Bioreactor Inoculation Control Using Online Biomass Sensing
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Solution Overview
Problem
Current bioprocesses face challenges in transferring inoculum between bioreactors due to manual sampling for viable cell density measurement, leading to inefficiencies, risks of contamination, and laborious volume control, which affects process stability and time efficiency.
Innovation Solution
A bioprocess device assembly with a biomass sensor and control unit that enables online monitoring of biomass parameters, particularly viable cell density, to automate the transfer of inoculum based on real-time measurement data, using a transfer system controlled by a control unit to ensure precise inoculation volume and process stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of time
If manual sampling is used to measure viable cell density, then process operator effort is reduced, but process time is wasted due to delayed detection of optimal inoculation timing
Solution Approach 1:
The system enables self-service by automatically monitoring biomass concentration and triggering transfer operations without operator intervention. The biomass sensor continuously measures VCD, and the control unit automatically initiates the transfer when threshold criteria are met, eliminating the need for manual sampling and operator decision-making while preventing time loss.
Solution Approach 2:
Manual mechanical sampling operations are replaced by an automated sensor-based measurement system. The biomass sensor and control unit substitute for manual sampling procedures, enabling continuous real-time monitoring without physical intervention, thus eliminating both time delay and operator effort.
2Measurement precision
If frequent manual sampling is performed to determine viable cell density, then measurement accuracy is improved, but operator effort and contamination risk increase
Solution Approach 1:
Manual sampling operations are completely replaced by an automated biomass sensor system that continuously monitors VCD in real-time. This substitution maintains high measurement precision through continuous data collection while eliminating operator effort and associated contamination risks.
Solution Approach 2:
The biomass sensor provides continuous real-time monitoring of viable cell density, replacing discrete manual sampling events. This continuous measurement approach maintains high measurement accuracy throughout the entire process while eliminating the need for repeated operator interventions.
3Manufacturing precision
If manual volume control is used for inoculum transfer, then device complexity is reduced, but manufacturing precision is compromised due to laborious and error-prone operations
Solution Approach 1:
Manual volume measurement and transfer operations are replaced by an automated control system that precisely controls the transfer pump. The control unit receives real-time VCD data, calculates the exact inoculation volume needed, and automatically controls the pump to transfer the precise volume, eliminating human error while managing system complexity through integrated automation.
Solution Approach 2:
The system implements feedback control by continuously monitoring biomass concentration and using this information to automatically calculate and adjust the required inoculation volume. The control unit receives real-time data from the biomass sensor and adjusts the transfer volume accordingly, ensuring precise inoculation while automating the complex calculations and control decisions.
4Reliability
If multiple manual operations are performed for sampling and transfer, then ease of operation is maintained, but reliability decreases due to increased contamination risk
Solution Approach 1:
The system performs self-service by automatically monitoring biomass, calculating required volumes, and executing transfers without operator intervention. This eliminates multiple manual operations that expose the process to contamination, thereby improving reliability while the automated nature of the system maintains operational simplicity.
Solution Approach 2:
The automated system performs continuous monitoring and coordinated operations without interruption or exposure to contamination. By eliminating discrete manual sampling and transfer steps, the system maintains process integrity and reliability while simplifying operations through automation.
Data Source
AI summary
A bioprocess device assembly includes at least a first bioreactor and a second bioreactor, and a transfer system for transferring a certain volume of a medium contained in the first bioreactor into the second bioreactor. A biomass sensor is associated to the first bioreactor. A control unit is configured for receiving measurement data from the biomass sensor and controlling the transfer system. An inoculation method makes use of such a device assembly wherein the biomass sensor measures at least one parameter of biomass contained in the first bioreactor; the biomass sensor sends measurement data to the control unit; and the control unit evaluates the measurement data and, based on an evaluation of the measurement data decides whether the viable cell density is sufficient for inoculation, determines a necessary inoculation volume, and controls the transfer system to transfer the determined inoculation volume from the first bioreactor into the second bioreactor.