Bioreactor Multiport TFF Loop Layout for Single-Port Perfusion
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing bioreactors with limited ports face challenges in performing perfusion or concentrated fed-batch processes, particularly in single-use bioreactors, as they require multiple ports for tangential flow filtration (TFF) which is preferred for lower stress on mammalian cells and consistent process conditions.
Innovation Solution
A multiport device is designed to connect a loop, such as a TFF loop, to a single port of a bioreactor, featuring a first flow path for withdrawing fluid and a second flow path for supplying fluid, with a minimum distance between their ends to ensure proper mixing and reduce shear stress on cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tangential flow filtration (TFF) mode is used for perfusion/concentrated fed-batch, then cell stress is reduced and process consistency is improved, but the number of ports required increases
Solution Approach 1:
The patent combines the functions of multiple ports into a single multiport device that integrates both medium withdrawal and return pathways. This merging allows TFF mode to be implemented in single-port bioreactors, reducing the port requirement from multiple to one while maintaining process consistency and low cell stress benefits.
Solution Approach 2:
The multiport device serves multiple functions through a single component: it enables both medium withdrawal and return operations, supports TFF mode operation, and maintains compatibility with single-use bioreactors. This multi-functionality resolves the contradiction by making the system adaptable to single-port configurations without sacrificing TFF advantages.
2Device complexity
If alternating tangential flow (ATF) is used to reduce port requirements, then the number of ports is reduced, but not the whole content of the hollow fiber filter unit can be pumped back into the bioreactor
Solution Approach 1:
The multiport device merges withdrawal and return functions into one integrated system, enabling complete recirculation of hollow fiber filter unit content back to the bioreactor. This resolves the ATF limitation where only partial content could be returned, thereby improving productivity and yield while maintaining single-port operation.
3Device complexity
If the mouth of the second flow path is positioned close to the first end of the first flow path, then device complexity is reduced, but immediate recirculation of returned medium occurs
Solution Approach 1:
The patent applies local quality by positioning the mouth of the second flow path at a specific distance (at least 5 mm) from the first end of the first flow path. This spatial differentiation ensures proper mixing of returned medium with bioreactor contents, preventing immediate recirculation while maintaining a relatively simple flow path configuration.
Data Source
AI summary
A multiport device for connecting a loop, preferably a tangential flow filtration loop or a sensor loop, to one port of a bioreactor, preferably a single-use bioreactor, is configured to be fixed to the port of the bioreactor. The multiport device includes a first flow path configured for withdrawing fluid from the bioreactor, and a second flow path configured for supplying fluid to the bioreactor. The first flow path has a first end adapted to be in fluid connection with the bioreactor, and a second end adapted to be connected to an inlet of the loop. The second flow path has an outer end adapted to be connected to an outlet of the loop, and a mouth adapted to be in fluid connection with the bioreactor. The mouth of the second flow path is distanced from the first end of the first flow path by at least 5 mm, preferably 10 mm.