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JP-7856646-B2 - Fluid coupling network for sample collection from bioreactors

JP7856646B2JP 7856646 B2JP7856646 B2JP 7856646B2JP-7856646-B2

Inventors

  • トゥオモ・フリゴード
  • カミラ・エストマー・ニルソン
  • パトリシア・ロシュ
  • ビョルン・マルクス・オロヴソン
  • マグヌス・ウェッターホール
  • ニルス・スタフストローム
  • インニェル・サロモンソン

Assignees

  • サイティバ・スウェーデン・アクチボラグ

Dates

Publication Date
20260511
Application Date
20211013
Priority Date
20201029

Claims (16)

  1. A computer-implemented method for controlling a fluid coupling network (170), wherein the fluid coupling network (170) is configured to be fluidly coupled to a bioreactor (110), a gas supply source (120), a buffer supply source (140), a waste port (150), a processing system (160), and a conduit reservoir (208), the fluid coupling network (170) comprises a barrier unit (220) configured to aseptically separate the flow path within the fluid coupling network (170), the fluid coupling network (170) is controllable for sampling from the bioreactor (110), and the method is: Step (510) of obtaining a fluid sample from the bioreactor (110), which includes controlling the flow of fluid from the bioreactor (110) to the waste port (150) via the conduit reservoir (208) and the fluid connection network (170) in order to fill the conduit reservoir (208) with the fluid sample from the bioreactor (110), Step (530) of providing the fluid sample, which includes providing the fluid sample from the conduit reservoir (208) to the processing system (160) via the fluid connection network (170), Step (540) of returning the residual fluid sample to the bioreactor (110), wherein the residual fluid sample is contained by a portion of the fluid coupling network (170) separated by the barrier unit (220), and the step of returning the residual fluid sample includes controlling the flow of gas from the gas supply source (120) to the bioreactor (110) through the portion of the fluid coupling network (170), A computer-based method, including.
  2. The method according to claim 1, further comprising the step (520) of controlling the flow of buffer fluid from the buffer supply source (140) to the processing system (160) via the fluid connection network (170) to fill a certain area of the fluid connection network.
  3. The method according to claim 1 or 2, further comprising the step (550) of rinsing the conduit reservoir (208) by controlling the flow of buffer fluid from the buffer supply source (140) to the processing system (160) via the conduit reservoir (208) and the fluid connection network (170).
  4. The fluid connection network (170) is further configured to be fluidly connectable to a clean-in-place (CIP) supply source (130), and the method is The method according to any one of claims 1 to 3, further comprising the step of cleaning an area of the fluid-connecting network by controlling (560) the flow of cleaning fluid from the stationary cleaning (CIP) supply source (130) to the processing system (160) via the fluid-connecting network (170).
  5. The fluid connection network (170) is further configured to be fluidly connectable to a clean-in-place (CIP) supply source (130), and the method is The method according to any one of claims 1 to 4, further comprising the step of cleaning the conduit reservoir (208) by controlling (570) the flow of cleaning fluid from the stationary cleanup (CIP) supply source (130) to the conduit reservoir (208) and the waste port (150) via the fluid connection network (170).
  6. A fluid connection network (170) is configured to be fluidly connectable to a bioreactor (110), a gas supply source (120), a buffer supply source (140), a waste port (150), a processing system (160), and a conduit storage container (208), the fluid connection network (170) comprises a barrier unit (220) configured to separate the flow path in a sterile manner within the fluid connection network (170), and the fluid connection network (170) is controllable for sampling from the bioreactor (110). The fluid connection network (170) is configured to obtain a fluid sample, which is obtained by enabling the flow of fluid from the bioreactor (110) by providing a flow path from the bioreactor (110) to the waste port (150) via the conduit reservoir (208) in order to fill the conduit reservoir (208) with fluid from the bioreactor (110). The fluid connection network (170) is configured to provide the fluid sample, and the fluid sample is provided to the processing system (160) by providing a flow path from the conduit reservoir (208) to the processing system (160), and The fluid coupling network (170) is configured to return the residual fluid sample to the bioreactor (110), the residual fluid sample is included by a portion of the fluid coupling network (170) separated by the barrier unit (220), and the residual fluid sample is returned by providing a flow path from the gas supply source (120) to the bioreactor (110). The barrier unit (220) is configured to separate a portion of the fluid coupling network (170) in a sterile state, and the portion of the fluid coupling network (170) includes a flow path that fluidly connects the bioreactor (110) and the gas supply source (120).
  7. A first controllable valve (201) is fluidically connected to a first port (IP1) connectable to the bioreactor (110) and configured to allow or prevent fluid from flowing between the bioreactor (110) and the fluid connection network (170), A second controllable valve (206) is fluidically connected to the outlet of the first controllable valve (201) and the inlet of the conduit reservoir (208), and is configured to allow or prevent fluid received from either of the first controllable valves (201) from flowing into the conduit reservoir (208), A third controllable valve (207) is fluidically connected to the outlet of the conduit reservoir (208) and configured to allow or prevent fluid from flowing out of the conduit reservoir (208), A fourth controllable valve (209) is fluidically connected to the outlet of the third controllable valve (207) and the waste port (150), and is configured to allow or prevent fluid from flowing from the outlet of the third controllable valve (207) to the waste port (150), Furthermore, The fluid coupling network (170) according to claim 6, wherein the fluid coupling network (170) is controlled to obtain a fluid sample and provide a flow path by controlling the first controllable valve (201), the second controllable valve (206), the third controllable valve (207), and the fourth controllable valve (209) to an open state that allows fluid to flow.
