34 results about "Perfusion bioreactor" patented technology

The present invention relates to a construct for perfusion bioreactor cell culture. The construct comprises at least one flexible polymer sheet for rolling or folding in use, and a plurality of channels for transport of cell culture medium to cells and / or hosting cells in use. The present invention further relates to methods of forming a construct for perfusion bioreactor cell culture, a system for perfusion bioreactor cell culture, a method of culturing cells, and a comestible product obtainable by the system or method.

The present invention provides a continuous upstream manufacturing process for the production of bispecific antibody products, which comprise at least two binding domains. The process comprises at least the steps of (i) providing in a perfusion bioreactor at least one mammalian cell culture, which is capable of expressing the bispecific antibody product, (ii) growing the mammalian cell culture at a first perfusion rate until a set point viable cell density is reached, and (iii) maintaining perfusion culture at a second perfusion rate, wherein the bispecific antibody product concentration in the bioreactor is kept below a threshold value. The bispecific antibody product is then subject to subsequent downstream processing. Moreover, the invention provides a bispecific antibody product produced by the continuous upstream manufacturing process.

Provided herein are methods of selecting an optimal fixed orientation of a dissolved oxygen (DO) probe in a perfusion bioreactor and culturing a mammalian cell in a perfusion bioreactor having the DO probe positioned at the selected fixed orientation.

A process and system for producing an inoculum for downstream cell production is disclosed. The inoculum is produced in a perfusion bioreactor in which the nutrient media feed is increased as the biomass concentration increases within the bioreactor. A biomass sensor can be used to periodically or continuously monitor biomass concentration. This information can be fed to a controller for automatically increasing nutrient media feed rates in a manner that is directly proportional to producing an inoculum with an increase cell density. The process and system can also include an automated subsystem for maintaining constant volume levels within the perfusion bioreactor during the process.

In some embodiments the present invention provides perfusion bioreactors and cell culture scaffolds suitable for the preparation of tissue grafts, such as bone tissue grafts. In some embodiments, the perfusion bioreactors comprise a graft chamber and / or a graft chamber insert configured to hold a tissue graft having a certain shape and / or certain dimensions, and / or to allow culture of such tissue grafts under press-fit direct perfusion conditions. In some embodiments, the perfusion bioreactors comprise an equilibration chamber.

A method of culturing muscle cells 16 suitable for an edible product comprising: a perfusion module (Fig.2, 2) comprising porous hollow fibres 12; seeding muscle cells 16 onto the fibers 12; maintaini

A cell culture system is provided comprising a cell culture vessel enclosing an interior configured to culture cells in a liquid cell culture medium and a culture medium conditioning system. The culture medium adjusting system comprises a culture medium adjusting container and an oxygenation tower, and the culture medium adjusting container is used for adjusting a liquid culture medium. The oxygenation tower includes a housing containing an interior space, an oxygen deficient medium inlet fluidly connected to the interior space, an excess gas vent fluidly connected to the interior space, and a lower opening fluidly connected to the interior space. The lower opening is disposed at a lower end of the oxygenation tower and in a fluid path between the interior space and the medium conditioning container. The oxygenation tower is designed to mix the oxygen deficient medium with a gas comprising oxygen in a countercurrent manner and thus achieve better dissolved oxygen saturation in the medium.

The present invention provides an apparatus and method for in-well high throughput 3D cell culture, the 3D orifice plate plug-in perfusion bioreactor comprising: an inlet in fluid communication with a first chamber and an outlet in fluid communication with a second chamber; and a plurality of hairy structures extending downwardly from the lower surface of the bioreactor, each hairy structure comprising a supply channel fluidly communicating the first chamber with the hairy structure tip, and a return channel fluidly communicating the second chamber with the hairy structure tip, wherein the supply channel and the return channel are in fluid communication with each other at the tip of the hairy structure. According to the invention, the real biological environment of cells in vivo can be better simulated, which is crucial for realizing accurate drug screening and does not need to sacrifice the high throughput advantage of traditional 2D culture plate screening.

