Hollow Fiber Depth Filters for Bioprocess Fouling
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Solution Overview
Problem
Current tangential flow filtration systems face challenges with fouling and finite process capacities, particularly when filter flux limits are exceeded, complicating efforts to increase process capacities and maintain optimal biological activity in bioreactors.
Innovation Solution
The development of hollow fiber tangential flow depth filters with a porous wall formed from extruded polymer filaments, featuring a specific pore size and density, which allows for the separation of large and small particles while trapping intermediate-sized particles, and a pulsatile flow system to enhance filtration efficiency and extend operational periods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If filter flux is increased to increase process capacity, then productivity improves, but fouling increases and reliability deteriorates
Solution Approach 1:
The patent employs depth filtration media with controlled porosity and pore size distribution to achieve high flux operation without fouling. The porous structure allows intermediate particles to be trapped within the matrix while maintaining open pathways for cell passage, enabling operation at fluxes exceeding traditional limits without the fouling that would normally compromise reliability.
Solution Approach 2:
The filtration system uses different pore sizes in different regions of the filter media. Larger pores near the feed side allow cell passage while smaller pores deeper in the media trap intermediate particles. This spatial variation in pore quality enables the system to handle high flux loads without uniform fouling across the entire filter structure.
2Productivity
If filter surface area is increased to handle higher cell densities, then productivity improves, but device complexity increases
Solution Approach 1:
The patent uses hollow fiber filters where the filtration media is nested within the wall structure of tubular fibers. Cells flow through the lumen while intermediate particles are trapped within the fiber wall matrix. This nested configuration provides large surface area for filtration without requiring large external filter assemblies, maintaining system simplicity while handling high cell densities.
Solution Approach 2:
The invention transitions from surface filtration to depth filtration, utilizing the third dimension (wall thickness) of the hollow fiber structure. The filtration occurs throughout the volume of the fiber wall rather than just at the surface, effectively increasing the active filtration area without increasing the external footprint or structural complexity of the system.
3Reliability
If filtration is performed to remove metabolic waste, then biological activity is maintained, but loss of substance increases due to potential product loss
Solution Approach 1:
The depth filtration media has a gradient of pore sizes where larger pores are positioned to allow passage of small biological products while smaller pores trap metabolic waste and intermediate particles. This spatial differentiation in pore quality enables selective filtration that maintains biological activity by removing waste without capturing valuable product molecules.
Solution Approach 2:
The patent uses porous depth filtration media with carefully controlled pore size distribution that allows size-based separation. The porous structure provides tortuous flow paths that enable metabolic waste removal through adsorption and physical trapping while maintaining pore sizes large enough to permit free passage of dissolved biological products, minimizing substance loss.
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
These filters effectively separate bioreactor fluids, maintaining high cell viability and productivity by reducing fouling and increasing process yields, enabling extended operation without maintenance and supporting high cell densities.
Implementation Method 1
hollow fiber tangential flow depth filters... that comprise: a housing having an interior, a fluid inlet, a retentate fluid outlet, a permeate fluid outlet, and at least one hollow fiber comprising a porous wall
Implementation Method 2
Tangential flow filtration (also referred to as cross-flow filtration or TFF) systems are widely used in the separation of particulates suspended in a liquid phase
Implementation Method 3
the permeate flows through pores in the walls of the fibers into the spaces between the fibers and within the larger fluid vessel
Data Source
AI summary
The present disclosure relates to hollow fiber tangential flow filters, including hollow fiber tangential flow depth filters, for various applications, including bioprocessing and pharmaceutical applications, systems employing such filters, and methods of filtration using the same.