Bioreactor Systems and Methods of Operating Same
The systems and methods disclosed herein can generate product from cells using a bioreactor system. The bioreactor system can include a centrifuge. The bioreactor system can use a centrifuge to improve product yield. The centrifuge can be used to separate content received from the bioreactor. The separated content can be diverted back to the bioreactor, or filtered and/or collected.
1 . A system comprising:
a centrifuge in fluidic communication with a bioreactor, wherein the centrifuge is configured to receive and separate content from the bioreactor into a first portion and a second portion, wherein a composition of the first portion is different from a composition of the second portion;
a first fluidic pathway configured to transfer the first portion from the centrifuge back to the bioreactor; and
a second fluidic pathway configured to transfer the second portion from the centrifuge to a filtration unit.
2 . The system of claim 1 , wherein the centrifuge comprises:
an inlet port configured to receive content from the bioreactor;
a first outlet port connected to the first fluidic pathway; and
a second outlet port connected to the second fluidic pathway.
3 - 6 . (canceled)
7 . The system of claim 1 , wherein the second portion comprises a supernatant.
8 - 10 . (canceled)
11 . The system of claim 1 , wherein the centrifuge comprises disk stack separators and is configured to be operated continuously for an extended time duration of at least 10 days.
12 . (canceled)
13 . The system of claim 1 , wherein the centrifuge is releasably coupled to the bioreactor.
14 . The system of claim 1 , wherein the centrifuge is releasably coupled to the filtration unit.
15 . (canceled)
16 . The system of claim 1 , wherein the first fluidic pathway comprises a bleeding port, and wherein the bleeding port is arranged to remove a predefined volume of the first portion from the first fluidic pathway before a remaining volume of the first portion is transferred back to the bioreactor.
17 . (canceled)
18 . The system of claim 16 , wherein the predefined volume of the first portion is determined based on a volume of the content in the bioreactor.
19 - 20 . (canceled)
21 . The system of claim 1 , further comprising the bioreactor, wherein the bioreactor is configured to receive media at a predefined rate per day, and wherein the predefined rate is based on one or more of a volume of the content in the bioreactor, a predefined volume of the first portion that is removed through bleeding, or a volume of perfusate generated by the filtration unit.
22 - 25 . (canceled)
26 . The system of claim 1 , further comprising the filtration unit, wherein the filtration unit is configured to enable tangential flow filtration (TFF) of the second portion to generate a perfusate and a retentate.
27 . (canceled)
28 . The system of claim 26 , wherein the perfusate is removed at a predefined volumetric rate per day, and wherein the predefined volumetric rate is based on a volume of the content in the bioreactor.
29 - 30 . (canceled)
31 . The system of claim 26 , further comprising a third fluidic pathway configured to transfer the retentate from the filtration unit back to the bioreactor for re-use in production of a product.
32 . A method comprising:
performing centrifugation on content received from a bioreactor, thereby separating the received content into a first portion and a second portion, wherein a composition of the first portion is different from a composition of the second portion; and
transferring the first portion back to the bioreactor, and transferring the second portion to a filtration unit.
33 . (canceled)
34 . The method of claim 32 , wherein a cell concentration of the first portion is higher than a cell concentration of the content in the bioreactor, and wherein the cell concentration of the first portion is based at least on the cell concentration of the content in the bioreactor and a spin force exerted by the centrifugation on the received content.
35 . (canceled)
36 . The method of claim 32 , wherein the second portion comprises supernatant.
37 . (canceled)
38 . The method of claim 32 , further comprising removing a predefined volume of the first portion before transferring a remaining volume of the first portion back to the bioreactor, wherein the predefined volume of the first portion is determined based on a volume of the content in the bioreactor.
39 - 40 . (canceled)
41 . The method of claim 32 , wherein the bioreactor receives media at a predefined rate per day, and wherein the predefined rate is based on one or more of a volume of the content in the bioreactor, a predefined volume of the first portion that is removed through bleeding, or a volume of perfusate generated by the filtration unit.
42 - 44 . (canceled)
45 . The method of claim 32 , further comprising: performing tangential flow filtration (TFF) on the second portion using the filtration unit to thereby generate a perfusate and a retentate.
46 . The method of claim 45 , further comprising removing the perfusate at a predefined volumetric rate, wherein the predefined volumetric rate is based on a volume of the content in the bioreactor.
47 - 48 . (canceled)
49 . The method of claim 45 , further comprising transferring the retentate from the filtration unit back to the bioreactor for re-use in production of a product.
50 - 54 . (canceled)