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Publication Number

US-10876090-B2

Patent

Publication Date

2020-12-29

Expiration Date


Abstract

The invention provides a structured cell growth matrix or assembly comprising a one or more spacer layers and one or more cell immobilization layers. The invention further provides a bioreactor comprising said matrix or assembly.

Core Innovation

A spiral configuration cell growth matrix assembly is provided including a plurality of cell immobilization layers and a plurality of spacer layers. Each cell immobilization layer includes a surface that allows cells to adhere and grow, and each spacer layer contains a tortuous path producing structure adjacent to each cell immobilization layer, forming a channel allowing passage of cells and medium along the surfaces.

The tortuous path producing structure of each spacer layer is adapted to direct the cells into the one or more cell immobilization layers and adhere at a depth therein. The matrix assembly includes an open central portion including a core about which the spacer layers and the cell immobilization layers are positioned, and at least one spacer layer is unattached to an adjacent cell immobilization layer.

The assembly includes an innermost spacer layer and an outermost spacer layer, and a thickness ratio of at least one of the plurality of cell immobilization layers to at least one of the plurality of spacer layers is between 1:2 and 2:1. The cell immobilization layers are made of a woven or nonwoven fabric, and the spiral configuration positions the layered structure around the core to create passage channels and depth-directed cell adhesion.

Claims Coverage

The independent claim set includes one independent claim (clm-00001). The inventive features relate to the spiral layered matrix architecture, tortuous-path spacer structures forming channels that guide cells into immobilization layers, specific layer material/form factors, an open central core, optional unattached spacer interfaces, innermost/outermost spacer definition, and a thickness-ratio relationship between immobilization and spacer layers.

Spiral cell growth matrix assembly with layered immobilization and spacer arrangement

A cell growth matrix assembly comprising a spiral configuration including a plurality of cell immobilization layers and a plurality of spacer layers, where each immobilization layer has a surface which allows cells to adhere and grow, and each spacer layer containing a tortuous path producing structure is positioned adjacent to each immobilization layer.

Tortuous path producing spacer structure forming channels for cells and medium

The tortuous path producing structure of each spacer layer produces a channel allowing passage of cells and medium along the surface of the plurality of cell immobilization layers and is adapted to direct the cells into the one or more cell immobilization layers and adhere at a depth therein.

Open central portion with core for positioning spacer and immobilization layers

The cell growth matrix assembly includes an open central portion including a core about which the plurality of spacer layers and the plurality of cell immobilization layers are positioned.

Unattached spacer layer adjacent to immobilization layer

At least one of the plurality of spacer layers is unattached to an adjacent one of the plurality of cell immobilization layers.

Innermost and outermost spacer layers defining boundary within spiral

The cell growth matrix assembly comprises an innermost spacer layer and an outermost spacer layer.

Thickness ratio between immobilization layers and spacer layers

A thickness ratio of at least one of the plurality of cell immobilization layers to at least one of the plurality of spacer layers is between 1:2 and 2:1.

Overall, the claim coverage centers on a spiral multi-layer cell growth matrix in which tortuous-path spacer structures form channels that guide cells into immobilization layers for depth adhesion, combined with an open central core, defined spacer layer attachments and boundaries (innermost/outermost), and a thickness-ratio relationship between immobilization and spacer layers.

Stated Advantages

Improving flow homogeneity while reducing pressure drop.

Enhancing infiltration into immobilization layers.

Generating turbulence to drive cells/medium along immobilization-layer surfaces.

Providing controlled cell culture surface reproducibility.

Enabling improved nutrient/toxic metabolite transport.

Improving homogeneous cell distribution.

Providing efficient packing and reduced cost/labor.

Providing high cell density surface in minimum volume.

Documented Applications

Integration with a bioreactor, including stationary axial flow versus rotating tangential/spiral flow configurations, optionally in a single-use configuration.

Use of the spiral/rolled configuration of the matrix assembly in a bioreactor inner space, with positioning of volume fraction within the bioreactor.

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