WO1979001121A1 - Procede de separation de suspensions liquides contenant des globules sanguins par filtration - Google Patents

Procede de separation de suspensions liquides contenant des globules sanguins par filtration Download PDF

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Publication number
WO1979001121A1
WO1979001121A1 PCT/US1979/000358 US7900358W WO7901121A1 WO 1979001121 A1 WO1979001121 A1 WO 1979001121A1 US 7900358 W US7900358 W US 7900358W WO 7901121 A1 WO7901121 A1 WO 7901121A1
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WO
WIPO (PCT)
Prior art keywords
membrane
filtration
blood
flow path
shear rate
Prior art date
Application number
PCT/US1979/000358
Other languages
English (en)
Inventor
L Friedman
M Lysaght
F Castino
B Solomon
Original Assignee
Department Of Commerce
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Filing date
Publication date
Application filed by Department Of Commerce filed Critical Department Of Commerce
Publication of WO1979001121A1 publication Critical patent/WO1979001121A1/fr

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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
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • 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
    • A61M1/3403—Regulation parameters
    • 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
    • A61M1/3403—Regulation parameters
    • A61M1/3406—Physical characteristics of the filtrate, e.g. urea
    • 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
    • A61M1/3403—Regulation parameters
    • A61M1/341—Regulation parameters by measuring the filtrate rate or volume
    • 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
    • A61M1/3601—Extra-corporeal circuits in which the blood fluid passes more than once through the treatment unit
    • A61M1/3603—Extra-corporeal circuits in which the blood fluid passes more than once through the treatment unit in the same direction
    • 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
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/33—Controlling, regulating or measuring
    • A61M2205/3331—Pressure; Flow
    • 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
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/33—Controlling, regulating or measuring
    • A61M2205/3331—Pressure; Flow
    • A61M2205/3334—Measuring or controlling the flow rate

Definitions

  • This invention relates to the fractionation of blood cell-containing liquid suspensions and, more particularly, to a process for effecting such 5 fractionation by filtration through a raicroporous membrane.
  • Certain highly desirable blood processing procedures require the ability to effect an efficient separation of a liquid suspension of blood cellular 0 components into a cellular component-containing fraction and a cellular component-free liquid fraction without causing damage to the cellular components.
  • the preservation of red blood cells, white blood cells or platelets which have been separated from 5 whole blood for future use in transfusions can be effectively achieved by freezing a prepared suspension of the blood cells in an electrolyte solution containing a suitable concentration of a cryoprotective agent, such as glycerol or dimethyl sulfoxide.
  • the prepared blood cell suspension must be fractionated subsequent to thawing and prior to use so as to remove the cryoprotective agent therefrom or at
  • Platelets frozen storage is desirable in order to reduce outdating and allow the provision of "matched" or autologous cells. Techniques currently in use are not satisfactory and the microporous system may be suitable for such an application. Similarly, white cell storage is a problem and transfusion of unfrozen products are still basically experimental. However, it is expected that utilization will increase, and that frozen storage will be needed for their efficient management.
  • Another highly desirable blood processing procedure involving the separation of a liquid suspensio of blood cellular components into a cellular component-, containing fraction and a cellular component-free liquid fraction, is plasmapheresis.
  • Plasmapheresis is defined as the process of removal of whole blood from the body of a blood donor by venesection, separation of its plasma portion, and reintroduction of the cellular portion into the donor's bloodstream.
  • the cell-free plasma thus collected may either be used directly for patient care or further processed into specific plasma derivatives for clinical use.
  • the return of the cellular components to the donor provides this plasma collection procedure with the advantage that it enables donations by the donor at more frequent intervals.
  • plasmapheresis also has therapeutic implications in plasma exchange procedures for the treatment of various clinical disorders.
  • the filtrate flux i.e., filtration rate per area of membrane. Since, in certain cases, the filtrate flux will be governed primarily by the transmembrane pressure, i.e., the pressure differential between the upstream and downstream sides of the membrane providing the filtration driving force, the transmembrane pressure should be maintained sufficiently high so as to maximize the filtrate flux.
