Spheroid cell culture well article and methods thereof

A spheroid cell culture article including: a frame having a chamber including: an opaque side wall surface; a top aperture; a gas-permeable, transparent bottom; and optionally a chamber annex surface and second bottom, and at least a portion of the transparent bottom includes at least one concave arcuate surface, is disclosed. Methods of making and using the article are also disclosed.

REINFORCED MICROPLATE

A microplate is fitted with a reinforcing member that enhances the rigidity of the microplate and decreases the magnitude of thermally-induced deformation. An example reinforced microplate includes a deck including a plurality of wells formed therein, and a reinforcing member attached to an underside of the deck.

CELL CULTURE MEDIA EXTENDING MATERIALS AND METHODS

This disclosure provides a cell culture media extending material capable of releasing nutrients into the cell culture environment slowly over time. In embodiments, this material is a part of a cell culture vessel. In embodiments, the material is a coating or a film on a surface of a cell culture material. In additional embodiments, the material is a surface upon which cells are cultured, such as a cell culture vessel or a microcarrier.

VESSELS AND METHODS FOR CRYOPRESERVATION

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, as defined herein. 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 by the methods and apparatus disclosed herein.

Multilayered cell culture apparatus

A multilayered cell culture apparatus for the culturing of cells is disclosed. The cell culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between the cell culture chambers and the external environment. The flask body also includes an aperture that will allow access to the cell growth chambers by means of a needle or cannula. The size of the apparatus, and location of an optional neck and cap section, allows for its manipulation by standard automated assay equipment, further making the apparatus ideal for high throughput applications.

MULTILAYERED CELL CULTURE APPARATUS

A multilayered cell culture apparatus for the culturing of cells is disclosed. The cell culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between the cell culture chambers and the external environment. The flask body also includes an aperture that will allow access to the cell growth chambers by means of a needle or cannula. The size of the apparatus, and location of an optional neck and cap section, allows for its manipulation by standard automated assay equipment, further making the apparatus ideal for high throughput applications. 1. A cell growth apparatus comprising:a plurality of cell growth chambers, each having a gas permeable, liquid impermeable membrane, an opposing surface, and at least one side wall connected to at least one of the gas permeable, liquid impermeable membrane and the opposing surface;at least one tracheal space in communication with at least one gas permeable, liquid impermeable membrane of at least one cell growth chamber;wherein the at least one tracheal space comprises peripheralsupports on a peripheral edge of the tracheal space; wherein the supports on the peripheral edge of the tracheal space are spaced apart to create a plurality of gaps to allow gasses to flow from an external environment into the tracheal space through the plurality of gaps between peripheral supports; and,an entry portal and an exit portal;wherein the entry portal and the exit portal provide fluid access to the plurality of cell culture chambers.2. The cell growth apparatus of wherein the fluid access to the plurality of cell culture chambers is arranged in parallel.3. The cell growth apparatus of wherein the cell growth chambers are arranged in staggered configuration.4. The cell growth apparatus of wherein the fluid access to the ...

MULTILAYERED CELL CULTURE APPARATUS

A multilayered cell culture apparatus for the culturing of cells is disclosed. The cell culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between the cell culture chambers and the external environment. The flask body also includes an aperture that will allow access to the cell growth chambers by means of a needle or cannula. The size of the apparatus, and location of an optional neck and cap section, allows for its manipulation by standard automated assay equipment, further making the apparatus ideal for high throughput applications. 1. A cell growth apparatus comprising:a plurality of cell growth chambers, each having a gas permeable, liquid impermeable membrane, an opposing surface, and at least one side wall connected to at least one of the gas permeable, liquid impermeable membrane and the opposing surface;at least two tracheal spaces, each tracheal space in communication with at least one gas permeable, liquid impermeable membrane of at least one cell growth chamber;wherein the at least two tracheal spaces comprises peripheral supports on a peripheral edge of the tracheal space; wherein the supports on the peripheral edge of the tracheal space are spaced apart to create a plurality of gaps to allow gasses to flow from an external environment into the tracheal space through the plurality of gaps between peripheral supports.2. The cell growth apparatus of wherein the fluid access to the plurality of cell culture chambers is arranged in parallel.3. the cell growth apparatus of wherein the cell growth chambers are arranged in staggered configuration.4. The cell growth apparatus of wherein the fluid access to the plurality of cell culture chambers is arranged in series.5. The cell growth apparatus of further comprising a fluid flow ...

SPHEROID CELL CULTURE ARTICLE AND METHODS THEREOF

A spheroid cell culture article including: 119-. (canceled)20. A cell culture article comprising: a side wall', 'a top aperture; and', 'a gas-permeable , liquid impermeable bottom comprising at least one concave surface, wherein at least a portion of the bottom is transparent and wherein at least a portion of the bottom comprises a low-adhesion or no-adhesion material in or on the at least one concave surface., 'a chamber comprising21. The article of further comprising a liner having a porous membrane situated within a portion of the chamber to divide the chamber into an upper chamber and a lower chamber.22. The article of further comprising a chamber annex for receiving a pipette tip for aspiration claim 20 , the chamber annex comprises a surface adjacent to and in fluid communication with the chamber claim 20 , the chamber annex having a second bottom spaced away and at an elevation above the gas-permeable claim 20 , transparent bottom claim 20 , wherein the second bottom deflects fluid dispensed from a pipette away from the transparent bottom.23. The article of further comprising a liner having a porous membrane situated within a portion of the chamber to form an upper chamber and a lower chamber the porous membrane providing separation of a second cellular material in the upper chamber claim 22 , from a first cellular material in the lower chamber .24. The article of wherein the article comprises from 1 to about 2 claim 20 ,000 of said chambers claim 20 , wherein each chamber is physically separated from any other chamber.25. The article of wherein the at least one concave surface comprises a plurality of concave surfaces within the same chamber.26. The article of wherein the at least one concave surface comprises a hemispherical surface claim 20 , a conical surface having a taper of 30 to about 60 degrees from the side walls to the bottom claim 20 , or a combination thereof.27. The article of wherein the side wall surface comprises a vertical cylinder claim 20 ...

SYSTEM AND METHOD FOR ANALYZING EXTRACELLULAR VESICLES WITH AN OPTICAL BIOSENSOR

Various implementations of a system and method for analyzing extracellular vesicles (EVs) are disclosed having a number of innovative features. In one implementation, a method for analyzing EVs includes binding EVs to an optical waveguide biosensor and phenotyping the bound EVs. Phenotyping can include binding a labeled ligand to the EVs and/or rupturing the EVs and analyzing their cargo. In another implementation, a system for analyzing EVs includes EVs bound to an optical waveguide biosensor and a labeled ligand bound to the EVs. In another implementation, a kit for analyzing EVs includes a micro plate having wells containing optical waveguide biosensors functionalized with a binding agent configured to bind to EVs and at least one of: (a) labeled ligands configured to bind to the extracellular vesicles or (b) a reagent configured to rupture the extracellular vesicles. 1. A method comprising:positioning a sample on an optical waveguide biosensor, the sample including extracellular vesicles;binding the extracellular vesicles to the optical waveguide biosensor;detecting the extracellular vesicles bound to the optical waveguide biosensor; andanalyzing a characteristic of the extracellular vesicles bound to the optical waveguide biosensor.2. The method of claim 1 , wherein the characteristic of the extracellular vesicles includes the number of extracellular vesicles in the sample claim 1 , the size of extracellular vesicles in the sample claim 1 , and/or the type of extracellular vesicles in the sample.3. The method of claim 1 , wherein analyzing the characteristic of the extracellular vesicles comprises binding ligands to the extracellular vesicles.4. The method of claim 3 , wherein the ligands include a first ligand that binds to a first marker on the extracellular vesicles and a second ligand that binds to a second marker on the extracellular vesicles.5. (canceled)6. The method of claim 1 , wherein analyzing the characteristic of the extracellular vesicles ...

CELL CULTURE SYSTEMS

An integrated cell culture system may include one or more cell culture vessels, manipulation apparatus, pumping apparatus, cell release apparatus, monitoring apparatus, and a control apparatus. The control apparatus may be used to monitor and control the system to facilitate effective cell culturing. The cell release apparatus may be used to release a plurality of cells adhered to the cell culture surfaces of the cell culture vessels. 1. A cell culture system comprising:at least one cell culture vessel configured to culture cells using a plurality of parallel cell culture surfaces, wherein the at least one cell culture vessel comprises at least one port configured to allow material to flow into and out of the at least one cell culture vessel;manipulation apparatus configured to rotate the at least one cell culture vessel about a first rotation axis and about a second rotation axis, wherein the first rotation axis is perpendicular to the second rotation axis, wherein each of the first rotation axis and the second rotation axis are parallel a ground surface;pumping apparatus fluidly coupled to the at least one port of the at least one cell culture vessel and configured to pump material into and out of the at least one cell culture vessel through the at least one port;monitoring apparatus configured to monitor one or more parameters of the at least one cell culture vessel, the manipulation apparatus, and the pumping apparatus; andcontrol apparatus operably coupled to the manipulation apparatus, the pumping apparatus, and the monitoring apparatus, wherein the control apparatus is configured to coordinate movement of the at least one cell culture vessel using the manipulation apparatus with the pumping of material into and out of the at least one culture vessel using the pumping apparatus.2. The system of claim 1 , wherein the control apparatus is further configured to:move, using the manipulation apparatus, the at least one cell culture vessel into at least one fill ...

