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Publication Number
US-12275929-B2
Publication Date
2025-04-15
Expiration Date
Abstract
A cell expansion system for culturing and expanding cells in hydrogel tubes is disclosed herein. The cell expansion system includes a cap having an extruder located within the cap and a tubular housing in fluid connection with the cap. The extruder has at least a first and second inlet. The tubular housing includes a cell compatible buffer. The extruder extends from within the cap into the tubular housing. The cell expansion system allows for expanding cells that can significantly reduce the production time and cost, while increasing the production capacity.
Core Innovation
The invention discloses an automatable cell expansion system for expanding cells using a cap connected to a tubular housing defining an internal space, where the cap comprises an extruder. The extruder includes at least a first inlet and at least a second inlet, disposed within the internal space such that distal ends of the first inlet and the second inlet are connected to the cap at respective openings. The first inlet is operable for introducing a cell solution into the cap, and the second inlet is operable for introducing a hydrogel-forming solution into the cap.
The tubular housing is in fluid connection with the extruder and comprises a cell compatible buffer. The system is configured to enable hydrogel tube fiber/crosslinking formation using calcium ions and/or barium ions, with the resulting microscale hydrogel structures used for low-hydrodynamic-stress culturing and subsequent cell expansion. The disclosed system further provides for cell release by dissolving the hydrogel, including chemical dissolution using EDTA, EGTA, or an alginate lyase solution, and optionally by mechanical force.
The disclosed approach is described in connection with hydrogel tubes, including alginate hydrogel tubes, referenced as AlgTubes, and supporting performance results, including high T-cell expansion fold and yield with low DNA damage and preserved phenotype. Demonstrated applicability is described for endothelial cells, neural stem cells, and personalized iPSC-derived DA progenitors, and the document describes automated prototype use with closed-tube processing and scale-up/scale-out concepts using tubular volume scaling.
Claims Coverage
Independent claim clm-00001 covers a cell expansion system with two main inventive features.
Cap-connected extruder with cell solution and hydrogel-forming solution inlets
A cap connected to a tubular housing defining an internal space, the cap comprising an extruder comprising at least a first inlet and at least a second inlet, the extruder disposed within the internal space such that distal ends of the first inlet and the second inlet are connected to the cap at respective openings in the cap, the first inlet operable for introducing a cell solution into the cap, and the at least second inlet operable for introducing a hydrogel-forming solution into the cap.
Tubular housing with cell compatible buffer in fluid connection with extruder
The tubular housing in fluid connection with the extruder, wherein the tubular housing comprises a cell compatible buffer.
The claim set centers on forming microscale cell-compatible hydrogel structures via a cap extruder that simultaneously receives a cell solution and a hydrogel-forming solution, while maintaining cell compatibility through a tubular housing containing a cell compatible buffer.
Stated Advantages
Enables low-hydrodynamic-stress culturing.
Provides high-yield and high-viability cell expansion.
Supports subsequent cell release by dissolving the hydrogel, including chemical dissolution with EDTA, EGTA, or alginate lyase.
Describes high T-cell expansion fold and yield with low DNA damage and preserved phenotype.
Documented Applications
Expanding T cells, including primary human T cells.
Expanding endothelial cells.
Expanding neural stem cells.
Expanding personalized iPSC-derived DA progenitors.
Automated prototype cell expansion using closed-tube processing.
Scale-up and scale-out implementations using tubular volumes.
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