Abstract: Multi-layer cell culture devices and systems for culturing suspension and adherent cells via continuous gravity flow of culture media without the use of motorized equipment minimize the risk of contamination of the cell culture. A multi-layer cell culture device includes at least first and second chambers configured to contain fluid and to be fluidly connected such that fluid in the first chamber unidirectionally and continuously flows by gravity flow from the first chamber and into the second chamber. A multi-layer cell culture device can further include a third chamber configured to contain fluid and positioned below the second chamber such that fluid in the second chamber unidirectionally and continuously flows by gravity flow from the second chamber and into the third chamber. Methods of culturing cells using these devices and systems are also described.

Abstract: A pipette structure (160B) includes first and second body sections (164, 166) connected at a junction and including first and second fluid passages, respectively, with the pipette structure including (i) a bellows joint (165) permitting pivotal movement between the first and second body sections (164, 165), and/or (ii) the second fluid passage of the second body section includes greater width dimension at a sample introduction end than a width dimension at the junction. Such a pipette structure may be embodied in a unitary measuring pipette or an extension tip device for a measuring pipette. A method is provided for transferring material between an interior of a cell culture housing that includes a structured surface defining an array of microwells suitable for three-dimensional culture of multi-cell aggregates and an external environment. A method for fabricating a pipette structures is further provided.

Abstract: A cell culture vessel includes a vessel body, support columns, and a stabilizer device. The vessel body defines a cell culture chamber enclosed between a bottom wall and a top wall. The support column is within the cell culture chamber and extends between the top wall and the bottom wall. The stabilizer device covers a width and length of the cell culture chamber and has a column engaging structure that is sized to slidingly engage the support column such that the stabilizer device is movable along the support column as a liquid culture medium is received in the cell culture chamber. The support column guides the stabilizer device along a length of the support column as the stabilizer device rises with rising liquid level in the cell culture chamber during a liquid culture medium filling operation.

Abstract: A structured bag for cell culture is provided herein. The structured bag includes a top portion, a bottom portion having a shape, and a sidewall extending between the top portion and the bottom portion and at least partially defining an interior compartment for receiving fluid. The bottom portion is configured to maintain the shape to support the structured bag such that the structured bag is free standing when placed on a surface.

Abstract: A pipette may comprise a length, a longitudinal axis, and an inner curved surface enclosing a space. The pipette may have a tip region having a tip thickness. The tip region may be connected to a body region having a body thickness. The tip thickness may be greater than the body thickness. The body region may be connected to a mouth region having a mouth thickness. The mouth thickness may be greater than the body thickness. The inner curved surface may not contain bumps or ridges either between the tip region and the body region or between the body region and the mouth region. The pipette may be formed by blow molding or vacuum forming.

Abstract: A cell culture apparatus includes a cell culture module including multiple cell culture chambers. A manifold connects the multiple cell culture chambers together along a side of the cell culture module. The manifold includes a side wall base structure connected to the side of the cell culture module and a column structure that is formed as a monolithic part of the side wall base structure. The column structure defines a fluid flow pathway through the manifold and to inlets to the cell culture chambers to allow filling and emptying of the cell culture chambers of liquid medium.

Abstract: An article including either a frame having an interior cavity, and a flexible liner situated within the interior cavity; or a deformable frame having an interior cavity. Either frame can receive a sample, such as liquid having suspended live cells, and cooling freezes the sample to a solid sample. The solid sample can be readily ejected from the article having either a frame with the flexible liner, or the deformable frame, without extensive thawing. The solid sample can be rapidly displaced from the article.

Abstract: A microcavity dish (10) for cultivating cells includes a dish body including a sidewall (16) that encloses a cell culture chamber within the dish body. The dish body has a top and a bottom (12). The bottom includes a cell culturing substrate comprising an array of microcavities (46). The sidewall includes a transition portion (30) that divides the sidewall into an upper portion and a lower portion that is offset inward relative to the upper portion defining a liquid medium delivery surface (26) that extends at least partially along an interior surface (28) of the sidewall and slopes toward the bottom.

Abstract: A fluidic device for culturing cells includes a microplate and plate lid. The microplate includes multiple wells and channels, the channels extending between the wells such that the channels interconnect the wells. The plate lid releasably engages the microplate to thereby enclose the wells and the channels The wells include a culture surface such that a cell culture medium received therein is deposited over the culture surface. At least one channel that extends between adjacent ones of the wells is spaced from the culture surfaces of the adjacent wells defining a gap between the at least one channel and the culture surfaces of the adjacent wells for collection of the cell culture medium.

Abstract: A remote monitoring system configured to non-invasively measure a cell culture is provided. The system includes a plurality of cell culture layers comprising a cell culture chamber configured to operate as a closed-system, the at least one cell culture chamber having at least one surface to which cells adhere. The system further includes at least one monitoring layer comprising an outer wall surrounding a monitoring layer cell culture chamber configured to operate as a closed-system and having at least one surface to which cells adhere, the at least one monitoring layer comprising at least one indentation in the outer wall. The system also includes at least one monitoring module disposed in at least one of the at least one indentation and comprising at least one of a confluence monitor and an analyte monitor.

