Collapsible Harvest Bag with Integrated Filter for Bioreactor Media Recovery
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Solution Overview
Problem
Current methods for separating microcarrier beads or cells from culture medium in bioreactors are inefficient, prone to clogging, and require substantial time, especially in continuous or perfusion modes, where nutrients are continuously added and products are harvested throughout the culture period.
Innovation Solution
A nonporous, collapsible harvest and microcarrier recovery bag with an integrated filter attached to its inner wall surface, allowing fluid to flow through while retaining microcarrier beads, preventing filter clogging and enabling faster and more efficient separation and recycling of culture medium.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If external filtering methods are used to separate microcarrier beads from culture medium, then product can be harvested, but the filter clogs and dead cells accumulate in the bioreactor
Solution Approach 1:
The invention extracts the filter from the bioreactor system, placing it in a separate harvest bag. This removes the filter from the confined bioreactor space where clogging would occur, allowing the filter to be easily replaced and cleaned without disrupting the bioreactor operation. The filter is taken out of the system during harvesting and can be discarded or regenerated separately.
Solution Approach 2:
The harvest bag serves as an intermediary device between the bioreactor and the filtration system. It provides a dedicated space for filtering culture medium away from the bioreactor, allowing dead cells and microcarrier beads to be separated in a controlled environment without clogging the bioreactor itself. The intermediary bag captures and contains the filtration process.
2Productivity
If conventional separation methods (settling and decanting or external filtering) are used, then microcarrier beads can be separated from culture medium, but the process requires substantial time and is inefficient
Solution Approach 1:
The invention segments the harvesting process into distinct functional zones within the harvest bag: a filtration zone with filter material for separating microcarrier beads, and a collection zone for the filtered culture medium. This segmentation allows simultaneous filtration and collection, eliminating the need for sequential settling and decanting operations that consume time.
Solution Approach 2:
The filter is pre-positioned in the harvest bag before harvesting begins. This preliminary arrangement of the filtration system eliminates the time required to set up filtration during the harvesting process. The filter is already in place to immediately begin separating microcarrier beads as culture medium flows through the bag.
3Reliability
If Tangential Flow Filtration is used to avoid filter clogging, then particles are carried along by flow, but the device requires large area, high flow rates, and high pressures that may damage cells or microcarrier beads
Solution Approach 1:
The invention applies different qualities to different parts of the harvest bag system. The filter material has specific pore sizes and properties optimized for retaining microcarrier beads while allowing culture medium to pass. The harvest bag itself has a structure that promotes gentle flow patterns without requiring high pressures. Each component is locally optimized for its specific function.
Solution Approach 2:
The invention changes the flow parameters from the high-pressure, high-flow-rate requirements of Tangential Flow Filtration to a lower-pressure, gravity-assisted or gentle pump-driven flow system. The filter is positioned and sized to create appropriate flow distribution without requiring extreme parameters. This parameter adjustment reduces the risk of damaging cells or microcarrier beads while still preventing filter clogging.
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 solution significantly reduces filter clogging, enhances separation efficiency, and allows for the recycling of microcarrier beads or cells back into the bioreactor, improving fluid retrieval and reducing contamination risks, making it suitable for both batch and continuous modes.
Implementation Method 1
a filter having a perimeter, a first surface and a second surface, and fixedly attached around its entire perimeter to a portion of the inner wall surface of the nonporous vessel, thereby forming an integrated interior bag within the nonporous vessel
Data Source
AI summary
Disclosed herein is a single use continuous recovery, flow-through harvest vessel and corresponding method for harvesting culture medium and simultaneously either leaving the microcarrier beads behind in the vessel or flowing microcarrier beads and medium back into a bioreactor.