HIGH DENSITY 3D HEPATOCYTE SPHEROID PLATFORM FOR DRUG ADME STUDIES

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. 1. An assay method for evaluating the interaction of one or more low clearance candidate compounds with hepatocytes , comprising: 'a top aperture; and a liquid impermeable bottom comprising a bottom surface, wherein at least a portion of the bottom comprises a low-adhesion or no-adhesion material in or on the bottom surface;', 'culturing hepatocytes in a cell culture article to form a spheroid, wherein the cell culture article comprises a chamber, the chamber comprising an array of microcavities, each microcavity structured to constrain the hepatocytes to grow in a 3D spheroid confirmation to form a hepatocyte spheroid; wherein each microcavity of the chamber comprisescontacting the 3D hepatocyte spheroid with one or more low clearance candidate compounds; andmeasuring the in vitro intrinsic clearance of the one or more candidate compounds.2. The assay method of claim 1 , wherein the culture is a long-term culture.3. (canceled)4. The assay method of claim 1 , wherein the liquid impermeable bottom comprising the bottom surface is gas-permeable.5. The assay method of ...

MULTILAYERED CELL CULTURE APPARATUS

A multilayered cell culture apparatus for the culturing of cells is disclosed. The cell culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between the cell culture chambers and the external environment. The flask body also includes an aperture that will allow access to the cell growth chambers by means of a needle or cannula. The size of the apparatus, and location of an optional neck and cap section, allows for its manipulation by standard automated assay equipment, further making the apparatus ideal for high throughput applications. 1. A cell growth apparatus comprising:a plurality of cell growth chambers, each having a gas permeable, liquid impermeable membrane, an opposing surface, and at least one side wall connected to at least one of the gas permeable, liquid impermeable membrane and the opposing surface;at least one tracheal space in communication with at least one gas permeable, liquid impermeable membrane of at least one cell growth chamber;wherein the at least one tracheal space comprises peripheral supports on a peripheral edge of the tracheal space; wherein the supports on the peripheral edge of the tracheal space are spaced apart to create a plurality of gaps to allow gasses to flow from an external environment into the tracheal space through the plurality of gaps between peripheral supports; and,an entry portal and an exit portal;wherein the entry portal and the exit portal provide fluid access to the plurality of cell culture chambers.2. The cell growth apparatus of wherein the fluid access to the plurality of cell culture chambers is arranged in parallel.3. The cell growth apparatus of wherein the cell growth chambers are arranged in staggered configuration.4. The cell growth apparatus of wherein the fluid access to the ...

REMOTE MONITORING SYSTEM FOR CELL CULTURE

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. 1. A remote monitoring system configured to non-invasively measure a cell culture , the system comprising: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;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; andat 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.2. The system of claim 1 , further comprising a communication component configured to transmit data from the at least one monitoring module to a remote location.3. The system of claim 1 , wherein the at least one monitoring module comprises both a confluence monitor and an analyte monitor.4. The system of claim 1 , wherein at least one of the confluence monitor and the analyte monitor is configured monitor a cell ...

VESSELS AND METHODS FOR CRYOPRESERVATION

An article including, either: 1. An article comprising:a frame having an interior cavity; anda flexible liner situated within the interior cavity;the frame has a first open end for receiving a sample into the flexible liner, and the frame has a second open end, for engaging a holster for the article, and for receiving an ejector to displace the flexible liner and the sample contents from a location within the cavity.2. The article of wherein the frame is a hollow cylinder or hollow conic having first and second open ends.3. The article of further comprising a closure member for reversibly sealing the received sample in the interior cavity claim 1 , and the closure member comprises at least one of: a screw cap adapted to engage screw threads on the frame; a press fit plug having an optional strap to engage the frame claim 1 , or a combination thereof.4. The article of wherein the frame comprises a plurality of frames claim 1 , the flexible liner comprises a plurality of flexible liners claim 1 , the ejector comprises a plurality of ejectors claim 1 , and the closure member comprises a plurality of closure members.5. The article of wherein the ejector is: integral with the article; worn by an operator;attached to a stationary external support; attached to a robotic external support; or a combination thereof.6. The article of further comprising at least one ejector.7. The article of further comprising at least one ejector integral with the article and the at least one ejector comprises at least one retractable member.8. The article of further comprising at least one ejector integral with the article claim 1 , the at least one ejector comprises a plurality of ganged ejectors aligned with and attached to a plurality of cryotubes separated by at least one spring member.9. The article of further comprising a holster where the holster holds the article and permits the closure member to be removed with a single human hand or a single mechanical gripper.10. The article of ...

COMPOSITION AND METHOD FOR CELL CULTURE SUSTAINED RELEASE

An ex vivo cell culture sustained release composition, including:

CELL CULTURE SYSTEM WITH MANIFOLD

A cell culture apparatus includes cell culture units having cell culture chambers, each with at least one manifold. The manifold connects the cell culture unit to a fluid flow channel. The manifold has a dam which allows liquid to pool in the manifold and allows for the creation of an airspace in the manifold, which reduces hydrostatic pressure inside the apparatus and enables the stacking of multiple cell culture units. Embodiments include cascading manifolds, manifolds having reservoirs, and manifolds having valves. 116-. (canceled)17. A cell culture apparatus having a cascading manifold , comprising: each cell culture chamber comprising a top surface, a bottom surface configured to culture cells comprising gas permeable, liquid impermeable film, and a plurality of cell culture chamber openings; and,', 'a plurality of spacer layers between the plurality of cell culture chambers, adjacent to the gas permeable, liquid impermeable film and exterior to each of the cell culture chambers; and,, 'a plurality of cell culture units, each cell culture unit comprising a plurality of stacked cell culture chambers;'}a cascading manifold comprising an inlet, an overflow outlet and a plurality of openings in fluid communication with each of the plurality of cell culture chamber openings of the cell culture chambers of a cell culture unit;wherein fluid, introduced into a cascading manifold of a first cell culture unit through its inlet, flows into each cell culture chamber of the first cell culture unit through the plurality of cell culture chamber openings until each cell culture chamber of the cell culture unit is filled with fluid and then, once each cell culture chamber of the cell culture unit is filled, the cascading manifold fills with fluid and fluid cascades out of the cascading manifold through its overflow outlet;wherein the overflow outlet of the cascading manifold of a first cell culture unit is coupled to the inlet of a second manifold of a second cell culture unit; ...

MULTILAYERED CELL CULTURE APPARATUS

A multilayered cell culture apparatus for the culturing of cells is disclosed. The cell culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between the cell culture chambers and the external environment. The flask body also includes an aperture that will allow access to the cell growth chambers by means of a needle or cannula. The size of the apparatus, and location of an optional neck and cap section, allows for its manipulation by standard automated assay equipment, further making the apparatus ideal for high throughput applications. 1a plurality of cell growth chambers, each having a gas permeable, liquid impermeable surface and an opposing surface; andat least one tracheal chamber in communication with at least one gas permeable, liquid impermeable surface of at least one cell growth chamber.. A cell growth apparatus comprising: This application is a continuation of U.S. application Ser. No. 14/814,267, filed on Jul. 30, 2015, which is a continuation of U.S. application Ser. No. 14/254,280, filed on Apr. 16, 2014, which is a continuation of U.S. application Ser. No. 13/904,171, filed on May 29, 2013, which is a continuation of U.S. application Ser. No. 13/591,566, filed on Aug. 22, 2012, which is a continuation of U.S. application Ser. No. 12/783,217, filed on May 19, 2010, which is a divisional of U.S. application Ser. No. 11/433,859, filed on May 11, 2006, which claims the benefit of priority to U.S. Provisional Application Ser. No. 60/702,896 filed on Jul. 26, 2005 and entitled “Multilayered Cell Culture Apparatus” which is incorporated by reference herein in.The present invention relates generally to the cellular biological field and, in particular, to a cell cultivating flask.In vitro culturing of cells provides material necessary ...

MICROCAVITY DISHES WITH SIDEWALL INCLUDING LIQUID MEDIUM DELIVERY SURFACE

A microcavity dish () for cultivating cells includes a dish body including a sidewall () that encloses a cell culture chamber within the dish body. The dish body has a top and a bottom (). The bottom includes a cell culturing substrate comprising an array of microcavities (). The sidewall includes a transition portion () 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 () that extends at least partially along an interior surface () of the sidewall and slopes toward the bottom. 1. A microcavity dish for cultivating cells , the microcavity dish comprising:a dish body comprising a sidewall that encloses a cell culture chamber within the dish body, the dish body having a top and a bottom, where the bottom comprises a cell culturing substrate comprising an array of microcavities;the sidewall comprising a transition portion 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 that extends at least partially along an interior surface of the sidewall and slopes toward the bottom.2. The microcavity dish of claim 1 , wherein the transition portion extends between opposite sides of the sidewall.3. The microcavity dish of claim 1 , wherein the cell culturing substrate is formed separately from the dish body and is connected thereto.4. The microcavity dish of claim 1 , further comprising a lid that connects to the top of the dish body claim 1 , wherein the lid comprises a seal member that seals against the top of the dish body.5. The microcavity dish of claim 4 , wherein the lid further comprises a vent to release air pressure within the cell culture chamber.6. The microcavity dish of claim 4 , wherein the lid comprises an internal threaded surface that engages an external thread of the dish body to close the lid against the dish body.7. The microcavity dish of ...