Abstract: The present disclosure relates to methods for evaluating the interaction of a candidate compound on 3D hepatocyte spheroid in an invitro culture, including evaluating the metabolism of a candidate compound, for use in various biochemical and molecular biology studies. The methods are performed in labware that combine 3D spheroid culture with micro-patterned design that allows for multiple to several hundreds of spheroids to be treated under the same conditions and to produce sufficient materials (e.g., parent drug, drug metabolites, DNA, RNA, and proteins from cells) and higher detection signal intensity for ADME/Tox (absorption, distribution, metabolism, excretion and toxicity) studies. The methods allow for, among other uses, the investigation and generation of accurate invitro intrinsic clearance data and thus more accurate prediction of in vivo clearance, particularly with low clearance compounds.

Abstract: A spheroid cell culture article including: a chamber including: an opaque side wall surface; a top aperture; and a gas-permeable, liquid impermeable bottom including at least one concave surface, wherein at least a portion of the bottom is transparent, wherein at least a portion of the bottom includes a low-adhesion or no-adhesion material in or on the at least one concave surface, and wherein the gas permeable, liquid impermeable bottom includes polystyrene.

Abstract: A cell separation device configured for separating cells from microcarriers or spheroids in a liquid is provided. The cell separation device includes a vessel comprising a first port, a second port, and a cavity; and a porous mesh disposed within the cavity to divide the cavity into a first compartment and a second compartment, wherein the first port is in communication with the first compartment of the cavity, the first port located to a first side of the porous mesh, wherein the second port is in communication with the second compartment of the cavity, the second port located to a second side of the porous mesh, and wherein the porous mesh is positioned within the cavity to have a substantially vertical orientation or an inclined orientation with respect to a flow of liquid through the porous mesh.

Abstract: A cell monitoring plate comprises a flat surface on which multiple cell culturing vessels may be stacked. The flats surface has multiple optical imaging systems embedded therein to fully image a cell culture vessels stacked on the plate. Each one of the multiple optical imaging systems provides both illumination and imaging through a single aperture in the surface of the monitoring plate.

Abstract: A cell culture vessel has a wall and cell culture surface having a plurality of microcavities for culturing cells in three-dimensional conformation, referred to as “spheroids”. The inner surface of the wall and the cell culture surface define a cell culture chamber of the vessel. The wall is attached to the cell culture surface in a way that does not provide flat surfaces on or around the cell culture surface so that the vessel provides an environment suitable for the production of a homogeneous population of three-dimensional cell clusters, or spheroids.

Abstract: The disclosure provides a cell culture vessel (100) having a surface (316) for culturing cells that has a microcavity array (115), suitable for culturing cells in 3D, either integrally provided in the bottom surface of the vessel, or provided by an insert (216) having an array of microcavities, placed on or affixed to the bottom surface of the vessel. The disclosure provides baffles (113) in the cell culture chamber and dams (130) in the neck of the vessel which control the flow of liquid into and out of microcavities to allow the microcavities to be filled and emptied with minimal turbulence, thus creating less disturbance for spheroids resting in the microcavities.

Abstract: A cell culture apparatus includes one or more plates having a first major surface and an opposing second major surface. The first major surface comprises a structured surface defining a plurality of wells. Each well has an interior surface defining an upper aperture and a nadir, wherein the upper aperture of each well has a diametric dimension in a range from 100 micrometers to 2000 micrometers. The apparatus also includes a plurality of spacers extending from the first major surface along a length of the bottom surface. A plurality of flow channels are defined between adjacent rails.

Abstract: A cell culture vessel (100) includes a wall including an inner surface defining a cell culture chamber of the vessel. A substrate (215) of non-porous material is positioned in the cell culture chamber between a first region of the cell culture chamber and a second region of the cell culture chamber. The substrate includes a plurality of microcavities (220), each microcavity of the plurality of microcavities includes a concave surface defining a well and an opening, the concave surface of each microcavity includes at least one aperture including a dimension less than or equal to about 15 microns defining a path from the well to the second region. A cell culture vessel including a substrate including a plurality of microcavities and a layer of porous material is also provided. Methods of culturing cells in the cell culture vessel are also provided.

Abstract: Methods, systems, and devices for non-invasive measurement of cell cultures are described that provide for remote monitoring of cell status. The system includes a cell culture vessel, at least one monitoring layer, at least one measurement device, and a communication component. The cell culture vessel may include at least one cell culture chamber configured for cell growth and for closed-system operation. The monitoring layer is external to the at least one cell culture chamber. In some cases, the communication component is configured to transmit data from the monitoring layer to a remote location.

Abstract: The present disclosure relates to apparatuses, systems and methods for culturing cells. In particular, devices and methods are provided for generation and culture of 3d cell aggregates.