Cell Bed Formation Recirculation Loop to Reduce Centrifuge Cell Loss
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Solution Overview
Problem
Existing bioprocessing systems face significant cell loss during initial cell bed formation in continuous centrifugation, leading to decreased overall yields and inefficient use of resources, particularly in the production of fragile eukaryotic cells like mammalian cells.
Innovation Solution
A recirculation loop system is introduced to redirect cells back to the cell bag instead of waste, utilizing a combination of centrifugal and flowing forces to form a stable fluidized bed, enhancing cell accumulation and reducing waste during the initial formation stage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If continuous centrifugation is used to process large volumes of material at high centrifugal forces, then processing efficiency and material process time are improved, but significant cell loss occurs during initial cell bed formation
Solution Approach 1:
The system performs preliminary action by forming a stable cell bed before full processing begins. The recirculation loop allows cells to be returned to the bioreactor during the initial phase, enabling the cell bed to form properly without losing cells to waste, thus preparing the system for efficient processing afterward
Solution Approach 2:
The recirculation loop implements discarding and recovering by redirecting cells that would normally be discarded to waste back to the bioreactor. This recovery mechanism prevents cell loss during initial cell bed formation while maintaining continuous processing efficiency
2Loss of substance
If reverse flow of continuous centrifuge pumps is used to re-process cells lost to waste, then cell recovery is improved, but increased stress on cells and process time occur
Solution Approach 1:
The recirculation loop enables continuity of useful action by maintaining continuous cell recovery without interrupting the processing flow. Cells are continuously redirected to the bioreactor during the initial phase, achieving complete recovery without the need for reverse flow operations that would increase process time
Solution Approach 2:
The system performs preliminary cell recovery action during the initial cell bed formation phase through the recirculation loop. This preliminary recovery prevents cell loss before it occurs, eliminating the need for subsequent reverse flow operations and reducing overall process time
3Reliability
If disposable equipment is used in cell culture, then contamination risk is reduced, but water usage and waste generation increase
Solution Approach 1:
The recirculation loop implements discarding and recovering by preventing cell loss to waste in the first place. By redirecting cells back to the bioreactor during initial bed formation, the system reduces the volume of waste requiring disposal, thereby reducing waste generation while maintaining disposable equipment for contamination prevention
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 recirculation loop significantly increases cell recovery by 30-40%, ensuring efficient cell bed formation and improved overall production yields without disrupting cellular processes.
Implementation Method 1
rotating a chamber about a substantially horizontal axis to create a centrifugal force
Implementation Method 2
flowing a first stream containing media and biomaterials from a container into the chamber through the inlet, wherein flowing the first stream acts to create a flowing force which opposes the centrifugal force
Data Source
AI summary
Methods and systems are disclosed for manipulating inert materials and biomaterials, including cell cultures, to efficiently form effective cell beds while preventing excess flow through of cells to permeate waste during bioprocessing. Gentle centrifugation concentrates a large volume of cells produced from bioreactors into the desired concentrated volume and cell density. When cells pass through the centrifuge, the majority fraction of cells are retained in the centrifuge disposable chamber pods as a cell bed. A recirculation loop redirects the remaining minority fraction of cells back to the cell bag instead of proceeding to waste. This prevents initial cell loss during cell bed formation in the chamber pods, increases overall cell yields at harvest, and conserves materials, for example. Growing and harvesting natural killer cells, in particular, increased yields by over 30% when the recirculation loop was employed.