable from a donated blood unit of about 500 ml, including anticoagulant.
  • the plasma fraction can also be obtained by plasmapheresis, in which the blood of the blood donor is withdrawn and centrifuged whereupon the red blood cells are returned to the donor.
  • Plasmapheresis is advantageous because it is a cheaper method of obtaining plasma in the case where red blood cells are not needed, because each withdrawal yields more plasma (in total 600 ml in the case of two-cycle plasmapheresis) , and because plasmapheresis can be carried out more frequently than blood donation.
  • Relatively expensive automated equipment for plasma ⁇ pheresis is known, such as the Haemonetic or Haemoscience machines which are made in the United States.
  • BG blood donor
  • rocker mixes the blood with the anticoagulant.
  • the flexible tube is cut off under the action of heat so that the ends of the flexible tube are sealed, and the bag is carried to a centrifuge in which separation takes place.
  • the bag is transferred to a squeezing device in which the plasma collected in the upper portion of the bag is expelled into a different bag.
  • the object of the present invention is to provide a method and an apparatus permitting small-scale semi- automated utilization of plasmapheresis, e.g. in mobile units, such as blood buses, and having the following advantages over manual plasmapheresis:
  • a large stationary centrifuge can be dispensed with.
  • a centrifuge of the type described in Swedish patent application No. 8602242-3 may be used.
  • This patent applica ⁇ tion discloses a centrifuge in which the processing space " of the rotor includes an annular separation compartment and a central compartment. The volume of the separation compartment can be reduced during the centrifugation to - displace a centrifugally separated component into the central compartment. An oscillating reciprocatary movement can be imparted to the rotor, and the processing space can be subjected to overpressure or vacuum.
  • blood is withdrawn from the blood donor direct into an annular primary container forming part of a closed flexible processing assembly which is positioned in the processing space of the centrifuge rotor.
  • the centrifuge may be positioned immediately adjacent the blood donor coach. During the withdrawal the rotor is oscillated to mix the blood with anticoagulant with which the primary container has been primed beforehand or which is supplied at the same time as the blood.
  • the next step consists in centrifugation of the blood in the primary container to separate blood cells and plasma. After a given centrifug- ing time, the plasma is expelled to a secondary container forming part of the processing assembly and disposed in the central region of the annular primary container. This transfer of the plasma may preferably be effected by increasing the rotational speed of the centrifuge so that a centrifugally operated valve opens a connecting duct between the primary container and the secondary container and at the same time subjecting the primary container to a squeezing pressure.
  • the invention also relates to a closed flexible processing assembly for use in carrying out the method.
  • the processing assembly comprises an annular primary container, a secondary container positioned in the central region of the annulus, and a closable connecting duct between the portion of the primary container closest to the centre of rotation and the secondary container, and a " " flexible tube connected to the primary container for supply of blood to the processing assembly and withdrawal of blood cell suspension from the processing assembly.
  • Fig. 1 is an elevational view of one embodiment of a processing assembly according to the invention
  • Fig. 2 is a plan view of the processing assembly
  • Fig. 3 is a diagrammatical cross-sectional view of the centrifuge rotor according to SE 8602242-3;
  • Figs. 4a-4e show the various steps of the method according to the invention.
  • Figs. 1 and 2 show a processing assembly 1 comprising an annular primary container 2 and a secondary container 3 in the centre of the annulus.
  • a flexible tube 4 is connec ⁇ ted to the primary container, passes through a sealing body 5 and ends in a sterile connector 6.
  • a collapsible flexible tube 7 connects the portion of the primary container 2 closest to the centre of rotation with the secondary container 3.
  • the flexible tube 7 is provided with a check valve 21 which permits liquid flow from the primary container to the secondary container but closes to flow in the opposite direction.
  • the flexible tube 7 is also passed through the sealing body 5 and forms a loop 8 on its outer side and then returns through the sealing body.
  • the sealing body 5 which may consist of a rubber stopper, for example, serves to seal the separation space of the rotor from the surrounding atmosphere after the processing assembly has been brought in position in the separation space.
  • the processing assembly can be made from pieces of plastic foil which are interconnected by an outer annular joint 9 and an inner annular joint 10. In this way, an annular primary container 2 and a disc-like secondary container 3 in the central region of the annulus are formed.
  • the inner joint is provided with a perforation 11 in the middle so that the containers can be disconnected from one another.
  • the plastic foil preferably is made of PVC or polyethylene, and the joining can be effected by heat sealing in well-known manner.
  • the flexible tubes 4 and 7 are welded in similar manner to the plastic sheet, if desired with a reinforcing neck at the point of attachment.
  • Fig. 3 is a diagrammatic cross-section of a rotor which is suitable for use in carrying out the present invention.
  • a centrifuge rotor of the illustrated design is described in greater detail in Swedish patent application No. 8602242-3.
  • the processing assembly 1 is positioned in the processing space 12, 13 of the rotor.
  • Numeral 12 designates an annular separation compartment and
  • numeral 13 designates a central compartment communicating with the separation compartment.
