Bioreactor pH Calibration Deviation Detection Using Headspace CO2
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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 readings, which can result in incorrect comparisons between bioreactors and affect the optimization of cell culture processes.
Innovation Solution
A method utilizing CO2 concentration measurements in the gas phase above the medium to determine if a pH measuring device is calibrated correctly, comparing CO2 concentrations and pH values between tanks to identify calibration issues and offset effects, allowing for the computation of an absolute expected pH value and enabling recalibration without removing the pH device from the tank.
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 sampling offset effects, leading to calibration errors
Solution Approach 1:
The patent introduces CO2 concentration as an intermediary parameter to establish a reference relationship. By measuring CO2 concentration in the headspace and using the known pH-CO2 equilibrium relationship, the system creates an indirect reference standard that avoids direct contact with calibration solutions and eliminates sampling offset effects, thereby resolving the contradiction between measurement precision and calibration reliability
Solution Approach 2:
The patent replaces the mechanical/physical calibration process (withdrawing the pH device, exposing it to reference solutions, re-introducing it) with a computational approach based on CO2 concentration measurements and equilibrium calculations. This substitution eliminates the harmful effects of autoclavation and sampling on calibration reliability while maintaining measurement precision
2Measurement precision
If medium samples are repeatedly withdrawn for pH measurement, then pH values can be monitored, but the risk of infection of the tank increases
Solution Approach 1:
The patent uses CO2 concentration in the tank headspace as an intermediary to determine pH values. By measuring CO2 concentration and applying the pH-CO2 equilibrium relationship, the system obtains pH information without withdrawing medium samples, thus eliminating the infection risk while maintaining pH monitoring capability
Solution Approach 2:
The patent replaces the mechanical sampling process (withdrawing medium samples with syringes or pumps) with a gas-phase measurement approach. CO2 concentration is measured in the headspace using gas analysis techniques, and pH is calculated computationally, eliminating direct contact between the external environment and the sterile medium, thus preventing infection
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 allows for accurate comparison of pH values between tanks, reduces contamination risks, and minimizes calibration errors by enabling online recalibration of pH measuring devices, ensuring precise control of bioreactor conditions.
Implementation Method 1
pH measuring devices are commonly used for measuring the pH value of a medium in a tank
Implementation Method 2
receiving, by a comparison unit, 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 (M1) in the first tank
Data Source
Figure 1
Figure 2~3
Figure 4A~4B
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.