  • transmembrane pressure too high a trans ⁇ membrane pressure will cause the blood cellular components to be forced to the membrane surface and interact there- with, leading to irreversible damage or hemolysis of the cells or possibly even to plugging of the membrane pores.
  • Proper control of the transmembrane pressure so as to provide optimal filtration rate per area of membrane without causing damage to the cellular compon- ents is further complicated by the pressure drop from the inlet end to the outlet end of the blood flow path, which causes corresponding variations in the trans ⁇ membrane pressure through the system. A relatively high pressure drop could lead to a very low transmembrane pressure in the outlet region.
  • the transmembrane pressure in the inlet region must be correspondingly higher so as to compensate for the pressure drop through the system.
  • a further factor influencing the transmembrane pressure through the system is the requirement that the pressure at the outlet end of the filtration flow path be at least sufficient to overcome the sum of the return venous blood pressure and the pressure drop in the return needle and tubing assembly if an accessory blood pump is to be avoided.
  • a primary object of the present invention to provide an improved process for the separation of a liquid suspension of blood cellular components into a cellular component-containing fraction and a cellular component-free liquid fraction by filtration under pressure through a microporous membrane, which enables the transmembrane pressure providing the filtration driving force to be controllably maintained at a level providing optimal filtration rate per area of membrane without causing damage to the cellular components.
  • Another object of the invention is to provide a filtration process in accordance with the preceding object, which is capable of effecting the separation o cell-free plasma from whole blood at a plasma flux sufficient to provide 500 ml of plasma in approximatel thirty minutes.
  • a further object of the invention is to provide a filtration process in accordance with the preceding objects, which is capable of being utilized in a continuous flow plasmapheresis system as an improved blood separation technique requiring a substantially shorter period of donor time than that required by the standard centrifugal techniques conventionally employe in carrying out the plasmapheresis procedure.
  • Still another object of the invention is to provi a filtration process in accordance with the first of t foregoing objects, which is capable of being utilized as a simple, efficient and economical technique for effecting removal of cryoprotective agent from previou frozen, thawed preparations of red blood cells, white blood cells or platelets.
  • a still further object of the invention is to provide a relatively simple filtration process for the deglycerolization of a previously frozen, thawed glycerol-containing red blood cell suspension, which i capable of efficiently and economically reducing the glycerol concentration in the suspension from a cryo- protectively effective level to a physiologically tolerable level without causing hemolysis of the red blood cells.
  • OM components is separated into a cellular component- containing fraction and a cellular component-free liquid fraction by filtration throug a microporous membrane while being conducted in laminar flow across the surface of the membrane along a flow path which is substantially parallel to the upstream side of the membrane under pressure conditions at the inlet and out ⁇ let ends of the flow path sufficient to maintain the laminar flow and to provide a filtration driving force from the upstream side to the downstream side of the membrane.
  • the cellular component-containing fraction is recovered from the outlet end of the flow path, and the cellular component-free liquid fraction is recovered as filtrate from the downstream side of the membrane.
  • the improvement, of the present invention which enables the transmembrane pressure providing the filtration driving force to be maintained at a level providing optimal filtration rate per area of membrane without causing lysis or damage to the cellular components, consists of controlling the membrane wall shear rate of the suspension along the flow path so that such shear rate will be sufficiently high to cause axial migration of cells and inhibit interactions of the cellular components with the membrane surface at the requisite transmembrane pressure and sufficiently low so as not to itself induce mechanical lysis or damage to the cellular components.
  • a filtration laodule of reasonably compact size capable o effecting the separation of substantially hemoglobin- free and cell-free plasma from whole blood at a plasma flux sufficient to yield 500 ml of plasma in approximately thirty minutes and at pressure condition at the outlet end of the blood flow path sufficient to enable reinfusion of the cellular component- containing fraction into the donor's bloodstream witho the necessity for a specific accessory blood pump for this purpose.
  • the improvement of the present invention broadens the applicability of the filtration process to also render it a relatively simp efficient and economical technique for effecting remov of cryoprotective agent from a previously frozen, thaw preparation of blood cells.