The present disclosure describes a modular bioreactor system. The system includes a housing; a plurality of interchangeable bioreactor modules, each module configured to be received within the housing, the plurality of interchangeable bioreactor modules including a uniaxial bioreactor module, a biaxial bioreactor module, a pulsatile bioreactor module, a fill-void bioreactor module, and / or a perfusion bioreactor module; a media exchanger subsystem configured to be connected to one of the plurality of interchangeable bioreactor module received within the housing; a sensor monitoring module configured to be connected to the media exchanger subsystem and the one of the plurality of interchangeable bioreactor modules received within the housing, with the sensor monitoring module optionally configured to be received within the housing; and a controller operatively associated with the housing, the plurality of interchangeable bioreactor modules, the sensor monitoring module, and the media exchanger subsystem.

The present invention provides a continuous upstream manufacturing process for the production of bispecific antibody products, which comprise at least two binding domains. The process comprises at least the steps of (i) providing in a perfusion bioreactor at least one mammalian cell culture, which is capable of expressing the bispecific antibody product, (ii) growing the mammalian cell culture at a first perfusion rate until a set point viable cell density is reached, and (iii) maintaining perfusion culture at a second perfusion rate, wherein the bispecific antibody product concentration in the bioreactor is kept below a threshold value. The bispecific antibody product is then subject to subsequent downstream processing. Moreover, the invention provides a bispecific antibody product produced by the continuous upstream manufacturing process.

A process and system for producing an inoculum for downstream cell production is disclosed. The inoculum is produced in a perfusion bioreactor in which the nutrient media feed is increased as the biomass concentration increases within the bioreactor. A biomass sensor can be used to periodically or continuously monitor biomass concentration. This information can be fed to a controller for automatically increasing nutrient media feed rates in a manner that is directly proportional to producing an inoculum with an increase cell density. The process and system can also include an automated subsystem for maintaining constant volume levels within the perfusion bioreactor during the process.

The present disclosure describes a modular bioreactor system. The system includes a housing; a plurality of interchangeable bioreactor modules, each module configured to be received within the housing, the plurality of interchangeable bioreactor modules including a uniaxial bioreactor module, a biaxial bioreactor module, a pulsatile bioreactor module, a fill-void bioreactor module, and / or a perfusion bioreactor module; a media exchanger subsystem configured to be connected to one of the plurality of interchangeable bioreactor module received within the housing; a sensor monitoring module configured to be connected to the media exchanger subsystem and the one of the plurality of interchangeable bioreactor modules received within the housing, with the sensor monitoring module optionally configured to be received within the housing; and a controller operatively associated with the housing, the plurality of interchangeable bioreactor modules, the sensor monitoring module, and the media exchanger subsystem.

The present invention provides a perfusion bioreactor, which at least includes: a culture chamber, in which a biological scaffold is arranged; a circulation pump, which is connected to the culture chamber; a supply chamber, which is respectively connected to the culture chamber and the circulation pump, and the supply chamber is used to hold a culture medium, and the supply chamber is connected to the outside world; a catheter, and the catheter includes a first catheter, a second catheter, a third catheter and a fourth catheter; when the supply chamber contains a culture medium, one end of the second catheter in the supply chamber is located below the liquid surface of the culture medium, and one end of the fourth catheter in the supply chamber is located above the liquid surface of the culture medium. The perfusion bioreactor of the present invention can simulate the in vivo microenvironment as much as possible during the in vitro construction of organs and tissues, ensure the supply of nutrients to cells and the discharge of excreta, the reactor is a sterile environment, stable, cell growth and vitality are vigorous, and the culture cycle and cost are reduced.

Provided herein are systems and methods for enhancing recovery of products using constant pressure and / or low flow rate tangential flow filtration.

A reactor for use with a media and a standard microtiter well plate having a top surface and a well with a side wall, a bottom portion, and a transparent bottom, and a target substance at the bottom of the well. The reactor has a support layer with a lower surface that extends substantially parallel to the top surface of the well plate. A perfusion plug extends outward from the lower surface of said support layer. The perfusion plug has a distal end that is at a distance from the bottom of the well to form a bottom flow channel at the bottom portion of the well. An inlet channel extends through the support layer and through or around the perfusion plug. The inlet channel is in fluid communication with the bottom flow channel. An outlet channel extends through said support layer and through or around the perfusion plug, the outlet channel in fluid communication with the bottom flow channel. The media can travel through the inlet channel to the bottom flow channel to contact the target substance, then through the outlet channel to exit the reactor.

