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US 11,634,676 B2Granted
Intracellular delivery using microfluidics-assisted cell screening (MACS)
AssigneePresident and Fellows of Harvard College
InventorsCharles James Baker, Ghee Chuan Lai, Dirk Landgraf, Burak Okumus, Johan Paulsson
Life of this patent
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Abstract
Described herein are methods inducing the uptake of an agent by a cell. Aspects of the invention relate to physically compressing the cell to induce perturbations (e.g., holes) in the cell membrane or wall. An agent is taken up by the cell through induced perturbations.
Claims19
A method for uptake of an agent into a cell or population thereof using a microfluidic device, the method comprising:
- passing a first flow fluid through a flow channel of the microfluidic device, the flow channel being at least partially bounded on a first side by a flexible layer of the microfluidic device and being at least partially bounded on an opposing second side by a rigid layer of the microfluidic device, the first flow fluid including a plurality of a first type of cell therein and a first agent;
- pressurizing a control channel formed in the flexible layer of the microfluidic device such that the flexible layer physically compresses at least one of the first type of cell in the first flow fluid against the rigid layer to induce at least one temporary perturbation in a membrane of the at least one of the first type of cell;
- and
- causing a portion of the first agent to be taken up by the at least one of the first type of cell through the at least one temporary perturbation in the membrane of the at least one of the first type of cell.
1 more element
A method of using a microfluidic device, the method comprising:
- passing a first flow fluid through a flow channel of the microfluidic device, the flow channel being at least partially bounded on a first side by a flexible layer of the microfluidic device and being at least partially bounded on an opposing second side by a rigid layer of the microfluidic device, the first flow fluid including a plurality of a first type of cells therein and a first agent;
- pressurizing, to a first pressure, a control channel formed in the flexible layer of the microfluidic device such that the flexible layer physically compresses at least one of the first type of cells in the first flow fluid against the rigid layer to induce at least one temporary perturbation in a membrane of the at least one of the first type of cell and permitting the at least one of the first type of cell to take up a portion of the first agent therethrough;
- passing a second flow fluid through the flow channel of the microfluidic device, the second flow fluid including a plurality of a second type of cells therein that is different from the first type of cells and a second agent;
- and
- pressurizing, to a second pressure that is different from the first pressure, the control channel formed in the flexible layer of the microfluidic device such that the flexible layer physically compresses at least one of the second type of cells in the second flow fluid against the rigid layer to induce at least one temporary perturbation in a membrane of the at least one of the second type of cells and permitting the at least one of the second type of cells to take up a portion of the second agent therethrough.
2 more elements
A method comprising:
- a. passing a flow fluid through a flow channel of a microfluidic device, the flow channel being formed by a flexible layer and a cover layer, the flexible layer including a control channel therein that extends generally perpendicular to the flow channel, the fluid including an agent and a plurality of cells therein;
- a. pressurizing the control channel;
- b. forming a constriction in the flow channel;
- c. physically compressing at least one of the plurality of cells in the fluid between the flexible layer and the cover layer at the formed constriction;
- d. inducing at least one temporary perturbation in a membrane of the at least one of the plurality of cells;
- and
- e. causing the at least one of the plurality of cells to take up a portion of the agent through the at least one temporary perturbation of the membrane.
4 more elements
Dependencies are inferred from the claim text.