  • the filtration process carried out under the controlled operating conditions of the present invention and in a continuous recirculation mode of operation has been found to be capable of reducing the glycerol concentra tion in a unit of frozen red blood cells from a cryo- protectively effective level to a physiologically tolerable level in a period of approximately thirty minutes, without causing any significant hemolysis of the red blood cells.
  • Figure 1 is a schematic flow diagram of a continuous flow plasmapheresis system incorporating th improved filtration process of the present invention
  • Figure 2 is a schematic flow diagram of a system for the removal of cryoprotective agent from a previou frozen, thawed blood cell suspension, incorporating the improved filtration process of the present invention.
  • microporous membranes suitable for use in carrying out the filtration process of the present invention are known filter materials having holes of controlled shape and size running through their thickness and capable of effecting separation of very small particulate or molecular components from suspensions or solutions.
  • Such microporous membranes are commercially available in various pore sizes.
  • poly ⁇ carbonate microporous membranes are commercially available under the trademark NUCLEPORE from the Nuclepore Corporation, and cellulosic ester microporous membranes are commercially available from Millipore Corporation.
  • microporous membranes are normally supplied in thin sheet form, they can also be used in carrying out the filtration process of the present invention in other configurations, for example, hollow fibers.
  • Suitable pore sizes found effective for filtering cell-free plasma from whole blood or cryoprotective agent from previously frozen, thawed blood cell suspensions range broadly from about 0.2 to about 1.5 microns in diameter, and preferably from about 0.40 to about 0.60 microns in diameter.
  • transmembrane pressures required for effectively carrying out the filtration process of the present invention will vary with the total effective void area of the membrane which, in turn, will be a function of both the membrane pore size and the total membrane surface area employed. Furthermore, as pointed out above, the transmembrane pressure at the inlet end of the filtration flow path will have to be sufficiently high so as to compensate for the pressure drop through the system and insure efficient operation at the outlet end of the filtration flow path. For proper control of the filtration operating conditions in accordance with the present invention, the transmembrane pressures requir for efficient operation should not be below about 50 Eg and should not exceed about 500 mm Hg.
  • the critical parameter is the wall shear r at the.membrane surface of the blood cell-containing liquid suspension along the filtration flow path.
  • Su membrane wall shear rate is a function of both the fl rate of the liquid suspension along the filtration fl path and the geometry of the filtration flow channel, and, for rectangular flow channels, can be expressed the relationship:
  • S is the membrane wall shear rate in sec
  • Q the inlet flow rate of the blood cell-containing liqu suspension in cm /sec
  • h is 1/2 of the flow channel height above the membrane surface in cm
  • w is the width of the flow channel across the membrane surface cm.
  • the membrane wall shear rate should be maintained at a minimum of about 500 sec " . It is also important to keep such shear rate sufficiently low so that it will not itself induce mechanical lysis or damage to the cellular components.
  • the upper limit of the shear rate depends upon the particular type of cellular components in the suspension being filtered. If the cellular components consist only of red blood cells, the upper limit of the shear rate will be about 50,000 sec " . On the other hand, if the cellular components include white blood cells or platelets, the upper limit of the shear rate will be about 10,000 sec " .
  • the membrane wall shear rate should be maintained within the range of about 500 to about 5,000 sec.
  • the selected shear rate can be achieved by proper coordination of the inlet suspension flow rate with the filtration flow channel dimensions in accordance with the relationship of these parameters defined above. If necessary, adjustment of the inlet suspension flow rate to maintain the requisite membrane wall shear rate may be provided, for example, by means of suitable pumps.
  • the blood flow which can normally be obtained from an antecubital vein is about 60 ml/min.
  • the blood rate from the donor may be suitab augmented by a recirculated flow system leading from th outlet end of the filtration flow path back to. the inlet end thereof.
  • FIG. 1 of the drawings a schematic flow diagram is provided illustrating the use of the improved filtration process of the present invention as the blood fractionating technique in a continuous flow plasmapheresis system.