FLUIDIC DEVICES INCLUDING MICROPLATES WITH INTERCONNECTED WELLS

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. 1. A fluidic device for culturing cells , comprising:(a) a microplate comprising a multiple wells and multiple channels, wherein the channels extend between the wells such that the channels interconnect the wells; and(b) a plate lid that releasably engages the microplate to thereby enclose the wells and the channels;wherein the wells include a culture surface such that a cell culture medium received therein is deposited over the culture surface;wherein 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.2. The fluidic device of claim 1 , wherein the channels are sized to facilitate circulation of the medium across the plurality of wells to thereby generate a shear force along the culture surfaces.3. The fluidic device of claim 1 , wherein the channels include a sidewall extending between the wells claim 1 , wherein the sidewalls are sized to partially retain the cell culture medium within the channels.4. The fluidic device of claim 1 , wherein the culture surface comprises a gas permeable microcavity substrate.5. The fluidic device of claim 1 , wherein the plate lid ...

CELL CULTURE VESSEL

A cell culture vessel () includes a wall including an inner surface defining a cell culture chamber of the vessel. A substrate () 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 (), 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. 1. A cell culture vessel comprising:a wall comprising inner surfaces defining a cell culture chamber of the vessel;a substrate of non-porous material 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 comprising a plurality of microcavities, each microcavity of the plurality of microcavities comprising a concave surface defining a well and an opening defining a path from the first region into the well, the concave surface of each microcavity comprising at least one aperture comprising a dimension less than or equal to about 15 microns defining a path from the well to the second region; anda first aperture extending through the wall in fluid communication with the first region.2. The cell culture vessel of claim 1 , further comprising a port extending through the wall in fluid communication with the second region claim 1 , the port comprising a gas-permeable filter.3. The cell culture vessel of claim 1 , further comprising a conduit connecting the first aperture to the second region.4. The cell culture vessel of claim 1 , further ...

MULTILAYERED CELL CULTURE APPARATUS

A multilayered cell culture apparatus for the culturing of cells is disclosed. The cell culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between the cell culture chambers and the external environment. The flask body also includes an aperture that will allow access to the cell growth chambers by means of a needle or cannula. The size of the apparatus, and location of an optional neck and cap section, allows for its manipulation by standard automated assay equipment, further making the apparatus ideal for high throughput applications. 1. A cell growth apparatus comprising:at least three cell growth chambers, each comprising a gas permeable, liquid impermeable membrane having a surface area for cell growth, an opposing surface, and side walls;at least two tracheal spaces contained within the cell growth apparatus, each tracheal space in communication with an external environment and also in communication with the gas permeable, liquid impermeable membrane of a cell growth chamber;a manifold providing access to the at least three cell growth chambers;{'sup': '2', 'wherein each cell growth chamber is configured to contain liquid and wherein a ratio of liquid volume contained in each cell growth chamber per unit surface area for cell growth is in the range of about 0.25 to 0.50 ml/cm.'}2. The apparatus of claim 1 , wherein the cell growth chambers claim 1 , the at tracheal spaces and the manifold comprise an integral unit.3. The apparatus of claim 2 , wherein each cell growth chamber alternates with a tracheal space successively.4. The apparatus of claim 3 , whereby said cell growth chambers are adjoined with and are in gaseous communication with said tracheal spaces through the gas permeable claim 3 , liquid impermeable membrane.5. The ...

PERFUSION BIOREACTOR PLATFORM

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. 1. A cell culture apparatus comprising:one or more plates having a first major surface and an opposing second major surface, wherein the first major surface comprises a plurality of microwells; wherein each microwell has an interior surface defining an upper aperture and a nadir; and wherein walls of the microwells have decreasing thickness from the microwell's upper aperture to the microwell's nadir; anda plurality of spacers extending from the first major surface, wherein a plurality of cell culture media flow channels are defined between adjacent plates.2. The cell culture apparatus of claim 1 , wherein the spacers extend from the first major surface along a length of the plate claim 1 , wherein a plurality of cell culture media flow channels are defined between adjacent spacers.3. The cell culture apparatus of claim 1 , wherein the upper aperture of each microwell has a diametric dimension in a range from 100 micrometers to 2000 micrometer.4. The cell culture apparatus according to claim 1 , wherein the cell culture apparatus comprises a plurality of said plates stacked on one another.5. The cell culture apparatus according to claim 1 , further comprising an inlet and an outlet claim 1 , wherein each of the plurality of media flow channels is in fluid communication with the inlet and the outlet.6. The cell culture apparatus according to claim 5 , further comprising an inlet ...

CELL CULTURE APPARATUSES WITH MANIFOLDS INCLUDING COLUMN STRUCTURES

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. 122-. (canceled)23. A cell culture apparatus , comprising:a cell culture module comprising multiple cell culture chambers;each cell culture chamber having a top, a bottom and sidewalls, defining an interior space for culturing cells;wherein each cell culture chamber has at least one inlet in a sidewall of the cell culture chamber through which liquid can flow into and out of the cell culture chamber;wherein the multiple cell culture chambers are stacked one above the other to form the cell culture module;a manifold comprising a side wall base structure and a column;wherein the manifold is aligned along a side of the cell culture module;wherein the manifold provides a fluid pathway from a manifold opening to each of the cell culture chambers through cell culture chamber inlets;and wherein the column provides an enlarged volume inside the manifold to enable fluid to flow through the manifold to the cell culture chamber inlets.24. The cell culture apparatus of claim 23 , wherein the manifold opening extends above the top-most stacked cell culture module.25. The cell culture apparatus of claim 23 , comprising multiple cell culture modules and the manifold comprises manifold segments where each manifold segment is associated with one of the cell culture modules.26. The cell culture apparatus of claim 25 , wherein each manifold segment comprises a side wall base structure segment and a column ...

CELL CULTURE APPARATUS FOR CO-CULTURE OF CELLS

A multilayered cell culture apparatus for the co-culturing of at least two cell types is disclosed. The cell co-culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between some cell culture chambers and the external environment. In addition, some cell culture chambers may have limited access to air creating relatively lower oxygen content cell culture chambers. The size of the apparatus, and location of an optional neck section, allows for its manipulation by standard automated assay equipment, further making the apparatus amenable to high throughput applications. 141-. (canceled)42. A multi-layer cell culture vessel for the co-culture of cells comprising:a first manifold providing access to a first plurality of cell culture chambers through ports in each of the first plurality of cell culture chambers, but does not provide access to a second plurality of cell culture chambers,a second manifold providing access to the second plurality of cell culture chambers through ports in each of the second plurality of cell culture chambers, but does not provide access to the first plurality of cell culture chambers;wherein the first plurality of cell culture chambers are adjacent to and alternate with the second plurality of cell culture chambers to form a multi-layer cell culture vessel, and wherein each of the first cell culture chambers are separated from each of the adjacent second cell culture chambers by a gas permeable liquid permeable membrane; and,at least one tracheal chamber adjacent to two cell culture chambers and separated from at least one of the adjacent cell culture chambers by a gas permeable, liquid impermeable membrane.43. The vessel of wherein the gas permeable claim 42 , liquid impermeable membrane comprises microporous membrane ...

CELL CULTURE VESSEL

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. 1. A cell culture vessel comprising:a cell culture surface consisting essentially of a plurality of microcavities;a wall attached to the cell culture surface, the cell culture surface and an inner surface of the wall define a cell culture chamber of the vessel.2. The cell culture vessel of claim 1 , each microcavity of the plurality of microcavities comprises a concave bottom and an opening.3. The cell culture vessel of claim 2 , further comprising a necked opening.4. The cell culture vessel of claim 3 , further comprising and dam in the necked opening.5. The cell culture vessel of claim 2 , further comprising a lid.6. The cell culture vessel of claim 4 , further comprising a lid.7. The cell culture vessel of claim 6 , wherein the lid comprises a hinged opening.8. The cell culture vessel of claim 4 , wherein the lid comprises a sliding opening.9. The cell culture vessel of claim 6 , wherein the necked opening comprises a bend.10. The cell culture vessel of claim 1 , wherein the wall comprises a recess and the cell culture surface is attached to the recess.11. The cell culture vessel of claims 9 , wherein the wall comprises a protrusion and the cell culture surface is attached to the protrusion.12. A cell culture vessel comprising:a cell culture surface comprising a plurality of microcavities, the microcavities having a non-flat sinusoidal shape;a wall attached to the cell culture surface, the cell culture surface ...

HANDLING FEATURES FOR MICROCAVITY CELL CULTURE VESSEL

The disclosure provides a cell culture vessel () having a surface () for culturing cells that has a microcavity array (), suitable for culturing cells in 3D, either integrally provided in the bottom surface of the vessel, or provided by an insert () having an array of microcavities, placed on or affixed to the bottom surface of the vessel. The disclosure provides baffles () in the cell culture chamber and dams () 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. 1. A cell culture vessel comprising:a cell culture chamber comprising a top, a bottom, sidewalls and a necked opening extending through a wall of the cell culture chamber in fluid communication with the cell culture chamber;a cell culture surface having an array of microcavities;{'sub': 'b', 'a baffle have in a baffle length (L) between a wall opposite the necked opening and the array of microcavities;'}{'sub': i', 'c, 'wherein the array of microcavities extends a Length (L) which is less than a length of the cell culture chamber (L); and,'}{'sub': b', 'i', 'c, 'wherein the baffle length (L) plus the Length of the array of microcavities (L) equals the length of the cell culture chamber (L);'}so that when the vessel is oriented so that the necked opening is up, there is a reservoir between the baffle and the top of the cell culture chamber.2. The cell culture vessel of claim 1 , wherein the bottom comprises the array of microcavities.3. The cell culture vessel of claim 2 , wherein the array of microcavities is integral to the interior surface of the bottom.4. The cell culture vessel of claim 3 , wherein the bottom surface of the array of microcavities is planar.5. The cell culture vessel of claim 3 , wherein the bottom surface of the array of microcavities comprises an array of microprojections.6. The cell culture vessel ...

