Bioreactor apparatus and cell culturing system
First Claim
1. A bioreactor apparatus and cell culturing system providing means for cell sampling, dilution, and fixation, comprising:
- a sealed housing enclosing a cell growth reactor vessel;
said cell growth reactor vessel rotatable about its axis including a cylindrical side wall connecting a first reactor cover plate and a second reactor cover plate, a first fluid rotary union in said first reactor cover plate providing an inlet for fluid communication with a fluid medium source, a second fluid rotary union in said second reactor cover plate including at least one exit outlet for medium and cells and at least one exit outlet in fluid communication with a filter for retaining cells and passage of medium;
means for rotating said reactor vessel about its axis;
means for collecting fluid and cell samples comprising a rotary sample collector including a first stationary collector plate and a second rotatable collector plate in sealed connection at their centers and in fluid communication with said exit outlet for medium and cells;
said rotary sample collector comprising multiple sample collectors in said first stationary collector plate which are alignable with an inlet in said second rotatable collector plate with capability for collecting cells on filters, fixing the cells and collecting the cells;
means for delivering medium and circulating medium to and from said reactor vessel;
means for controlling the humidity within said sealed housing;
means for rotating said second rotatable collector plate;
a computer with graphical user interface for automatically and/or robotically controlling rotation of the reactor vessel, rotation of said second plate, controlling the feeding of fresh medium, controlling perfusing the reactor vessel, controlling taking timed collection samples of fluid from said reactor vessel, and selecting between collecting cells or cell-free supematant; and
an electrical power source in electrical communication with said means for rotating said reactor vessel, said means for rotating said second collector plate, and said means for delivering and circulating medium.
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Accused Products
Abstract
A bioreactor apparatus and cell culturing system is provided for the automated cultivation and processing of living cells remotely both on earth and in low gravity which utilizes a generally cylindrical reactor vessel that may be optionally rotated about its cylindrical axis while allowing the entrance of fresh or recycled fluid and the removal, optionally, of spent medium, medium to be recycled or filtered or unfiltered medium for the collection of samples. A method of exchanging gases between the culture medium and ambient gases is provided. A fresh-medium storage bag and peristaltic pump is used for batch feeding, perfusion or sample collection. An enclosure and manifold representing an additional level of chemical containment and a series of pinch valves for the periodic collection of samples of suspended cells or cell-free medium is disposed therein together with a humidity control system. The bioreactor is computer controlled in order to control all functions including rotation of the reactor vessel, feeding fresh medium, perfusing the reactor vessel, timed collection of samples of fluid from the reactor, selecting between collecting cells or cell-free supernatant. A sealed compartment for sample-collection bags provides a level of chemical containment for safety. A sealed external housing is used for all components of the device except the power supply and computer. An external loop and electronic video microscope provides real-time and recorded and/or transmitted observation of cells in the suspension.
81 Citations
26 Claims
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1. A bioreactor apparatus and cell culturing system providing means for cell sampling, dilution, and fixation, comprising:
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a sealed housing enclosing a cell growth reactor vessel; said cell growth reactor vessel rotatable about its axis including a cylindrical side wall connecting a first reactor cover plate and a second reactor cover plate, a first fluid rotary union in said first reactor cover plate providing an inlet for fluid communication with a fluid medium source, a second fluid rotary union in said second reactor cover plate including at least one exit outlet for medium and cells and at least one exit outlet in fluid communication with a filter for retaining cells and passage of medium; means for rotating said reactor vessel about its axis; means for collecting fluid and cell samples comprising a rotary sample collector including a first stationary collector plate and a second rotatable collector plate in sealed connection at their centers and in fluid communication with said exit outlet for medium and cells; said rotary sample collector comprising multiple sample collectors in said first stationary collector plate which are alignable with an inlet in said second rotatable collector plate with capability for collecting cells on filters, fixing the cells and collecting the cells; means for delivering medium and circulating medium to and from said reactor vessel; means for controlling the humidity within said sealed housing; means for rotating said second rotatable collector plate; a computer with graphical user interface for automatically and/or robotically controlling rotation of the reactor vessel, rotation of said second plate, controlling the feeding of fresh medium, controlling perfusing the reactor vessel, controlling taking timed collection samples of fluid from said reactor vessel, and selecting between collecting cells or cell-free supematant; and an electrical power source in electrical communication with said means for rotating said reactor vessel, said means for rotating said second collector plate, and said means for delivering and circulating medium. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
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17. A closed-loop bioreactor apparatus and cell culturing system, comprising:
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a cell growth reactor vessel rotatable about its axis including a cylindrical side wall connecting a first reactor cover plate and a second reactor cover plate, a first fluid rotary union in said first reactor cover plate providing an inlet for fluid communication with a fluid medium source, a second fluid rotary union in said second reactor cover plate including at least one exit outlet for medium and cells and at least one exit outlet in fluid communication with a filter for retaining cells and passage of medium; means for rotating said reactor vessel about its axis; means for collecting fluid and cell samples comprising a rotary sample collector including a first stationary collector plate and a second rotatable collector plate in sealed connection at their centers and in fluid communication with said exit outlet for medium and cells; said rotary sample collector further comprises means for rotating an inlet in second rotatable collector plate into a compartment in said first stationary collector plate with filter means to remove waste liquid from an input cell suspension, means for collecting cells in chambers in liquid suspension, and means to store fixed cells for later recovery and examination; means for delivering medium and circulating medium to and from said reactor vessel to form a closed loop; means for rotating said second rotatable collector plate; means for exchanging gases between said medium and ambient gas environments; a computer with graphical user interface for automatically and/or robotically controlling said reactor vessel; an observation system wherein said observation system comprises a camera and a dual optical path configuration allowing for an observation of said cell growth reactor vessel contents and a second microscopic observation path with a 5-micron resolution of said cell sample; an electrical power source in electrical communication with said means for rotating said reactor vessel, said means for rotating said second collector plate, and said means for delivering and circulating medium. - View Dependent Claims (18, 19, 20, 21, 22, 23, 24, 25, 26)
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Specification