The subject invention pertains to methods and devices for generating mature oocytes from immature oocytes and improving oocyte quality for improved success of assistant reproductive technology (ART). The methods include the use of tunneling nanotube-forming cells and oocytes, wherein the tunneling nanotube-forming cells transfer autologous genomic materials, biomolecules and cellular components to the oocytes. The devices of the invention include microfluidic device to improve the efficiency of the transfer of biomolecules and cellular components between tunneling nanotube-forming cells and oocytes.

A packed-bed bioreactor system for culturing cells is provided, the system including a cell culture vessel having at least one interior reservoir, an inlet fluidly connected to the reservoir, and an outlet fluidly connected to the reservoir; and a cell culture matrix disposed in the reservoir. The cell culture matrix includes a structurally defined multi-layered substrate for adhering cells thereto, and each layer of the multi-layered substrate has a physical structure and a porosity that are substantially regular and uniform.

A method includes introducing a suspension including cells suspended in a cell culture medium through a feed port or a drain port into a cavity of a cell culture vessel, the suspension being in an amount sufficient to cover a gas permeable, liquid impermeable membrane positioned at a bottom of the cell culture vessel, the feed port being disposed through a surface of the cell culture vessel and configured to permit additional cell culture medium into the cavity, and the drain port being disposed through the surface of the cell culture vessel and configured to permit removal of the cells, cell culture medium, and used cell culture medium from the cavity, allowing the cells to settle on the gas permeable, liquid impermeable membrane by gravity, removing the used cell culture medium through the drain port and introducing the additional cell culture medium through the feed port such that a constant volume is maintained in the cell culture vessel until the cells expand to a desired cell density, wherein the removing and introducing are performed subsequent to allowing the cells to settle on the gas permeable, liquid impermeable membrane, resuspending the cells in the cell culture medium in the cell culture vessel, wherein the resuspending is performed after the desired cell density is attained, and removing the resuspended cells and the cell culture medium through the drain port.

A media conditioning vessel is provided for a perfusion bioreactor system. The media conditioning vessel includes a vessel having an interior cavity to hold a volume of liquid cell culture media; a media inlet to return cell culture media from a perfusion bioreactor to the vessel; and a media outlet to transfer cell culture media out of the vessel to the perfusion bioreactor. Sensors to measure or detect a characteristic of the cell culture media are provided in the form of inline sensors in at least one of the media inlet and the media outlet or patch sensors attached to a sidewall or bottom of the media conditioning vessel.

Provided herein are isolation processes and the associated hardware to allow fluid streams to be isolated from a sterilized system (e.g., a sterile process vessel) that contains a sterile process. The isolation processes described herein allow for continuous removal of fluid streams (e.g., waste streams, liquid containing recombinant therapeutic proteins) from a sterilized system (e.g., a biological manufacturing system), which provides for less manual manipulation of the sterilized system and a decreased risk of contaminating the sterilized system.

A non-transitory computer readable medium includes instructions configured to adapt a controller to maintain a first target environment in a bioreactor vessel containing a population of cells for a first incubation period to produce a population of genetically modified cells from the population of cells, initiate a flow of media to the bioreactor vessel, maintain a second target environment in the bioreactor vessel for a second incubation period to produce an expanded population of genetically modified cells.

Provided is a product production method which includes: a step of culturing a cell which produces a product and is contained in a cell suspension accommodated in a culture vessel; a separation treatment step of extracting the cell suspension from the culture vessel and separating the cell suspension by a tangential filtration method using a separation membrane; a step of returning a return liquid to the culture vessel; a step of supplying a fresh medium into the culture vessel; and a step of collecting the product, and in which with respect to a live cell concentration Nc, a pore diameter Dp of the separation membrane, a filtration area S of the separation membrane, and a volume Vf of a primary side flow path of the separation membrane, a number density Nd of fine particles having a particle size of 8 Dp to 30 Dp other than live cells in the cell suspension satisfies NcNdS/(32VfDp.sup.2).

The present invention relates to a method and microfluidic device for introducing compounds into red blood cells.

A bioreactor outlet air conditioning system (10) has a bioreactor vessel (100) and a heat exchanger. The heat exchanger has a fluid flow path (196) from a headspace (108) in the vessel for venting air from the vessel, and a temperature control element (300) in thermal contact with the fluid flow path (196). The fluid flow path (196) may be defined by a disposable portion of the bioreactor vessel (100). A method of controlling evaporation within a bioreactor vessel (100), dependent on the required evaporation rate, adjusts the temperature of the temperature control element (300) to control the rate of evaporation of the liquid media (106) from the vessel (100), and may include monitoring fluids in the fluid flow path (196) to detect at least water content of the fluids exiting the vessel to adjust the temperature and control the rate of evaporation dependent on the detected water content levels.

Herein is reported a feed mixing device for adding feed solutions with a non-physiologically pH value to a cell cultivation vessel comprising a chamber for mixing the feed solutions prior to their addition to the cell cultivation vessel as well as its use. With the feed mixing device as reported herein feed components can be provided in solution at a pH value at which they have good solubility and/or good stability whereby the pH value can be clearly different from the pH value of the cultivation medium, i.e. different from the physiological pH value. This allows performing the cultivation with more flexibility compared to a cultivation in which the pH value of the feed solution is limited to a small range around the pH value of the cultivation.