Vessel, preferably spherical or oblate spherical for growing or culturing cells, cellular aggregates, tissues and organoids and methods for using same
First Claim
1. A culture vessel comprising:
- a housing defining a chamber having at least one inlet and at least one outlet, the housing adapted to rotate about a longitudinal substantially horizontal axis;
at least one filter within the chamber in fluid communication with an outlet, the filter having openings of a size that allows the passage of a fluid culture medium and cellular metabolic waste but prevents the passage of cells and cellular aggregates;
the chamber having a substantially unobstructed horizontal axis; and
a pump in fluid communication with at least one of an inlet or an outlet, wherein the chamber is symmetrical about an axis.
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Accused Products
Abstract
An improved culture vessel or bioreactor for growing cells, cellular aggregates, tissue particles or tissue “organoids” and methods for using same which includes a housing having at least one chamber defined by a curved wall symmetrical about an axis. The perfused version of the vessel has at least one inlet and at least one outlet and at least one filter in fluid communication with at least one of the inlets or outlets structured to pass culture media but retain cells, cellular aggregates or tissues within the culture chamber. The batch culture version of the vessel has at least part of the vessel wall made of a gas permeable material. The vessel housing is rotated about the horizontal or proximate horizontal axis to suspend the cells, in an unobstructed, three-dimensional or toroidal flow. The chamber has a substantially ellipsoid, oblate ellipsoid, spherical or oblate spherical shape and an unobstructed volume for growth of cells, cellular aggregates or tissues. The perfused version of the invention has a pump in fluid communication with an inlet or outlet to maintain a flow of oxygen and nutrient rich culture media through the vessel to sustain respiration and metabolism. A gas exchange device is used to maintain desired concentration of gases. Operational modes include either continuous perfusion flow or a batch culture. Methods are disclosed to produce biological products, cells and tissues and to filter waste materials and toxins from fluids (such as a liver assist device).
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Citations
63 Claims
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1. A culture vessel comprising:
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a housing defining a chamber having at least one inlet and at least one outlet, the housing adapted to rotate about a longitudinal substantially horizontal axis;
at least one filter within the chamber in fluid communication with an outlet, the filter having openings of a size that allows the passage of a fluid culture medium and cellular metabolic waste but prevents the passage of cells and cellular aggregates;
the chamber having a substantially unobstructed horizontal axis; and
a pump in fluid communication with at least one of an inlet or an outlet, wherein the chamber is symmetrical about an axis. - View Dependent Claims (3, 5, 6, 7, 9, 10, 11, 12, 14, 15, 16, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32)
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2. A culture vessel comprising:
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a housing defining a chamber having at least one inlet and at least one outlet, the housing adapted to rotate about a longitudinal axis;
at least one filter in fluid communication with an outlet, the filter having openings of a size that allows the passage of a fluid culture medium and a cellular metabolic waste but prevents the passage of cells and cellular aggregates;
the chamber, in cross-section through a longitudinal axis, having wall portions spherical, oblate spherical, extended spherical or extended oblate spherical wall portions; and
a pump in fluid communication with at least one of an inlet or outlet.- View Dependent Claims (4, 8, 13)
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17. A culture vessel comprising:
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a housing defining a chamber having at least one access port located on the housing;
a gas permeable membrane located within the housing, the gas permeable membrane allowing for the transfer of gases between the chamber and a space outside of the chamber;
the chamber, in cross-section through a longitudinal horizontal axis, having wall portions spherical, oblate spherical, extended spherical or extended oblate spherical wall portions; and
means for rotation about the horizontal axis. - View Dependent Claims (18, 19, 20)
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33. A method for growing cells, cellular aggregates or tissues in a rotatable culture vessel, comprising the steps of:
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filling a rotatable culture vessel having a culture chamber with an unobstructed longitudinal axis with fluid culture media, wherein the culture chamber is symmetrical about an axis;
introducing cells, cellular aggregates and/or tissues into the media;
maintaining media flow through the vessel to provide oxygen and materials to the growing cells and to remove cellular metabolic wastes; and
rotating the vessel to suspend the growing cells in the media. - View Dependent Claims (35, 36, 37, 38, 39, 40, 41)
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34. A method for growing cells, cellular aggregates or tissues in a rotatable culture vessel, comprising the steps of:
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providing a gas permeable membrane for providing oxygen to a culture chamber and removing carbon dioxide and;
filling a rotatable culture vessel having the culture chamber with an unobstructed longitudinal horizontal axis with fluid culture media, wherein the culture chamber is symmetrical about an axis;
introducing cells, cellular aggregates and/or tissues into the media and;
rotating the vessel to suspend the growing cells in the media.
