Tangential Flow Filter Reverse Flushing in Perfusion Systems
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Solution Overview
Problem
Fouling of tangential flow filters in perfusion systems leads to reduced filter efficiency, increased processing time, and limited cell density, restricting continuous processing duration and performance in bioprocessing applications.
Innovation Solution
A method and system that utilize a control unit to manage flow control devices, enabling reverse flow of feed or permeate fluids to clean the tangential flow filter, maintaining filter integrity and allowing for continuous bioprocessing without manual intervention.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If continuous perfusion processing is performed through the tangential flow filter, then productivity and process intensification are improved, but filter fouling increases leading to reduced filter efficiency and increased processing time
Solution Approach 1:
The system implements periodic reverse flushing cycles where the flow direction through the tangential flow filter is temporarily reversed to remove accumulated foulants. This periodic action restores filter efficiency without stopping the overall continuous processing operation, resolving the contradiction between extended processing duration and maintained filter performance
Solution Approach 2:
The system uses a portion of its own permeate output to automatically flush and clean the filter during operation. This self-service mechanism allows the filter to clean itself without external intervention or manual intervention, maintaining efficiency while enabling continuous processing
2Quantity of substance
If high cell density is achieved in the bioreactor, then product yield is improved, but filter clogging increases restricting process duration
Solution Approach 1:
The system performs preliminary reverse flushing before complete filter clogging occurs, preventing the accumulation of foulants that would restrict flow. This preliminary maintenance action allows the system to sustain high cell density operations for extended durations by proactively managing filter condition
3Reliability
If manual filter cleaning is performed, then filter efficiency is restored, but processing time increases and automation is reduced
Solution Approach 1:
The system automatically performs reverse flushing operations using its own permeate output without requiring manual intervention. This self-service capability restores filter efficiency continuously during operation, eliminating downtime associated with manual cleaning and maintaining high productivity
Solution Approach 2:
The reverse flushing operation is integrated into the continuous processing flow, allowing the filter to be cleaned without interrupting the overall bioprocess. The useful action of filtration continues uninterrupted while the filter is automatically maintained, preventing loss of processing time
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
The system reduces filter clogging, enhances filter life, permits higher cell density cultures, and facilitates continuous bioprocessing by automatically cleaning the filter during operations, thereby improving processing efficiency and yield.
Implementation Method 1
The most common filtration processes are microfiltration (MF), ultrafiltration (UF), and reverse osmosis (RO). Such filtration processes are pressure driven and are used for separation of macromolecules from a fluid using a filter.
Implementation Method 2
operating the control unit to control the at least one feed flow control device to direct at least one of a) a further flow of a second quantity of the feed fluid from the bioreactor, b) a portion of the permeate fluid, and c) a portion of a nutrient fluid from a source, along a second direction opposite to the first direction via the tangential flow filter for a predefined duration to clean the tangential flow filter
Data Source
AI summary
A method includes inducing a first quantity of a feed fluid (28) to flow along a first direction (72) from a bioreactor (12) to a tangential flow filter (16) to separate the first quantity of the feed fluid (28) into a permeate fluid (42) and a retentate fluid (48). Further, the control unit (66) is operated to control at least one feed flow control device (24, 26) to inhibit the flow of first quantity of the feed fluid (28). Furthermore, the control unit (66) is operated to control the at least one feed flow control device (24, 26) to direct at least one of further flow of a second quantity of the feed fluid (28) from the bioreactor (12), a portion of the permeate fluid (42), and a portion of a nutrient fluid, along a second direction (74) opposite to the first direction (72) via the tangential flow filter (16).