To provide an improved process for producing an inoculum of a microorganism for later transfer to a larger production bioreactor.SOLUTION: A process for producing an inoculum for a subsequent cell culture production process comprises: introducing a cell culture into a perfusion bioreactor; feeding a nutrient medium at a flow rate to the perfusion bioreactor and withdrawing a fluid medium from the perfusion bioreactor; determining biomass concentrations over time within the perfusion bioreactor using a biomass sensor, the biomass sensor being in communication with a controller; and adjusting the nutrient medium flow rate into the perfusion bioreactor based on biomass concentrations sensed by the biomass sensor, the controller being configured to adjust the medium flow rate based on information received from the biomass sensor.SELECTED DRAWING: Figure 1

A method for preparing mammalian cells for a perfusion cell culture process that improves cell growth and productivity is provided. Also provided is a cell culture method that includes subjecting mammalian cells to one or more perfusion procedures, which includes generating a solid phase and a liquid phase with a continuous flow centrifuge and utilizing at least a portion of the solid phase to sustain, maintain, and / or initiate a new cell culture. Also provided are perfusion bioreactor systems and components thereof.

A bioreactor system for culturing cells is provided. The bioreactor system includes a vessel comprising an inlet, an outlet, and an internal cavity disposed between the inlet and the outlet and for perfusion of a cell culture medium therethrough. The system further includes a cell culture substrate disposed in the internal cavity in a fixed bed configuration, the surface of the cell culture substrate having a surface area for culturing cells thereon during operation of the bioreactor system. By adjusting the surface area of the cell culture substrate, the bioreactor system can be scaled up or down depending on the number of cells to be cultured.

The present application discloses a perfusion bioreactor system having an inner cavity and a scaffold with matching porosity to balance the flow of fluid through the bioreactor. The scaffold can be manufactured using additive manufacturing techniques or other manufacturing techniques to match the geometry of the defect (e.g., facial bone abnormalities). The inner cavity is manufactured in a similar manner and has a cavity that matches the shape of the scaffold to form a unified structure when assembled with the scaffold. By matching the shape of the scaffold and the inner cavity, free space within the internal volume of the bioreactor is eliminated. Stem cells can flow through the bioreactor and attach to the scaffold and then be cultured to grow a tissue graft.

The utility model belongs to the technical field of perfusion type bioreactors, and particularly relates to an adjustable throttling control device of a perfusion type bioreactor, which comprises a support frame, the support frame is provided with a reactor body through support ribs, the lower end of the reactor body is fixedly connected with a runner pipe, the lower end of the runner pipe is contacted with a throttling pipe, and the lower end of the throttling pipe is provided with a throttling valve. An inserting rod is fixedly connected to the inner wall of the second connecting disc of the throttling pipe and slidably connected with the first connecting disc of the runner pipe, a fixing rod is fixedly connected to the side face of the runner pipe, and the outer side of the fixing rod is slidably sleeved with a moving piece. The handle is pushed to drive the rotating shaft to rotate so as to drive the rotating disc to rotate, the rotating disc is positioned under the structures such as the positioning rod and the inserting hole, the rotating disc is stable after the position is adjusted, the opening and closing angle of the rotating disc is adjusted for use, and then the circulation amount of the throttle pipe is adjusted.

Provided herein is a perfusion bioreactor having a flow chamber including a flow chamber top, a flow chamber bottom, and an interior space defined between the flow chamber top and the flow chamber bottom. Along the length of the flow chamber, the interior space includes an inlet portion, an outlet portion, and a central portion arranged therebetween. A sealing member is arranged between the flow chamber top and the flow chamber bottom. Further, the inlet portion includes at least one funnel element having a diameter in the transverse direction that increases over a respective length of the inlet portion in the longitudinal direction. A method for culturing cells is also provided herein.

A process and system for producing inoculum for downstream cell production is disclosed. The inoculum is produced in a perfusion bioreactor in which nutrient media feed is increased as biomass concentration within the bioreactor increases. A biomass sensor can be used to monitor biomass concentration periodically or continuously. This information can be supplied to a controller for automatically increasing the nutrient media feed rate in direct proportion to the production of inoculum with increasing cell density. The process and system can also include an automated subsystem for maintaining a constant volume level within the perfusion bioreactor during the process.