  • the system employs a filtration module 10 provided with a continuo filtration flow channel 12 extending therethrough from its inlet end 14 to its outlet end 16 across the surface of the upstream side of a microporous filtratio membrane 18 disposed within the filtration module so as to form one wall of the filtration flow channel 12.
  • the filtration module 10 is provided with a filtrate ex port 20 on the downstream side of the membrane 18.
  • the filtrate exit port 20 is connected via conduit 22 to a filtrate collector 24.
  • the filtration module 10 is connected to the vein of ⁇ blood donor 30 via a blood supply conduit 32 provided with a blood pump 34 and connected to the inlet end 14 of the filtration flow channel 12, and a blood cell return conduit 36 connected to the outlet end 16 of the filtration flow channel 12.
  • An anti ⁇ coagulant supply container 38 is connected, via a conduit 40 provided with a pump 42, into the blood supply conduit 32 between the donor 30 and the blood pump 34.
  • a recirculation conduit 44 provided with a pump 46 is connected at its one end into the blood cell return conduit 36 adjacent to the outlet end 16 of the filtration flow channel 12, and at its other end into the blood supply conduit 32 between the blood pump 34, and the filtration module 10 and adjacent to the inlet end 14 of the filtration flow channel 12, to thereby provide a recirculation flow loop leading from the outlet end 16 to the inlet end 14 of the filtration flow channel 12.
  • the blood supply conduit 32, the filtration flow channel 12, the blood cell return conduit 36, and the recircula ⁇ tion conduit 34 are all first of all primed with saline solution.
  • the donor is connected into the system, and whole blood is withdrawn from the donor into the blood supply conduit 32, wherein anticoagulant, pumped by pump 42 through conduit 40 from the anticoagulant supply container 38, is added thereto.
  • the whole blood is then driven by pump 34 into the inlet end 14 of the filtration flow channel 12.
  • cell-free plasma passes through the microporous membrane 18 to the downstream side thereof, while the cellular components of the blood are retained on the upstream side of the membrane.
  • the cell-free plasma thereby separated from the blood leaves the filtration module 10 through the filtrate exit port 20 and flows through the conduit 22 into the filtrate collector 24.
  • the cellular component-containing fraction of the blood exits from the outlet end 16 of the filtration flov channel 12 into the blood cell return conduit 36 for reinfusion back into the donor 30. Under the action of the pump 46 in the recirculation conduit 44, a portion of the cellular component-containing fraction will be diverted from the blood cell return conduit 36 ⁇ and recirculated via recirculation conduit 44 and blood supply conduit 32 back to the inlet end 14 of the filtration flow channel 12.
  • the membrane wall shear rate of the blood flowing through the filtration flow channel 12 must be maintained sufficiently high to inhibit lysis-causing interactions of the blood cells with the membrane surface under the transmembrane pressure conditions existing in the filtration module under the action of the pumps 34 and 46, so as to avoid injury to the blood cells being returned to the donor and to insure that the plasma collected- by the procedure is free of hemoglobin.
  • the recirculation flow rate through the recirculation conduit 44 should be such that in combination with the flow rate of the whole blood co ing from the donor, it is sufficient to maintain the requisite membrane wall shear rate.
  • the recirculated flow may be dispensed with, in which case . the entire blood cell-containing fraction exiting from the outlet end 16 of the filtration flow channel 12 would be transferred back to the donor.
  • FIG. 2 a schematic flow diagram is provided illustrating the use of the improved filtration process of the present invention in a system for the removal of cryoprotective agent from a previously frozen, thawed blood cell preparation.
  • the system employs a filtration module 110, similar to filtration module 10 described above, provided with a continuous filtration flow channel 112
  • the filtration module 110 is provided with a filtrate exit port 120 on the downstream side of the membrane 118.
  • the filtration exit port 120 is connected via conduit 122 to a filtrate collector 124.
  • the filtration module 110 is connected in a recir ⁇ culated flow arrangement to a blood cell suspension reservoir 150 via a suspension supply conduit 152 provided with a pump 154 and connected to the inlet end 114 of the filtration flow channel 112, and a suspension return conduit 156 connected to the outlet end 116 of the filtration flow channel 112.
