Single-Port Bioreactor Multiport Device for TFF Loop Mixing
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Solution Overview
Problem
Existing bioreactor systems require multiple ports for perfusion and concentrated fed-batch processes, which is problematic for single-use bioreactors due to potential leakage risks and the need for complex controllers, while tangential flow filtration (TFF) offers benefits over alternating tangential flow (ATF) but still faces challenges in port requirements.
Innovation Solution
A multiport device that connects a loop, such as a TFF loop, to a single port of a bioreactor, with flow paths designed to ensure effective mixing and minimize immediate recirculation, using a one-piece design with flexible hoses to reduce damage risks and allow for efficient TFF operation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If multiple ports are used for perfusion and concentrated fed-batch processes, then process functionality is improved, but leakage risk and device complexity increase
Solution Approach 1:
The patent combines the inlet and outlet flow paths into a single port connection point. The multiport device integrates multiple flow paths (first flow path for withdrawing fluid, second flow path for supplying fluid) that all connect to a single port on the bioreactor, eliminating the need for multiple separate ports and thus reducing leakage risks while maintaining full perfusion functionality
Solution Approach 2:
The single port is designed to serve multiple functions simultaneously. The multiport device enables the same port to handle both fluid withdrawal and supply operations, making the port universal for perfusion processes. This is achieved through the strategic positioning of the mouth of the second flow path at a different location than the first end of the first flow path, allowing distinct flow paths to converge at one port
2Productivity
If multiple ports are used for TFF loop connection, then process performance is improved, but manufacturing complexity and cost increase
Solution Approach 1:
The patent merges multiple flow paths into a single port connection, simplifying the bioreactor structure. Instead of requiring multiple ports for TFF loop connection, the invention uses one port with internally differentiated flow paths, reducing manufacturing complexity while maintaining process performance
Solution Approach 2:
The patent segments the flow paths within the single port connection. The first flow path and second flow path are separated into distinct channels within the multiport device, allowing independent fluid withdrawal and supply operations through a single port. This segmentation enables complex perfusion processes without requiring multiple external ports
3Volume of moving object
If flow paths are positioned close together, then device compactness is improved, but immediate recirculation and mixing efficiency deteriorate
Solution Approach 1:
The patent applies different spatial positioning strategies to different parts of the flow paths. The mouth of the second flow path is positioned at a location that is distanced from the first end of the first flow path, creating local spatial separation to prevent immediate recirculation. This local quality differentiation ensures adequate mixing efficiency while maintaining overall device compactness
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables perfusion and concentrated fed-batch processes in single-port bioreactors, maintaining consistent flow and reducing stress on cells, while using simpler controllers and minimizing leakage risks.
Implementation Method 1
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.
Implementation Method 2
Several developments have led to the application of hollow fiber or flat filter devices to retain the cells and/or the product to obtain higher cell densities and higher product titer.
Implementation Method 3
TFF provides for more constant flow across the surface of the membrane resulting in less or delayed fouling of the membrane
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.