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42. A method for using cellular mechanisms to secrete biological products in the media or to remove biological waste materials or toxins from the media, comprising the steps of:
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filling a rotatable culture vessel having a culture chamber with an unobstructed longitudinal axis with fluid culture media;
introducing cells, cellular aggregates, or tissues into the media to form a mixture;
providing oxygen and nutrients to the cells, cellular aggregates, or tissues; and
secreting biological products or removing waste materials using cellular mechanisms. - View Dependent Claims (45, 46, 47)
removing a vessel containing depleted cells, cellular aggregates, or tissues from the series and adding a vessel containing fresh cells, cellular aggregates, or tissues to the series.
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43. A method for using cellular mechanisms to secrete biological products into the media or to remove biological waste materials or toxins from the media, comprising the steps of:
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introducing culture media into a culture vessel chamber having a spherical, oblate spherical, an extended spherical, or continuous curved wall symmetrical about an axis, an inlet and an outlet, the chamber having at least one filter in fluid communication with the inlet or outlet, the filter structured to pass culture media and to retain cells, cellular aggregates or tissues;
introducing cells, cellular aggregates, or tissues into the media to form a mixture;
rotating the culture chamber vessel about the horizontal or proximate horizontal axis;
providing oxygen and nutrients to the cells, cellular aggregates, or tissues; and
secreting biological products, or removing waste materials using cellular mechanisms of the cells, cellular aggregates, or tissues.
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44. A method for using cellular mechanisms to secrete biological products into the media or to remove biological waste materials or toxins from the media, comprising the steps of:
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providing a gas permeable membrane within a culture vessel chamber, the gas permeable membrane allowing for the transfer of gases between the chamber and a space outside of the chamber;
introducing culture media into the culture vessel chamber having a spherical, oblate spherical, an extended spherical, or continuous curved wall symmetrical about an axis, an inlet and an outlet, introducing cells, cellular aggregates, or tissues into the culture media in the vessel to form a mixture;
rotating the culture chamber vessel about the horizontal or proximate horizontal axis;
providing oxygen and nutrients to the cells, cellular aggregates, or tissues; and
secreting biological products, or removing waste materials using cellular mechanisms of the cells, cellular aggregates, or tissues; and
providing at least one access port for inserting or removing material from the vessel.
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48. A culture vessel comprising:
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a cylindrical vessel having first and second end walls and a cylindrical wall therebetween, at least one inlet, at least one outlet, and at least one filter, the at least one filter having openings of a size that allows the passage of a fluid culture medium and cellular metabolic waste but prevents the passage of cells and cellular aggregates;
a growth chamber defined by the cylindrical wall, the fist and second end walls, and the at least one filter, the growth chamber having an unobstructed horizontal axis, wherein the growth chamber is symmetrical about an axis;
means for rotating the tubular vessel about a substantially horizontal longitudinal axis, said rotation means capable of rotating the vessel at a variety of speeds; and
a pump for maintaining a flow of fluid culture medium through the growth chamber, the pump capable of maintaining a variety of flow rates and reversing the direction of flow. - View Dependent Claims (49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63)
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Specification