Aseptic Microcarrier Package With Internal Flow Channel Transfer
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Solution Overview
Problem
The challenge in bioprocessing is to aseptically transfer pre-sterilized microcarriers into a bioreactor without compromising sterility and to perform cell growth phases in a closed system, while avoiding damage from gamma sterilization-induced free radicals.
Innovation Solution
Aseptic bioprocess packages with a 2D flexible container featuring an interior compartment, inlet, outlet, and a channel-forming feature that maintains a fluid flow path, allowing for sterilization, hydration, washing, and aseptic transfer of microcarriers without exposing them to the atmosphere.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If gamma sterilization is used to sterilize microcarriers, then sterilization efficiency is improved, but cellular damage from free radicals increases
Solution Approach 1:
The patent extracts the harmful free radicals generated during gamma sterilization by introducing a free radical scavenger into the system. The scavenger captures and neutralizes the free radicals, preventing them from damaging the microcarriers and cells while allowing the sterilization process to proceed effectively.
Solution Approach 2:
The free radical scavenger acts as an intermediary substance between the gamma radiation and the microcarriers/cells. It intercepts the harmful free radicals generated during sterilization and converts them into harmless substances, thereby protecting the biological materials from damage while maintaining sterilization efficacy.
2Reliability
If a closed system is used for cell growth, then sterility is maintained, but fluid removal from the system becomes difficult
Solution Approach 1:
The patent extracts fluid from the closed system through a port fitting that allows selective removal of supernatant or culture media. The port fitting is designed to enable fluid extraction without compromising the closed system's sterility barrier, allowing operators to remove unwanted fluid while maintaining the sterile environment.
Solution Approach 2:
The patent employs hydraulic principles through the port fitting design, which utilizes pressure differential to facilitate fluid removal. By applying pressure to the external surface of the flexible container, fluid can be forced out through the port fitting in a controlled manner, enabling easy fluid removal from the closed system.
3Ease of operation
If microcarriers are transferred through the atmosphere, then transfer flexibility is improved, but sterility is compromised
Solution Approach 1:
The patent introduces a sterile transfer mechanism as an intermediary between the sterilized microcarriers and the bioreactor. This intermediary system allows transfer to occur without direct atmospheric exposure, maintaining sterility while providing operational flexibility. The transfer can be performed through sealed connections or under controlled conditions.
Solution Approach 2:
The patent employs an inert or controlled atmosphere environment for the transfer process. By conducting transfers in a sterile hood, laminar flow cabinet, or other controlled environment that maintains sterility, the system preserves the sterile status of microcarriers while enabling flexible transfer operations to the bioreactor.
4Ease of operation
If dissolvable microcarriers are used, then cell separation ease is improved, but sterilization complexity increases
Solution Approach 1:
The patent extracts the need for complex sterilization procedures by using a free radical scavenger that simplifies the sterilization process for dissolvable microcarriers. The scavenger protects the microcarriers during gamma sterilization, allowing them to be sterilized effectively without requiring elaborate protective measures or multiple sterilization steps.
Solution Approach 2:
The patent changes the chemical parameters of the sterilization environment by introducing the free radical scavenger. This modification allows dissolvable microcarriers to withstand gamma sterilization without degradation, transforming the sterilization process from one that would damage the microcarriers to one that effectively sterilizes them while preserving their dissolvable properties.
Data Source
AI summary
An aseptic bioprocess package is provided herein. The aseptic bioprocess package includes a 2D flexible container including an interior compartment, a height having an upper half and a lower half, an inlet and an outlet, the inlet and the outlet being disposed on the same half of the 2D flexible container and a channel-forming feature in the interior compartment of the container, the channel-forming feature being configured to maintain a fluid flow path that fluidly connects the interior compartment of the flexible container with the outlet.