STRUCTURED BAG FOR CELL CULTURE

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. 1. A structured bag for cell culture comprising:a top portion;a bottom portion having a shape; anda sidewall extending between the top portion and the bottom portion and at least partially defining an interior compartment for receiving fluid,wherein 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.2. The structured bag of claim 1 , wherein at least one of the portions of the structured bag is formed from a flexible material.3. The structured bag of claim 2 , wherein the flexible material comprises a plastic film or laminate having high gas permeability.4. (canceled)5. (canceled)6. The structured bag of claim 1 , wherein the bottom portion and at least one of the top portion and the sidewall is formed from a flexible material claim 1 , and wherein the flexible material of the bottom portion is thicker than the flexible material of the at least one of the top portion and the sidewall.7. The structured bag of claim 1 , wherein the bottom portion comprises a rigid substrate.8. The structured bag of claim 7 , wherein the rigid substrate comprises geometric patterns that support three dimensional cell culture.9. The structured bag of claim 8 , wherein the geometric patterns comprise microwells.10. The structured bag of claim 1 , further comprising a dip tube in the interior compartment claim 1 , wherein the dip tube comprises a proximal end and a distal end claim 1 , the proximal end being in fluid communication with a port in the fitment ...

SYSTEM AND METHOD FOR IMAGING AND ILLUMINATION FOR CELL CONFLUENCE MEASUREMENT

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. 1. An apparatus comprising:a housing having a flat top surface;one or more apertures disposed in the flat top surface;one or more optical imaging systems disposed within the housing and configured to image a culture in a cell culture vessel placed on the flat top surface of the housing.2. The apparatus of claim 1 , the one or more optical imaging systems each comprising:an imaging component; andan illumination component.3. The apparatus of claim 2 , the illumination component configured to direct light at an oblique angle to a surface above the culture in the cell culture vessel such that the light is reflected off of the surface such as to illuminate the culture from a side opposite the imaging component.4. The apparatus of claim 3 , wherein the surface reflecting the light is the bottom surface of the cell culture vessels stacked on top of the cell culture vessel placed on the flat top surface of the housing.5. The apparatus of claim 2 , the imaging component being disposed in the housing offset from one of the apertures in the top surface of the housing claim 2 , further comprising:a mirror located directly underneath the aperture and angled to direct light from the culture to the imaging component.6. The apparatus of claim 5 , the imaging component having a focal length fixed to image the culture in the cell culture vessel placed directly on the top surface of the housing.7. The apparatus of claim 5 , the imaging component having a movable focal length which may be adjusted to image cultures located in cell culture vessels stacked on the cell culture vessel placed directly on ...

CELL CULTURE VESSELS WITH STABILIZER DEVICES

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. 1. A cell culture vessel , comprising:a vessel body that defines a cell culture chamber enclosed between a bottom wall and a top wall;a support column within the cell culture chamber extending between the top wall and the bottom wall;a stabilizer device covering a width and length of the cell culture chamber having 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;wherein 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.2. The cell culture vessel of claim 1 , wherein a cell culture surface is located along the bottom wall and defines a cell culturing area claim 1 , the stabilizer device having a footprint on the cell culture surface that is at least 50 percent of the cell culturing area.3. The cell culture vessel of claim 2 , wherein the stabilizer device comprises a material having a density no greater than about 1.0 g/cmat room temperature ...

CELL CULTURE INSERT

A cell culture insert for use in culturing cells to promote the formation of spheroids and methods of using these spheroid-promoting cell culture inserts. The cell culture insert includes a porous membrane and one or more sidewalls that are non-adherent to cells and cause the cells in the insert to associate with each other and form spheroids. 1. A cell culture insert comprising:a body sized for insert into a reservoir of a cell culture device, said body having a first open end, a second end defining an opening, and one or more sidewalls extending from the first open end to the second end; wherein the one or more sidewalls are sloped; anda porous membrane disposed over the opening of the second endwherein the porous membrane comprises an array of microwells.2. A cell culture insert according to claim 1 , wherein said opening of said second end has a diametric dimension in a range from 100 μm to 1000 μm.3. A cell culture insert according to claim 1 , wherein said opening of said second end has a diametric dimension in a range from 200 μm to 750 μm.4. A cell culture insert according to wherein at least a portion of the one or more sidewalls are non-adherent to cells.5. A cell culture insert according to claim 1 , wherein at least a portion of the porous membrane is non-adherent to cells.6. A cell culture insert according to claim 1 , wherein at least a portion of the porous membrane is adherent to cells.7. A cell culture insert according to claim 1 , wherein a portion of the one or more sidewalls proximate the second end at least partially define a spheroid confinement volume.8. A cell culture insert according to claim 7 , wherein a depth of the confinement volume is in a range from 100 μm to 500 μm.9. A cell culture insert according to further comprising a reservoir claim 1 , wherein a first cell culture insert is configured to be positioned in the interior of the reservoir to retain the second end of the first cell culture insert above the bottom of the reservoir.10 ...

PIPETTE STRUCTURE AND METHODS UTILIZING SAME

A pipette structure (B) includes first and second body sections () connected at a junction and including first and second fluid passages, respectively, with the pipette structure including (i) a bellows joint () permitting pivotal movement between the first and second body sections (), 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. 1. A pipette structure comprising:a first body section defining a first fluid passage;a second body section comprising a sample introduction end, being connected to the first body section at a junction, and defining a second fluid passage in fluid communication with the first fluid passage;wherein the pipette structure comprises at least one of the following features (i) or (ii):(i) the junction comprises a bellows joint permitting pivotal movement between the first body section and the second body section; or(ii) the second fluid passage comprises a non-uniform width between the sample introduction end and the junction, with a width dimension at the sample introduction end that is greater than a width dimension at the junction.2. The pipette structure of claim 1 , wherein the junction comprises a bellows joint permitting pivotal movement between the first body section and the second body section.3. The pipette structure of claim 1 , wherein the second fluid passage comprises a non-uniform width between the sample introduction end and the junction claim 1 , with a width dimension at the ...

Multilayered cell culture apparatus

A multilayered cell culture apparatus for the culturing of cells is disclosed. The cell culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between the cell culture chambers and the external environment. The flask body also includes an aperture that will allow access to the cell growth chambers by means of a needle or cannula. The size of the apparatus, and location of an optional neck and cap section, allows for its manipulation by standard automated assay equipment, further making the apparatus ideal for high throughput applications.

SPHEROID CELL CULTURE WELL ARTICLE AND METHODS THEREOF

A spheroid cell culture article including: 1. A cell culture article comprising: an opaque side wall surface;', 'a top aperture; and', 'a gas-permeable, liquid impermeable transparent bottom surface adjacent the opaque side wall surface, wherein at least a portion of the bottom surface comprises at least one concave arcuate surface., 'a frame having a chamber comprising2. The article of further comprising a low-adhesion or no-adhesion coating on the at least one concave arcuate surface.3. The article of further comprising a chamber annex for receiving a pipette tip for aspiration claim 1 , the chamber annex comprises a surface adjacent to and in fluid communication with the chamber claim 1 , the chamber annex having a second bottom spaced away and at an elevation above the gas-permeable claim 1 , transparent bottom claim 1 , and the second bottom in use deflects fluid dispensed from a pipette away from the transparent bottom.4. The article of further comprising a porous membrane situated within a portion of the chamber claim 3 , situated within a portion of the auxiliary second chamber claim 3 , or both the chamber and the auxiliary second chamber claim 3 , the porous membrane providing isolation or separation of second cellular material in an upper portion of the chamber claim 3 , in an upper portion of the auxiliary second chamber claim 3 , or both chambers claim 3 , from the first cellular material in a lower portion of one or both chambers near the transparent bottom.5. The article of wherein the chamber comprises from 1 to about 1 claim 1 ,000 chambers claim 1 , each chamber is physically separated from any other chamber claim 1 , and each chamber has a single concave arcuate surface.6. The article of wherein the at least one concave arcuate surface comprises a plurality of adjacent concave arcuate surfaces within the same chamber.7. The article of wherein the at least one concave arcuate surface comprises a hemi-spherical surface claim 1 , a conical surface ...

