US5081035A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Bioreactor system
Assignee: University of Michigan-Ann Arbor
•
Filing: 1991-02-11
•
Granted: 1992-01-14
•
Expires: 2011-02-11
Abstract
Abstract A system for continuous perfusion culturing of anchorage-dependent and anchorage-independent mammalian cell lines, inter alia, wherein in vivo capillary bed conditions are simulated by providing a bioreactor having a growth chamber wherein the cells are grown between a multitubular array comprising at least three functionally separate, inert non-degradable and structurally strong tubes or sets of tubes. A constant nutrient gradient is maintained along the entire length of the tubes by perfusing medium through the tubes at a flow rate which is sufficient to expose all areas of the chamber to fresh medium by convective forces rather than diffusion. Oxygen transfer and removal of toxic wastes is improved by the invention herein. In a preferred embodiment, porous inert expanded Teflon tubes are employed having an inner diameter of approximately between 1 and 2 millimeters.
Inventors
- 👤 Craig R. Halberstadt
- 👤 A. Rees Midgley
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 17:26
CPC Classifications
C; C12; C12M; C12M29/00; C12M29/10; C12M23/00; C12M23/24; C12M29/12; C12M35/00; C12M35/04; C12M35/08; C12M41/00; C12M41/30; C12M41/32
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
258 words
An apparatus for maintaining and culturing cells in vitro therein, the apparatus comprising: a housing; a first permeable tube arranged in said housing for supplying a liquid medium, said first permeable tube being arranged in said housing along a first path therein which has a first predetermined length, said first permeable tube having first and second ports at respective ends thereof and positioned and arranged so as to communicate with the exterior of said housing, said first path being substantially randomly disposed within the housing; a second permeable tube arranged in said housing for receiving the liquid medium supplied by said first permeable tube and containing a product produced by the cells, said second permeable tube being arranged in said housing along a second path having a second predetermined length, said second path being maintained throughout said second predetermined length of said second path in close proximity to substantially the entire first predetermined length of said first path by being intertwined therewith so as to provide a varying distance between said first and second paths throughout said first and second predetermined lengths, and having first and second ports at respective ends thereof and positioned and arranged so as to communicate with the exterior of said housing, whereby a convective flow of the liquid medium is maintained in a region in the vicinity of said first and second paths; and enclosure means for providing a fluid-tight closure for said housing, said first permeable tube and said second permeable tube being disposed within said fluid-tight closure of said enclosure means.
Claim 2
Independent Claim
258 words
An apparatus for maintaining and culturing cells in vitro therein, the apparatus comprising: a housing; a first permeable tube arranged in said housing for supplying a liquid medium, said first permeable tube being arranged in said housing along a first path therein which has a first predetermined length, said first permeable tube having first and second ports at respective ends thereof and positioned and arranged so as to communicate with the exterior of said housing, said first path being substantially randomly disposed within the housing; a second permeable tube arranged in said housing for receiving the liquid medium supplied by said first permeable tube and containing a product produced by the cells, said second permeable tube being arranged in said housing along a second path having a second predetermined length, said second path being maintained throughout said second predetermined length of said second path in close proximity to substantially the entire first predetermined length of said first path by being intertwined therewith so as to provide a varying distance between said first and second paths throughout said first and second predetermined lengths, and having first and second ports at respective ends thereof and positioned and arranged so as to communicate with the exterior of said housing, whereby a convective flow of the liquid medium is maintained in a region in the vicinity of said first and second paths; and enclosure means for providing a fluid-tight closure for said housing, said first permeable tube and said second permeable tube being disposed within said fluid-tight closure of said enclosure means.
Claim 3
Dependent Claim
24 words
The apparatus of claim 1 wherein there is further provided pulsed-pressure medium supply means for supplying said liquid medium to said first permeable tube.
Claim 4
Dependent Claim
27 words
The apparatus of claim 1 wherein at least one of said first and second permeable tubes has an internal diameter of approximately between 1 and 2 millimeters.
Claim 5
Dependent Claim
27 words
The apparatus of claim 1 further including spool means for supporting said first and second permeable tubes so as to be substantially randomly disposed within said housing.
Claim 6
Dependent Claim
39 words
The apparatus of claim 1 wherein there is further provided a third permeable tube for propagating a gas having a predetermined composition, wherein said third permeable tube is intertwined with said first permeable tube and said second permeable tube.
Claim 7
Dependent Claim
25 words
The apparatus of claim 5 wherein said first, second, and third permeable tubes are arranged to be intertwined in a braided manner with one another.