  • In the cover 14 of the rotor there is an opening 15 above the central compartment. When the processing assembly has been brought in position in the rotor, this opening is sealed by pulling the sealing body 5 upwardly into the opening 15 whereupon the processing space of the rotor may be subjected to overpressure or vacuum by way of a connection 16.
  • valved connector 6 of the flexible tube 4 and the tube loop 8, which is inserted in a centrifugally operated pinch valve 17, are positioned outside the sealed separa ⁇ tion space.
  • a pressure medium 18, e.g. a rubber body, is deformed as a result of the centrifugation and exerts a pressure on the primary container 2 positioned in the separation compartment 12.
  • the rotor is driven by a programme-controlled motor (not shown) .
  • a processing assembly is positioned in the rotor, and the processing space of the rotor is sealed by means of the sealing body 5.
  • the tube loop 8 is inserted in the pinch valve 17.
  • Figs. 4a-4e show the various steps of the procedure which is then carried out.
  • Fig. 4a shows withdrawal of blood during agitation.
  • the connector 6 is attached to a standard withdrawal kit which is also linked to a blood donor (BG) .
  • BG blood donor
  • CPD anticoagulant
  • the primary container may be primed with anticoagulant before ⁇ hand.
  • anticoagulant is continuously supplied through the blood withdrawal kit as shown in Fig. 4 or by priming the primary container with one unit of anticoagulant. If the negative hydrostatic pressure from the blood donor to the primary container is insufficient for normal withdrawal of blood, the processing space of the centrifuge may be subjected to vacuum.
  • a vacuum pump is connected to the passage 16 (Fig. 3) to provide the desired increased vacuum.
  • the blood of the donor now flows into the primary container 2.
  • the centrifuge is programmed during this phase to oscillate the rotor at a predetermined amplitude and a predetermined frequency.
  • the primary container suitably is designed to accommo ⁇ date a blood donation (usually 500 ml) so that the with ⁇ drawal of the blood is discontinued automatically when this quantity has been withdrawn.
  • the centrifuge may be equipped with an alarm device which is activated when the primary container has been filled. Attention is thereby called to an attendant who disconnects the blood with ⁇ drawal kit from the connector 6, and in the customary manner saline is fed to the blood donor to replace a portion of the withdrawn blood and to keep the blood withdrawal tubes clean.
  • the centrifuging step I (Fig. 4b) is initiated by switching the centrifuge from oscillation to rotation, and the rotor is accelerated to a selected separation speed.
  • the blood cells settle in the peripheral part of the primary container while the plasma is collected in the portion of the annulus 2 closest to the centre.
  • the connecting tube 7 is kept closed by the centrifugal valve 17, for example.
  • centrifuging step II (Fig. 4c) is initiated.
  • the separated plasma is caused to flow to the secondary container 3 by way of the check valve 21.
  • This is accomplished by re- * ducing the volume of the separation compartment while the centrifugation is going on so that the primary container 2 is compressed and the plasma fraction is displaced to the secondary container 3.
  • this is done with the aid of a rubber body 18 (Fig. 3) positioned in the rotor, which rubber body has greater density than the blood and/or is acted on by radially displaceable weight segments. During the centrifugation the rubber body exerts a pressure on the primary container in the separation compartment.
  • centrifuged blood volume cannot move, because the valve 17 is closed. While centrifuging step II is carried out, the valve 17 is opened and the rubber body 18 is deformed into the separation compartment and expels a corresponding volume of plasma into the secondary container, In accordance with a preferred embodiment, centrifuging step II is carried out at a higher centrifuge speed than centrifuging step I. The transfer of the plasma then takes place while the separated phases are subjected to the action of a centrifugal field which is even stronger than that existing during the settling phase (centrifuging step I) . The danger of resuspending blood cells in the plasma fraction during the transfer therefore is very small.
  • the valve 17 may be a centrifugal valve set to be closed at the lower speed and to open at the higher speed.
  • the rubber body 18 and the weight segments or corresponding means may also be adapted to provide the required transfer pressure only when the higher speed has been reached.
  • the transfer may also by monitored by photocells, e.g. at the tube loop 8, which then has to be transparent. If cells reach the light path of the photocell, the transfer is discontinued, e.g. by reducing the centrifuge speed so that the centrifugal valve 17 closes and/or the pressure action of the rubber body ceases.
  • the centrifuge is stopped and the resuspension step is initiated (Fig. 4d) .
  • Liquid diluent physiological saline
  • the processing space of the centrifuge may then be subjected to vacuum in the same way as during the withdrawal of blood so that the introduction of the saline into the primary container is facilitated.
  • the retrans- fusion step (Fig. 4e) is commenced.
  • a new flexible tube is attached to the connector 6, and the processing space on the rotor is subjected to a predetermined overpressure, e.g. by pumping air into it by way of the passage 16.
  • the contents of the primary container then flow through the attached flexible tube by way of an air trap and a connecte transfusion kit with a filter and back to the blood donor.
  • the primary container 2 is empty, a single-cycle plasmapheresis is completed.
  • the secondary container 3 is made large enough to accommodate two batches of plasma, and the procedure is repeated with the same processing assembly.
  • the cover 14 is then removed, and the flexible tube 7 is sealed and cut, e.g. by means of a pair of heat-sealing jaws.
  • the secondary container with the recovered plasma is torn away from the primary container along the perforation 11 of the joint 10. Then the secondary container can immediately be frozen to save the quality of the plasma.

