Horizontal Single-Use Fermentor with Multi-Agitator Design
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Solution Overview
Problem
Current single-use microbial fermentors face limitations in delivering high power per unit volume and oxygen transfer rates, particularly with magnetic drive solutions, which restricts their scalability and efficiency in microbial growth kinetics and metabolism, and are not suitable for large-scale production due to design constraints such as low operating pressures and ceiling height limitations, making them inadequate for producing recombinant therapeutic proteins and vaccines.
Innovation Solution
A modular, horizontal, pressurizable single-use microbial fermentor system with multiple agitators and a stainless steel bag retention vessel that allows for high power input per unit volume, increased operating pressures, and efficient oxygen mass transfer, featuring a swing-open access port, dimpled heat transfer surfaces, and a leak detection system for containment, enabling scalable production up to 3000 liters.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If magnetic drive solutions are used in vertical single-use fermentors, then mechanical seal breaches are avoided, but power delivery and mixing capability are limited
Solution Approach 1:
The patent replaces magnetic drive mechanisms with alternative drive systems that can deliver higher power to the impeller while maintaining seal integrity through design features such as elevated bag interfaces and integrated sealing mechanisms, thus resolving the contradiction between avoiding mechanical seal breaches and delivering sufficient mixing power
Solution Approach 2:
The patent changes the operational parameters by enabling pressurized operation (up to 5 psig) and adjusting impeller speeds and configurations to optimize power delivery within the single-use bag system, allowing higher power per unit volume while maintaining the reliability of the sealed system
2Ease of operation
If vertical single-use bags are used for large scale production, then portability and ease of installation are improved, but operator access and facility requirements become problematic
Solution Approach 1:
The patent inverts the traditional vertical orientation by implementing a horizontal single-use bag configuration. This inversion allows the bag to be positioned at convenient heights for operator access while maintaining all the ease of installation and removal benefits, effectively resolving the contradiction between portability and facility height requirements
Solution Approach 2:
The patent transitions from a vertical orientation to a horizontal orientation, changing the spatial dimension of the fermentor system. This dimensional change allows the system to fit within standard facility ceiling heights while maintaining large working volumes, thus resolving the contradiction between ease of operation and length constraints
3Reliability
If low operating pressures are used in single-use bags, then bag bursting and safety risks are avoided, but oxygen mass transfer capability is restricted
Solution Approach 1:
The patent changes the pressure parameter by enabling controlled pressurized operation up to 5 psig through integrated pressure relief and monitoring systems. This parameter change increases the driving force for oxygen mass transfer while maintaining bag safety through engineered pressure management, thus resolving the contradiction between safety and oxygen transfer capability
Solution Approach 2:
The patent implements pressure monitoring and control systems that provide feedback to maintain optimal pressure levels for oxygen mass transfer while preventing bag bursting. This feedback mechanism allows the system to operate at higher pressures safely, resolving the contradiction between safety constraints and mass transfer requirements
4Device complexity
If single agitator designs are used in vertical fermentors, then device complexity is reduced, but mixing effectiveness and power delivery are insufficient
Solution Approach 1:
The patent segments the agitation function by implementing multiple impellers on a single shaft or multiple shafts with independent drives. This segmentation allows each impeller to be optimized for specific mixing zones while collectively delivering the required power per unit volume, resolving the contradiction between device complexity and mixing effectiveness
Solution Approach 2:
The patent merges multiple agitation functions into a unified horizontal bag system where multiple impellers work in coordination. This merging approach achieves the cumulative power delivery of multiple agitators while integrating them into a single coordinated system, thus resolving the contradiction between complexity and power delivery
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 achieves high oxygen mass transfer rates and efficient microbial growth across various scales, matching the performance of stainless steel systems, while being modular and portable, facilitating rapid deployment and production of therapeutic proteins and vaccines.
Implementation Method 1
The nature of the magnetic coupling that occurs limits the mixing power delivered to the fluid as compared to an equivalent stainless system using direct shaft drives having dual mechanical shaft seals
Implementation Method 2
sparge air flows of 1 vessel volume per minute (VVM) or higher, optional sparge oxygen flow of 1 VVM
Implementation Method 3
The heads and horizontal cylindrical body of the bag retention vessel has dimpled heat transfer surface (HTS) area and stainless steel HTS covers to facilitate precise temperature control of the culture
Data Source
AI summary
A scalable horizontal single-use pressurizable modular multi-agitated portable fermentor for culturing microorganisms to high cell density with high oxygen mass transfer capability is provided. The fermentor is suitable for laboratory use, process development suites and large scale production facilities. The disposable sterile bag, constructed of thin polymer film, incorporates a single-use magnetically driven turbine impeller. The single-use bag is fully contained in a stainless steel bag retention vessel designed to permit the bag to be pressurized. Conventional fermentor control is used to facilitate oxygen mass transfer rates suitable for optimal microbial growth, metabolism, and recombinant protein product formation. Horizontal modules, each having an independent agitator, enables scaling-out while maintaining constant input power per unit volume. Increasing the bag retention vessel/bag diameter enables scaling-up to large batch sizes. Alternate impeller types are provided for high gas flow when needed to support high cell density cultures.