  8. A fifth controllable valve (205) is fluidly connected to a second port (IP2) connectable to the buffer supply source (140) and configured to allow or prevent fluid from flowing from the buffer supply source (140) to the fluid connection network (170), A sixth controllable valve (210) is fluidically connected to the outlet of the third controllable valve (207) and to a port (OP2) connectable to the processing system (160), and is configured to allow or prevent fluid from flowing to the processing system (160), Furthermore, The fluid coupling network (170) is controlled to provide the fluid sample and the flow path by controlling the second controllable valve (206), the third controllable valve (207), the fifth controllable valve (205), and the sixth controllable valve (210) to an open state that allows fluid to flow, and by controlling the first controllable valve (201) and the fourth controllable valve (209) to a closed state that prevents fluid from flowing. The fluid coupling network (170) according to claim 7.
  9. The system further comprises a seventh controllable valve (202) which is fluidly connected to a third port (IP3) connectable to a gas supply source (120) and configured to allow or prevent gas from flowing from the gas supply source (120) to the portion of the fluid connection network (170), The fluid coupling network (170) is controlled to return the residual fluid sample to the bioreactor (110) and to provide a flow path by controlling the first controllable valve (201) and the seventh controllable valve (202) to an open state that allows fluid to flow, and by controlling the second controllable valve (206), the third controllable valve (207), the fourth controllable valve (209), the fifth controllable valve (205), and the sixth controllable valve (210) to a closed state that prevents fluid from flowing, according to claim 8.
  10. The system further comprises an eighth controllable valve (211) which is fluidically connected to the inlet of the second controllable valve (206) and the outlet of the third controllable valve (207), and is configured to allow or prevent fluid from flowing between the inlet of the second controllable valve (206) and the outlet of the third controllable valve (207), The fluid coupling network (170) is configured to fill a certain area of the fluid coupling network (520) and provide a flow path by controlling the fifth controllable valve (205), the sixth controllable valve (210), and the eighth controllable valve (211) to an open state that allows fluid to flow, and by controlling the first controllable valve (201), the second controllable valve (206), the third controllable valve (207), the fourth controllable valve (209), and the seventh controllable valve (202) to a closed state that prevents fluid from flowing, as described in claim 9.
  11. The fluid coupling network (170) is configured to rinse the conduit reservoir (208) and provide a flow path by controlling the second controllable valve (206), the third controllable valve (207), the fifth controllable valve (205), and the sixth controllable valve (210) to an open state that allows fluid to flow, and by controlling the first controllable valve (201), the fourth controllable valve (209), the seventh controllable valve (202), and the eighth controllable valve (211) to a closed state that prevents fluid flow, as described in claim 10.
  12. The system further comprises a ninth controllable valve (204) which is fluidly connected to a fourth port (IP4) that can be connected to a CIP (Cleaning Intensive Care) supply source (130), The fluid coupling network (170) is configured to clean the area of the fluid coupling network and provide a flow path by controlling the sixth controllable valve (210), the eighth controllable valve (211), and the ninth controllable valve (204) to an open state that allows fluid to flow, and by controlling the first controllable valve (201), the second controllable valve (206), the third controllable valve (207), the fourth controllable valve (209), the fifth controllable valve (205), and the seventh controllable valve (202) to a closed state that prevents fluid from flowing, as described in claim 10.
  13. The fluid coupling network (170) is configured to clean the conduit reservoir (208) and provide a flow path by controlling the second controllable valve (206), the third controllable valve (207), the fourth controllable valve (209), and the ninth controllable valve (204) to an open state that allows fluid to flow, and by controlling the first controllable valve (201), the fifth controllable valve (205), the sixth controllable valve (210), the seventh controllable valve (202), and the eighth controllable valve (211) to a closed state that prevents fluid flow, as described in claim 10.
  14. A control unit (CU) for a fluid coupling network (170) that can control a bioreactor (110) to take samples, Processing circuit configuration (412), A storage device (415) includes an instruction that can be executed by the processing circuit configuration (412), which causes the processing circuit configuration (412) to perform the method described in any one of claims 1 to 5, A control unit (CU) equipped with this.
  15. A computer program comprising a computer-executable instruction, which, when executed in a processing circuit configuration (412) included in a control unit (CU), causes the control unit to perform any of the steps of the method described in any one of claims 1 to 5.
  16. A computer program product comprising a computer-readable storage medium on which the computer program described in claim 15 is embodied.