  • a diluent reservoir 158 is connected into the suspension return conduit 156 via a conduit 160 provided with a pump 162.
  • the suspension reservoir 150 contains a previously frozen, thawed suspension of blood cellular components, i.e., either red blood cells, white blood cells or platelets, in an electrolyte solution containing a cryoprotectively effective concentration of a cryoprotective agent, such as glycerol or dimethylsulfoxide.
  • a cryoprotective agent such as glycerol or dimethylsulfoxide.
  • the diluent reservoir 158 contains cryoprotective agent-free electrolyte solution.
  • the blood cell suspension is pumped from the suspension reservoir 150 by means of pump 154 through the suspension supply conduit 152 into the inlet end 114 of the filtration flow channel 112.
  • the suspension flows along the filtration flow channel 112
  • a portion of the electrolyte solution and a portion of the cryoprotective agent pass through the microporous membrane 118 to the downstream side thereof, while the blood cells are retained on the upstream side of the membrane.
  • the cell-free cryoprotective agent-containing filtrate leaves the filtration module 110 through the filtrate exit port 120 and passes through the conduit
  • OMPI »- IIPPOO cell-containing fraction exits from the outlet end 11 of the filtration flow channel 112 into the suspensio return conduit 156 through which it is returned to th suspension reservoir 150 for recirculation through th system.
  • the recirculating fraction is diluted with additional amounts of electrolyte solution pumped by means of pump 162 from the diluent reservoir 15 ⁇ thro the conduit 160 and into the suspension return condui 156, so as to at least partially compensate for the reduction in the electrolyte solution to blood cell r in the recirculating fraction resulting from electrol solution removal -in the filtration module.
  • the recirculation is carried out continuously at least un the cryoprotective agent concentration in the resulti blood cell suspension in the suspension reservoir 150 has been reduced to a physiologically tolerable level that such suspension is ready for transfusion in huma
  • a physiologically tolerable level for example, in the case of glycerol, which is the mo frequently employed cryoprotective agent, the physiologically tolerable level is about 0.1 moles pe liter.
  • the membrane wall shear rate of th blood cell suspension flowing through the filtration flow channel 112 must be maintained sufficiently high inhibit lysis-causing interactions of the blood cells with the membrane surface at the transmembrane pressu conditions existing in the filtration module under th action of the pump 154, in order to avoid injury to t blood cells.
  • the diluent flow rate from diluent reservoir 158 should be such that in combinat with the flow rate of the recirculating fraction, it sufficient to maintain the requisite membrane wall shear rate.
  • the filtration module f use in carrying out the process of the present invent may be varied somewhat from that indicated schematica in the accompanying drawings, so long as the filtration flow channel dimensions are properly coordinated with the inlet suspension flow rate so as to provide the requisite membrane wall shear rate.
  • the filtration module may be designed to have a plurality of parallel filtration flow channels spaced across the width of the membrane surface, with an inlet flow distributor for dividing and directing the flow of incoming suspension to the inlet ends of the respective channels, and an outlet flow collector for reuniting the flow of outgoing suspension from the outlet ends of the respective channels.
  • the preferred filtration module design for use in carrying out the process of the present invention is that described and claimed in the application filed simultane ⁇ ously herewith corresponding to the U. S. patent application of Barry A. Solomon and Michael J. Lysaght, Serial No. 909,459, filed May 25, 1978, entitled "FILTRATION APPARATUS FOR SEPARATING BLOOD CELL- CONTAINING LIQUID SUSPENSIONS", and incorporated herein by reference.
  • the filtration flow channels gradually and uniformly increase in width from their inlet ends to their outlet ends.
  • the filtration module is provided with a total of six parallel filtration flow channels, each of the diverging width design, and arranged in a configuration similar to the multiple channel configuration described above, but in upper and lower sets of three channels sandwiched between two microporous membranes so that the upper membrane forms the membrane wall of the upper set of channels, and the lower membrane forms the membrane wall of the lower set of channels.
