Dissolved CO2 Measurement In Bioprocess from R&D to Production

Dissolved CO2 in Bioprocess

CO2 has many important roles in growth and maintenance of cell and bacteria cultures. CO2 acts as an additive product which affects a wide range of metabolic and critical process parameters. It is important to track dCO2 in your cultures for:

• Intracellular/Extracellular pH changes
• Glycosylation and Molecule Stability
• Lactate production
• