Bioreactor pH Calibration Checking via Headspace 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 bioreactors to identify pH measuring device calibration issues and offset effects by comparing CO2 concentrations and pH values between reference and monitored tanks, allowing for accurate calibration and minimization of sampling-induced errors without the need for offline measurements.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If tank-external pH measuring devices are used for measuring pH value of samples, then the risk of infection is reduced, but the measured pH value may deviate from the actual pH value due to offset effects
Solution Approach 1:
The patent introduces CO2 concentration as an intermediary parameter to indirectly determine pH calibration status. Instead of directly measuring pH with tank-external devices that cause offset effects, the system measures CO2 concentration in the headspace and uses it as a mediator to calculate or infer the pH calibration offset, thereby maintaining both low infection risk and measurement accuracy
Solution Approach 2:
The patent replaces the mechanical/chemical pH measurement system with an optical/electronic CO2 sensing system. By substituting direct pH electrode measurement with CO2 concentration measurement (using optical or electronic sensors), the system eliminates the need for physical contact with the medium that causes contamination while maintaining measurement capability through the CO2-pH relationship
2Measurement precision
If pH measuring devices are calibrated with reference solutions requiring withdrawal and re-introduction, then calibration accuracy can be improved, but the autoclaving process may affect the calibrated device
Solution Approach 1:
The patent performs calibration verification using CO2 concentration measurements before the autoclaving process occurs. By checking the pH calibration status in advance through the CO2 intermediary method, the system can identify calibration drift before autoclaving, allowing for timely recalibration without subjecting the calibrated device to the harsh autoclaving process
Solution Approach 2:
The patent implements a feedback mechanism where CO2 concentration measurements continuously monitor pH calibration status. This feedback loop allows the system to detect calibration drift and trigger recalibration procedures, ensuring calibration accuracy is maintained without requiring repeated withdrawal and re-introduction of the pH device for routine checks
3Measurement precision
If regular sampling is performed for pH measurement, then pH value monitoring is improved, but contamination risk and offset effects increase
Solution Approach 1:
The patent uses CO2 concentration in the headspace as an intermediary to monitor pH status without sampling the liquid medium. By measuring CO2 gas phase concentration and using it to infer pH calibration and status, the system achieves continuous pH monitoring capability while completely avoiding the contamination risks associated with liquid sampling
Solution Approach 2:
The patent replaces the liquid sampling and pH electrode measurement system with a gas-phase CO2 sensing system. This substitution eliminates the need to breach the sterile barrier for sampling while maintaining pH monitoring capability through the measurement of CO2 concentration that equilibrates between the headspace and liquid medium
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 precise calibration of pH measuring devices, reduces contamination risks, and ensures accurate comparison of bioreactor states by using CO2 concentrations to determine and correct calibration differences and offset effects, thereby maintaining optimal environmental conditions for cell cultures.
Implementation Method 1
a first time being a time when the medium in the first tank 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.