Abstract

The method comprises withdrawal of a quantity of blood from a blood donor to an annular primary container (2) forming part of a closed flexible processing assembly positioned in a processing space provided in a centrifuge rotor and conformed to the processing assembly. During the withdrawal, the rotor is caused to perform an oscillating movement for agitating the blood whereupon the blood is centrifuged in the primary container to be separated into blood cells and plasma. While the centrifugation is going on the primary container is then compressed to expel the plasma fraction to a secondary container (3) positioned in the central region of the annular primary container. Liquid diluent is then fed to the primary container to resuspend the blood cell fraction while agitation is again accomplished by oscillating the rotor, whereupon the blood cell fraction is returned to the blood donor. The apparatus is a closed flexible processing assembly for use in carrying out the method according to the invention and comprises an annular primary container (2), a secondary container (3) positioned in the central region of the annular primary container, a collapsible connecting duct (7) connecting the portion of the primary container closest to the centre of rotation with the secondary container, and a flexible tube (4) connected to the primary container.

Description

Method and apparatus for plasmapheresis
This invention relates to a method and an apparatus for carrying out plasmapheresis.
Half of the blood is so-called plasma, a yellowish liquid containing various proteins. The other half of the blood contains cellular material, such as red blood cells, white blood cells and platelets. Plasma is used in transfu¬ sions and as raw material for the pharmaceutical industry in connection with the production of pharmaceuticals, such as albumin, gamma globulin and Factor VIII (haemophilia medicament) .
Plasma may be obtained in pure form by centrifugation, about 200 ml of red blood cells and about 250 ml of plasma being obtainable from a donated blood unit of about 500 ml, including anticoagulant. The plasma fraction can also be obtained by plasmapheresis, in which the blood of the blood donor is withdrawn and centrifuged whereupon the red blood cells are returned to the donor. Plasmapheresis is advantageous because it is a cheaper method of obtaining plasma in the case where red blood cells are not needed, because each withdrawal yields more plasma (in total 600 ml in the case of two-cycle plasmapheresis) , and because plasmapheresis can be carried out more frequently than blood donation. Relatively expensive automated equipment for plasma¬ pheresis is known, such as the Haemonetic or Haemoscience machines which are made in the United States.
Apart from the high cost for the plasma production, these machines are only suitable for withdrawal in large blood banks, and for that reason plasmapheresis has to be carried out manually in most cases, especially when withdrawal is carried out in mobile units.
When plasmapheresis is carried out manually, blood is withdrawn from a blood donor (BG) and conveyed through a flexible tube to a bag positioned on a combined weighing scale and rocker. The scale discontinues the blood with¬ drawal and gives a warning when a sufficient amount of blood(about 450 ml) has been withdrawn, and the rocker mixes the blood with the anticoagulant. Thereupon the flexible tube is cut off under the action of heat so that the ends of the flexible tube are sealed, and the bag is carried to a centrifuge in which separation takes place. In the next step the bag is transferred to a squeezing device in which the plasma collected in the upper portion of the bag is expelled into a different bag. Saline is then added to the original bag containing the blood cells which are retransfused to the blood donor. Normally, this procedure is repeated with one and the same blood donor, that is, so-called two-cycle plasmapheresis is carried out, yielding 500-600 ml of plasma, including the origin¬ ally added anticoagulant.
This system has many disadvantages: - „
Many manipulative steps including connections and disconnections of flexible tubes are required;
- Separation of plasma from the centrifuged bag takes place manually and with the fractions held separated only under the action of the normal gravity, which means that high quality is not achieved, that is, that cellular material is left in the plasma. In order that high quality may be achieved, it is neces¬ sary to carry out repeated centrifugations and to transfer the plasma to a further secondary bag, which means added costs; - The method lends itself to confusion, because the bag is physically separated from the blood donor; The method is time-consuming in that it takes about one hour. It is easy to recruit persons for donating blood, which takes about 15 minutes, but it is more difficult to find persons who can sacrifice one hour.
The object of the present invention is to provide a method and an apparatus permitting small-scale semi- automated utilization of plasmapheresis, e.g. in mobile units, such as blood buses, and having the following advantages over manual plasmapheresis:
- Increased speed;
Improved plasma quality (fewer cells left in the plasma) ; Simplified procedure and reduced number of manipu¬ lative steps.
Increased safety because of reduced danger of confusion; - A large stationary centrifuge can be dispensed with.
This object is achieved by a method and an apparatus as defined in the claims.