  • the invention is further illustrated by way of the following examples, in which the filtration module employed was designed in accordance with the above- described preferred embodiment of the filtration module of the above-identified Solomon, et al application.
  • the filtration module had a total filtration area of 402 cm 2, divided evenly among its six filtration flow channels. Each channel had a height of " 0.051 cm, an effective filtration length of 40.6 cm, a width of 1.1 cm at the inlet end of the filtration area and gradually and uniformly widening to 2.2 cm at the outlet end of the
  • Each of the two filtration membranes employed in the filtration module was a polycarbonate microporous membrane having an average pore diameter of 0.6 microns.
  • a simulated continuous flow plasmapheresis procedure was carried out utilizing the system illustrated in Figure 1 and operated as described above, but employing a simulated donor consisting of a blood supply container connected to the donor end of the blood supply conduit 32, and a blood collection container connected to the donor end of the blood cell return conduit 36.
  • the blood supply container was filled with freshly collected CPD anticoagulated whole human blood of normal hemato- crit.
  • the filtrate line was operated at atmospheric pressure.
  • the inlet blood pump 34 was operated at a flow rate of 70 ml/ in, and the recirculation pump 46 was operated at a flow rate of 200 ml/min, providing an inlet suspension flow rate into the filtration module of 270 ⁇ l/min, a transiaembraixe pressure of 180 mm Hg and a membrane wall shear rate of 2,000 sec at the inlet end of the filtration flow channels, and a transmembrane pressure of 100 mm Hg and a membrane wall shear rate of 1,000 sec " at the outlet end of the filtration flow channels.
  • the procedure resulted in the collection of 500 ml of plasma in the filtrate collector 24 in an operating time of approximately 30 minutes.
  • the plasma so collected was cell-free with an acceptably low level of hemoglobin content, indicating substantially hemolysis- free operation of the system.
  • the filtrate line was operated at atmospheric pressure, the diluent pump 162 was operated at a diluent flow rate of 30-40 ml/min, and the inlet suspension pump 154 was operated at an inlet suspension flow rate of 270 ml/min, providing a transmembrane pressure of 150 mm Hg and a membrane wall shear rate of 2,000 sec at the inlet end of the filtration flow channels, and a trans ⁇ membrane pressure of 70 mm Hg and a membrane wall shear rate of 1,000 sec at the outlet end of th ⁇ filtration flow channels.
  • the process was operated in a continuous recircu ⁇ lation mode until the glycerol concentration in the red blood cell suspension in the suspension reservoir 150 had been reduced to a level of about 0.1 moles per liter.
  • the filtrate recovered in the filtrate collector 124 contained glycerol, was cell-free, and had a free hemoglobin concentration not significantly greater than that of the original red blood cell suspension, indicating substantially hemolysis-free operation of the filtration system.

Abstract

Une suspension liquide contenant des cellules sanguines est separee en une fraction contenant des cellules et une fraction sans globules, par filtration. La suspension sous pression est conduite par un ecoulement laminaire a travers la surface d'une membrane microporeuse (18, 118) le long d'un passage d'ecoulement (12, 112) qui est sensiblement parallele au cote amont de la membrane (18, 118), la fraction avec cellules etant recuperee la sortie (16, 116) du passage d'ecoulement (12, 112) et la fraction sans cellules etant recuperee comme filtrat (24, 124). Le procede s'effectue dans des conditions procurant un taux de filtration par unite de surface de membrane (18, 118) eleve sans endommager les cellules sanguines. Ceci est realise par commande du taux de separation de la suspension sur la paroi de la membrane le long du passage d'ecoulement (12, 112) de sorte que l'on ait un taux de separation suffisamment eleve pour induire une migration axiale des cellules et inhiber les interactions des cellules avec la surface de la membrane (18, 118) dans les conditions de pression requises. Ce taux est maintenu assez bas pour eviter qu'il n'endommage les cellules. Les applications utiles du procede comprennent la separation du plasma du sang par plasmapherese a ecoulement continu, et l'enlevement d'agents cryoprotecteurs de preparations degelees, prealablement congelees, de globules rouges, de globules blancs, ou de plaquettes.