CRYOPRESERVATION DEVICES

Vial assemblies comprising a tubular body and a flexible bottom or flexible liner are described herein, wherein the flexible bottom or liner is configured to compress at least partially upon the application of force. Methods for storing and removing frozen samples from such vial assemblies are also described herein. 1. A vial assembly comprising:a tubular body comprising a cavity, a first end, a second end for dispensing a sample, and a tube wall comprising a first material; anda flexible bottom comprising a second elastomeric material overmolded on an interior surface of the tube wall proximate the first end,wherein the flexible bottom does not extend past the first end of the tubular body.2. The vial assembly of claim 1 , wherein an interior surface of the tube wall proximate the flexible bottom comprises one or more features configured to retain an integral ejector.3. The vial assembly of claim 1 , wherein the tube wall comprises at least two flanges proximate the flexible bottom claim 1 , wherein the flanges are configured to hinge inwardly and apply force to the flexible bottom.4. The vial assembly of claim 1 , wherein the flanges further comprise at least one gusset configured to apply force to the flexible bottom.5. A vial assembly comprising:a tubular body comprising a cavity, a first end, a second end, and a tube wall comprising a first material; anda flexible bottom comprising a second elastomeric material overmolded on the first end of the tubular body,wherein the flexible bottom further comprises at least two flanges attached to the tube wall and configured to hinge inwardly and apply force to a surface of the flexible bottom.6. A vial assembly comprising:a substantially rigid tubular body comprising a cavity, a first end, a second end, and a tube wall comprising a first material; anda flexible liner comprising a second elastomeric material positioned in the cavity of the tubular body and extending past the first end of the substantially rigid tubular ...

CRYOGENIC VIAL ASSEMBLIES

Vial assemblies comprise a tubular body and a cap, the cap including a first portion configured to abut a lip of an open end of the tubular body, a threaded portion configured to couple to threading on an internal surface of the tubular body, and a second portion protruding from the threaded portion and extending into a cavity of the tubular body. Methods for storing and removing frozen samples from such vial assemblies are also described. 1. A vial assembly comprising:a tubular body comprising a cavity, an open end comprising a lip, and a closed end, wherein an internal surface of the tubular body proximate the open end comprises threading; anda cap configured to couple to the open end of the tubular body, wherein the cap comprises:a first portion configured to abut the lip of the open end;a threaded portion configured to couple to at least a portion of the threading on the internal surface of the tubular body; anda second portion protruding from the threaded portion and extending into the cavity of the tubular body.2. The vial assembly of claim 1 , wherein the cap is configured to couple to the open end of the tubular body by rotation to engage the threaded portion of the cap to the threading on the internal surface of the tubular body.3. The vial assembly of claim 1 , wherein the tubular body comprises a first portion having an internal surface comprising threading and a second portion having an internal surface not comprising threading.4. The vial assembly of claim 3 , wherein a diameter of the first portion of the tubular body is greater than a diameter of the second portion of the tubular body.5. The vial assembly of claim 1 , wherein the internal surface of the tubular body comprising threading extends from the open end to the closed end of the tubular body.6. The vial assembly of claim 1 , wherein the first portion comprises an upper portion having a height extending above the lip of the open end claim 1 , the upper portion comprising a textured surface.7. ...

COMPOSITION AND METHOD FOR CELL CULTURE SUSTAINED RELEASE

An ex vivo cell culture sustained release composition, including: 1. An ex vivo cell culture sustained release composition , comprising: a sustenant in an amount of from 60 to 96 wt %; and', 'a non-biodegradable binder in an amount of from 1 to 20 wt %; and, 'a mixture comprisinga non-biodegradable and water insoluble encapsulant coat that encapsulates the mixture, in an amount of from 1 to 20 wt %, based on 100 wt % of the total composition.2. The composition of wherein the composition has a dosage form of at least one of a tablet claim 1 , a pellet claim 1 , a powder claim 1 , a pill claim 1 , or a combination thereof.3. The composition of wherein the sustenant has a water solubility of at least 0.01 to 10 wt % and comprises at least one sustenance ingredient selected from at least one o″: a nutrient claim 1 , a protein claim 1 , a vitamin claim 1 , a growth factor claim 1 , a performance enhancing molecule claim 1 , an inhibitor claim 1 , an amino acid claim 1 , a metal ion claim 1 , an organic acid claim 1 , a reducing agent claim 1 , a chelator claim 1 , an anti-oxidant claim 1 , or a combination thereof.4. The composition of wherein the sustenant is a sugar.5. The composition of wherein the sustenant is glucose.6. The composition of wherein the binder and the encapsulant are the same chemical entity and have the same or different molecular weight.7. The composition of wherein the binder claim 1 , the encapsulant claim 1 , or both claim 1 , are not chemically crosslinked claim 1 , and the binder further includes a plasticizer.8. The composition of wherein the sustained release composition is free of a hydrogel.9. The composition of wherein the sustained release composition has a release half-life of from 1 to 15 days.10. A method for sustainably providing a sustenant to an ex vivo cell culture in aqueous media claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'contacting the cell culture and the sustained release composition of .'}11. The ...

UNITARY SEROLOGICAL PIPETTE AND METHODS OF PRODUCING THE SAME

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. 1. A method for producing pipettes comprising the steps of:(a) providing a parison or preform, the parison or preform having a longitudinal axis and an inner curved surface enclosing a space;(b) inserting the parison or preform into a mold, the mold having at least two mold cavities, wherein each mold cavity has proximal and distal mold end features; and(c) blow-molding or vacuum forming the parison or preform to form at least two pipettes in the shape of the at least two mold cavities, each of the at least two pipettes having proximal and distal ends.2. The method of claim 1 , wherein step (c) involves blow-molding the parison or preform.3. The method of claim 1 , wherein step (c) involves vacuum forming the parison or preform.4. The method of claim 1 , wherein the proximal and distal mold end features are orifices.5. The method of claim 1 , wherein the at least two pipettes are arranged in the at least two mold cavities such that the proximal ends of at least two pipette are in close proximity to each other.6. The method of claim 1 , wherein the at least two pipettes are arranged in the at least two mold cavities such that the distal ends of at least two pipette are in close proximity to each other.7. The method of claim 1 , further comprising a step prior to step (b) of printing the at least two mold cavities to create mold ...

UNITARY SEROLOGICAL PIPETTE AND METHODS OF PRODUCING THE SAME

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. 1. A pipette comprising:a length, a longitudinal axis, and an inner curved surface enclosing a space;a tip region having a tip diameter and a tip thickness, wherein the tip region is connected toa body region having a body diameter and a body thickness, wherein the body diameter is greater than the tip diameter, and wherein the body region is connected toa mouth region having a mouth diameter and a mouth thickness,wherein the body thickness is less than one of the tip thickness or the mouth thickness, andwherein the inner curved surface is substantially smooth in the transition regions between the tip region and the body region or between the body region and the mouth region.2. The pipette of wherein the body thickness is less than the tip thickness.3. The pipette of wherein the body thickness is less than the mouth thickness.4. The pipette of claim 1 , wherein the inner curved surface is substantially smooth along the length of the pipette.5. The pipette of claim 1 , wherein the tip thickness is 0.3 mm or greater.6. The pipette of claim 1 , wherein the tip thickness is 0.6 mm or greater.7. The pipette of claim 1 , wherein the body thickness is 0.6 mm or less.8. The pipette of claim 1 , wherein the body thickness is 0.4 mm or less.9. The pipette of claim 1 , wherein the mouth thickness is 0.3 mm or greater.10. The pipette of claim 9 ...

CELL SEPARATION DEVICE AND METHOD FOR USING SAME

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. 1. A cell separation device configured for separating cells from microcarriers or spheroids in a liquid , the cell separation device comprising:a vessel comprising a first port, a second port, and a cavity; anda 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, andwherein 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.2. The cell separation device of claim 1 , wherein the first port is located at one end of the vessel and the second port is located at an opposing end of the vessel.3. The cell separation device of claim 2 , wherein the first port and the second port are off-set from one another on the vessel such that the porous mesh has the substantially vertical orientation within the cavity when ...

PERFUSION BIOREACTOR PLATFORM

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. 1. A cell culture apparatus comprising:one or more plates having a first major surface and an opposing second major surface, wherein the first major surface comprises a plurality of microwells; anda plurality of spacers extending from the first major surface, wherein a plurality of cell culture media flow channels are defined between adjacent plates.2. The cell culture apparatus of claim 1 , wherein the spacers extend from the first major surface along a length of the plate claim 1 , wherein a plurality of cell culture media flow channels are defined between adjacent spacers.3. The cell culture apparatus of claim 1 , wherein each well has an interior surface defining an upper aperture and a nadir claim 1 , wherein the upper aperture of each well has a diametric dimension in a range from 100 micrometers to 2000 micrometer.4. The cell culture apparatus according to claim 1 , wherein the cell culture apparatus comprises a plurality of said plates stacked on one another.5. The cell culture apparatus according to claim 1 , further comprising an inlet and an outlet claim 1 , wherein each of the plurality of media flow channels is in fluid communication with the inlet and the outlet.6. The cell culture apparatus according to claim 5 , further comprising an inlet manifold that defines the inlet and defines a plurality of inlet flow channel apertures claim 5 , wherein each of the plurality of ...

MULTILAYERED CELL CULTURE APPARATUS

A multilayered cell culture apparatus for the culturing of cells is disclosed. The cell culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between the cell culture chambers and the external environment. The flask body also includes an aperture that will allow access to the cell growth chambers by means of a needle or cannula. The size of the apparatus, and location of an optional neck and cap section, allows for its manipulation by standard automated assay equipment, further making the apparatus ideal for high throughput applications.

