Abstract: A fixed-bed bioreactor system is provided that includes a vessel with a media inlet, a media outlet, and an interior cavity disposed between and in fluid communication with the media inlet and media outlet. The vessel further includes a cell culture substrate disposed in the interior cavity between the media inlet and the media outlet in a packed-bed configuration, the cell culture substrate including a plurality of porous disks in a stacked arrangement. The interior cavity includes a cell culture section and a spacer section, the cell culture substrate defining the cell culture section and the spacer section being disposed between the cell culture section and the media outlet, and each of the plurality of porous disks has a surface configured to culture cells thereon.

Abstract: A cell culture apparatus may include a substrate defining a well. The well may define an interior surface, an exterior surface, an upper aperture and a nadir. The substrate may define a thickness between the interior and exterior surfaces that has a thickness proximate the nadir that is greater than or equal to a thickness proximate the upper aperture.

Abstract: A bioreactor system is provided that includes a cell culture vessel having a first end, a second end, and at least one reservoir between the first and second ends; and a cell culture matrix disposed in the at least one reservoir. The cell culture matrix has a structurally defined substrate with a surface for adhering cells thereto. The bioreactor system flows material through the at least one reservoir and through the cell culture matrix in a flow direction from the first end to the second end, and the cell culture matrix exhibits isotropic fluid flow permeability therethrough.

Abstract: A cell culture article includes a substrate having a polymer coating that is conducive to colony passaging of cells cultured on the coating. Example polymer coatings are formed from polygalacturonic acid (PGA), alginate, or combinations thereof. Cells cultured on the polymer coating can be separated from the substrate as a colony or layer of cells by exposing the polymer coating to (i) a chelating agent, (ii) a proteinase-free enzyme, or (iii) a chelating agent and a proteinase-free enzyme.

Abstract: A cell culture substrate (200, 308) for a fixed bed bioreactor and a fixed bed bioreactor having such a cell culture substrate is provided. The substrate has a structurally defined surface for culturing cells thereon, where the structurally defined surface defines an ordered and regular array of openings through a thickness of the cell culture substrate. At least a portion of the cell culture substrate includes a sample substrate, the sample substrate being defined by a separation boundary between the sample substrate and a remainder of the cell culture substrate, and the separation boundary allows separation of the sample substrate from the remainder of the cell culture substrate. A bioreactor (300) having ports for aseptic removal of the sample substrate is also provided.

Abstract: A cell culture bioreactor is disclosed that has a cell culture vessel with an interior reservoir to contain a cell substrate, an inlet fluidly connected to the reservoir, and an outlet fluidly connect to the reservoir. The bioreactor also has a sensor system for measuring impedance within the reservoir. The sensor system includes a pair of electrodes that are spaced apart from each other with at least a portion of the cell substrate disposed between the pair of electrodes. Each electrode of the pair of electrodes includes a plurality of pores to allow at least one of cells and culture media to flow through the electrode.

Abstract: A fixed-bed bioreactor system is provided that includes a vessel with a media inlet, a media outlet, and an interior cavity disposed between and in fluid communication with the media inlet and media outlet. The vessel further includes a cell culture substrate disposed in the interior cavity between the media inlet and the media outlet in a packed-bed configuration, the cell culture substrate including a plurality of porous disks in a stacked arrangement. The interior cavity includes a cell culture section and a spacer section, the cell culture substrate defining the cell culture section and the spacer section being disposed between the cell culture section and the media outlet, and each of the plurality of porous disks has a surface configured to culture cells thereon.

Abstract: A cell culture matrix is provided that has a substrate with a first side, a second side opposite the first side, a thickness separating the first side and the second side, and a plurality of openings formed in the substrate and passing through the thickness of the substrate. The plurality of openings allow flow of at least one of cell culture media, cells, or cell products through the thickness of the substrate, and provides a uniform, efficient, and scalable matrix for cell seeding, proliferation, and culturing. The substrate can be formed from a woven polymer mesh material that provides a high surface area to volume ratio for cells and good fluid flow through the matrix. Bioreactor systems incorporating the cell culture matrix and related methods are also provided.

Abstract: A fixed-bed cell culture matrix formed from a rolled cell culture substrate is provided that includes a cell culture vessel having an inlet, an outlet, and an interior reservoir fluidly disposed in a fluid pathway between the inlet and the outlet. A cell culture matrix is disposed in the reservoir in a wound configuration around a winding axis. The cell culture matrix includes a structurally defined substrate from a substrate material defining a plurality of pores, the substrate material being designed for adhering cells thereto. A plurality of permeability zones are provided in the cell culture matrix, which include an opening in the substrate, where the opening being larger than a diameter of any of the plurality of pores. The plurality of permeability zones are arranged with a variable periodicity along a length of the substrate in the wound configuration.

Abstract: A fixed-bed bioreactor system (300) is provided that includes a vessel with a media inlet (310), a media outlet (312), and an interior cavity disposed between and in fluid communication with the media inlet and media outlet; a cell culture substrate disposed in the interior cavity between the media inlet and the media outlet in a packed-bed configuration, the cell culture substrate having a plurality of porous disks (308) in a stacked arrangement; and a harvesting volume (2010,2020) to hold a fluid, the harvesting volume being in fluid communication with the interior cavity, wherein each of the plurality of porous disks comprises a surface configured to culture cells thereon. The harvesting volume can be inside or outside of the vessel.

