Material Transfer Screen for Gentle Bioreactor Medium Exchange
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Solution Overview
Problem
Current methods for medium exchange in bioreactors, particularly for large-scale cell and gene therapy applications, result in cell damage, nutrient starvation, and incomplete removal of spent medium, exacerbated by prolonged process times and larger volumes, posing a bottleneck for commercial-scale manufacturing.
Innovation Solution
A material transfer device with a housing and screen configuration that separates cell aggregates or microcarriers from spent medium, allowing for rapid and efficient medium exchange while maintaining a closed system, using a control system to automate fluid flow and minimize stress on cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If settling method is used for medium exchange, then medium exchange is achieved, but cell damage occurs through unwanted agglomeration, nutrient starvation, and deviation of key process parameters
Solution Approach 1:
A screen is introduced as an intermediary component between the bioreactor contents and the removal system. The screen allows spent medium to pass through while retaining cell aggregates and microcarriers, enabling medium exchange without direct settling or filtration that would cause cell damage. This mediator resolves the contradiction by separating the medium removal function from the cell handling function.
Solution Approach 2:
The patent replaces the mechanical settling process (which requires pausing agitation and allows prolonged exposure to harmful conditions) with a continuous flow system using a screen filter. This substitution eliminates the need for temporary cessation of mixing and prevents cell damage while achieving complete medium exchange.
2Quantity of substance
If settling method is used for medium exchange, then medium exchange is achieved, but spent medium cannot be completely removed without losing cells
Solution Approach 1:
The screen acts as a selective intermediary that physically separates medium from cells based on size differences. It allows complete removal of spent medium through its pores while retaining all cell aggregates and microcarriers on the other side, preventing cell loss while achieving complete medium exchange.
Solution Approach 2:
A porous screen structure is used with pore sizes specifically selected to allow spent medium to pass through while blocking cell aggregates and microcarriers. This porous material enables complete medium removal without cell loss by exploiting the size difference between medium molecules and cellular structures.
3Quantity of substance
If settling method is used in larger volumetric scales, then medium exchange capacity is increased, but process time increases and issues are exacerbated
Solution Approach 1:
The screen-based system enables continuous medium exchange without requiring pausing of agitation or waiting for settling. The continuous flow through the screen maintains uninterrupted useful action, allowing rapid medium exchange even at large volumetric scales without the time delays inherent in settling methods.
Solution Approach 2:
The patent replaces the time-consuming mechanical settling process with a rapid filtration approach using a screen. This substitution eliminates the prolonged waiting period required for cells to settle in large volumes, enabling fast medium exchange at any scale by driving flow through the screen rather than relying on gravity-driven settling.
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 device minimizes cell stress and contamination risk by ensuring aseptic conditions and rapid medium exchange, facilitating scalable manufacturing of therapeutic cells.
Implementation Method 1
The screen is adapted to prevent the cell aggregates or the microcarriers from passing through the screen while allowing the spent medium to pass through the screen
Implementation Method 2
The first pair of ports may be used to carry medium containing cell aggregates or microcarriers into and out of the housing
Data Source
AI summary
Material transfer devices and related systems and methods are disclosed. In accordance with an example, a material transfer device includes a housing including a first housing portion and a second housing portion and a screen. The first housing portion includes a first inlet port, a first outlet port, and a first transfer opening. The second housing portion has a second inlet port, a second outlet port, and a second transfer opening. The first transfer opening is disposed adjacent to and in communication with the second transfer opening. The screen is disposed between the housing portions adjacent to the first and second transfer openings.