MULTILAYERED CELL CULTURE APPARATUS

A multilayered cell culture apparatus for the culturing of cells is disclosed. The cell culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between the cell culture chambers and the external environment. The flask body also includes an aperture that will allow access to the cell growth chambers by means of a needle or cannula. The size of the apparatus, and location of an optional neck and cap section, allows for its manipulation by standard automated assay equipment, further making the apparatus ideal for high throughput applications. 1. (canceled)2. A method of culturing cells in a gas permeable multi-shelf cell culture apparatus , the method comprising:adding cells and media into a gas permeable multi-shelf apparatus comprising two or more culture compartments, each compartment including a shelf comprised of gas permeable, liquid impermeable material for cells to reside upon, each shelf connected to an opposing surface, a fluid pathway shared by said culture compartments, and each said shelf is in contact with a gas space, whereby said apparatus is incubated in the presence of ambient gas suitable for cell culture, oriented in a position such that said culture compartments are located one above the other, each said shelf is in a horizontal position with said gas space located below it, cells reside upon at least a portion of each said shelf, said culture compartments include media in contact with said shelf and said opposing surface, and ambient gas resides within each said gas space and is in contact with each shelf.3. The method of claim 2 , wherein a culture compartment support is in contact with a portion of each said shelf.4. The method of claim 3 , wherein said culture compartment support includes projections that make contact ...

DEVICES AND METHODS FOR GENERATION AND CULTURE OF 3D CELL AGGREGATES

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. 1. A cell culture substrate comprising an array of microwells , each microwell comprising an opening into the microwell defined by a top well edge , corrugated microwell sidewalls , and a rounded well-bottom , wherein the corrugated microwell sidewalls are aligned to produce microwells in the gaps between the corrugated sidewalls.27-. (canceled)8. The cell culture substrate of wherein at least the rounded well-bottom comprises a non-adherent surface.9. The cell culture substrate of wherein at least the rounded well-bottom comprises gas permeable material.1011-. (canceled)12. The cell culture substrate of wherein the cell culture substrate comprises at least a portion of a cell culture container.13. The cell culture substrate of wherein the cell culture container is selected from the group consisting of a multiwell plate claim 12 , a dish claim 12 , a flask claim 12 , a tube claim 12 , a multi-layer flask claim 12 , a soft-sided flask and a bag.14. The cell culture substrate of claim 1 , wherein microwells are configured to allow fluid communication between at least one of said microwells and a single liquid reservoir.1521-. (canceled)22. A method of culturing spheroids comprising: charging the cell culture container of with culture media and spheroid forming cells.23. The cell culture substrate of claim 1 , wherein the microwell sidewalls are corrugated from the opening of the microwell to the bottom of the microwell.24. The cell culture substrate of claim 1 , wherein a lower portion of each microwell extends below the corrugated sidewalls and forms a rounded well-bottom.25. The cell culture substrate of claim 1 , wherein the microwell sidewalls are corrugated with a planar periodicity having regions where the sidewalls are far apart and then come closer together.26. The cell culture ...

DEVICES AND METHODS FOR GENERATION AND CULTURE OF 3D CELL AGGREGATES

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. 1. A cell culture substrate comprising an array of microwells , each microwell comprising an opening into the microwell defined by a rounded top well edge , at least one microwell side-wall , and a rounded well-bottom.2. The cell culture substrate of wherein each microwell claim 1 , in cross-section claim 1 , has a sinusoidal well shape.3. The cell culture substrate of further comprising one or more ridges claim 1 , wherein the ridge is round claim 1 , angular claim 1 , needle-shaped or hexagonal.4. The cell culture substrate of further comprising one or more fissures claim 1 , wherein the fissure is round claim 1 , angular claim 1 , needle-shaped or hexagonal.5. The cell culture substrate of wherein the rounded well bottom has a thickness of between 10 and 100 μm.6. The cell culture substrate of wherein walls of the microwells are relatively thicker proximate to the opening into the microwell and relatively thinner at the bottom of the microwell.7. The cell culture substrate of wherein the substrate comprises 2-10000 of said microwells per square centimeter of surface of said cell culture substrate.8. The cell culture substrate of wherein at least the rounded well-bottom comprises a non-adherent surface.9. The cell culture substrate of wherein at least the rounded well-bottom comprises gas permeable material.10. The cell culture substrate of wherein the microwell sidewalls are discontinuous.11. The cell culture substrate of wherein the microwell sidewalls are corrugated.12. The cell culture substrate of wherein the cell culture substrate comprises at least a portion of a cell culture container.13. The cell culture substrate of wherein the cell culture container is selected from the group consisting of a multiwell plate claim 12 , a dish claim 12 , a flask claim 12 , a tube claim 12 ...

ULTRASONIC APPARATUS AND METHOD FOR CELL RELEASE

An apparatus () for cell release from a cell culture article (), including: an ultrasonic source (); a stage comprising a base () and a raised portion () that defines a cell culture article confinement area; and a mechanism for relative scan motion between the ultrasonic source and the cell culture article confined to the stage. Also disclosed is a method for cell release and harvesting from a cell culture article (), including: securing a cell culture article in the disclosed cell release apparatus; and accomplishing relative motion scanning between the energized ultrasonic source and the cell culture article for a time, as defined herein. 1. An apparatus for cell release from a surface of a cell culture article , comprising:an ultrasonic source;a stage comprising a base and a raised portion that defines a cell culture article confinement area; anda mechanism for relative scan motion between the ultrasonic source and the cell culture article confined to the stage.2. The apparatus of wherein the mechanism for providing relative scan motion between the ultrasonic source and a cell culture article confined to the stage comprises: a race and a motive source claim 1 , wherein the race traverses at least a portion of the long dimension of the cell culture article confined to the stage.3. The apparatus of wherein the relative scan motion between the ultrasonic source and a cell culture article confined to the stage is linear and continuous.4. The apparatus of wherein the relative scan motion between the ultrasonic source and a cell culture article confined to the stage is from about 0.1 to about 3 inches per second claim 1 , and the ultrasonic source generates ultrasonic waves at a frequency from about 19 to about 21 kHz.5. The apparatus of wherein the ultrasonic source is an ultrasonic horn emitting at from about 10 to about 80 kHz.6. The apparatus of wherein the ultrasonic source is an ultrasonic horn emitting at from about 15 to 25 kHz.7. The apparatus of wherein the ...

MULTILAYERED CELL CULTURE APPARATUS

A multilayered cell culture apparatus for the culturing of cells is disclosed. The cell culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between the cell culture chambers and the external environment. The flask body also includes an aperture that will allow access to the cell growth chambers by means of a needle or cannula. The size of the apparatus, and location of an optional neck and cap section, allows for its manipulation by standard automated assay equipment, further making the apparatus ideal for high throughput applications. 121-. (canceled)22. A static cell growth apparatus comprising:only one compartment; andsaid compartment is liquid impermeable, capable of holding medium, and includes more than one gas permeable shelf for cells to reside upon; and each shelf has a culture space between it and an opposing surface; anda manifold connects each culture space, and the culture spaces reside one above the other when the shelves are in a horizontal position; and the outside surface of each shelf is in contact with projections that are spaced apart to create a space for ambient gas to contact each shelf.23. The apparatus of claim 22 , whereby said compartment is capable of being completely filled with media for optimal cell-nutrient exchange.24. The apparatus of claim 22 , wherein said opposing surface is gas permeable claim 22 , liquid impermeable.25. The apparatus of claim 22 , whereby a uniformity of conditions for cellular growth includes a determined media volume per unit surface area.26. The apparatus of claim 22 , wherein said compartment has a substantially rectangular footprint and a substantially uniform height.27. A static cell growth apparatus comprising:a liquid impermeable housing, the inside of which is able to contain ...

MULTILAYERED CELL CULTURE APPARATUS

A multilayered cell culture apparatus for the culturing of cells is disclosed. The cell culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between the cell culture chambers and the external environment. The flask body also includes an aperture that will allow access to the cell growth chambers by means of a needle or cannula. The size of the apparatus, and location of an optional neck and cap section, allows for its manipulation by standard automated assay equipment, further making the apparatus ideal for high throughput applications. 1. (canceled)2. A cell culture vessel comprising:a top plate;a bottom tray opposed to the top plate;a manifold; anda plurality of vertically spaced and aligned cell growth chambers that are between the top plate and the bottom tray, each cell growth chamber defined by a gas permeable, liquid impermeable membrane bottom surface and a top surface, said top and bottom surfaces attached to a pair of side walls, and end walls, wherein the top surface of a first cell growth chamber and the gas permeable, liquid impermeable membrane bottom surface of a second cell growth chamber adjacent the first cell growth chamber define a tracheal space, said tracheal space being in gaseous communication with the external environment through openings between the side walls of adjacent cell growth chambers, and wherein one of the end walls comprises at least two openings that allow fluid communication between the cell growth chambers and the manifold.3. The cell culture vessel of claim 2 , wherein the manifold comprises an aperture with a necked opening.4. The cell culture vessel of claim 3 , wherein the aperture is covered by a cap.5. The cell culture vessel of further comprising:one or more internal supports extending from the ...

Optical cell culture monitoring and analyte measuring system

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.