When carrying out the method according to the invention, a centrifuge of the type described in Swedish patent application No. 8602242-3 may be used. This patent applica¬ tion discloses a centrifuge in which the processing space " of the rotor includes an annular separation compartment and a central compartment. The volume of the separation compartment can be reduced during the centrifugation to - displace a centrifugally separated component into the central compartment. An oscillating reciprocatary movement can be imparted to the rotor, and the processing space can be subjected to overpressure or vacuum. When carrying out the method according to the present invention, blood is withdrawn from the blood donor direct into an annular primary container forming part of a closed flexible processing assembly which is positioned in the processing space of the centrifuge rotor. The centrifuge may be positioned immediately adjacent the blood donor coach. During the withdrawal the rotor is oscillated to mix the blood with anticoagulant with which the primary container has been primed beforehand or which is supplied at the same time as the blood. The next step consists in centrifugation of the blood in the primary container to separate blood cells and plasma. After a given centrifug- ing time, the plasma is expelled to a secondary container forming part of the processing assembly and disposed in the central region of the annular primary container. This transfer of the plasma may preferably be effected by increasing the rotational speed of the centrifuge so that a centrifugally operated valve opens a connecting duct between the primary container and the secondary container and at the same time subjecting the primary container to a squeezing pressure. Thereupon the centrifugation is discontinued, and liquid diluent (physiological saline) is fed to the primary container while agitation is again effected by oscillating the rotor, and the thus resuspend- ed blood cell fraction is retransfused to the blood donor. The invention also relates to a closed flexible processing assembly for use in carrying out the method. The processing assembly comprises an annular primary container, a secondary container positioned in the central region of the annulus, and a closable connecting duct between the portion of the primary container closest to the centre of rotation and the secondary container, and a " " flexible tube connected to the primary container for supply of blood to the processing assembly and withdrawal of blood cell suspension from the processing assembly. The invention will be described in greater detail hereinafter with reference to the accompanying drawings, in which:
Fig. 1 is an elevational view of one embodiment of a processing assembly according to the invention;
Fig. 2 is a plan view of the processing assembly; Fig. 3 is a diagrammatical cross-sectional view of the centrifuge rotor according to SE 8602242-3;
Figs. 4a-4e show the various steps of the method according to the invention.
Figs. 1 and 2 show a processing assembly 1 comprising an annular primary container 2 and a secondary container 3 in the centre of the annulus. A flexible tube 4 is connec¬ ted to the primary container, passes through a sealing body 5 and ends in a sterile connector 6. A collapsible flexible tube 7 connects the portion of the primary container 2 closest to the centre of rotation with the secondary container 3. The flexible tube 7 is provided with a check valve 21 which permits liquid flow from the primary container to the secondary container but closes to flow in the opposite direction. The flexible tube 7 is also passed through the sealing body 5 and forms a loop 8 on its outer side and then returns through the sealing body. The sealing body 5, which may consist of a rubber stopper, for example, serves to seal the separation space of the rotor from the surrounding atmosphere after the processing assembly has been brought in position in the separation space. The processing assembly can be made from pieces of plastic foil which are interconnected by an outer annular joint 9 and an inner annular joint 10. In this way, an annular primary container 2 and a disc-like secondary container 3 in the central region of the annulus are formed. Suitably, the inner joint is provided with a perforation 11 in the middle so that the containers can be disconnected from one another. The plastic foil preferably is made of PVC or polyethylene, and the joining can be effected by heat sealing in well-known manner. The flexible tubes 4 and 7 are welded in similar manner to the plastic sheet, if desired with a reinforcing neck at the point of attachment.
Fig. 3 is a diagrammatic cross-section of a rotor which is suitable for use in carrying out the present invention. A centrifuge rotor of the illustrated design is described in greater detail in Swedish patent application No. 8602242-3. The processing assembly 1 is positioned in the processing space 12, 13 of the rotor. Numeral 12 designates an annular separation compartment and numeral 13 designates a central compartment communicating with the separation compartment. In the cover 14 of the rotor there is an opening 15 above the central compartment. When the processing assembly has been brought in position in the rotor, this opening is sealed by pulling the sealing body 5 upwardly into the opening 15 whereupon the processing space of the rotor may be subjected to overpressure or vacuum by way of a connection 16. When this is done, the valved connector 6 of the flexible tube 4 and the tube loop 8, which is inserted in a centrifugally operated pinch valve 17, are positioned outside the sealed separa¬ tion space. A pressure medium 18, e.g. a rubber body, is deformed as a result of the centrifugation and exerts a pressure on the primary container 2 positioned in the separation compartment 12. The rotor is driven by a programme-controlled motor (not shown) .
In use of the apparatus of Figs. 1 and 2, a processing assembly is positioned in the rotor, and the processing space of the rotor is sealed by means of the sealing body 5. The tube loop 8 is inserted in the pinch valve 17. Figs. 4a-4e show the various steps of the procedure which is then carried out.
