CARTRIDGE FOR USE IN A SYSTEM FOR DELIVERY OF A PAYLOAD INTO A CELL
A cartridge for delivering a payload to cells of a cell suspension is provided, wherein the cartridge comprises an input channel that delivers the cell suspension to a first plurality of branch channels, and wherein the first plurality of branch channels each deliver the cell suspension into a respective one or a plurality of microfluidic chips or filters. Cell suspension exiting a microfluidic chip or filter flows into a respective one of a second plurality of branch channels, and is then delivered to an output channel by which it exits the cartridge. The cartridge may comprise a plurality of removable covers that hold the chips or filters in place against a body of the cartridge in which the input channel, output channel, and branch channels are formed.
1 . A cartridge for delivering a payload to cells of a cell suspension, the cartridge comprising:
a cartridge body comprising a first surface configured to receive a first plurality of constriction-containing elements and a second surface configured to receive a second plurality of constriction-containing elements, each of the first plurality of constriction-containing elements and the second plurality of constriction-containing elements comprising a respective constriction configured to perturb membranes of cells of the cell suspension to facilitate delivery of the payload to the cells;
a first removable cover configured to hold the first plurality of constriction-containing elements in place against the first surface of the cartridge body and to hold the second plurality of constriction-containing elements in place against the second surface of the cartridge body, wherein the first removable cover comprises an input port configured to receive flow of a cell suspension;
a second removable cover configured to hold the first plurality of constriction-containing elements in place against the first surface of the cartridge body and to hold the second plurality of constriction-containing elements in place against the second surface of the cartridge body, wherein the second removable cover comprises an output port configured to direct flow of the cell suspension out of the cartridge.
2 . The cartridge of claim 1 , wherein the first removable cover and the second removable cover are each slidable over the cartridge body, the first plurality of constriction-containing elements, and the second plurality of constriction-containing elements.
3 . The cartridge of claim 1 , wherein the first removable cover and the second removable cover are slidable onto and off of the cartridge body in opposed directions.
4 . The cartridge of claim 1 , wherein the first removable cover and the second removable cover are each configured to encircle the cartridge body.
5 . The cartridge of claim 1 , wherein the cartridge body comprises:
an input chamber formed in the cartridge body and opening toward a first side of the cartridge body to which the first removable cover attaches, wherein the input chamber is configured to be fluidly connected to and receive flow of the cell suspension from the input port; and
an output chamber formed in the cartridge body and opening toward a second side of the cartridge body to which the second removable cover attaches, wherein the output chamber is configured to be fluidly connected to and direct flow of the cell suspension to the output port.
6 . The cartridge of claim 5 , wherein the cartridge body comprises:
a first plurality of branch channels, wherein each of the first plurality of branch channels intersects the input chamber and opens at a respective one of a first plurality of openings to the first surface of the cartridge body and at a second plurality of openings to the second surface of the cartridge body; and
a second plurality of branch channels, wherein each of the second plurality of branch channels intersects the output chamber and opens at a respective one of a third plurality of openings to the first surface of the cartridge body and at a fourth plurality of openings to the second surface of the cartridge body.
7 . The cartridge of claim 6 , wherein the first removable cover and second removable cover are configured to slide in a direction perpendicular to the first plurality of branch channels and the second plurality of branch channels.
8 . The cartridge of claim 6 , wherein the first plurality of branch channels and the second plurality of branch channels are associated with one another in pairs of corresponding branch channels, such that fluid may flow from one branch channel of a pair through a constriction-containing element and into another branch channel of the same pair.
9 . The cartridge of claim 8 , wherein the branch channels of one or more of the pairs of corresponding branch channels are spaced apart from one another in a direction perpendicular to the direction of flow in the input port and output port and perpendicular to the direction of flow of fluid in the branch channels.
10 . The cartridge of claim 6 , wherein:
each of the first and second pluralities of openings is formed in a respective one of a first plurality of recessed cavities formed on the first surface of the cartridge body; and
each of the third and fourth pluralities of openings is formed in a respective one of a second plurality of recessed cavities formed on the first surface of the cartridge body.
11 . The cartridge of claim 5 , wherein the cartridge body comprises:
a first raised lip configured to form a seal against an inside surface of the first removable cover; and
a second raised lip configured to form a seal against an inside surface of the second removable cover.
12 . The cartridge of claim 11 , wherein:
the first raised lip is configured to retain a first o-ring in a first ridge; and
the second raised lip is configured to retain a second o-ring in a second ridge.
13 . The cartridge of claim 11 , wherein:
the first raised lip encircles an opening of the input chamber; and
the second raised lip encircles an opening of the output chamber.
14 . The cartridge of claim 5 , wherein one of the input chamber and the output chamber has a width of less than 5 mm.
15 . The cartridge of claim 6 , wherein one of the branch channels has a diameter of less than 4 mm.
16 . The cartridge of claim 6 , wherein one of the branch channels has a length of less than 25 mm.
17 . The cartridge of claim 6 , wherein the first plurality of branch channels and the second plurality of branch channels each comprise more than four branch channels.
18 . The cartridge of claim 1 , wherein the cartridge has an overall fluid throughput of greater than 1 L/min.
19 . The cartridge of claim 1 , wherein the cartridge has a length of less than 15 cm.
20 . The cartridge of claim 1 , wherein one or more of the first plurality of constriction-containing elements has a length of less than 50 mm.
21 . The cartridge of claim 1 , wherein the cartridge comprises one or more of polycarbonate, polypropylene, and polymethyl methacrylate.