SYSTEMS AND METHODS FOR ENHANCED TRANSDUCTION
Described herein are systems and methods for automated cell transduction within a cell processing system. A system for cell processing may include a cell processing cartridge having a transduction system. The transduction system may include a fluidic manifold, one or more modules for performing a cell processing protocol, and a tube having a surface area to volume ration of between about 1,260 mm 2 /mL and about 5,080 mm 2 /mL. A method for cell processing may first include flowing cells through a tube of a flow cell of a cell processing cartridge for a first time period to achieve a transduction efficiency of at least 50%. Second, the method may include expanding the cells within a bioreactor module of the cell processing cartridge for a second time period.
1 . A method for cell processing comprising:
flowing cells through at least one tube of a flow cell of a cell processing cartridge for a first time period to achieve a transduction efficiency of at least 50%; and
expanding the cells within a bioreactor module of the cell processing cartridge for a second time period.
2 . The method of claim 1 , wherein following the cells through the at least one tube comprises:
transferring the cells from a mixing chamber of the bioreactor module to the flow cell via a fluidic manifold of the cell processing cartridge; and
transferring the cells from the flow cell to the mixing chamber via the fluidic manifold of the cell processing cartridge.
3 . The method of claim 1 , wherein the transduction efficiency is measured.
4 . The method of claim 1 , wherein the transduction efficiency is estimated.
5 . The method of claim 1 , wherein the cells flow through the at least one tube via a fluidic manifold of the cell processing cartridge.
6 . The method of claim 1 , wherein the transduction efficiency is equal to or greater than 60%.
7 . The method of claim 1 , wherein the transduction efficiency is equal to or greater than 70%.
8 . The method of claim 1 , wherein the first time period is between about 60 minutes and about 90 minutes.
9 . The method of claim 1 , wherein the second time period is between about 5 days and about 7 days.
10 . The method of claim 1 further comprising maintaining a constant flow rate of the cells through the at least one tube over the first time period.
11 . The method of claim 10 , wherein the flow rate is between about 5 mL/min and about 100 mL/min.
12 . The method of claim 1 , wherein the cells are suspended in a cell solution comprising a density of between about 5×10 5 cells/mL and about 2×10 6 cells/mL.
13 . The method of claim 1 , wherein the cells comprise T-cells.
14 . The method of claim 1 further comprising, prior to flowing the cells through the at least one tube, isolating the cells from blood via apheresis.
15 . The method of claim 1 , wherein the cells are suspended in a cell solution, the method further comprising, prior to transducing the cells, introducing one or more transduction reagents into the cell solution.
16 . The method of claim 15 , wherein the one or more transduction reagents comprise one or both of a lentiviral vector and a virus.
17 . The method of claim 1 , wherein the at least one tube comprises a surface area to volume ratio of between about 1,260 mm 2 /mL and about 5,080 mm 2 /mL.
18 . The method of claim 1 , wherein the at least one tube comprises a diameter of between about 1.57 mm and about 3.18 mm.
19 . A system for cell processing comprising:
a cell processing cartridge comprising:
a transduction system comprising:
a fluidic manifold;
one or more modules for cell processing; and
at least one tube having a surface area to volume ratio of between about 1,260 mm 2 /mL and about 5,080 mm 2 /mL.
20 . The system of claim 19 , wherein the one or more modules comprise a bioreactor module and a flow cell.
21 . The system of claim 20 , wherein the at least one tube is coupled to the flow cell.
22 . The system of claim 19 , wherein the bioreactor module comprises a mixing chamber container configured to receive a volume of cell solution.
23 . The system of claim 19 , wherein the at least one tube comprises a diameter of between about 1.57 mm and about 3.18 mm.
24 . The system of claim 19 further comprising a pump configured to maintain a constant flow rate of cells through the at least one tube.
25 . The system of claim 22 , wherein the flow rate is between about 5 mL/min and about 100 mL/min.
26 . The system of claim 19 further comprising a docking station configured to receive the cell processing cartridge.
27 . The system of claim 19 further comprising a reagent vault configured to store one or more reagents for cell processing.
28 . The system of claim 27 , wherein the one or more reagents comprise one or more transduction reagents.
29 . The system of claim 27 further comprising a sterile liquid transfer device configured to exchange the one or more reagents between the reagent vault and the cell processing cartridge.
30 . The system of claim 29 , wherein the sterile liquid transfer device is fluidically coupled to the fluidic manifold via a sterile liquid transfer port.