PCT/US1979/000358 1978-05-25 1979-05-24 Procede de separation de suspensions liquides contenant des globules sanguins par filtration WO1979001121A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US90945878A 1978-05-25 1978-05-25
US909458 1978-05-25

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WO1979001121A1 true WO1979001121A1 (fr) 1979-12-27

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EP (1) EP0016014A1 (fr)
JP (1) JPS55500370A (fr)
WO (1) WO1979001121A1 (fr)

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3006455A1 (de) * 1980-02-05 1981-08-13 Takeda Chemical Industries, Ltd., Osaka Verfahren und vorrichtung zur niederdruck-filtration von plasma aus blut
WO1981002979A1 (fr) * 1980-04-14 1981-10-29 Baxter Travenol Lab Dispositif de fractionnement du sang
FR2519555A1 (fr) * 1982-01-11 1983-07-18 Rhone Poulenc Sa Appareillage et procede de plasmapherese alternative avec appareil a membrane
EP0088570A1 (fr) * 1982-03-04 1983-09-14 Dunlop Limited Moyen de contrôle d'un fluide
EP0101890A1 (fr) * 1982-07-30 1984-03-07 Karl Dr. Aigner Cathéter à double lumière pour un dispositif d'épuration in-vivo du sang
EP0112173A2 (fr) * 1982-12-16 1984-06-27 E.I. Du Pont De Nemours And Company Procédé pour plasmaphorèse
US4605503A (en) * 1983-05-26 1986-08-12 Baxter Travenol Laboratories, Inc. Single needle blood fractionation system having adjustable recirculation through filter
US4619639A (en) * 1980-02-05 1986-10-28 Asahi Medical Co., Ltd. Method and apparatus for low pressure filtration of plasma from blood
US4708713A (en) * 1984-11-16 1987-11-24 Anisa Medical, Inc. Method and system for removing immunosuppressive components from the blood of mammals
US4746436A (en) * 1981-06-25 1988-05-24 Baxter Travenol Laboratories, Inc. Membrane plasmapheresis apparatus and process which utilize a flexible wall to variably restrict the flow of plasma filtrate and thereby stabilize transmembrane pressure
US4844871A (en) * 1986-05-13 1989-07-04 Fresenius Ag Method of determining the partial pressure of gases in blood and an apparatus for performing the method
US4865726A (en) * 1987-12-22 1989-09-12 Promac B.V. Device for making potable water
EP0490212A1 (fr) * 1990-12-07 1992-06-17 SIFRA S.p.A. Appareil à rendement élevé pour hemodialyse, hemofiltration plasmapherese, et hemodiafiltration
FR2702962A1 (fr) * 1993-03-22 1994-09-30 Hospal Ind Dispositif et procédé de contrôle de la balance des fluides sur un circuit extracorporel de sang.
