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.

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 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 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 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 packed-bed bioreactor system is provided, the system including a cell culture vessel having a first end, a second end, and a reservoir between the first and second ends; and a cell culture matrix disposed in the reservoir. The cell culture matrix includes a structurally defined substrate with a plurality of interwoven fibers having surfaces for adhering cells thereto. The substrate is disposed within the reservoir in a wound configuration creating a plurality of layers of substrate in the wound configuration, and none of the plurality of layers of substrate are separated by a spacer material.

Abstract: A cell culture vessel (100) has walls and a substrate having a plurality of microcavities (120), where each microcavity of the plurality of microcavities includes a concave well and an opening to allow the microcavity to be filled with liquid. A flange (170) surrounds the substrate having an array of microcavities. A channel (175, 176) surrounds the flange, providing a moat around the microcavity substrate. The flange is angled. Methods of culturing cells in the cell culture vessel are also provided.

Abstract: A sensing cell culture vessel having one or more sensors on or in the vessel is configured to collect readings of various parameters or characteristics of a cell culture located within the sensing cell culture vessel and transmit the readings. The sensing cell culture vessels may be accompanied by a sensing plate having means for reading the one or more sensors and transmitting the one or more sensors to a server hosting electronic lab notebook for analyzing and storage of the readings. Sensing plates may further be equipped with cameras for imaging cell cultures located in the sensing cell culture vessels and transmitting the images to the server hosting the electronic lab notebook for analyzing and storage of the images. Embodiments of the invention allow for the continuous and automatic monitoring of cell cultures.

Abstract: A modular and stacked cell culture system that includes a standalone cell culture subunit with an interior cavity to house a cell culture substrate in a cell culture space, a fluid inlet to supply fluid to the cell culture space, and a fluid outlet to remove fluid from the cavity. The cavity is arranged for fluid to flow in from the fluid inlet, then through the cell culture space, and then out through the fluid outlet. The subunit further includes an alignment feature on at least one of a top and a bottom of the standalone cell culture subunit, wherein the alignment feature aligns with an alignment feature of another standalone cell culture subunit, such that multiple standalone cell culture subunits are stackable.

Abstract: A connected ecosystem for a laboratory environment comprises an electronic lab notebook, and instrumented biosafety cabinet, and one or more sensing vessels containing cell cultures. The electronic lab notebook interfaces with the instrumented biosafety cabinet to provide instructions, guidance, and monitoring of a user during the set up of the experimental protocol and to receive commands from the user via one of several input modalities. After the experimental protocol has been set up in the instrumented biosafety cabinet, cell cultures may be moved to an incubator where the connected ecosystem may provide automatic monitoring of the cultures. The automatic monitoring is provided by sensors integrated into cell culture vessels and supplemented by images of the cell cultures captured by a camera. The user may be informed of deviations from expected results detected based on the automatic monitoring.

Abstract: An aseptic bioprocess package is provided herein. The aseptic bioprocess package includes a 2D flexible container including 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 and a channel-forming feature in the interior compartment of the 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.

Abstract: A cell culture system is provided that includes a cell culture vessel having an interior cavity to house a cell culture substrate in a cell culture space, and at least one port for at least one of fluid inlet to the interior cavity and fluid outlet from the interior cavity. The system further includes a piston having a distal end disposed in the cell culture vessel above the cell culture space, the distal end of the piston being sealed with an airtight seal within the interior cavity. The system also includes a driver coupled to the piston to move the piston so as to increase and decrease a distance between the distal end and the cell culture space. The driver can pressurize the interior cavity via actuation of the piston to harvest cells from the cell culture space through the at least one port.

Abstract: Kits for making a spheroid-stabilizing hydrogel in a calcium-free or calcium-chelated cell culture media include (a) a gelation agent including a polygalacturonic acid (PGA) compound or an alginic acid compound, wherein the PGA compound includes at least one of: (i) pectic acid or salts thereof, or (ii) partially esterified pectic acid having a degree of esterification from about 1 to about 40 mol % or salts thereof; (b) a crosslinking agent, wherein the crosslinking agent includes a salt of a divalent ion; and (c) a proton donor, wherein the proton donor includes lactones, esters, or other compounds that hydrolyze in aqueous solutions to form acids over a period of from 10 minutes to 1 hour. Resultant spheroid-stabilizing hydrogels and methods of preparing the same.

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.