SPHEROID CELL CULTURE ARTICLE AND METHODS THEREOF

A spheroid cell culture article including: 119-. (canceled)20. A cell culture article comprising: an opaque side wall;', 'a top aperture; and', 'a gas-permeable, liquid impermeable bottom comprising at least one concave surface, wherein at least a portion of the bottom is transparent, wherein at least a portion of the bottom comprises a low-adhesion or no-adhesion material in or on the at least one concave surface, and wherein the gas permeable, liquid impermeable bottom comprises polystyrene., 'a chamber comprising21. The article of further comprising a liner having a porous membrane situated within a portion of the chamber to divide the chamber into an upper chamber and a lower chamber.22. The article of further comprising a chamber annex for receiving a pipette tip for aspiration claim 20 , the chamber annex comprises a surface adjacent to and in fluid communication with the chamber claim 20 , the chamber annex having a second bottom spaced away and at an elevation above the gas-permeable claim 20 , transparent bottom claim 20 , wherein the second bottom deflects fluid dispensed from a pipette away from the transparent bottom.23. The article of further comprising a liner having a porous membrane situated within a portion of the chamber to form an upper chamber and a lower chamber the porous membrane providing separation of a second cellular material in the upper chamber claim 22 , from a first cellular material in the lower chamber.24. The article of wherein the article comprises from 1 to about 2 claim 20 ,000 of said chambers claim 20 , wherein each chamber is physically separated from any other chamber.25. The article of wherein the at least one concave surface comprises a plurality of concave surfaces within the same chamber.26. The article of wherein the at least one concave surface comprises a hemi-spherical surface claim 20 , a conical surface having a taper of 30 to about 60 degrees from the opaque side walls to the bottom claim 20 , or a combination ...

CELL CULTURE MEDIA EXTENDING MATERIALS AND METHODS

This disclosure provides a cell culture media extending material capable of releasing nutrients into the cell culture environment slowly overtime. In embodiments, this material is a part of a cell culture vessel. In embodiments, the material is a coating or a film on a surface of a cell culture material. In additional embodiments, the material is a surface upon which cells are cultured, such as a cell culture vessel or a microcarrier. 120-. (canceled)21. A cell culture vessel comprising:a surface; and a first layer disposed between the surface and a second layer, the first layer comprising a hygroscopic polymer and at least one sequestered nutrient; the second layer comprising the hygroscopic polymer without the at least one sequestered nutrient, and wherein the hygroscopic polymer comprises poly(ethylene-co-vinyl acetate) (EVA);', 'wherein the EVA has an ability to attract and hold water molecules from the surrounding environment; and', 'wherein the hygroscopic polymers swell to less than 50% water by weight in an aqueous environment., 'a cell culture media extending material disposed on the surface, wherein the cell culture media extending material comprises22. The cell culture vessel of claim 21 , wherein the cell culture media extending material comprises at least one coating.23. The cell culture vessel of claim 21 , wherein the cell culture media extending material comprises a film.24. The cell culture vessel of claim 21 , wherein the vessel comprises at least one cell culture compartment claim 21 , each cell culture compartment comprising a bed claim 21 , a ceiling and at least one wall.25. The cell culture vessel of claim 24 , wherein at least two of the bed claim 24 , the ceiling and the at least one wall comprise the cell culture media extending material.26. The cell culture vessel of claim 21 , wherein the hygroscopic polymer comprises ethyl cellulose materials claim 21 , poly(ethyl cellulose) claim 21 , PDMS claim 21 , or poly(ether/amide) copolymers.27. ...

SENSING VESSELS FOR CELL CULTURES

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. 1. A sensing vessel comprising:a cell culture vessel; andone or more sensors disposed on or in the cell culture vessel, each of the one or more sensors capable of sensing a particular parameter or characteristic of the of a cell culture disposed within the cell culture vessel.2. The sensing vessel of claim 1 , the one or more sensors being active sensors having means for transmitting readings from the sensors.3. The sensing vessel of claim 2 , the one or more sensors further comprising a proximity tag for transmitting readings from the sensors.4. The sensing vessel of claim 2 , the one or more sensors further comprising a wireless transmitter for transmitting readings from the sensors.5. The sensing vessel of claim 1 , the one or more sensors being passive sensors.6. A sensing plate comprising:a surface on which one or more sensing vessels having one or more sensors may be placed;one or more cameras for imaging cell cultures disposed within the one or more sensing vessels or for imaging passive sensors located on or in the sensing vessels; anda wired or wireless connection for transmitting images collected from the one or more cameras.7. The sensing ...

Cell culture insert

A cell culture insert for use in culturing cells to promote the formation of spheroids and methods of using these spheroid-promoting cell culture inserts. The cell culture insert includes a porous membrane and one or more sidewalls that are non-adherent to cells and cause the cells in the insert to associate with each other and form spheroids.

Remote monitoring system for cell culture

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.

Cell storage and transportation medium and system and method of transport of cell aggregates

The present disclosure relates to agarose and methylcellulose storage and transport mediums, systems for cell storage and transport, and cell storage and transport methods. The instantly-disclosed agarose and methylcellulose storage and transport medium is ideally suited for 3D spheroid cell culture storage and transport. In particular aspects, the storage and transport mediums, systems, and methods are used in combination with or performed in labware that combine 3D spheroid culture with a gas permeable, micro-patterned design that allows for protection and prolonged maintenance of spheroid cell (e.g. hepatocytes) viability and functionality during storage and transport.

Radial flow fixed bed bioreactor and methods of using the same

A modular cell culture system includes a standalone cell culture subunit with an interior cavity to house a cell culture substrate in a cell culture space, a radial flow manifold below the cell culture space, a fluid inlet to supply fluid to a center of the manifold, 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 manifold, 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. The manifold can supply fluid at a uniform rate across a width of the cell culture space, and the alignment feature aligns with an alignment feature of another standalone cell culture subunit, such that multiple standalone cell culture subunits are stackable.

Gravity flow cell culture devices, systems, and methods of use thereof

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.

21-acyloxy-3 & -hydroxy pregnanes

Optical cell culture monitoring and analyte measuring system

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 (105, 205, 305, 405, 505, 605, 705, 805), 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.

Bioreactor system

A cell culture system is provided that includes at least one multi-layered vessel for culturing cells, and a cabinet comprising an interior cavity enclosed by one or more sidewalls. The cabinet being configured to house the multi-layered vessel within the interior cavity. The multi-layered vessel includes a cell culture space within the multi-layered vessel. The cabinet can change an orientation of the multi-layered vessel from an upright orientation to a tilted orientation.

Cell separation device and method for using same

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.

Cell separation device and method for using same

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.

System and method for analyzing extracellular vesicles with an optical biosensor

Various implementations of a system and method for analyzing extracellular vesicles (EVs) are disclosed having a number of innovative features. In one implementation, a method for analyzing EVs includes binding EVs to an optical waveguide biosensor and phenotyping the bound EVs. Phenotyping can include binding a labeled ligand to the EVs and/or rupturing the EVs and analyzing their cargo. In another implementation, a system for analyzing EVs includes EVs bound to an optical waveguide biosensor and a labeled ligand bound to the EVs. In another implementation, a kit for analyzing EVs includes a micro plate having wells containing optical waveguide biosensors functionalized with a binding agent configured to bind to EVs and at least one of: (a) labeled ligands configured to bind to the extracellular vesicles or (b) a reagent configured to rupture the extracellular vesicles.

Cell culture media extending materials and methods

This disclosure provides a cell culture media extending material capable of releasing nutrients into the cell culture environment slowly over time. In embodiments, this material is a part of a cell culture vessel. In embodiments, the material is a coating or a film on a surface of a cell culture material. In additional embodiments, the material is a surface upon which cells are cultured, such as a cell culture vessel or a microcarrier.

Cryogenic vial assemblies

Vial assemblies comprise a tubular body and a cap, the cap including a first portion configured to abut a lip of an open end of the tubular body, a threaded portion configured to couple to threading on an internal surface of the tubular body, and a second portion protruding from the threaded portion and extending into a cavity of the tubular body. Methods for storing and removing frozen samples from such vial assemblies are also described.

System and method for analyzing extracellular vesicles with an optical biosensor

Various implementations of a system and method for analyzing extracellular vesicles (EVs) are disclosed having a number of innovative features. In one implementation, a method for analyzing EVs includes binding EVs to an optical waveguide biosensor and phenotyping the bound EVs. Phenotyping can include binding a labeled ligand to the EVs and/or rupturing the EVs and analyzing their cargo. In another implementation, a system for analyzing EVs includes EVs bound to an optical waveguide biosensor and a labeled ligand bound to the EVs. In another implementation, a kit for analyzing EVs includes a micro plate having wells containing optical waveguide biosensors functionalized with a binding agent configured to bind to EVs and at least one of: (a) labeled ligands configured to bind to the extracellular vesicles or (b) a reagent configured to rupture the extracellular vesicles.

Pipette structure and methods utilizing same

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.

Cell culture systems

An integrated cell culture system may include one or more cell culture vessels, manipulation apparatus, pumping apparatus, cell release apparatus, monitoring apparatus, and a control apparatus. The control apparatus may be used to monitor and control the system to facilitate effective cell culturing. The cell release apparatus may be used to release a plurality of cells adhered to the cell culture surfaces of the cell culture vessels.

Bioreactor system

A cell culture system is provided that includes at least one multi-layered vessel for culturing cells, and a cabinet comprising an interior cavity enclosed by one or more sidewalls. The cabinet being configured to house the multi-layered vessel within the interior cavity. The multi-layered vessel includes a cell culture space within the multi-layered vessel. The cabinet can change an orientation of the multi-layered vessel from an upright orientation to a tilted orientation.

Urządzenia do kriokonserwacji

Cell culture apparatuses with manifolds including column structures

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.

