Cell Bed Formation with Recirculation 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 is introduced in the bioprocessing system, redirecting a minority fraction of cells back to the cell bag from the waste line, using a combination of centrifugal and opposing flowing forces to form a stable fluidized bed, minimizing cell loss and enhancing yield.
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 throughput 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 main processing begins. The recirculation loop continuously recycles cells during the initial phase to build up sufficient cell bed mass in the centrifuge, ensuring that when production starts, the cell bed is already established and ready to efficiently capture cells without significant loss to waste.
Solution Approach 2:
The recirculation loop implements discarding and recovering by diverting cells that would normally be lost to waste back to the cell bag. During initial cell bed formation, cells in the waste stream are recirculated back through the system, allowing them to be recovered and reused for building the cell bed, thereby converting what would be a loss into a productive resource.
2Loss of substance
If reverse flow recirculation is used to re-process lost cells, then cell recovery is improved, but increased stress on cells and potential high pressure risks occur
Solution Approach 1:
Instead of reversing the flow direction to pump cells back through the centrifuge (which creates high stress and pressure), the system uses the natural forward flow direction. The recirculation loop captures cells from the waste outlet and returns them to the cell bag through a low-stress pathway, maintaining the natural flow direction while achieving cell recovery.
Solution Approach 2:
The recirculation loop acts as an intermediary system between the centrifuge and cell bag. Rather than directly reversing flow through the centrifuge, the loop provides a separate, low-stress recirculation pathway that mediates cell return, avoiding the high pressure and stress associated with reverse flow through the centrifugal system.
3Loss of substance
If reverse flow recirculation is used to recover cells, then cell yield is improved, but overall process time increases
Solution Approach 1:
The recirculation loop enables continuous useful action by operating throughout the entire process duration. Rather than adding separate reverse flow steps that interrupt production, the loop continuously recirculates cells during normal forward flow operation, maintaining uninterrupted processing while simultaneously recovering cells.
Solution Approach 2:
The system merges cell recovery with the normal production flow. The recirculation loop is integrated into the existing forward flow system, combining the production function with the recovery function in a single continuous operation, rather than adding separate recovery steps that would extend process 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 recirculation loop increases cell collection yield by 25-32%, achieving an average recovery of 86% of biomaterials, thereby improving the efficiency and reducing waste in bioprocessing systems.
Implementation Method 1
rotating a chamber about a substantially horizontal axis to create a centrifugal force
Implementation Method 2
forming a fluidized bed consisting of a majority fraction of biomaterials in the chamber, wherein the centrifugal force and the flowing force substantially immobilize the biomaterials in the fluidized bed
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.