Terumo Bct, Inc.

Pure H20 Bio-technologies, Inc.

Mark E Jones

Brian J Nankervis

Domicinda M Hill

Nathan D Frank

Dennis J Hlavinka

Thomas J Felt

Jon A Dodd

Thomas G Dilorenzo

Michael E Kinzie

Boah Vang

Kristina E Fuerst

Joseph P Doxey

Dennis Bordeaux

Dalip Sethi

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

Implementations are described that relate to methods and systems for growing cells in a hollow fiber bioreactor. In implementations, the cells may be exposed to a number of growth factors including a combination of recombinant growth factors. In other implementations, the cells may be grown in co-culture with other cells, e.g., hMSC's. In implementations, the cells may include CD34+ cells. A coated membrane includes a membrane having a first coating configured to promote cellular adhesion to the membrane and a second coating that includes a soluble protein moiety.

Cell capture and expansion

Embodiments are described that relate to methods and systems for growing cells in a hollow fiber bioreactor. In embodiments, the cells may be exposed to a number of growth factors including a combination of recombinant growth factors. In other embodiments, the cells may be grown in co-culture with other cells, e.g., hMSC's. In embodiments, the cells may include CD34+ cells.

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

Described are embodiments for expanding cells in a bioreactor. In embodiments, methods and systems 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.

One or more embodiments are described directed to a method and system for concentrating components of a fluid circulated through a cell growth chamber such as a cell growth chamber. Accordingly, embodiments include methods and systems that utilize a tangential flow filter to concentrate components of a fluid that in embodiments includes expanded cells. In embodiments, a concentrated fluid component and a concentrated cell component are generated by flowing the fluid with expanded cells across a tangential flow filter. The concentrated cell component may be recirculated to the tangential flow filter to reach some desired concentration of cells. The concentrated fluid component may be collected to utilize cellular-produced constituents in the concentrated fluid component.

Concentrating components of fluid circulated through a cell growth chamber

A water disinfection delivery treatment system first filters the supply by a particle and then a carbon filter. The partially treated flow is split in two and a first part passes through a first cutoff valve and is fed into a disinfection (iodine) chamber, filter or feeder via a flow restricter. The chamber output passes through a second solenoid driven cutoff valve. The second part is fed to a third cutoff valve and this valve's output is summed with the second valve's output and then fed into a holding tank. The tank retain's a volume such that the water remains therein for at least a period sufficient to permit a minimum 3 log reduction of pathogenic microbes. A final carbon filter is downstream of the tank as is a meter and dispenser. A method is also provided for delivering potable drinking water.

Growing community of inventors

Littleton, CO, United States of America

Mark E Jones