Disposable Fluid Circuit for Small Volume Cell Processing

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Solution Overview

Problem

Current cell washing systems are inefficient for processing small volumes of cellular suspensions, requiring large volumes of wash media and often resulting in cell loss and contamination due to the use of intermediate large volume containers for storage and transfer.

Innovation Solution

A system comprising a disposable fluid circuit with a spinning membrane separator, flow control cassette, and reusable hardware, including syringe pumps and a controller, that minimizes internal volume and allows direct filling of small volume containers, ensuring precise control and reduced contamination risks.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If large volume processing systems are used, then processing capability is improved, but wash media volume requirement increases and cell loss increases

Engineering Contradiction:
Improveprocessing capabilityVSAvoidwash media volume
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The system divides the processing into distinct stages using a spinning membrane separator that separates wash media from cell suspension, allowing efficient processing with reduced media volumes. The disposable fluid circuit is segmented into multiple pathways for independent control of wash media flow and cell product flow.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The spinning membrane separator creates localized regions of high shear stress for efficient separation while maintaining gentle handling of cells in the retentate. The system applies different flow rates and pressures to different parts of the fluid circuit to optimize both processing efficiency and cell recovery.

Inventive Principle:
Principle #3Local quality

2Productivity

If large volume processing systems are used, then processing capability is improved, but cell loss increases

Engineering Contradiction:
Improveprocessing capabilityVSAvoidcell loss
Core Design Contradiction:
ProductivityVSLoss of substance

Solution Approach 1:

The system performs preliminary washing and concentration steps using the spinning membrane separator before final product collection, minimizing cell loss during transfer operations. The disposable fluid circuit is pre-primed and ready for immediate use, reducing cell exposure time and potential loss.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The disposable fluid circuit eliminates the need for extensive sterilization and cleaning between uses, reducing cell loss during system preparation. The single-use nature ensures no cross-contamination and minimal cell adhesion to reusable surfaces.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Reliability

If intermediate large volume containers are used for storage and transfer, then product storage is improved, but contamination risk increases

Engineering Contradiction:
Improveproduct storageVSAvoidcontamination risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The system extracts the cell product directly from the processing circuit into the final delivery syringe, eliminating the intermediate storage step in large volume containers. This direct transfer pathway removes the contamination risk associated with multiple transfer operations and intermediate storage.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The spinning membrane separator acts as an intermediary device that enables direct coupling between the processing circuit and the final product container, allowing sterile transfer without intermediate storage. The membrane barrier maintains sterility while enabling efficient product transfer.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Quantity of substance

If disposable fluid circuit with minimized internal volume is used, then wash media volume is reduced, but device complexity increases

Engineering Contradiction:
Improvewash media volumeVSAvoiddevice complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The system merges multiple functions into the spinning membrane separator, which simultaneously performs separation, washing, and concentration operations. The flow control cassette integrates multiple valves and flow paths into a single compact unit, reducing overall system complexity while maintaining minimized internal volume.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The disposable fluid circuit is designed as a universal platform that can process different cell types and volumes while maintaining minimized internal volume. The standardized connectors and flow paths allow the same circuit design to be used for various applications, reducing complexity through design standardization.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentEP3569266B1Fill and finish systems for small volume processing
Publication Date: 2023.04.19 FENWAL INC
  • EP3569266B1 patent drawingFigure 1
  • EP3569266B1 patent drawingFigure 2
  • EP3569266B1 patent drawingFigure 3

AI summary

A system for processing fluids and filling a container with a product includes a disposable fluid circuit and reusable hardware configured to accept the disposable fluid circuit. The disposable fluid circuit includes a spinning membrane separator, first and second syringes, and a flow control cassette. The reusable hardware includes a drive coupled to the spinning membrane separator, first and second syringe pumps, the first and second syringes coupled to the first and second syringe pumps respectively, and a controller. The system also includes a syringe pump for filling low-volume containers, which syringe pump may be one of the first and second syringe pumps, or may be a third syringe pump. The syringe pump for filling low-volume containers may include a filtered vacuum/pressure source and a position detector.