Fig. 4a shows withdrawal of blood during agitation. The connector 6 is attached to a standard withdrawal kit which is also linked to a blood donor (BG) . Blood is withdrawn from the blood donor and at the same time anticoagulant (CPD) is added. Alternatively, if only - single-cycle plasmapheresis is to be carried out, the primary container may be primed with anticoagulant before¬ hand. When two-cycle plasmapheresis is carried out, anticoagulant is continuously supplied through the blood withdrawal kit as shown in Fig. 4 or by priming the primary container with one unit of anticoagulant. If the negative hydrostatic pressure from the blood donor to the primary container is insufficient for normal withdrawal of blood, the processing space of the centrifuge may be subjected to vacuum. In the centrifuge according to SE 8602246-3 a vacuum pump is connected to the passage 16 (Fig. 3) to provide the desired increased vacuum. The blood of the donor now flows into the primary container 2. To ensure that the anticoagulant is thoroughly mixed with the blood, the centrifuge is programmed during this phase to oscillate the rotor at a predetermined amplitude and a predetermined frequency.
The primary container suitably is designed to accommo¬ date a blood donation (usually 500 ml) so that the with¬ drawal of the blood is discontinued automatically when this quantity has been withdrawn. The centrifuge may be equipped with an alarm device which is activated when the primary container has been filled. Attention is thereby called to an attendant who disconnects the blood with¬ drawal kit from the connector 6, and in the customary manner saline is fed to the blood donor to replace a portion of the withdrawn blood and to keep the blood withdrawal tubes clean. At the same time, the centrifuging step I (Fig. 4b) is initiated by switching the centrifuge from oscillation to rotation, and the rotor is accelerated to a selected separation speed. In centrifuging step I the blood cells settle in the peripheral part of the primary container while the plasma is collected in the portion of the annulus 2 closest to the centre. In this step the connecting tube 7 is kept closed by the centrifugal valve 17, for example.
After a calculated time has elapsed, centrifuging step II (Fig. 4c) is initiated. In this step the separated plasma is caused to flow to the secondary container 3 by way of the check valve 21. This is accomplished by re- * ducing the volume of the separation compartment while the centrifugation is going on so that the primary container 2 is compressed and the plasma fraction is displaced to the secondary container 3. In one embodiment of the centrifuge described in SE 8602242-3, this is done with the aid of a rubber body 18 (Fig. 3) positioned in the rotor, which rubber body has greater density than the blood and/or is acted on by radially displaceable weight segments. During the centrifugation the rubber body exerts a pressure on the primary container in the separation compartment. However, the centrifuged blood volume cannot move, because the valve 17 is closed. While centrifuging step II is carried out, the valve 17 is opened and the rubber body 18 is deformed into the separation compartment and expels a corresponding volume of plasma into the secondary container, In accordance with a preferred embodiment, centrifuging step II is carried out at a higher centrifuge speed than centrifuging step I. The transfer of the plasma then takes place while the separated phases are subjected to the action of a centrifugal field which is even stronger than that existing during the settling phase (centrifuging step I) . The danger of resuspending blood cells in the plasma fraction during the transfer therefore is very small. When two centrifuge speeds are used, the valve 17 may be a centrifugal valve set to be closed at the lower speed and to open at the higher speed. The rubber body 18 and the weight segments or corresponding means may also be adapted to provide the required transfer pressure only when the higher speed has been reached. The transfer may also by monitored by photocells, e.g. at the tube loop 8, which then has to be transparent. If cells reach the light path of the photocell, the transfer is discontinued, e.g. by reducing the centrifuge speed so that the centrifugal valve 17 closes and/or the pressure action of the rubber body ceases.
After a predetermined time has elapsed, the centrifuge is stopped and the resuspension step is initiated (Fig. 4d) . Liquid diluent (physiological saline) is now fed to the primary container by way of the connector 6 while the * rotor is again oscillated. The processing space of the centrifuge may then be subjected to vacuum in the same way as during the withdrawal of blood so that the introduction of the saline into the primary container is facilitated. When the cell concentrate remaining in the primary containe has been diluted to the desired concentration, the retrans- fusion step (Fig. 4e) is commenced. A new flexible tube is attached to the connector 6, and the processing space on the rotor is subjected to a predetermined overpressure, e.g. by pumping air into it by way of the passage 16. The contents of the primary container then flow through the attached flexible tube by way of an air trap and a connecte transfusion kit with a filter and back to the blood donor. When the primary container 2 is empty, a single-cycle plasmapheresis is completed. When two-cycle plasmapheresis is carried out, the secondary container 3 is made large enough to accommodate two batches of plasma, and the procedure is repeated with the same processing assembly. The cover 14 is then removed, and the flexible tube 7 is sealed and cut, e.g. by means of a pair of heat-sealing jaws. The secondary container with the recovered plasma is torn away from the primary container along the perforation 11 of the joint 10. Then the secondary container can immediately be frozen to save the quality of the plasma.

