Terumo Bct, Inc.

Brian J Nankervis

Mark E Jones

Thomas G Dilorenzo

Dennis J Hlavinka

Nathan D Frank

Jon A Dodd

Michael E Kinzie

Domicinda M Hill

Glen Delbert Antwiler

Casey V Medina

Edward Allan Stanton, Iv

Monique Givens

Boah Vang

Albert Winsman

Kristina E Fuerst

David M Gibbons

Edward Allan Iv Stanton

Display screen or portion thereof with a graphical user interface for displaying cell culture process steps and measurements of an associated bioreactor device

Embodiments described herein generally provide for expanding cells in a cell expansion system. The cells may be grown in a bioreactor, and the cells may be activated by an activator (e.g., a soluble activator complex). Nutrient and gas exchange capabilities of a closed, automated cell expansion system may allow cells to be seeded at reduced cell seeding densities, for example. Parameters of the cell growth environment may be manipulated to load the cells into a particular position in the bioreactor for the efficient exchange of nutrients and gases. System parameters may be adjusted to shear any cell colonies that may form during the expansion phase. Metabolic concentrations may be controlled to improve cell growth and viability. Cell residence in the bioreactor may be controlled. In embodiments, the cells may include T cells. In further embodiments, the cells may include T cell subpopulations, including regulatory T cells (Tregs), for example.

Expanding cells in a bioreactor

Embodiments described herein generally provide for expanding cells in a cell expansion system. The cells may be grown in a bioreactor, and the cells may be activated by an activator (e.g., a soluble activator complex). Nutrient and gas exchange capabilities of a closed, automated cell expansion system may allow cells to be seeded at reduced cell seeding densities, for example. Parameters of the cell growth environment may be manipulated to load the cells into a particular position in the bioreactor for the efficient exchange of nutrients and gases. System parameters may be adjusted to shear any cell colonies that may form during the expansion phase. Metabolic concentrations may be controlled to improve cell growth and viability. Cell residence in the bioreactor may be controlled. In embodiments, the cells may include T cells. In further embodiments, the cells may include T cell subpopulations, including regulatory T cells (Tregs), helper, naïve, memory, or effector, for example.

Cell expansion

Embodiments described herein generally provide for the expansion of cells in a cell expansion system using an active promotion of a coating agent(s) to a cell growth surface in some embodiments. A coating agent may be applied to a surface, such as the cell growth surface of a hollow fiber in a bioreactor, by controlling the movement of a fluid in which a coating agent is suspended, by changing flow rates, by changing flow directions, by rotation of the bioreactor, and/or combinations thereof.

Coating a bioreactor in a cell expansion system

Embodiments described herein generally provide for the expansion of cells in a cell expansion system using an active promotion of a coating agent(s) to a cell growth surface. A coating agent may be applied to a surface, such as the cell growth surface of a hollow fiber, by controlling the movement of a fluid in which a coating agent is suspended. Using ultrafiltration, the fluid may be pushed through the pores of a hollow fiber from a first side, e.g., an intracapillary (IC) side, of the hollow fiber to a second side, e.g., an extracapillary (EC) side, while the coating agent is actively promoted to the surface of the hollow fiber. In so doing, the coating agent may be hydrostatically deposited onto a wall, e.g., inner wall, of the hollow fiber.

Methods and systems for coating a cell growth surface

Embodiments described herein generally relate to passively replacing media in a closed cell expansion system to reduce or prevent the dilution of chemical signaling used to inhibit signaling pathways that keep a cell population in the lag phase of cell growth. To prevent such dilution, active inlet fluid flow to the system may be halted. To replace fluid lost by the system, a bag containing media may be attached to the waste line in replacement of the waste or outlet bag connected thereto. By turning off one or more pumps, media from the replacement bag is added to the system at the rate of evaporation. Chemical signaling dilution may be prevented while conserving system resources. Enhancement of chemical signaling to reduce the lag phase of cell growth may further be accomplished by adding molecules, such as chemical-signaling proteins, from a direct source to the system.

Passive replacement of media

Described are embodiments for expanding cells in a bioreactor. In one embodiment, methods are provided that distribute cells throughout the bioreactor and attach cells to specific portions of a bioreactor to improve the expansion of the cells in the bioreactor. Embodiments may be implemented on a cell expansion system configured to load, distribute, attach and expand cells.

Embodiments described herein generally provide for expanding cells in a cell expansion system. The cells may be grown in a bioreactor, and the cells may be activated by an activator (e.g., a soluble activator complex). Nutrient and gas exchange capabilities of a closed, automated cell expansion system may allow cells to be seeded at reduced cell seeding densities, for example. Parameters of the cell growth environment may be manipulated to load the cells into a particular position in the bioreactor for the efficient exchange of nutrients and gases. System parameters may be adjusted to shear any cell colonies that may form during the expansion phase. Metabolic concentrations may be controlled to improve cell growth and viability. Cell residence in the bioreactor may be controlled. In embodiments, the cells may include T cells. In further embodiments, the cells may include T cell subpopulations, including regulatory T cells (Tregs), helper, na&#xef;ve, memory, or effector, for example.

Embodiments for loading and expanding particular cell types are described. Embodiments may include the use of hollow fiber membranes with particular characteristic such as hollow fibers with inner diameters that provide mechanical stimulus (e.g., radius of curvature greater than a dimension of a cell). In addition, embodiments may provide for manipulation of flow rates and other features that also provide mechanical stimuli and promote or enhance the growth of particular types of cells.

Cell growth with mechanical stimuli

Embodiments provide for introducing a first fluid into a bioreactor and while introducing the first fluid into the bioreactor, circulating a second fluid with a reagent at a first flow rate through the bioreactor. The bioreactor may be maintained in a first orientation for a first period of time to allow at least a first portion of the reagent to coat the bioreactor. The second fluid may then be circulated at a second flow rate slower than the first flow rate to allow a second portion of the reagent to coat the bioreactor. Introduction of the first fluid may promote coating of the bioreactor by ultrafiltration. The introduction of the first fluid may be stopped. A third fluid may be circulated through the bioreactor to remove a portion of the reagent not coated on the bioreactor.

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Thornton, CO, United States of America

Brian J Nankervis