Bioreactor Filtration Segmentation for Continuous Perfusion
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Solution Overview
Problem
Current bioreactor systems lack the capability to simultaneously harvest high molecular biological products at an adequate flow speed while removing impurities, leading to suboptimal cell density and productivity in continuous perfusion processes.
Innovation Solution
Incorporating both an ultrafiltration impurity filter unit and a product harvest module into the bioreactor, allowing independent regulation of impurity removal and product harvest, enabling higher cell density and product concentration by retaining cells and high molecular weight compounds within the reactor.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If a single filter is used to remove impurities while retaining cells and product, then impurity removal is achieved, but product harvest speed and cell density are suboptimal
Solution Approach 1:
The single filter system is segmented into two independent filter units: a first filter unit for impurity removal and a second filter unit for product harvest. This segmentation allows each filter to be optimized for its specific function, enabling simultaneous impurity removal and product harvest at adequate flow speeds while maintaining high cell density in the bioreactor.
2Quantity of substance
If continuous perfusion process is used to maintain high cell density, then cell concentration is improved, but impurity accumulation limits productivity
Solution Approach 1:
The first filter unit is specifically designed to extract and remove impurities from the bioreactor system while retaining cells and high molecular weight compounds. This continuous impurity extraction enables the system to maintain high cell density and productivity by eliminating the harmful accumulation of waste products that would otherwise limit the continuous perfusion process.
3Productivity
If flow rate through filter is increased to harvest product faster, then productivity improves, but cell retention and product concentration decrease
Solution Approach 1:
The system dynamically regulates the flow rates through the two filter units independently. The second filter unit (product harvest) operates at a flow rate optimized for maintaining product concentration and cell retention, while the first filter unit (impurity removal) operates at a higher flow rate to remove impurities. This dynamic flow rate optimization enables simultaneous achievement of high productivity and high product concentration.
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
This configuration significantly increases cell density and product yield, with cell density rising from 45 million cells/ml to 60 million cells/ml and product concentration from 425 mg/L to 850 mg/L, improving overall biopolymer production efficiency.
Implementation Method 1
the bioreactor comprises an impurity filter unit and a product harvest module wherein (i) the impurity filter unit allows impurities with a MW below the MW of the biopolymer of interest to be removed while retaining cells and the biopolymer of interest in the bioreactor
Implementation Method 2
the product harvest module allows biopolymer of interest and impurities to be removed while retaining cells in the bioreactor
Data Source
AI summary
A method for improving productivity in microbial fermentations and mammalian cell culture bioreactors.