Bioreactor pH Sensor Drift Detection via CO2 Equilibrium Comparison
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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 readings, which can result in incorrect 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 by comparing CO2 and pH values between reference and monitored tanks, allowing for the detection of calibration errors and offset effects without the need for offline measurements, thereby enabling accurate pH value determination and device recalibration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If pH measuring devices are calibrated using commercially available reference solutions requiring withdrawal and re-introduction from the tank, then calibration can be performed, but the pH measuring device may be affected by autoclavation and require re-calibration, increasing complexity and potential errors
Solution Approach 1:
The patent extracts the calibration function from the traditional offline reference solution method and implements it within the online measurement system using CO2 concentration measurements and pH-CO2 equilibrium relationships. This eliminates the need to withdraw the pH measuring device from the tank for calibration, removing the autoclavation step and associated complexity while maintaining calibration accuracy through the mathematical relationship between CO2 concentration and pH at equilibrium
Solution Approach 2:
The system performs self-calibration by utilizing the inherent pH-CO2 equilibrium relationship in the bioreactor medium. The pH measuring device and CO2 measuring device work together to automatically determine calibration parameters without external intervention or removal from the tank. The system uses measured CO2 concentration and known medium composition to calculate expected pH values, enabling continuous self-validation and recalibration
2Measurement precision
If offline pH measurements are performed by withdrawing medium samples, then pH values can be measured, but offset effects occur due to temperature, pressure, or air composition differences during sampling and transport
Solution Approach 1:
The patent replaces the mechanical sampling and transport process with an online in-situ measurement system. Instead of physically withdrawing samples and transporting them to a pH meter, the system uses a pH measuring device positioned within the bioreactor to measure pH values directly at the measurement location. This eliminates all offset effects associated with sampling, temperature changes, pressure changes, and air composition variations during transport
Solution Approach 2:
The patent introduces CO2 concentration measurement as an intermediary parameter to establish a reference relationship with pH values. By measuring CO2 concentration in the gas phase above the medium and using the known pH-CO2 equilibrium relationship for the specific medium composition, the system creates an indirect but accurate reference that avoids all the problems of direct sample handling while still enabling calibration and offset effect identification
3Ease of operation
If tank-external pH measuring devices are used for measuring pH values of medium samples, then measurements can be performed, but the process increases contamination risk and may not accurately reflect actual tank conditions
Solution Approach 1:
The patent transitions from external offline measurement to internal online measurement by positioning the pH measuring device within the bioreactor medium. This dimensional change from outside-to-inside measurement enables continuous real-time monitoring of actual tank conditions without the need to withdraw samples. The system measures pH values in the exact location where they are needed, eliminating contamination risks associated with opening tank seals and introducing external devices while providing trustworthy data that truly reflects tank conditions
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 ensures accurate comparison and synchronization of bioreactor states by correcting calibration errors and minimizing contamination risks, allowing for precise monitoring and control of bioreactor conditions without the need for sample-based calibration.
Implementation Method 1
a first pH value being a measured value provided by a first pH measuring device (108; 146)
Implementation Method 2
the first time being a time when the medium in the first tank is in pH-CO2 equilibrium state with the first gas volume at a predefined temperature and pressure
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.