Description

This invention relates to a controllable fluid coupling network for sampling from a bioreactor. The invention further relates to a method, a barrier unit, a control unit, a computer program, and a computer program product. A bioreactor is typically a vessel in which chemical processes involving organisms or biochemically active substances derived from such organisms are carried out. In the biotechnology industry, bioreactors are often used, sometimes operating for extended periods. Specifically, bioreactors are used in the biotechnology industry to grow organisms such as cells, bacteria, or fungi. Organisms can produce substances such as biomacromolecules (e.g., proteins) or various types of viruses/viral components. In such bioreactors suitable for producing organisms or biochemically active substances, periodic sampling of the fluid within the bioreactor is necessary. Therefore, it is crucial to avoid contamination and/or loss of sterility during such sampling. In other words, it is necessary to avoid contamination of the container or the environment it contains during sampling. Sampling is required, for example, to monitor and control the state and levels of nutrients required for cell growth. Traditionally, bioreactor sampling can be performed manually, typically using a subcutaneous needle inserted through a membrane. Manual sampling can be a time-consuming and costly process, and increases the risk of contamination of the bioreactor fluid. Some conventional systems include automated sample collection from bioreactors, such as the sample collection system described in Patent Document 1. However, this conventional method has the drawback of discarding a relatively large volume of fluid each time a fluid sample is obtained. Therefore, there is a need for improved methods and fluid networks for bioreactor sampling. U.S. Patent Application Publication No. 2014/087413 This is a diagram of a bioprocess system comprising a fluid coupling network according to one or more embodiments of the present disclosure.This figure shows details of a fluid coupling network according to one or more embodiments of the present disclosure.This figure shows the operating state of a controllable valve according to one or more embodiments of the present disclosure.This is a diagram of a control unit according to one or more embodiments of the present disclosure.This is a flowchart of a method according to one or more embodiments of the present disclosure.This is a diagram of an embodiment of a barrier unit according to one or more embodiments of the present disclosure.This is a diagram of a further embodiment of a barrier unit according to one or more embodiments of the present disclosure.This is a diagram of a further embodiment of a barrier unit according to one or more embodiments of the present disclosure.This is a diagram of a further embodiment of a barrier unit according to one or more embodiments of the present disclosure. A more complete understanding of embodiments of the present invention and an understanding of additional advantages of the present invention will be provided to those skilled in the art by considering the following detailed descriptions of one or more embodiments. It should be understood that similar reference numerals are used to identify similar elements shown in one or more of the figures. In this description and the corresponding claims, "or" is to be understood as a mathematical OR (logical disjunction) encompassing both "and" and "or," and not as an XOR (exclusive disjunction). The indefinite article "one (a)" in this description and the claims is not limited to one, but can also be understood as "one or more," i.e., plural. In this disclosure, “bioreactor” means a container/receptacle configured to carry out a chemical process within a vessel, the chemical process involving organisms or biochemically active substances derived from such organisms. Examples of bioreactors include disposable reactors (e.g., Cytiva WAVE/Xcellerex) and stainless steel reactors. Examples of process modes used in bioreactors include perfusion culture, fed-batch culture, and batch culture. In this disclosure, the term “fluid-connected network” typically refers to an arrangement for providing flow paths to and from a bioreactor, such as from a bioreactor to a bioprocess system or biological analysis system, including a chromatograph. In this disclosure, the term “flow path” means an assembly of components configured to transport fluid, such as a conduit fluidly connected to one or more fluid valves. A flow path typically comprises a fluid inlet, a fluid outlet, and one or more conduits connecting to any intermediate devices such as filters, ventilators, sensors, and valves. In this disclosure, the term "gas source" refers to a configuration for supplying gas, such as a cylindrical canister of compressed air. In this disclosure, the term “buffer source” means a configuration for providing a buffer fluid, such as a contain