Closed Sterile Cell Processing With Centrifugal and Magnetic Separation
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Solution Overview
Problem
Current methods for processing cellular therapy products require significant infrastructure and manual handling, posing risks of contamination and complexity, and necessitate separate facilities for sterility maintenance.
Innovation Solution
A fully automated system integrating sample processing and separation steps into a single device, using a magnetic separation column with a nonmagnetic housing and a fluid-permeable matrix of metallic spheres, along with a centrifugation chamber and optical detection for sterile processing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If manual cell transfer and multiple separate devices are used for cellular therapy processing, then flexibility in handling different cell types is maintained, but contamination risk increases and operational complexity increases
Solution Approach 1:
The patent combines multiple separate cell processing devices and steps into a single integrated closed system. The system integrates cell separation, washing, concentration, and formulation steps within one closed chamber, eliminating the need for manual transfers between multiple devices and thereby reducing contamination risk while maintaining operational flexibility.
Solution Approach 2:
The integrated system is designed to perform multiple cell processing functions (separation, washing, concentration, formulation) within a single device that can handle different cell types and therapy protocols. This multi-functional design maintains the flexibility needed for various cellular therapies while eliminating the complexity of managing multiple separate devices.
2Reliability
If clean room infrastructure and multiple separate facilities are used to maintain sterility, then cell product sterility is ensured, but infrastructure cost and operational complexity increase
Solution Approach 1:
The system merges all cell processing operations into a single closed chamber that maintains sterility throughout the entire process. The closed system design with integrated filtration and sterile barriers eliminates the need for separate clean room facilities for different processing steps, thereby ensuring sterility while reducing infrastructure requirements.
Solution Approach 2:
The patent employs sterile barriers, filters, and closed system components as intermediaries that maintain sterility without requiring extensive clean room infrastructure. These intermediary elements allow the system to achieve pharmaceutical-grade sterility in a more compact and less complex facility environment.
3Measurement precision
If multiple separate processing devices are used with manual transfer, then in-process controls can be implemented, but processing time increases and productivity decreases
Solution Approach 1:
The integrated system combines all processing steps within a single continuous workflow in one closed chamber. In-process controls are implemented through integrated sensors and monitoring systems that track cell concentration, purity, and other parameters continuously throughout the process, eliminating the time losses associated with manual transfers and batch processing between separate devices.
Solution Approach 2:
The system enables continuous processing where cell separation, washing, concentration, and formulation occur in an unbroken sequence within the same closed system. This continuous action eliminates idle time between steps and maintains constant monitoring, thereby improving both productivity and measurement precision simultaneously.
4Adaptability or versatility
If manual cell handling and transfer steps are performed, then adaptability to different processing protocols is maintained, but user errors increase and reliability decreases
Solution Approach 1:
The integrated system is designed with programmable control that can accommodate different cell processing protocols and parameters. The system maintains protocol flexibility through software configuration and adjustable processing conditions while eliminating manual handling steps that are prone to user error, thereby improving reliability without sacrificing adaptability.
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 system ensures sterility, minimizes user errors, and allows for direct use of processed cellular products, reducing contamination risks and operational complexity while enabling bedside processing.
Implementation Method 1
Magnetic separation is a procedure for selectively retaining magnetic materials in a chamber or column disposed in a magnetic field. A target substance, including biological materials, may be magnetically labeled by attachment to a magnetic particle by means of a specific binding partner, which is conjugated to the particle.
Implementation Method 2
A matrix of material of suitable magnetic susceptibility may be placed in the chamber, such that when a magnetic field is applied to the chamber a high magnetic field gradient is locally induced close to the surface of the matrix. This permits the retention of weakly magnetized particles and the approach is referred to as high gradient magnetic separation (HGMS).
Implementation Method 3
a rotating container (or centrifugation chamber) having at least one sample chamber, wherein the sample processing unit is configured to provide a first processing step to a sample or to rotate the container so as to apply a centrifugal force to a sample deposited in the chamber and separate at least a first component and a second component of the deposited sample
Data Source
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AI summary
The invention pertains to a method of manufacturing a defined population of target cells from a mixed population of blood cells using an apparatus that is configured for processing such cells using a sterile tubing set,wherein the tubing set comprises: (a) an input port configured to receive and deliver the sample to a rotating container, (b) said rotating container, which is configured to rotate about an axis and thereby to apply centrifugal force to a sample contained in a processing chamber in the container so as to separate cells from the sample from other components of the sample; (c) an output port configured to transfer cells processed by the rotating container to a cell separation column; (d) said separation column, which is configured to separate labeled cells from unlabeled cells; and (e) an output port configured to transfer cells separated by the cell separation column to a product collection container. According to the invention, the the method comprises: (1) delivering the sample through the input port into the tubing set; and (2) operating the apparatus such that the sample is processed by the rotating container and by the separation column in the tubing set whereby the target cells are delivered into the product collection container while maintaining sterility of the target cells throughout the aforelisted components of the tubing set.