Centrifuge System With Single-Use Fluid Path For High Cell Concentration
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Solution Overview
Problem
Current centrifugal separation systems face challenges in processing high concentrations of cells and cell debris, leading to reduced throughput rates, increased contamination risks, and longer processing times, especially when dealing with low viability cell cultures and high viscosity cell concentrates.
Innovation Solution
The development of pre-sterilized, single-use fluid path components and a centrifuge design that includes a solid wall centrifuge with a multiple use rigid bowl and single-use components, featuring a flexible membrane and centripetal pumps, allowing for continuous or semi-continuous operation at high cell concentrations, minimizing feed turbidity, and enabling efficient discharge of cell concentrates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional centrifugal separation systems are used to process high concentrations of cells and cell debris, then cell separation function is maintained, but throughput rate decreases and processing time increases
Solution Approach 1:
The system divides the cell separation process into distinct functional zones within the centrifuge: an acceleration zone for initial cell-debris separation, a separation zone for continuous differentiation of cells from debris, and a discharge zone for removing concentrated cells. This segmentation allows each zone to optimize its function, maintaining high throughput even with high cell concentrations.
Solution Approach 2:
The centrifuge performs preliminary acceleration of the cell suspension before it enters the main separation zone. This preliminary action ensures that cells and debris are properly oriented and separated from the bulk fluid early in the process, enabling more efficient continuous separation downstream and preventing processing bottlenecks.
2Reliability
If conventional centrifugal systems process low viability cell cultures, then cell separation is achieved, but contamination risk increases
Solution Approach 1:
The system employs disposable, pre-sterilized centrifuge bowls and fluid path components that are discarded after a single use. This eliminates cross-contamination risks between batches and removes the need for complex cleaning and sterilization procedures, maintaining high reliability while preserving processing efficiency through continuous operation.
Solution Approach 2:
The centrifuge system operates with closed, sterile fluid paths and disposable components that create an inert, contamination-free environment. This prevents introduction of contaminants during processing, especially important when handling low viability cell cultures that are more susceptible to contamination.
3Productivity
If high angular velocities are used to process high cell concentrations, then settling velocity increases for efficient separation, but shear forces increase which may damage cells
Solution Approach 1:
The centrifuge design creates different local conditions in different zones: the acceleration zone operates at conditions optimized for rapid initial separation, while the main separation zone maintains conditions that provide gentle, continuous separation. This local optimization allows high settling velocities where needed while protecting cells from excessive shear forces in other regions.
Solution Approach 2:
The system uses dynamic control of feed rate and rotational velocity to maintain optimal separation conditions. By continuously adjusting operational parameters, the centrifuge can maintain high angular velocities for efficient separation while preventing excessive shear forces that would damage cells, adapting to varying cell concentrations and properties.
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 high-capacity, efficient processing of large volumes of cell suspensions with reduced contamination risks and processing times, maintaining cell viability, and improving overall production rates by maintaining high angular velocities and minimizing shear forces.
Implementation Method 1
The exemplary centrifuges discussed herein may be solid wall centrifuges that use pre-sterilized, single-use components, and may be capable of processing cell suspensions, with high cell concentrations... maintain a sufficiently high angular velocity to create a settling velocity suited to efficiently processing highly concentrated cell culture streams
Data Source
AI summary
An apparatus for separating cell suspension material into centrate and concentrate, includes a single use structure (178, 240, 250) releasably positioned in a cavity in a solid wall rotatable centrifuge bowl (172). The bowl and portions of single use structure rotate about an axis (174). A stationary inlet feed tube (184), a centrate discharge tube (212) and a concentrate discharge tube (230) extend along the axis of the rotating single use structure. A centrate centripetal pump (208) is in fluid connection with the centrate discharge tube. A concentrate centripetal pump (216) is in fluid connection with the concentrate discharge tube. A controller (274) operates responsive to sensors (264, 270) in respective centrate and concentrate discharge lines (262, 268), to control flow rates of a concentrate pump (272) and a centrate pump (266) to produce output flows of cell concentrate and generally cell free centrate.