Culture vessels containing 3d cell culture substrates with diffusion structures

A cell culture device comprises a multi-well cell culture plate comprising a plurality of wells, each well comprising a top, a bottom, and a sidewall disposed between the top and the bottom and having an interior surface comprising an ultra-low attachment surface. A plurality of scaffolds are disposed within wells of the multi-well cell culture plate, each scaffold comprising a cell-adherent surface. In some embodiments, the scaffold comprises a fiber scaffold. In some embodiments, the scaffold comprises an artificial vascular scaffold. In some embodiments, cell culture devices comprise a plurality of hydrogel scaffolds disposed in a multi-well cell culture plate, the plurality of hydrogel scaffolds comprising hydrogel fibers of differing lengths, wherein opposite ends of a hydrogel fiber are disposed in different wells within the multi-well cell culture plate to create interconnected wells.

Cell culture media extending materials and methods

This disclosure provides a cell culture media extending material capable of releasing nutrients into the cell culture environment slowly overtime. In embodiments, this material is a part of a cell culture vessel. In embodiments, the material is a coating or a film on a surface of a cell culture material. In additional embodiments, the material is a surface upon which cells are cultured, such as a cell culture vessel or a microcarrier.

Cell culture vessel

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.

Microcavity dishes with sidewall including liquid medium delivery surface

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.

Rolled adherent cell culture substrates for uniform flow in fixed bed reactors

A cell culture matrix for culturing cells in a fixed bed reactor is provided. The cell culture matrix includes a first substrate material with an ordered and regular array of openings passing through the layer, the openings being separated by the substrate material having a physical structure that is substantially regular and uniform and that is configured for growing cell thereon. The physical structure and array of openings are configured such that, when the first substrate material is rolled into a rolled substrate matrix comprising rolled layers of the first substrate material, a variation in packing density of the rolled layers is less than about 20x, less than about 10x, less than about 5x, or less than about 2x throughout the rolled substrate matrix.

Materiały i sposoby do przedłużania pożywki do hodowli komórkowej

Cell separation device and method for using same

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.

Multilayered cell culture apparatus

A multilayered cell culture apparatus for the culturing of cells is disclosed. The cell culture apparatus is defined as an integral structure having a plurality of cell culture chambers in combination with tracheal space(s). The body of the apparatus has imparted therein gas permeable membranes in combination with tracheal spaces that will allow the free flow of gases between the cell culture chambers and the external environment. The flask body also includes an aperture that will allow access to the cell growth chambers by means of a needle or cannula. The size of the apparatus, and location of an optional neck and cap section, allows for its manipulation by standard automated assay equipment, further making the apparatus ideal for high throughput applications.

Vessels and methods for cryopreservation

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, as defined herein. 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 by the methods and apparatus disclosed herein.

Cell culture apparatuses with manifolds including column structures

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.

Clamp assemblies for clamping tubing and controlling fluid flow

A clamp assembly for clamping flexible tubing includes a base member including a pair of sidewalls and a bottom that extends between the sidewalls. At least one of the sidewalls includes a clamp latching feature that extends inward from an inner surface of the at least one of the sidewalls. A locking lever is located between the sidewalls and is pivotally connected to the sidewalls at a pivot location such that the locking lever pivots relative to the base member. The locking lever includes a lever catch feature configured to cooperatively mate with the clamp latching feature.

Cell separation device and method for using same

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.

Cell culture vessel

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.

Cell culture autofill system

A cell culture system for culturing cells is provided. The cell culture system including a cell culture vessel with a cell culture chamber for culturing cells, an inlet through which liquid can flow for filling the cell culture vessel, and an outlet through which fluid can exit the cell culture vessel. The system also includes at least one fill sensor arranged to detect liquid within the cell culture vessel reaching a fill level at a predetermined position of the cell culture vessel during filling of the cell culture vessel, where the at least one fill sensor can generate a detection signal when liquid within the cell culture vessel reaches the fill level. Also included is an actuator to change an orientation of the cell culture vessel in response to the detection signal.

Cold-formed glass articles with overmolded carriers and methods of fabricating the same

A glass article comprises a glass substrate, a decorative ink layer disposed on a major surface of the glass substrate, and a carrier that is injection molded onto and bonded to the decorative ink layer. The carrier comprises a main body comprising a surface bonded to the ink layer without an adhesive layer being disposed between the decorative ink layer and the surface and a plurality of connection elements extending from the main body or incorporated into the main body. A support structure comprising a plurality of retention elements that are mechanically engaged with the plurality of connection elements to retain the glass substrate and the carrier on the support structure in a curved configuration.

Cell Visualization System for Multi-Layer Cell Culture Device

The present invention relates generally to a multi-layer system for containing cells in culture, and a system for visualizing cells cultured in the multi-layered system. More specifically, the present invention relates to a multi-layer cell culture device having a specialized bottom plate and a microscope adaptor which can accommodate a microscope to allow microscopic visualization of cells cultured in the device.

Bioreactor system

A cell culture system is provided that includes at least one multi-layered vessel for culturing cells, and a cabinet comprising an interior cavity enclosed by one or more sidewalls. The cabinet being configured to house the multi-layered vessel within the interior cavity. The multi-layered vessel includes a cell culture space within the multi-layered vessel. The cabinet can change an orientation of the multi-layered vessel from an upright orientation to a tilted orientation.

Konstrukcja pipety i sposoby jej zastosowania

System and method for imaging and illumination for cell confluence measurement

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.

Cell culture insert

A cell culture insert for use in culturing cells to promote the formation of spheroids and methods of using these spheroid-promoting cell culture inserts. The cell culture insert includes a porous membrane and one or more sidewalls that are non-adherent to cells and cause the cells in the insert to associate with each other and form spheroids.

Fluidic devices including microplates with interconnected wells

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.

Cryopreservation devices

Vial assemblies comprising a tubular body and a flexible bottom or flexible liner are described herein, wherein the flexible bottom or liner is configured to compress at least partially upon the application of force. Methods for storing and removing frozen samples from such vial assemblies are also described herein.

Cell culture autofill system

A cell culture system for culturing cells is provided. The cell culture system including a cell culture vessel with a cell culture chamber for culturing cells, an inlet through which liquid can flow for filling the cell culture vessel, and an outlet through which fluid can exit the cell culture vessel. The system also includes at least one fill sensor arranged to detect liquid within the cell culture vessel reaching a fill level at a predetermined position of the cell culture vessel during filling of the cell culture vessel, where the at least one fill sensor can generate a detection signal when liquid within the cell culture vessel reaches the fill level. Also included is an actuator to change an orientation of the cell culture vessel in response to the detection signal.

Multi-position supports for cell culture apparatuses

A multi-position support for a multi-layer cell culture apparatus includes a primary base that rests against a support member in an upright configuration. A support surface is offset vertically from the primary base in the upright configuration. The support surface supports the multi-layer cell culture apparatus with the multi-layer cell culture apparatus located thereon. An intermediate surface extends between the primary base and the support surface. The intermediate surface meets the primary base at an interface that extends at an oblique angle to sides of the primary base. The multi-position support has a tilted configuration where the multi-position support is rotated about the interface such that the support surface is closer to the support member than in the upright configuration with the support surface supporting the multi-layer cell culture apparatus thereon.

Microcavity plate

Microcavity plates ( 10 ) comprise a microcavity substrate and a base ( 303 ) comprising a bottom grid comprising a plurality of grid segments arranged in ordered rows and columns to form a plurality of openings, and an open well ( 307 ) comprising a plurality of sidewalls ( 309 ) extending vertically from a perimeter of the bottom grid. The microcavity substrate comprises a plurality of microcavities ( 315 ) arranged in ordered rows and columns that align with the plurality of openings in the bottom grid, each microcavity comprising a cavity disposed within an opening of the bottom grid. The microcavity plate may further comprise an upper grid ( 405 ) for placement on top of the bottom grid delineating the ordered rows and columns of the base.

Culture vessels containing 3d cell culture substrates with diffusion structures

A cell culture device comprises a multi-well cell culture plate comprising a plurality of wells, each well comprising a top, a bottom, and a sidewall disposed between the top and the bottom and having an interior surface comprising an ultra-low attachment surface. A plurality of scaffolds are disposed within wells of the multi-well cell culture plate, each scaffold comprising a cell-adherent surface. In some embodiments, the scaffold comprises a fiber scaffold. In some embodiments, the scaffold comprises an artificial vascular scaffold. In some embodiments, cell culture devices comprise a plurality of hydrogel scaffolds disposed in a multi-well cell culture plate, the plurality of hydrogel scaffolds comprising hydrogel fibers of differing lengths, wherein opposite ends of a hydrogel fiber are disposed in different wells within the multi-well cell culture plate to create interconnected wells.

Composition and method for cell culture sustained release

An ex vivo cell culture sustained release composition, including: a mixture comprising: a sustenant; and a non-biodegradable binder; and a non-biodegradable and water insoluble encapsulant coat that encapsulates the mixture, as defined herein. Also disclosed is a method for sustainably providing a sustenant to a cell culture in aqueous media, including contacting a cell culture with the sustained release composition.

Cell culture vessels with stabilizer devices

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.

Cell culture vessels with stabilizer devices

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.

Multi-position supports for cell culture apparatuses

A multi-position support for a multi-layer cell culture apparatus includes a primary base that rests against a support member in an upright configuration. A support surface is offset vertically from the primary base in the upright configuration. The support surface supports the multi-layer cell culture apparatus with the multi-layer cell culture apparatus located thereon. An intermediate surface extends between the primary base and the support surface. The intermediate surface meets the primary base at an interface that extends at an oblique angle to sides of the primary base. The multi-position support has a tilted configuration where the multi-position support is rotated about the interface such that the support surface is closer to the support member than in the upright configuration with the support surface supporting the multi-layer cell culture apparatus thereon.