Claims

Claims
1. Method for carrying out plasmapheresis, character¬ ised in that a quantity of blood is withdrawn from a blood donor to an annular primary container (2) forming part of a closed flexible processing assembly (1) positioned in a processing space (12,13) in the rotor of a centrifuge, said processing space being conformed to the processing assembly; during the withdrawal the rotor is caused to perform an agitating movement for agitation of the blood; the blood is centrifuged in the primary container to be separated into blood cells and plasma; during the centrifugation the primary container is compressed to expel the plasma fraction to a secondary container (3) disposed in the central region of the - annular primary container; liquid diluent is fed to the primary container for resuspending the blood cell fraction while agitation is carried out again by oscillating the rotor, and the blood cell fraction is returned to the blood donor.
2. Method according to claim 1, characterised in that the blood is centrifuged at a first speed with a collapsible connecting duct (7) between the primary container and the secondary container being closed and in that the rotational speed of the rotor is then increased to a second rotational speed at which the connecting duct is open.
3. Method according to claim 1, characterised in that the processing space (12,13) of the rotor is subjected to vacuum during the withdrawal of blood to the primary container.
4. Method according to claim 1, characterised in that the processing space (12,13) of the rotor is pressurized during the returning of the blood cells to the blood donor.
5. A closed flexible processing assembly for use in carrying out the method according to any of claims 1 to 5, characterised by an annular primary container (2) ; a secondary container (3) positioned in the central region of the annular primary container; a collapsible connecting duct (7) connecting the portion of the primary container closest to the centre of rotation with the secondary container; and a flexible tube (4) connected to the 5 primary container.
6. A processing assembly according to claim 5, characterised by a sealing body (5) for sealing the processing space (12,13) of the rotor from the surrounding atmosphere after the processing assembly has been posi- 0 tioned in said space with the flexible tube (4) accessible from outside.
7. A processing assembly according to claim 6, characterised in that the collapsible connecting duct between the primary container and the secondary container "5 comprises a flexible tube extending through the sealing " body (5) so as to form a loop (8) exteriorly of the sealing body.
8. A processing assembly according to claim 5, characterised in that the connecting duct (7) includes a 0 check valve (21) permitting liquid flow from the primary container to the secondary container.
9. A processing assembly according to claim 5, characterised in that the primary and secondary containers consist of pieces of plastic foil joined together by an 5 outer annular joint (9) and an inner annular joint (10) .
10. A processing assembly according to claim 9, characterised in that the inner annular joint (10) is perforated so that the containers can be disconnected from one another. 0
5
PCT/SE1987/000240 1986-05-16 1987-05-13 Method and apparatus for plasmapheresis WO1987006844A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT87903463T ATE90575T1 (en) 1986-05-16 1987-05-13 DEVICE FOR PLASMAPHORESIS.

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
SE8602242A SE459791B (en) 1986-05-16 1986-05-16 centrifuge
SE8602242-3 1986-05-16
SE8605456A SE461192B (en) 1986-05-16 1986-12-18 SETTING AND DEVICE COLLECTING THE BLOOD PLASMA WHEN PLUSING
SE8605456-6 1986-12-18

Publications (1)

Publication Number Publication Date
WO1987006844A1 true WO1987006844A1 (en) 1987-11-19

Family

ID=26659369

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE1987/000240 WO1987006844A1 (en) 1986-05-16 1987-05-13 Method and apparatus for plasmapheresis

Country Status (6)

Country Link
US (1) US4990132A (en)
EP (1) EP0304431B1 (en)
JP (1) JPH01502560A (en)
AU (1) AU7399787A (en)
DE (1) DE3786263T2 (en)
WO (1) WO1987006844A1 (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989002273A1 (en) * 1987-09-15 1989-03-23 Omega Medicinteknik Ab Method of washing blood cells and container assembly therefor
WO1990004019A1 (en) * 1988-10-11 1990-04-19 Baxter International Inc. System for magnetic affinity cell separation from cell concentrates
US5723050A (en) * 1993-07-08 1998-03-03 Omega Medicinteknik Ab Bag set for use in centrifugal separation
US6656105B2 (en) 1999-05-31 2003-12-02 Gambro, Inc. Centrifuge for processing blood and blood components in ring-type blood processing bags
US6689042B2 (en) 1997-02-12 2004-02-10 Gambro, Inc. Centrifuge and container system for treatment of blood and blood components
US6740239B2 (en) 1999-10-26 2004-05-25 Gambro, Inc. Method and apparatus for processing blood and blood components
US9079194B2 (en) 2010-07-19 2015-07-14 Terumo Bct, Inc. Centrifuge for processing blood and blood components
US11535868B2 (en) 2020-04-29 2022-12-27 Bristol-Myers Squibb Company Miniaturized dystrophins having spectrin fusion domains and uses thereof

