Bioreactor pH Calibration Deviation Detection Using CO2 Equilibrium
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Solution Overview
Problem
Existing pH measuring devices in bioreactors face calibration errors and offset effects due to sampling processes, leading to inaccurate pH value measurements, which can result in incorrect comparison and synchronization of bioreactor states and potential contamination risks.
Innovation Solution
A method utilizing CO2 concentration measurements in tanks to identify pH measuring device calibration issues by comparing CO2 concentrations and pH values between reference and monitored tanks, allowing for the determination of accurate pH values and minimizing offset effects without the need for offline measurements.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If offline pH measurements are performed by withdrawing medium samples, then pH values can be measured, but calibration errors and offset effects occur leading to inaccurate measurements
Solution Approach 1:
The patent extracts the pH measuring device from the bioreactor for offline calibration measurements. The device is removed, calibrated externally using reference solutions, and then reinserted. This extraction allows calibration without interference from bioreactor conditions but introduces contamination risks and potential calibration drift during removal/reinsertion processes.
Solution Approach 2:
The patent uses reference solutions with known pH values as intermediaries for calibrating the pH measuring device. These standard buffer solutions serve as a mediator between the calibration process and the actual bioreactor medium, providing a reliable reference point for accuracy adjustment.
2Measurement precision
If pH measuring devices are calibrated using reference solutions, then calibration accuracy can be improved, but contamination risks increase due to removal and reinsertion processes
Solution Approach 1:
The pH measuring device is extracted from the bioreactor to perform calibration with reference solutions outside the bioreactor environment. This allows accurate calibration but exposes the device and potentially the bioreactor to contamination during removal and reinsertion.
Solution Approach 2:
The patent implements sterilization protocols and careful handling procedures as preventive measures before the calibration process to minimize contamination risks. The device is sterilized and handled in a controlled manner during the calibration process to prevent introduction of contaminants.
3Object-affected harmful factors
If tank-external pH measuring devices are used for sample measurements, then contamination risks are reduced, but offset effects cause measured pH values to deviate from actual bioreactor pH
Solution Approach 1:
The patent separates the pH measurement function into two distinct modes: online measurement within the bioreactor using a tank-internal device, and offline calibration using a tank-external device with reference solutions. Each device serves its specific purpose, allowing contamination-free calibration while maintaining accurate in-situ measurement.
Solution Approach 2:
The patent uses CO2 concentration measurements as an intermediary parameter to bridge the gap between offline calibration data and online measurements. By correlating CO2 levels with pH values, the system can transfer calibration information from the external device to the internal device without direct physical contact or sampling.
4Reliability
If CO2 concentrations are used to compute expected pH values, then calibration deviations can be identified, but additional measurements and computations are required
Solution Approach 1:
The patent utilizes the CO2 measuring device to serve multiple functions: monitoring bioreactor conditions, detecting calibration deviations through expected pH computation, and providing a reference for synchronizing multiple bioreactors. This multi-functionality reduces the need for separate calibration verification systems.
Solution Approach 2:
The system implements a feedback mechanism where CO2 concentration measurements are used to compute expected pH values, which are then compared with actual measurements from the pH device. When deviations are detected, the system provides feedback to trigger recalibration or alert operators, creating a self-verifying system.
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
This approach enables accurate comparison and synchronization of pH values between tanks, reduces contamination risks, and allows for real-time monitoring and control of bioreactor states by identifying calibration differences and offset effects, ensuring precise operational conditions.
Implementation Method 1
a first time being a time when the medium in the first bioreactor is in pH-CO2 equilibrium state with the first gas volume
Data Source
AI summary
The invention relates to a comparison unit (130) configured for determining if a first pH measuring device of a first tank (104; 106) is affected by a pH-measuring problem, the comparison unit being configured for:receiving a first CO2 concentration and a first pH value, the first CO2 concentration being a CO2 concentration of a first gas volume above a medium in a first tank, the first CO2 concentration and the first pH value being measured at a first time when the medium in the first tank is in pH-CO2 equilibrium state with the first gas volume and before said equilibrium state is modified by the metabolism of a cell culture in the first tank, the first pH value being a measured value provided by a first pH measuring device operatively coupled to the first tank (102);receiving a second CO2 concentration and a second pH value, the second CO2 concentration being a CO2 concentration of a second gas volume above a medium in a second tank, the second CO2 concentration and the second pH value being measured at a second time when the medium in the second tank is in pH-CO2 equilibrium state with the second gas volume and before said equilibrium state is modified by the metabolism of a cell culture, the second pH value being a measured value provided by a second pH measuring device;comparing the first and second pH values and CO2 concentrations for determining if comparing (206), by the comparison unit, the first and second pH values and comparing the first and second CO2 concentrations for determining if the first pH measuring device is affected by the pH-measuring problem.