EP0016014A1 - 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 filtrationInfo
- Publication number
- EP0016014A1 EP0016014A1 EP79900587A EP79900587A EP0016014A1 EP 0016014 A1 EP0016014 A1 EP 0016014A1 EP 79900587 A EP79900587 A EP 79900587A EP 79900587 A EP79900587 A EP 79900587A EP 0016014 A1 EP0016014 A1 EP 0016014A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- membrane
- filtration
- blood
- fraction
- flow
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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
- 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
- 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 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.
- 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.
- 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 " .
- 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.
- 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 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 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 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.
Landscapes
- Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Engineering & Computer Science (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- External Artificial Organs (AREA)
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.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US90945878A | 1978-05-25 | 1978-05-25 | |
US909458 | 1978-05-25 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0016014A4 EP0016014A4 (fr) | 1980-09-29 |
EP0016014A1 true EP0016014A1 (fr) | 1980-10-01 |
Family
ID=25427260
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP79900587A Withdrawn EP0016014A1 (fr) | 1978-05-25 | 1980-01-03 | Procede de separation de suspensions liquides contenant des globules sanguins par filtration |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0016014A1 (fr) |
JP (1) | JPS55500370A (fr) |
WO (1) | WO1979001121A1 (fr) |
Families Citing this family (19)
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 |
JPS56110625A (en) * | 1980-02-05 | 1981-09-01 | Takeda Chem Ind Ltd | Separating method of blood plasma and apparatus for the same |
JPS57500633A (fr) * | 1980-04-14 | 1982-04-15 | ||
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 |
US4668399A (en) * | 1982-02-16 | 1987-05-26 | E. I. Du Pont De Nemours And Company | Hollow fiber plasmapheresis process |
GB2117092A (en) * | 1982-03-04 | 1983-10-05 | Dunlop Ltd | Fluid control valve |
DE3228438C2 (de) * | 1982-07-30 | 1985-01-17 | Karl Dr. 6301 Pohlheim Aigner | Doppellumiger Katheter |
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 |
DE3616062A1 (de) * | 1986-05-13 | 1987-11-19 | Fresenius Ag | Verfahren zur bestimmung von gaspartialdruecken im blut sowie vorrichtung zur durchfuehrung des verfahrens |
US4865726A (en) * | 1987-12-22 | 1989-09-12 | Promac B.V. | Device for making potable water |
IT1242940B (it) * | 1990-12-07 | 1994-05-18 | Sifra S P A | Impianto ad alto rendimento per la attuazione di emodialisi, emofiltrazione plasmaferesi, emodiafiltrazione |
CA2074671A1 (fr) * | 1991-11-04 | 1993-05-05 | Thomas Bormann | Dispositif et methode permettant de separer le plasma d'un liquide biologique |
FR2702962B1 (fr) * | 1993-03-22 | 1995-04-28 | Hospal Ind | Dispositif et procédé de contrôle de la balance des fluides sur un circuit extracorporel de sang. |
GB9311988D0 (en) * | 1993-06-10 | 1993-07-28 | Pall Corp | Device and method for separating plasma from a blood product |
WO2000023140A1 (fr) * | 1998-10-16 | 2000-04-27 | 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 |
CN109395191A (zh) * | 2010-09-15 | 2019-03-01 | 旭化成医疗株式会社 | 血液净化装置及其控制方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2725608A1 (de) * | 1976-06-22 | 1978-01-05 | Mitsui Toatsu Chemicals | Verfahren und vorrichtung zum kontinuierlichen entfernen von blutsubstanzen in einem extrakorporalen kreislauf |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3483867A (en) * | 1968-06-13 | 1969-12-16 | Meyer Markovitz | Artificial glomerulus and a method for treating blood |
US3567031A (en) * | 1969-05-29 | 1971-03-02 | Amicon Corp | Autoagitating ultrafiltration apparatus |
US3705100A (en) * | 1970-08-25 | 1972-12-05 | Amicon Corp | Blood fractionating process and apparatus for carrying out same |
-
1979
- 1979-05-24 JP JP50088279A patent/JPS55500370A/ja active Pending
- 1979-05-24 WO PCT/US1979/000358 patent/WO1979001121A1/fr unknown
-
1980
- 1980-01-03 EP EP79900587A patent/EP0016014A1/fr not_active Withdrawn
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2725608A1 (de) * | 1976-06-22 | 1978-01-05 | Mitsui Toatsu Chemicals | Verfahren und vorrichtung zum kontinuierlichen entfernen von blutsubstanzen in einem extrakorporalen kreislauf |
Non-Patent Citations (1)
Title |
---|
See also references of WO7901121A1 * |
Also Published As
Publication number | Publication date |
---|---|
JPS55500370A (fr) | 1980-06-26 |
WO1979001121A1 (fr) | 1979-12-27 |
EP0016014A4 (fr) | 1980-09-29 |
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Legal Events
Date | Code | Title | Description |
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed | ||
AK | Designated contracting states |
Designated state(s): CH DE FR GB LU SE |
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STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
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18D | Application deemed to be withdrawn |
Effective date: 19820323 |
|
RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: LYSAGHT, MICHAEL J. Inventor name: FRIEDMAN, LEONARD I. Inventor name: CASTINO, FRANCO Inventor name: SOLOMON, BARRY A. |