Inflatable Bioreactor Bag Baffles Perfusion
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Solution Overview
Problem
Current bioreactor systems face challenges in achieving high cell densities due to insufficient aeration and nutrient supply, leading to limitations in cell culture productivity and product quality, particularly in perfusion cultures where filter clogging and nutrient depletion are significant issues.
Innovation Solution
The development of an inflatable bioreactor bag with centrally located tubular baffles that enhance mixing and aeration, combined with perfusion methods using microfilters or ultrafilters for continuous nutrient supply and waste removal, to maintain high viable cell densities and product concentrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional stainless steel bioreactor systems are used, then sterilization and cleaning can be performed, but the systems are costly, labor-intensive to sterilize, and difficult to reconfigure
Solution Approach 1:
The patent employs single-use disposable plastic bioreactor bags instead of reusable stainless steel systems. These bags are pre-sterilized and discarded after one use, eliminating the need for complex cleaning and sterilization procedures while reducing overall system complexity and cost.
2Ease of manufacture
If pillow style bags are used, then manufacturing cost is low, but aeration and mixing efficiency is insufficient for high cell densities
Solution Approach 1:
The patent divides the bag structure into multiple functional sections by incorporating internal baffles and partitions. These segments create distinct zones for aeration, mixing, and cell culture, improving mass transfer efficiency and enabling high cell density cultivation while maintaining the simplicity and low cost of plastic bag construction.
3Ease of operation
If batch mode operation is used, then operation is simple, but nutrient depletion occurs leading to low final cell densities
Solution Approach 1:
The patent implements continuous perfusion operation where fresh nutrient medium is continuously fed into the bioreactor while spent medium is removed. This continuous supply of nutrients maintains high cell densities throughout the cultivation period, overcoming the nutrient depletion limitation of batch mode while keeping the system relatively simple to operate.
4Productivity
If fed-batch mode is used, then cell density and product yield increase, but toxic metabolite build-up impairs product quality
Solution Approach 1:
The patent employs continuous perfusion operation where spent medium containing toxic metabolites is continuously removed and replaced with fresh medium. This continuous exchange maintains high cell density and product yield while preventing the accumulation of harmful metabolites that would otherwise impair product quality in fed-batch mode.
5Productivity
If perfusion operation is used, then high cell densities and product concentrations are achieved, but filter clogging occurs
Solution Approach 1:
The patent positions the filter at a specific location within the bag where cell density is lower and flow dynamics are more favorable. This localized placement reduces the likelihood of filter clogging while still enabling high cell density cultivation in the main culture volume, maintaining both productivity and filter reliability.
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 solution enables prolonged high-density cell cultures with improved mixing and aeration, maintaining cell viability and productivity, and preventing filter clogging, thus achieving higher yields and reducing the bioreactor size.
Implementation Method 1
The table rocks the bag providing constant movement of the cells in the bag and also efficient gas exchange from the turbulent air-liquid surface
Implementation Method 2
Bags with baffles along the edges to improve the mixing have been described but these are not sufficient to reach the cell densities desired today. Accordingly there is a need for improved aeration in rocking table bioreactors
Implementation Method 3
a hollow fiber filter with a low cut-off pore size is used to separate high molecular particles such as cells and target proteins such as antibodies, from low molecular waste products
Data Source
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AI summary
An inflatable bioreactor bag for cell cultivation, which comprising a top and a bottom sheet of flexible material, joined together to form two end edges and two side edges, wherein one baffle or a plurality of baffles extend from the bottom sheet in a region where the shortest distance to any one of the two end edges is higher than about one fourth of the shortest distance between the two end edges.