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5792372A (en) * 1987-01-30 1998-08-11 Baxter International, Inc. Enhanced yield collection systems and methods for obtaining concentrated platelets from platelet-rich plasma
US5370802A (en) 1987-01-30 1994-12-06 Baxter International Inc. Enhanced yield platelet collection systems and methods
US5656163A (en) 1987-01-30 1997-08-12 Baxter International Inc. Chamber for use in a rotating field to separate blood components
AU613148B2 (en) * 1987-11-25 1991-07-25 Baxter International Inc. Single needle continuous hemapheresis apparatus and methods
US6007725A (en) 1991-12-23 1999-12-28 Baxter International Inc. Systems and methods for on line collection of cellular blood components that assure donor comfort
US5549834A (en) 1991-12-23 1996-08-27 Baxter International Inc. Systems and methods for reducing the number of leukocytes in cellular products like platelets harvested for therapeutic purposes
US5690835A (en) 1991-12-23 1997-11-25 Baxter International Inc. Systems and methods for on line collection of cellular blood components that assure donor comfort
DE69223042T2 (en) * 1991-12-23 1998-06-10 Baxter Int CENTRIFUGE WOBEI BASKET AND COIL IS SEPARABLE TO PROVIDE ACCESS TO THE SEPARATION CHAMBER
US5324253A (en) * 1992-03-02 1994-06-28 Mcrea James C Cannula apparatus and system for heparin removal from blood
US5334130A (en) * 1992-05-13 1994-08-02 Savant Instruments, Inc. Centrifugal vacuum concentration with holder assembly
JP2776988B2 (en) * 1993-04-27 1998-07-16 ヘモネティクス・コーポレイション Apheresis device
US5427695A (en) 1993-07-26 1995-06-27 Baxter International Inc. Systems and methods for on line collecting and resuspending cellular-rich blood products like platelet concentrate
SE9600713L (en) * 1996-02-26 1997-10-17 Omega Medicinteknik Ab Method of separating cells, especially platelets and bag set therefor
SE9701423D0 (en) * 1997-04-16 1997-04-16 Omega Medicinteknik Ab Container set and device for blood separation
US6027441A (en) * 1997-07-01 2000-02-22 Baxter International Inc. Systems and methods providing a liquid-primed, single flow access chamber
AU2002253801A1 (en) 2000-11-02 2002-08-19 Gambro, Inc. Fluid separation devices, systems and methods
ATE527004T1 (en) * 2002-02-01 2011-10-15 Caridianbct Inc SYSTEM FOR COLLECTION AND PROCESSING OF WHOLE BLOOD
US20030173274A1 (en) * 2002-02-01 2003-09-18 Frank Corbin Blood component separation device, system, and method including filtration
DE60331794D1 (en) * 2002-04-16 2010-04-29 Caridianbct Inc Process for processing blood components
CA2705168A1 (en) * 2002-08-23 2004-03-04 Caridianbct, Inc. Methods and apparatuses for blood component separation
US7347932B2 (en) * 2003-08-25 2008-03-25 Gambro Bct, Inc. Apparatus and method for separating a volume of composite liquid into at least two components
WO2006009650A1 (en) * 2004-06-22 2006-01-26 Gambro, Inc. Bag assembly for the separation of a composite liquid and method for manufacturing it
DE602005018443D1 (en) * 2004-12-28 2010-02-04 Caridianbct Inc Apparatus and method for separating a lot of blood into four components
WO2007024518A2 (en) * 2005-08-22 2007-03-01 Gambro Inc. Apparatus and method for separating a composite liquid into at least two components
US7819793B2 (en) * 2006-06-07 2010-10-26 Caridianbct, Inc. Apparatus for separating a composite liquid into at least two components
CN102274803B (en) * 2006-09-06 2014-01-01 泰尔茂比司特公司 Apparatus and method for separating a composite liquid into at least two components
JP5405313B2 (en) * 2006-12-20 2014-02-05 テルモ ビーシーティー、インコーポレーテッド Apparatus and method for separating a composite liquid into at least two components
US20080234622A1 (en) * 2007-03-20 2008-09-25 Gambro Bct Inc. Methods and Systems for Preparing Blood Products
WO2008140561A1 (en) * 2007-05-14 2008-11-20 Caridianbct, Inc. Apparatus and method for separating a composite liquid into at least two components
EP2310851B1 (en) * 2008-07-31 2018-11-07 Terumo BCT, Inc. Method and apparatus for determining the yield of at least one component
US9028388B2 (en) 2010-06-07 2015-05-12 Terumo Bct, Inc. Multi-unit blood processor with volume prediction
EP2815776B1 (en) 2011-06-13 2016-02-03 Terumo BCT, Inc. System for blood separation with gravity valve for controlling a side-tapped separation chamber
EP2956187B1 (en) 2013-02-18 2017-11-01 Terumo BCT, Inc. System for blood separation with a separation chamber having an internal gravity valve
US10618060B2 (en) 2013-12-20 2020-04-14 Terumo Bct, Inc. Centrifuge safety mechanism
CA2957407C (en) 2014-08-14 2020-06-30 Terumo Bct, Inc. Processing particles

