EP0801674A4 - Apparatur zur kultivierung bioartifizieller leber - Google Patents

Apparatur zur kultivierung bioartifizieller leber

Info

Publication number
EP0801674A4
EP0801674A4 EP96938724A EP96938724A EP0801674A4 EP 0801674 A4 EP0801674 A4 EP 0801674A4 EP 96938724 A EP96938724 A EP 96938724A EP 96938724 A EP96938724 A EP 96938724A EP 0801674 A4 EP0801674 A4 EP 0801674A4
Authority
EP
European Patent Office
Prior art keywords
blood
bioreactor
hemoperfusion
circuit
media
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP96938724A
Other languages
English (en)
French (fr)
Other versions
EP0801674A1 (de
Inventor
Darrell Page
Robert Wojciechowski
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Minnesota Twin Cities
Original Assignee
Cellex Biosciences Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cellex Biosciences Inc filed Critical Cellex Biosciences Inc
Publication of EP0801674A1 publication Critical patent/EP0801674A1/de
Publication of EP0801674A4 publication Critical patent/EP0801674A4/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
    • C12M25/10—Hollow fibers or tubes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/022—Artificial gland structures using bioreactors
    • 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
    • A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
    • A61M1/1621—Constructional aspects thereof
    • A61M1/1623—Disposition or location of membranes relative to fluids
    • A61M1/1625—Dialyser of the outside perfusion type, i.e. blood flow outside hollow membrane fibres or tubes
    • 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
    • A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
    • A61M1/3475—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate with filtrate treatment agent in the same enclosure as the 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
    • A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
    • A61M1/3486—Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents
    • A61M1/3489—Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents by biological cells, e.g. bioreactor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M21/00—Bioreactors or fermenters specially adapted for specific uses
    • C12M21/08—Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/16—Microfluidic devices; Capillary tubes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/28—Constructional details, e.g. recesses, hinges disposable or single use
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/58—Reaction vessels connected in series or in parallel
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/10—Perfusion
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/34—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas
    • 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
    • A61M2205/75—General characteristics of the apparatus with filters
    • A61M2205/7554—General characteristics of the apparatus with filters with means for unclogging or regenerating filters

Definitions

  • blood is allowed to flow through the extraluminal shell space, with the semi-permeable hollow fibers serving to separate the blood from the hepatocyte-containing matrix.
  • An intraluminal stream of medium is allowed to flow through the newly created lumen space, to carry the growth factors and nutrients necessary to support cell growth.
  • the intraluminal stream can also be used to remove toxins and metabolic products.
  • the Sielaff et al. article provides a functional diagram of the cell culture hardware and software used in regulating pH, oxygen, and shell flow at both the prehemoperfusion and hemoperfusion phases.
  • the diagram depicts the use of a gas exchanger ("GEX") to provide a blend of air and CO 2 .
  • GEX gas exchanger
  • Figure 2 shows the assembly and bioreactors of Figure 1 in operation in the course of the hemoperfusion circuit
  • Figure 3 shows a perspective view of a preferred switching valve for use in an apparatus of the present invention
  • Electrode Company (Houston, TX), and the "GX" line of electrodes available from pHoenix Electrode Company (Houston, TX).
  • Preferred electrodes provide an optimal combination of such properties as accuracy, safety, storage/regeneration properties, temperature compensation, and compatibility with the patient's blood within the temperature, flow and other conditions of use.
  • First and second bioreactors can be prepared and used in the manner described in PCT Patent Application No. PCT//US91/07952 , the disclosure of which is incorporated herein by reference.
  • Suitable bioreactors for use in a system of the present invention can be constructed using available materials and methods.
  • the system also provides an incubator, preferably in the form of a forced draft convection system, designed to keep the cultureware at a controlled temperature.
  • a fan on the incubator circulates heated air from a coil heater to provide pre-set ambient air conditions.
  • Inside the incubator are typically rows of bulkhead fittings used for electrical cable interface and gas supply to the cultureware.
  • a variety of blood pump modules are suitable for use in the system of the present invention, in order to control and supervise the extracorporeal blood circuit.
  • a preferred blood pump module will include with the pump, an arterial and venous pressure sensor/alarm, a drip chamber air detector, arterial and venous solenoid clamps for blood line clamping for certain alarms, and an optional heparin pump. Such a module can be used to circulate the blood from the patient to the tube set and return it to the patient during the hemoperfusion phase of the procedure.
  • the instrument and consumable supplies are preferably installed on a cart to provide a mobile self-contained platform for operation.
  • Assorted docking grids, hangers and holders can be provided, e.g., for hanging media bags and waste containers on the cart, and for docking and securing the blood pump and power supply, and bioreactor support module.
  • Blood is allowed to flow through the extraluminal shell space, with the semi-permeable hollow fibers serving to separate the blood from the hepatocytes.
  • An intraluminal stream of medium is allowed to flow through the hollow fibers, to carry the growth factors and nutrients necessary to support cell growth and to provide toxin or metabolic product removal.
  • the selectively permeable hollow fibers allow diffusion of toxic waste products, such as ammonia and bilirubin from the blood to the intraluminal biomatrix.
  • the blood composition including the pH and/or blood gas levels can be continually monitored in order to ensure that they are within suitable limits. Variations of these parameters can be achieved by appropriate control of the gas composition and/or flow rate in the oxygenator.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Sustainable Development (AREA)
  • Vascular Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Hematology (AREA)
  • Anesthesiology (AREA)
  • Molecular Biology (AREA)
  • Cell Biology (AREA)
  • Urology & Nephrology (AREA)
  • Clinical Laboratory Science (AREA)
  • Emergency Medicine (AREA)
  • Immunology (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Transplantation (AREA)
  • Analytical Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Cardiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • External Artificial Organs (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
EP96938724A 1995-10-30 1996-10-30 Apparatur zur kultivierung bioartifizieller leber Withdrawn EP0801674A4 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US550162 1975-02-14
US55016295A 1995-10-30 1995-10-30
PCT/US1996/017559 WO1997016527A1 (en) 1995-10-30 1996-10-30 Cultureware for bioartificial liver

