Perfusion Bioreactor Feed Control for High-Density Inoculum
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Solution Overview
Problem
Existing inoculum processes in bioreactors are limited by nutrient limitations and inhibitory metabolite build-up, leading to low cell densities and extended incubation times, which negatively impact the efficiency of commercial-scale bioproduct production.
Innovation Solution
A perfusion bioreactor system that dynamically adjusts nutrient media flow rates based on real-time biomass measurements, using a biomass sensor and controller to maintain optimal feed rates, thereby increasing cell density and viable cell count.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional batch mode inoculum processes are used, then the process is simple to operate, but cell density is limited due to nutrient limitations and inhibitory metabolite build-up
Solution Approach 1:
The patent implements dynamic perfusion rate adjustment based on real-time biomass measurements. The perfusion rate is continuously modified according to the actual growth state of the cell culture, transitioning from static batch mode to dynamic continuous mode, enabling higher cell densities while managing nutrient supply and waste removal
Solution Approach 2:
The system employs feedback control by measuring biomass concentration in real-time and using this information to adjust the perfusion rate. The controller receives biomass data and automatically modulates the nutrient media flow rate to optimize cell density, preventing both nutrient depletion and inhibitory metabolite accumulation
2Duration of action of moving object
If conventional batch mode inoculum processes are used, then the equipment is simple, but incubation time is extended
Solution Approach 1:
The patent transitions from batch mode with idle periods between cycles to continuous perfusion mode where nutrient media is continuously supplied and waste is continuously removed. This continuous operation eliminates idle time and maintains optimal growth conditions throughout, significantly reducing incubation time and increasing process throughput
Solution Approach 2:
The system changes the operational parameters from static batch parameters to dynamic continuous parameters. By adjusting perfusion rate, media composition, and flow rates in real-time based on biomass measurements, the process achieves faster cell density accumulation and shorter incubation times while maintaining high productivity
3Ease of operation
If lower cell density inoculum is used, then the inoculum process is easier to control, but more time is needed in production bioreactor
Solution Approach 1:
The patent replaces manual control mechanisms with automated sensing and control systems. Biomass sensors continuously monitor cell density, and the controller automatically adjusts perfusion rates, eliminating the need for manual intervention and enabling precise control even at high cell densities, thus reducing production bioreactor time without sacrificing ease of operation
Data Source
AI summary
A process and system for producing an inoculum for downstream cell production is disclosed. The inoculum is produced in a perfusion bioreactor in which the nutrient media feed is increased as the biomass concentration increases within the bioreactor. A biomass sensor can be used to periodically or continuously monitor biomass concentration. This information can be fed to a controller for automatically increasing nutrient media feed rates in a manner that is directly proportional to producing an inoculum with an increase cell density. The process and system can also include an automated subsystem for maintaining constant volume levels within the perfusion bioreactor during the process.