# US 5,705,390 A · Bioreactor

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- Number: US 5,705,390 A
- Document ID: US5705390A
- Status: Granted
- Kind: A
- Application number: 08/422,626
- Filed: 1995-04-14
- Granted: 1998-01-06
- Earliest claimed: 1992-05-05
- Assignees: Interpharm Laboratories Ltd.
- Inventors: Avinoam Kadouri; Yehoshua Aloni; Mordechai Geron
- Web page: https://patentgrep.com/patent/US5705390A

## CPC

- C12M 25/16: {Particles; Beads; Granular material; Encapsulation (chemical or physical processes conducted in the presence of fluids and solid particles B01J8/00)}
- C12M 27/14: {Rotation or movement of the cells support, e.g. rotated hollow fibers}
- C12M 27/22: {Perforated plates, discs or walls}
- C12M 29/04: {Filters; Permeable or porous membranes or plates, e.g. dialysis}
- C12M 41/00: {Means for regulation, monitoring, measurement or control, e.g. flow regulation (controlling or regulating chemical, physical or physicochemical processes B01J19/0006; heating or cooling apparatus for laboratory use B01L7/00; electro optical investigation of individual particles, flow cytometers G01N15/14; automatic analysis G01N35/00; controlling or regulating in general G06N)}
- 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}

## Abstract

A radial flow bioreactor comprising a reaction vessel having an inlet and an outlet respectively for adding and withdrawing a culture medium and at least one cell basket within the reaction vessel for accommodating a plurality of cell carriers and having side wall perforations so dimensioned as to prevent passage of the cell carriers therethrough.

## Claims

### Claim 1

A radial flow bioreactor for cell propagation, comprising:
a reaction vessel having an inlet and an outlet for adding and withdrawing, respectively, culture medium;
at least one cell basket within the reaction vessel for accommodating a plurality of cell carriers therein with associated cells to be propagated, each of said at least one cell basket having
a base member;
a roof member;
an outer side wall, having perforations therein, wherein said base and roof members support said outer side wall around the respective outer peripheries thereof, said outer side wall having a longitudinal axis; and
an inner cylinder having a side wall with perforations, supported between said base and roof members and having a longitudinal axis coaxial with the longitudinal axis of said outer side wall, whereby a cavity is defined by said outer side wall and said side wall of said cylinder;
wherein said base and roof members each have an aperture therein at the appropriate ends of said inner cylinder so as to allow culture medium to flow into the inner cylinder from both ends thereof; and
circulation means for urging the culture medium through the apertures in said base and roof members of each said at least one cell basket, through the perforation in said side wall of said inner cylinder thereof, through the cavity thereof, and thence radially through the perforations of said outer side wall thereof, said circulation being of sufficiently low velocity so as not to create shear forces within each said cavity great enough to cause the cells to be destroyed or removed from their carriers when in use, said circulation means comprising a system of turbine blades coupled to the circumference of each said at least one cell basket so as to rotate therewith and thereby augment the radial circulation of the culture medium from the longitudinal axis through the cavity of each said at least on cell basket, and rotating means for rotating each of said at least one cell basket about the longitudinal axis thereof.

### Claim 2 (depends on 1)

A bioreactor in accordance with claim 1, further including a plurality of cell carriers disposed within said cavity of each said at least one cell basket.

### Claim 3 (depends on 2)

A bioreactor in accordance with claim 2, further including cells to be propagated attached to said cell carriers.

### Claim 4 (depends on 1)

A bioreactor in accordance with claim 1, wherein said at least one cell basket comprises a plurality of cell baskets disposed side by side in the reaction vessel.

### Claim 5 (depends on 1)

A bioreactor in accordance with claim 1, wherein said at least one cell basket is removable.

### Claim 6 (depends on 1)

A method for cultivating anchorage-dependent cells using a bioreactor in accordance with claim 1, comprising:
loading the at least one cell basket with cell carriers and the cells to be cultivated;
filling the reaction vessel with culture medium;
rotating the at least one cell basket at an appropriate speed to cause culture medium to enter the inner cylinder through both the roof member aperture and the base member aperture and pass through the cavity and out the perforations of the outer side wall at a velocity which is insufficient to create shear forces within the cavity great enough to cause the cells to be destroyed or removed from their cell carriers.

### Claim 7

A cell basket comprising:
a base member;
a roof member;
an outer side wall, having perforations therein, wherein said base and roof members support said outer side wall around the respective outer peripheries thereof, said outer side wall having a longitudinal axis;
an inner cylinder having a side wall with perforations, supported between said base and roof members and having a longitudinal axis substantially parallel to the longitudinal axis of said outer side wall, whereby a cavity is defined by said outer side wall and said side wall of said cylinder, wherein said base and roof members each have an aperture therein at the appropriate ends of said inner cylinder so as to allow culture medium to flow into the inner cylinder from both ends thereof; and
a system of turbine blades coupled to the circumference of said outer side wall in such a manner that when the cell basket is caused to rotate around the longitudinal axis thereof in a liquid medium the turbine blades will augment the flow of the culture medium through said base and roof members into said inner cylinder and radially through the perforations of said inner cylinder side wall, said cavity, and the perforations of said outer side wall.

### Claim 8 (depends on 7)

A cell basket in accordance with claim 7, further including a plurality of cell carriers disposed within said cavity.

### Claim 9 (depends on 8)

A cell basket in accordance with claim 8, further including cells to be propagated attached to said cell carriers.