Abstract: A cell culture matrix for a perfusion-flow fixed-bed reactor is provided. The cell culture matrix includes a substrate having a porous sheet for adhering cells thereto. The sheet has a first side, a second side opposite the first side, a thickness separating the first side and the second side, and a plurality of openings formed in the substrate, arrayed in a regular pattern, and passing through the thickness of the substrate. The porous sheet is wound into a cylindrical shape having a plurality of wound layers, and the cell culture matrix does not include a spacer material or physical barrier between the plurality of wound layers of the substrate.

Abstract: A cell culture matrix is provided that has a substrate with a first side, a second side opposite the first side, a thickness separating the first side and the second side, and a plurality of openings formed in the substrate and passing through the thickness of the substrate. The plurality of openings allow flow of at least one of cell culture media, cells, or cell products through the thickness of the substrate, and provides a uniform, efficient, and scalable matrix for cell seeding, proliferation, and culturing. The substrate can be formed from a woven polymer mesh material that provides a high surface area to volume ratio for cells and good fluid flow through the matrix. Bioreactor systems incorporating the cell culture matrix and related methods are also provided.

Abstract: A bioreactor system for culturing cells is provided. The system includes a cell culture vessel with an interior reservoir. an inlet and an outlet fluidly connected to the reservoir. A fluid flow path supplies fluid to the inlet and receives fluid from the outlet. and a media conditioning vessel is fluidly connected to the cell culture vessel. The system also includes an outlet sensor arranged at the outlet of the cell culture vessel. The outlet sensor can detect a property of cell culture media exiting the cell culture vessel via the outlet, and the bioreactor system can adjust a property of the cell culture media based on the property detected by the outlet sensor.

Abstract: A method for separating at least one target compound from a feed solution is provided. The method includes filling a bioprocess package with a chromatography resin. The bioprocess package includes a 2D flexible container comprising an interior compartment, a height having an upper half and a lower half, an inlet and an outlet, the inlet and the outlet being disposed on the same half of the 2D flexible container, the channel-forming feature being configured to maintain a fluid flow path that fluidly connects the interior compartment of the flexible container with the outlet. The method further includes flowing a feed solution into the bioprocess package to contact the chromatography resin such that substantially all of the at least one target compound binds to the chromatography resin, washing the chromatography resin in the bioprocess package, and eluting the chromatography resin.

Abstract: A cell culture vessel includes a base defining a base plane extending in a first direction and a second direction perpendicular to the first direction, a plurality of cell culture chambers stacked one atop another, each cell culture chamber having a top, a bottom and sidewalls, each of the top, bottom and sidewalls having an interior surface, wherein at least the bottom surface has an array of microcavities supporting the culture of cells as spheroids and each bottom surface is at an angle with respect to the plane of a table or surface upon which the vessel sits. Further, liquid can flow into each cell culture chamber via an inlet and out of each cell culture chamber via an outlet. The angled cell culture surface allows the cell culture chambers to be perfused or allows media changes without dislodging spheroids from microcavities.

Abstract: A cell culture matrix for a perfusion-flow fixed-bed reactor is provided. The cell culture matrix includes a substrate having a porous sheet for adhering cells thereto. The sheet has a first side, a second side opposite the first side, a thickness separating the first side and the second side, and a plurality of openings formed in the substrate, arrayed in a regular pattern, and passing through the thickness of the substrate. The porous sheet is wound into a cylindrical shape having a plurality of wound layers, and the cell culture matrix does not include a spacer material or physical barrier between the plurality of wound layers of the substrate.

Abstract: A fixed-bed bioreactor system is provided that includes a vessel with a media inlet, a media outlet, and an interior cavity disposed between and in fluid communication with the media inlet and media outlet. The vessel further includes a cell culture substrate disposed in the interior cavity between the media inlet and the media outlet in a packed-bed configuration, the cell culture substrate including a plurality of porous disks in a stacked arrangement. The interior cavity includes a cell culture section and a spacer section, the cell culture substrate defining the cell culture section and the spacer section being disposed between the cell culture section and the media outlet, and each of the plurality of porous disks has a surface configured to culture cells thereon.

Abstract: A cell culture article includes a substrate having a polymer coating that is conducive to colony passaging of cells cultured on the coating. Example polymer coatings are formed from polygalacturonic acid (PGA), alginate, or combinations thereof. Cells cultured on the polymer coating can be separated from the substrate as a colony or layer of cells by exposing the polymer coating to (i) a chelating agent, (ii) a proteinase-free enzyme, or (iii) a chelating agent and a proteinase-free enzyme.

Abstract: A packed-bed cell culture matrix and bioreactor system for culturing cells is provided. The system includes a cell culture vessel having an inlet, an outlet, and an interior reservoir fluidly connected to and disposed between the inlet and the outlet. A cell culture matrix is disposed in the reservoir, the cell culture matrix having a structurally defined substrate with a substrate material defining a plurality of pores, and the substrate material is for adhering cells thereto. A permeability zone is located in a portion of the cell culture matrix, the at least one permeability zone having a higher permeability than a standard permeability of the cell culture matrix outside of the permeability zone. The permeability zone has an opening in the substrate, where the opening is larger than a diameter of any of the plurality of pores.

Abstract: A cell culture matrix is provided that has a substrate with a first side, a second side opposite the first side, a thickness separating the first side and the second side, and a plurality of openings formed in the substrate and passing through the thickness of the substrate. The plurality of openings allow flow of at least one of cell culture media, cells, or cell products through the thickness of the substrate, and provides a uniform, efficient, and scalable matrix for cell seeding, proliferation, and culturing. The substrate can be formed from a woven polymer mesh material that provides a high surface area to volume ratio for cells and good fluid flow through the matrix. Bioreactor systems incorporating the cell culture matrix and related methods are also provided.