Publications (2)

Publication Number Publication Date
EP0801674A1 EP0801674A1 (de) 1997-10-22
EP0801674A4 true EP0801674A4 (de) 1999-07-07

Family

ID=24196001

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96938724A Withdrawn EP0801674A4 (de) 1995-10-30 1996-10-30 Apparatur zur kultivierung bioartifizieller leber

Country Status (3)

Country Link
EP (1) EP0801674A4 (de)
JP (1) JPH10512159A (de)
WO (1) WO1997016527A1 (de)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5955353A (en) * 1997-05-22 1999-09-21 Excorp Medical, Inc. Hollow fiber bioreactor with an extrafilament flow plug
EP1045024A1 (de) * 1999-04-12 2000-10-18 K.U. Leuven Research & Development Verwendung einer Humanen Hepatozytzelllinie für die Behandlung von chronischen und akuten Leberschwäche
AU2001294922A1 (en) 2000-10-02 2002-04-15 Thomas F. Cannon Automated bioculture and bioculture experiments system
US20020146817A1 (en) 2000-10-02 2002-10-10 Cannon Thomas F. Automated bioculture and bioculture experiments system
CN100335142C (zh) * 2004-12-24 2007-09-05 浙江大学 适用于人工肝的装置
JP2010519937A (ja) 2007-03-05 2010-06-10 カリディアンビーシーティー、インコーポレーテッド 細胞増殖システムおよび使用方法
US9057045B2 (en) 2009-12-29 2015-06-16 Terumo Bct, Inc. Method of loading and distributing cells in a bioreactor of a cell expansion system
WO2012048276A2 (en) 2010-10-08 2012-04-12 Caridianbct, Inc. Customizable methods and systems of growing and harvesting cells in a hollow fiber bioreactor system
WO2015073913A1 (en) 2013-11-16 2015-05-21 Terumo Bct, Inc. Expanding cells in a bioreactor
WO2015148704A1 (en) 2014-03-25 2015-10-01 Terumo Bct, Inc. Passive replacement of media
US10077421B2 (en) 2014-04-24 2018-09-18 Terumo Bct, Inc. Measuring flow rate
EP3198006B1 (de) 2014-09-26 2021-03-24 Terumo BCT, Inc. Geplante fütterung
US20180044624A1 (en) * 2015-02-20 2018-02-15 Tokyo Electron Limited Cell Culture Device, Cartridge for Culture Medium Replacement Use, and Method for Replacing Culture Medium
WO2017004592A1 (en) 2015-07-02 2017-01-05 Terumo Bct, Inc. Cell growth with mechanical stimuli
US11965175B2 (en) 2016-05-25 2024-04-23 Terumo Bct, Inc. Cell expansion
US11685883B2 (en) 2016-06-07 2023-06-27 Terumo Bct, Inc. Methods and systems for coating a cell growth surface
US11104874B2 (en) 2016-06-07 2021-08-31 Terumo Bct, Inc. Coating a bioreactor
JP6935201B2 (ja) 2017-01-20 2021-09-15 日本光電工業株式会社 細胞培養システム、細胞培養環境評価装置、及びプログラム
CN117247899A (zh) 2017-03-31 2023-12-19 泰尔茂比司特公司 细胞扩增
US11624046B2 (en) 2017-03-31 2023-04-11 Terumo Bct, Inc. Cell expansion

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4855057A (en) * 1986-09-30 1989-08-08 Yokogawa Electric Corporation Regeneration type body fluid treating circuit and method for treating body fluid

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4853324A (en) * 1985-12-02 1989-08-01 Viles Joseph M Liver assist device employing transformed cell lines
US4889812A (en) * 1986-05-12 1989-12-26 C. D. Medical, Inc. Bioreactor apparatus
AU9031591A (en) 1990-10-29 1992-05-26 Regents Of The University Of Minnesota A bioartificial liver
US5270192A (en) * 1991-02-07 1993-12-14 Monsanto Company Biological artificial liver
US5368555A (en) * 1992-12-29 1994-11-29 Hepatix, Inc. Organ support system

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4855057A (en) * 1986-09-30 1989-08-08 Yokogawa Electric Corporation Regeneration type body fluid treating circuit and method for treating body fluid

Also Published As

Publication number Publication date
EP0801674A1 (de) 1997-10-22
WO1997016527A1 (en) 1997-05-09
JPH10512159A (ja) 1998-11-24

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