Single-Use Cell Centrifuge With Continuous Concentrate Discharge
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Solution Overview
Problem
Existing centrifugal separation systems face challenges in efficiently processing high-concentration and low-viability cell cultures due to increased processing times, viscosity issues, and contamination risks, particularly when dealing with high turbidity feeds, which result in reduced throughput and product loss.
Innovation Solution
The use of pre-sterilized, single-use centrifuge systems with rotationally fixed feed and discharge components, including a flexible membrane and centripetal pumps, allows for continuous or semi-continuous discharge of cell concentrates, minimizing contamination risks and maintaining high angular velocity for efficient processing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional centrifugal separation systems are used for high-concentration cell cultures, then cell separation can be achieved, but processing time increases and throughput decreases
Solution Approach 1:
The system divides the centrifugal separation process into distinct functional zones: a feed zone with accelerated flow for rapid cell suspension introduction, a separation zone for centrifugal settling, and a discharge zone for continuous concentrate removal. This segmentation allows each zone to be optimized independently, enabling high-throughput processing of concentrated cell cultures without increasing overall processing time
Solution Approach 2:
The system implements continuous feeding and continuous concentrate discharge operations, eliminating batch processing interruptions. The feed tube maintains continuous suspension introduction while the concentrate discharge mechanism continuously removes separated cells, allowing the centrifugal separation to proceed without stopping and thereby maximizing throughput while reducing total processing time
2Speed
If high angular velocity is maintained for efficient separation, then settling velocity increases, but viscosity issues arise with high-concentration feeds
Solution Approach 1:
The system applies different flow conditions to different regions: the feed zone receives high-velocity accelerated flow to rapidly introduce suspension, while the separation zone maintains optimized angular velocity for settling. The concentrate discharge zone operates under controlled conditions to remove viscous material. This local differentiation allows high settling velocity where needed while managing viscosity effects through region-specific flow management
Solution Approach 2:
The system uses hydraulic principles to manage viscous high-concentration feeds, employing a feed accelerator that creates controlled turbulence and flow patterns. The centripetal pumps utilize hydraulic forces to discharge concentrate, and the overall system balances centrifugal forces with feed flow dynamics to prevent viscosity from becoming a limiting factor while maintaining high settling velocities
3Reliability
If single-use pre-sterilized components are used, then contamination risk is minimized, but device complexity increases
Solution Approach 1:
The single-use centrifugal separation system is designed as a nested structure where the flexible membrane forms the innermost separation chamber, supported by a rigid frame with integrated feed and discharge components. This nested configuration allows the entire single-use assembly to be pre-sterilized as one unit and then installed in the multiple-use centrifuge, simplifying the sterilization process while maintaining contamination prevention and reducing the complexity of integrating multiple separate components
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
These systems enable high-throughput processing of large volumes of high-concentration cell suspensions with reduced processing times and minimized contamination, achieving efficient cell separation and recovery.
Implementation Method 1
Devices and methods for centrifugal separation of cells in suspension
Implementation Method 2
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
Implementation Method 3
These structures permit the exemplary systems to 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/or a centrate pump (266) to produce output flows of cell concentrate and generally cell free centrate.