Apparatus for modification of cells
AssigneeThe Charles Stark Draper Laboratory, Inc.
InventorsHesham Azizgolshani, Jonathan R. Coppeta
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Abstract
Devices for treatment of cells are disclosed. The devices include an elongated housing and at least one hollow fiber semi-permeable membrane positioned within the housing having a plurality of pores dimensioned to prevent passage of the cells to be treated. Systems for treatment of cells including the device are disclosed. Methods of treating cells, including transducing cells and activating cells, are also disclosed. The methods include introducing a biosample with cells to be treated into the device, introducing media to suspend and release treated cells into the device, and discharging the treated cells from the device.
Claims22
A system for treatment of cells comprising:
- a treatment device comprising:
- an elongated housing having a luminal inlet on a first end, a luminal outlet on a second end, and a luminal recycle loop extending from the luminal outlet to the luminal inlet, and a housing inlet, a housing outlet, and a housing recycle loop extending from the housing outlet to the luminal inlet;
- and
- at least one hollow fiber semi-permeable membrane positioned within the elongated housing extending between the luminal inlet and the luminal outlet to define an interior flow chamber and an exterior flow chamber, the hollow fiber semi-permeable membrane including activation particles immobilized on a surface of the at least one hollow fiber semi-permeable membrane and the hollow fiber semi-permeable membrane having a plurality of pores dimensioned to prevent passage of cells to be treated and the activation particles and allow passage of inhibitory factors,
- the luminal inlet constructed and arranged to receive the cells to be treated and the activation particles;
- a source of a biosample comprising the cells to be treated fluidly connected to the luminal inlet;
- a source of a treatment agent comprising the activation particles fluidly connected to the luminal inlet;
- and
- at least one source of a media fluid independently fluidly connected to:
- one of the luminal inlet and the luminal outlet, and one of the housing inlet and the housing outlet.
A system for treatment of cells with activation particles comprising:
- a treatment device comprising:
- an elongated housing having a luminal inlet on a first end, a luminal outlet on a second end, and a housing inlet and a housing outlet, the elongated housing defining a housing recycle loop extending between the housing outlet and both the luminal inlet and the housing inlet, and a luminal recycle loop extending between the luminal outlet and the luminal inlet;
- and
- at least one hollow fiber semi-permeable membrane positioned within the elongated housing extending between the luminal inlet and the luminal outlet to define an interior flow chamber and an exterior flow chamber, the hollow fiber semi-permeable membrane having a plurality of pores dimensioned to prevent passage of cells to be treated and the activation particles, the activation particles being bound to a lumen-side surface and immobilized on the lumen-side surface of the hollow fiber semi-permeable membrane;
- a source of a biosample comprising the cells to be treated fluidly connected to the luminal inlet;
- and
- at least one source of a media fluid independently fluidly connected to:
- one of the luminal inlet and the luminal outlet, and
- one of the housing inlet and the housing outlet.
A device dimensioned for treatment of a target number of cells with activation particles, the device comprising:
- an elongated housing having a luminal inlet on a first end, a luminal outlet on a second end, and a housing inlet and a housing outlet, the elongated housing defining a housing recycle loop extending between the housing outlet and both the luminal inlet and the housing inlet, and a luminal recycle loop extending between the luminal outlet and the luminal inlet;
- and
- at least one primed hollow fiber semi-permeable membrane positioned within the elongated housing extending between the luminal inlet and the luminal outlet to define an interior flow chamber and an exterior flow chamber,
- the at least one hollow fiber semi-permeable membrane having a plurality of pores dimensioned to prevent passage of the cells to be treated and an interior surface area of between about 20 mm2 and about 250 mm2 for every 1 million cells to be treated and having a surface modified by surface-bound transduction enhancers, the activation particles being bound to and immobilized on a lumen side of the hollow fiber semi permeable, and the cells to be activated are distributed as a monolayer for interaction with the bound activation particles.
Dependencies are inferred from the claim text.