Spiral vane bioreactor

A bioreactor for use in a closed loop cell culture system under microgravity conditions for maintenance and growth of mammalian cells in suspension in a liquid environment while changing nutrients, said bioreactor including;

• an elongated, stationary, upright, tubular culture vessel containing a nutrient liquid, microcarrier beads, and mammalian cells completely filling the culture vessel;
• end cap means enclosing the ends of said culture vessel;
• rotatable tubular filter means co-axially disposed in said culture vessel and extending between said end cap means so as to define an annular culture chamber between said tubular filter means and the inner wall of the vessel;
• said filter means including a tubular membrane disposed over a perforated tubular member between said end cap means and barrier means disposed in said tubular member so as to define two separate interior sections, said perforations providing flow communication between an interior of said tubular member and said tubular membrane, said tubular membrane being permeable to liquids within said culture chamber but non-permeable with respect to the microcarrier beads;
• means for admitting an input liquid containing fresh nutrients and oxygen to said culture vessel in flow communication with one of said interior sections of said tubular member and means for exiting liquid from said culture vessel in flow communication with the other of said interior sections of said tubular member;
• means for rapidly alternating the communication of said means for admitting an input liquid and said means for exiting liquid with said interior sections so as to provide an effectively continuous backflush of the tubular member and membrane thereby preventing clogging without major alteration of the flow patterns within the vessel;
• flexible strip members disposed in said culture chamber lengthwise of said culture vessel and located between said filter means and the inner wall of said culture vessel;
• rotatable support means rotatably supporting said strip members and located at said end cap means for said culture vessel, wherein the opposite ends of said strip members are connected to said support means at an angular displacement with respect to the longitudinal axis of the culture vessel, and said strip members comprise spiral vanes which when rotated create lift vectors that move the microcarrier beads tangentially away from the high shear field near the filter means;
• and
• drive means for rotating said filter means and said support means independently of one another about the longitudinal axis of the culture vessel.

A closed loop system for growing mammalian cells in a microgravity environment, said system including;

• an elongated, stationary, upright, tubular culture vessel containing a nutrient liquid, microcarrier beads, and mammalian cells completely filling the culture vessel;
• end cap means enclosing the ends of said culture vessel;
• rotatable tubular filter means co-axially disposed in said culture vessel and extending between said end cap means so as to define an annular culture chamber between said tubular filter means and the inner wall of the vessel;
• said filter means including a tubular membrane disposed over a perforated tubular member between said end cap means, said perforations providing flow communication between an interior of said tubular member and said tubular membrane, said tubular membrane being permeable to liquids within said culture chamber but non-permeable with respect to the microcarrier beads;
• means for admitting an input liquid containing fresh nutrients and oxygen to said culture chamber at one end of said culture vessel and means for exiting liquid from said culture vessel in communication with said interior of said tubular member;
• flexible strip members disposed in said culture chamber lengthwise of said culture vessel and located between said filter means and the inner wall of said culture vessel;
• rotatable support means rotatably supporting said strip members and located at said end cap means for said culture vessel, wherein the opposite ends of said strip members are connected to said support means at an angular displacement with respect to the longitudinal axis of the culture vessel, and said strip members comprise spiral vanes which when rotated create lift vectors that move the microcarrier beads tangentially away from the high shear field near the filter means;
• drive means for rotating said filter means and said support means independently of one another about the longitudinal axis of the culture vessel;
• a main fluid circulation loop for receiving cell-free nutrient liquid from the culture vessel in flow communication with said means for admitting an input liquid and said means for exiting liquid, said loop including pump means positioned so as to provide liquid circulation, pressure regulator means positioned and arranged so as to control pressure differences between said circulation loop and said culture vessel, outflow sensor block means and inflow sensor block means positioned and arranged so as to detect various chemical parameters of the liquid, wherein said various chemical parameters are selected from the group consisting of oxygen concentration, carbon dioxide concentration, pH, and reduction-oxidation potential, said outflow sensor block being adjacent said means for exiting liquid, said inflow sensor block being adjacent said means for admitting an input liquid, a first manifold means constructed and arranged so as to provide for the addition of nutrients and acid or base fluids of pH adjustments to the liquid, dialysis means constructed and arranged so as to separate wastes from the liquid, semi-permeable membrane-type gas exchange means positioned and arranged so as to provide oxygen and removal of at least carbon dioxide or ammonia gases, said first manifold means, said dialysis means and said gas exchange means all being disposed at least between said outflow sensor block means and said inflow sensor block means, microgravity bubble trap means for elimination of free gas bubbles from the liquid, said bubble trap means disposed at least between said gas exchange means and said inflow sensor block means;
• and
• microprocessor means connected to said inflow sensor block means and said outflow sensor block means and at least one of said pump means, said first manifold means, said dialysis means, and said gas exchange means so as to control at least one of said pump means, said first manifold means, said dialysis means, and said gas exchange means in response to signals generated by said inflow and outflow sensor block means.