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Increase Yield and Consistency

New research shows that active control of dissolved CO₂ in bioproduction increases product yield and improves consistency of process scale-up and scale-down. Traditional electrochemical sensors indirectly measure DCO₂, are maintenance intensive, and are prone to measurement drift. CO₂NTROL is a Solid State Sensor that directly measures DCO₂ and provides maintenance free, real-time, and in-line control of this new critical process parameter.

CO₂NTROL

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Automated Control of DCO₂ Enables:

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.

Direct vs. Indirect

Traditional electrochemical sensors measure DCO₂ based on the Severinghaus principle. This indirect measurement method combines the challenges of measuring pH and electrochemical DO into one sensor. The result is significant maintenance effort and multiple sources of drift that must be compensated by time-consuming product calibration. Hamilton’s CO₂NTROL is a maintenance free, solid-state sensor that directly measures DCO₂ resulting in better measurement accuracy and lower cost of ownership.

Streamlined Workflow

The CO₂NTROL development team recognized that for CO₂ to become a critical control parameter the sensor had to be easy to use and maintain. To accomplish this we had to reduce the complexity and eliminate liquid solutions and replacement parts. The team developed a Solid State MIR design that is calibrated in certified gas and does not require a product calibration because of drift after sterilization processes.

Maintenance-Free Solid-State CO₂

Simple Calibration

In air and gas standard.

Measuring Range

Designed for bioproduction (5–1000 mbar).

Maintenance Free

No liquids or replacement parts to change.

Hygienic Design

Compatible with Autoclave, SIP, or CIP.

Inverted Installation

Not affected by mounting orientation.

No Ammonia Fouling

No interference from other dissolved gases.

Get CO₂NTROL

CO₂NTROL is the newest member to Hamilton’s Arc Intelligent Sensor line. Embedded electronics convert the MIR CO₂ measurement into standard digital and analog signals that are easily integrated into your control strategy.

ARCAIR
Seamless control of all Arc products from a PC or mobile device. CO2NTROL pairs with the newest ArcAir software to automatically store all sensor activities, diagnostic data, and health indicators throughout the life of the sensor. ArcAir is ready for GMP with Part 11 and Annex 11 compliance.
WIRELESS CONNECTIVITY

An optional Bluetooth adapter and ArcAir software enable wireless calibration, configuration, and monitoring of all sensor details.

INTEGRATED INTELLIGENCE
Arc sensors save space and cost with their integrated micro-transmitters. Calibration data is stored in the sensor head enabling high quality lab calibration.
PROCESS DATA
The CO2NTROL sensor transmits process data through a hardwired connection. Communication options include modbus RTU and 4-20 mA, with additional compatibility for OPC, Profibus, and Foundation Fieldbus coming soon.
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