The disclosure provides a filtration system for a cell culture apparatus and a method of cell culture. The filtration system comprises a bioreactor vessel and two or more alternating tangential flow (ATF) filters connected in parallel. A failure in either filter is detected by an in-line sensor, and an automated response system functions to sequester the malfunctioning filter by stopping the flow of liquid media through the filter. Media flow through the remaining operable filters can be increased so that the rate of perfusion through the bioreactor remains relatively unchanged. Such a system may prevent issues that arise from ATF filter failures in conventional perfusion bioreactors, thereby improving the long-term viability of cell cultures.

The present disclosure relates to a bioreactor assembly having a housing defining an interior chamber; a lid assembly removably coupled to the housing and enclosing the interior chamber; and a gimbal assembly disposable within the interior chamber. The gimbal assembly includes a cradle configured to hold an organ or organ scaffold and an arm assembly configured to move the cradle between a plurality of positions. The bioreactor assembly also includes an ultrasound imaging unit positioned to capture volumetric and / or spatial data of the organ or organ scaffold.

The present disclosure is directed to method (100) for separating a biomolecule from a fluid (2), wherein the biomolecule is produced by biological cells in a perfusion bioreactor (3), the method comprising: forwarding (110) a product fluid comprising the biomolecule and biological cells from the perfusion bioreactor (3) during a bioreactor product output time period; loading (210) a first separation device (4) with the product fluid obtained in step (110) during a first separation loading time period, which constitutes a first part of a first separation cycle time period; pausing (130) the forwarding of the product fluid from the perfusion bioreactor during a bioreactor non-product output time period; and pausing (220) the loading of the first separation device (4) during a second part of the first separation cycle time period. Also disclosed are a computer-implemented method performed by a controller configured to control a separation of a biomolecule from a fluid (2), and further a controller, a computer program, and a computer program product.

The present invention provides improved bioprocessing systems and methods for cell culture using the improved bioreactors, e.g., batch-fed or perfusion bioreactor cell culture systems for production of monoclonal or bi-specific antibodies, which are modified to include one or more membrane gas transfer modules in place of a sparger- or microsparger-based aeration systems to better regulate the levels of critical gases in a bioreactor cell culture, e.g., the dissolved levels of O2 and CO2, even at high cell densities, without subjecting the cells to bubble-burst associated cell death.

A 3D perfusion bioreactor system and method for more accurate modeling of in vivo environmental conditions and cellular behaviors. In some embodiments, the bioreactor includes a cavity for containing culture media and cells. A plurality of capillary tubes cross the cavity. Artery capillary tubes may transport culture media received from an inlet of the bioreactor, across the cavity, and into a return compartment. Vein capillary tubes may transport culture media from the return compartment, across the cavity, and to an outlet of the bioreactor. Metabolites may diffuse from the capillary tubes into the cavity for cellular consumption, and metabolic waste may diffuse from the cavity into the capillary tubes for removal from the bioreactor. In some embodiments, culture media discharged from the outlet may be processed via a waste treatment device and returned to the inlet.

A bioreactor system for culturing cells is provided. The bioreactor system includes a vessel comprising an inlet, an outlet, and an interior cavity disposed between the inlet and the outlet and for perfusing cell culture media therethrough. The system also includes a cell culture substrate disposed in the interior cavity in a fixed-bed configuration, the cell culture substrate having a surface having a surface area upon for culturing cells thereon during operation of the bioreactor system. The bioreactor system can scale up or down with a desired number of cells to be cultured by adjusting the surface area of the cell culture substrate.

The present invention provides improved bioprocessing systems and methods for cell culture using the improved bioreactors, e.g., batch-fed or perfusion bioreactor cell culture systems for production of monoclonal or bi-specific antibodies, which are modified to include one or more membrane gas transfer modules in place of a sparger-or microsparger-based aeration systems to better regulate the levels of critical gases in a bioreactor cell culture, e.g., the dissolved levels of O2 and CO2, even at high cell densities, without subjecting the cells to bubble-burst cell death.

Provided is a culture method for maintaining the productivity of a product by dynamically controlling cell discharge in order to appropriately control viable cell density. Provided is a method for culturing cells using a perfusion bioreactor, the method including: measuring the capacitance of living cells in a culture medium in a perfusion bioreactor; and discharging live cells in the culture medium in the perfusion bioreactor on the basis of a set value of the capacitance. The set value for the capacitance is changed at a predetermined time interval, and the change is performed on the basis of the numerical value of a viable cell density calculated on the basis of a parameter other than the capacitance.