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3244363A (en) * 1959-06-24 1966-04-05 George N Hein Centrifuge apparatus and bag therefor
SE354582B (en) * 1971-03-15 1973-03-19 Aga Ab
US4303193A (en) * 1979-01-22 1981-12-01 Haemonetics Corporation Apparatus for separating blood into components thereof

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4268393A (en) * 1980-05-05 1981-05-19 The Institutes Of Medical Sciences Apparatus for centrifugal separation of platelet-rich plasma
US4421503A (en) * 1981-07-09 1983-12-20 Haemonetics Corporation Fluid processing centrifuge and apparatus thereof
US4482342A (en) * 1982-06-17 1984-11-13 Haemonetics Corporation Blood processing system for cell washing

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3244363A (en) * 1959-06-24 1966-04-05 George N Hein Centrifuge apparatus and bag therefor
SE354582B (en) * 1971-03-15 1973-03-19 Aga Ab
US4303193A (en) * 1979-01-22 1981-12-01 Haemonetics Corporation Apparatus for separating blood into components thereof

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989002273A1 (en) * 1987-09-15 1989-03-23 Omega Medicinteknik Ab Method of washing blood cells and container assembly therefor
US5114396A (en) * 1987-09-15 1992-05-19 Omega Medicinteknik Ab Method of washing blood cells and container assembly thereof
WO1990004019A1 (en) * 1988-10-11 1990-04-19 Baxter International Inc. System for magnetic affinity cell separation from cell concentrates
US5723050A (en) * 1993-07-08 1998-03-03 Omega Medicinteknik Ab Bag set for use in centrifugal separation
US6689042B2 (en) 1997-02-12 2004-02-10 Gambro, Inc. Centrifuge and container system for treatment of blood and blood components
US6656105B2 (en) 1999-05-31 2003-12-02 Gambro, Inc. Centrifuge for processing blood and blood components in ring-type blood processing bags
US7097774B2 (en) 1999-05-31 2006-08-29 Gambro Inc Method for processing a blood product with a bag set having a multi-way connector
US7235041B2 (en) 1999-05-31 2007-06-26 Gambro Bct, Inc. Centrifuge for processing a blood product with a bag set having a processing bag
US6740239B2 (en) 1999-10-26 2004-05-25 Gambro, Inc. Method and apparatus for processing blood and blood components
US9079194B2 (en) 2010-07-19 2015-07-14 Terumo Bct, Inc. Centrifuge for processing blood and blood components
US11535868B2 (en) 2020-04-29 2022-12-27 Bristol-Myers Squibb Company Miniaturized dystrophins having spectrin fusion domains and uses thereof

Also Published As

Publication number Publication date
AU7399787A (en) 1987-12-01
US4990132A (en) 1991-02-05
EP0304431B1 (en) 1993-06-16
EP0304431A1 (en) 1989-03-01
DE3786263T2 (en) 1994-01-05
JPH01502560A (en) 1989-09-07
DE3786263D1 (en) 1993-07-22

Similar Documents

Publication Publication Date Title
EP0304431B1 (en) Apparatus for plasmapheresis
AU720556B2 (en) Separation set for blood component preparation
SE461192B (en) SETTING AND DEVICE COLLECTING THE BLOOD PLASMA WHEN PLUSING
US7166217B2 (en) Methods and apparatuses for blood component separation
EP1627651B1 (en) Method and apparatus for blood component separation
EP1077733B1 (en) Platelet collection system
SE462015B (en) SETTING AND DEVICE CLEANING BLOOD CELLS
CN1311880C (en) Automated system and method for withdrawing compounds from blood
US7235041B2 (en) Centrifuge for processing a blood product with a bag set having a processing bag
JPH02502522A (en) Platelet concentrate generator and method
KR20060113744A (en) Separation apparatus and method
WO1995031266A1 (en) Blood collection system
US20150224245A1 (en) Single collection bag blood collection system, method and apparatus
SE517032C2 (en) Method and apparatus for treating blood and blood components
US10391231B2 (en) Method and device for separating blood using a centrifuge
JPH09168574A (en) Method of separating blood components
JPS61500652A (en) flexible disposable centrifuge system

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU JP SU US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LU NL SE

WWE Wipo information: entry into national phase

Ref document number: 1987903463

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1987903463

Country of ref document: EP

WWG Wipo information: grant in national office

Ref document number: 1987903463

Country of ref document: EP