Claim 8
Dependent Claim
43 words
The apparatus of claim 5 wherein at least one of said first, second, and third permeable tubes is provided with a nonporous tubing affixed at an end thereof for connecting said one of said first, second, and third permeable tubes to a connector.
Claim 9
Dependent Claim
17 words
The apparatus of claim 5 wherein said third permeable tube is formed of a gas-permeable silicone rubber.
Claim 10
Dependent Claim
24 words
The apparatus of claim 5 wherein said first, second, and third permeable tubes have an intertubular distance which is less than approximately 2 millimeters.
Claim 11
Dependent Claim
16 words
The apparatus of claim 2 wherein said third permeable tube is formed of expanded polyfluorinated hydrocarbon.
Claim 12
Dependent Claim
25 words
The apparatus of claim 5 wherein at least one of said first, second, and third permeable tubes is formed of a microporous polyfluorinated hydrocarbon material.
Claim 13
Dependent Claim
17 words
The apparatus of claim 11 wherein said microporous polyfluorinated material has an overall porosity of approximately 70%.
Claim 14
Dependent Claim
24 words
The apparatus of claim 12 wherein said microporous polyfluorinated material has pores therein having a pore size of approximately between 2.0 and 4.0 microns.
Claim 15
Independent Claim
244 words
An apparatus for maintaining and culturing cells in vitro therein, the apparatus comprising: a housing; a first permeable tube formed of a microporous polyfluorinated hydrocarbon material having an internal diameter of approximately between 1 and 2 millimeters for supplying a liquid medium; a second permeable tube formed of a microporous polyfluorinated hydrocarbon material having an internal diameter of approximately between 1 and 2 millimeters for receiving a product fluid formed at least in part of the liquid medium supplied by said first permeable tube whereby a convective flow of the liquid medium is maintained in a region in the vicinity of said first and second permeable tubes; a third permeable tube formed of a microporous polymeric material for conducting a gas-containing fluid having a predetermined composition, said first, second and third permeable tubes being intertwined with respect to one another so as to have a distance therebetween which varies along their respective lengths; spool means for supporting said first, second, and third permeable tubes so as to be substantially randomly disposed within said housing; enclosure means for providing a fluid-tight closure for said housing said first, second, and third permeable tubes, and said spool means; and first, second, and third pairs of fluid coupling ports, each such pair of fluid coupling ports being coupled to a respective one of said first, second, and third permeable tubes at respective distal ends thereof, so as to provide fluid communication with the exterior of said enclosure means.
Claim 16
Independent Claim
244 words
An apparatus for maintaining and culturing cells in vitro therein, the apparatus comprising: a housing; a first permeable tube formed of a microporous polyfluorinated hydrocarbon material having an internal diameter of approximately between 1 and 2 millimeters for supplying a liquid medium; a second permeable tube formed of a microporous polyfluorinated hydrocarbon material having an internal diameter of approximately between 1 and 2 millimeters for receiving a product fluid formed at least in part of the liquid medium supplied by said first permeable tube whereby a convective flow of the liquid medium is maintained in a region in the vicinity of said first and second permeable tubes; a third permeable tube formed of a microporous polymeric material for conducting a gas-containing fluid having a predetermined composition, said first, second and third permeable tubes being intertwined with respect to one another so as to have a distance therebetween which varies along their respective lengths; spool means for supporting said first, second, and third permeable tubes so as to be substantially randomly disposed within said housing; enclosure means for providing a fluid-tight closure for said housing said first, second, and third permeable tubes, and said spool means; and first, second, and third pairs of fluid coupling ports, each such pair of fluid coupling ports being coupled to a respective one of said first, second, and third permeable tubes at respective distal ends thereof, so as to provide fluid communication with the exterior of said enclosure means.
References Cited (Backward Citations)
US3853712A
Cited
US3941662A
Cited
US3812016A
Cited
US3821087A
Cited
US3883393A
Cited
US3925165A
Cited
US4246120A
Cited
US3997396A
Cited
US4311798A
Cited
US4228242A
Cited
US4310630A
Cited
US4184922A
Cited
US4178209A
Cited
US4220725A
Cited
US4242459A
Cited
US4391912A
Cited
US4649114A
Cited
US4440853A
Cited
US4442206A
Cited
WO1984001959A1
Cited
US4537860A
Cited
US4559299A
Cited
US4546083A
Cited
US4647539A
Cited
US4808315A
Cited
DE3809163A1
Cited
JPS6425477A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1995-01-13 | 1995-07-15 | 1996-01-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-01-13 | 1999-07-15 | 2000-01-14 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-01-13 | 2003-07-15 | 2004-01-14 | $7700.00 | Window Closed / Lapsed |