Dissolved Carbon Dioxide (DCO₂) Sensors
Is Your Bioprocess in Control?
Dissolved carbon dioxide (DCO₂) is a critical process parameter (CPP) in biopharma production processes according to PAT guidelines. By influencing other parameters such as extracellular and intracellular pH, it has an effect on different metabolic pathways which are involved in cell growth or in product formation and quality.
Introducing CO₂NTROL
Automated Control of DCO₂ Enables:
Increased Titer
Reproducibility
Consistency
Bioreactor Size Impacts CO₂
Large and small bioreactors have Mass Transfer Coefficients (KLa) that change the dissolution and stripping characteristics from reactor to reactor. As a result the same control strategy will result in different CO₂ accumulation across R&D, PD, and Production scale reactors. Only real-time control of DCO₂ to an optimized profile will result in comparable mass transfer independent of scale.
| Optimizing Yield While the small surface area to volume ratio of a typical R&D reactor means that CO₂ accumulation is minimal. Real-time control of CO₂ is critical to define the optimal set-point and optimize product yield. | Scale Up Mimicking sparging and stripping strategies optimized for R&D will result in different conditions as the surface to volume ratio decreases. Active control of an optimal DCO₂ profile ensures consistency across scales. | Scale Down For existing processes that were developed without DCO₂ control, the efficiency of scale-down studies can be improved by actively controlling DCO₂ to mimic the profile seen in the production reactor. |
Impact of CO₂ on Process Performance
– Excessive Accumulation During a process excess CO₂ accumulation is common as cell concentration increases and more metabolic CO₂ is produced. This accumulation reduces intracellular pH resulting in slower enzymatic activity or delayed lactate shift. The outcome is lower production quantity and quality. | – Excessive Removal Aggressive aeration and mixing can prevent detrimental accumulation of CO₂. However, too little CO₂ can slow cell growth, metabolism, and productivity by starving cells of CO₂ needed for the formation of metabolic intermediates. Excessive removal can also reduce buffer capacity in bicarbonate systems. | – Uncontrolled CO₂ Range Media addition and process adjustments can result in large swings in dissolved CO₂ that may go unnoticed with infrequent offline monitoring and adjustment. Continuous inline control at the optimal level yields increased viable cell density, production phase duration, and titer. |
Specific Applications
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App Note - Real-time Monitoring of DCO2 in Addition to DO
In this application note, the utilization of a DCO2-probe in addition to a DO-probe at Ostwestfalen-Lippe University of Applied Sciences and Arts, is briefly described using cell cultivation with varying stirring speeds to demonstrate the value added of inline dissolved gas measurement.
Resources
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Catalog - Process Analytics
Download the Process Analytics sensor catalog to learn about the complete offering of Hamilton process sensors and accessories. -
Brochure - BioPharma
Innovative solutions for process analytics in biotechnological and pharmaceutical industries. -
Brochure - Arc Intelligent Sensors
Arc Intelligent sensors offer a new way to connect to your process control system.
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What should CO₂NTROL be reading in air?
The measurement range of the CO2NTROL sensor is 0.5 to 100% CO2 volume which is suitable for cell culture applications. The normal level of CO2 in air is approximately 0.04% which is technically below the measurement range of the sensor. Since the CO2 value is outside of the sensor measurement range, the error will be significant and the reading may appear to be noisy. Please note that this is acceptable and one of the reasons that air is used as a calibration point. -
Is the CO₂NTROL CO₂ sensor sanitary?
The tip of the CO2NTROL sensor has round "dots" that give the appearance of perforated metal. This surface is actually smooth. It is covered with a layer of translucent silicone that ensures a sanitary design. In fact, the design meets EHEDG sanitary requirements and has been certified. -
What is the output signal of the CO₂NTROL Sensor?
The CO2NTROL Sensor provides a Modbus RTU RS485 digital signal as standard. With the additional of the Wi 2G BlueTooth Wireless Adapter (Ref 243470) the sensor can provide two 4 to 20mA analog outputs in addition to the Modbus signal. Hamilton also offers signal converters for OPC, Profibus, and Profinet to ensure compatibility with various SCADA software and controllers.
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Best Practices: Zero Point Oxygen Calibration
There are several methods to achieving a good zero point calibration of optical and polarographic DO sensors. This paper looks at each procedure in depth. -
CO₂NTROL RS485 Sensor Calibration
Since CO2 measurement can be a new parameter for some users this article provides some basic question and answer topics related to calibration of this sensor. -
Cleaning Procedure for CO₂NTROL Sensors
This brief article highlights both inline and offline cleaning processes for the solid state sensing element used in the CO2NTROL RS485 CO2 Sensor.
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