US5601727A (en) * 1991-11-04 1997-02-11 Pall Corporation Device and method for separating plasma from a biological fluid
US5914042A (en) * 1993-06-10 1999-06-22 Pall Corporation Device and method for separating plasma from a blood product
EP1121175A1 (fr) * 1998-10-16 2001-08-08 Mission Medical, Inc. Systeme de traitement du sang
EP1673975A1 (fr) * 2004-12-27 2006-06-28 Friesland Brands B.V. Séparation de particules par forces de cisaillement
EP2617444A1 (fr) * 2010-09-15 2013-07-24 Asahi Kasei Medical Co., Ltd. Dispositif de purification de sang et son procédé de commande

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US3567031A (en) * 1969-05-29 1971-03-02 Amicon Corp Autoagitating ultrafiltration apparatus
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Cited By (26)

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Publication number Priority date Publication date Assignee Title
US4619639A (en) * 1980-02-05 1986-10-28 Asahi Medical Co., Ltd. Method and apparatus for low pressure filtration of plasma from blood
DE3006455A1 (de) * 1980-02-05 1981-08-13 Takeda Chemical Industries, Ltd., Osaka Verfahren und vorrichtung zur niederdruck-filtration von plasma aus blut
WO1981002979A1 (fr) * 1980-04-14 1981-10-29 Baxter Travenol Lab Dispositif de fractionnement du sang
US4746436A (en) * 1981-06-25 1988-05-24 Baxter Travenol Laboratories, Inc. Membrane plasmapheresis apparatus and process which utilize a flexible wall to variably restrict the flow of plasma filtrate and thereby stabilize transmembrane pressure
FR2519555A1 (fr) * 1982-01-11 1983-07-18 Rhone Poulenc Sa Appareillage et procede de plasmapherese alternative avec appareil a membrane
EP0085016A1 (fr) * 1982-01-11 1983-08-03 Rhone-Poulenc S.A. Appareillage utilisable en plasmaphérèse avec appareil à membrane semi-perméable
EP0088570A1 (fr) * 1982-03-04 1983-09-14 Dunlop Limited Moyen de contrôle d'un fluide
EP0101890A1 (fr) * 1982-07-30 1984-03-07 Karl Dr. Aigner Cathéter à double lumière pour un dispositif d'épuration in-vivo du sang
EP0112173A2 (fr) * 1982-12-16 1984-06-27 E.I. Du Pont De Nemours And Company Procédé pour plasmaphorèse
AU570019B2 (en) * 1982-12-16 1988-03-03 E.I. Du Pont De Nemours And Company Microporous hollow fiber plasmapheresis
EP0112173A3 (en) * 1982-12-16 1986-02-26 E.I. Du Pont De Nemours And Company Hollow fiber plasmapheresis module and process
US4605503A (en) * 1983-05-26 1986-08-12 Baxter Travenol Laboratories, Inc. Single needle blood fractionation system having adjustable recirculation through filter
US4708713A (en) * 1984-11-16 1987-11-24 Anisa Medical, Inc. Method and system for removing immunosuppressive components from the blood of mammals
US4844871A (en) * 1986-05-13 1989-07-04 Fresenius Ag Method of determining the partial pressure of gases in blood and an apparatus for performing the method
US4865726A (en) * 1987-12-22 1989-09-12 Promac B.V. Device for making potable water
EP0490212A1 (fr) * 1990-12-07 1992-06-17 SIFRA S.p.A. Appareil à rendement élevé pour hemodialyse, hemofiltration plasmapherese, et hemodiafiltration
US5601727A (en) * 1991-11-04 1997-02-11 Pall Corporation Device and method for separating plasma from a biological fluid
EP0629413A1 (fr) * 1993-03-22 1994-12-21 Hospal Industrie Dispositif et procédé de contrôle de la balance des fluides sur un circuit extracorporel de sang
US5470483A (en) * 1993-03-22 1995-11-28 Hospal Industrie Device and method for controlling the balance of fluids in an extracorporeal blood circuit
FR2702962A1 (fr) * 1993-03-22 1994-09-30 Hospal Ind Dispositif et procédé de contrôle de la balance des fluides sur un circuit extracorporel de sang.
US5914042A (en) * 1993-06-10 1999-06-22 Pall Corporation Device and method for separating plasma from a blood product
EP1121175A1 (fr) * 1998-10-16 2001-08-08 Mission Medical, Inc. Systeme de traitement du sang
EP1121175A4 (fr) * 1998-10-16 2005-09-21 Mission Medical Inc Systeme de traitement du sang
EP1673975A1 (fr) * 2004-12-27 2006-06-28 Friesland Brands B.V. Séparation de particules par forces de cisaillement
EP2617444A1 (fr) * 2010-09-15 2013-07-24 Asahi Kasei Medical Co., Ltd. Dispositif de purification de sang et son procédé de commande
EP2617444A4 (fr) * 2010-09-15 2014-12-24 Asahi Kasei Medical Co Ltd Dispositif de purification de sang et son procédé de commande

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JPS55500370A (fr) 1980-06-26
EP0016014A4 (fr) 1980-09-29
EP0016014A1 (fr) 1980-10-01

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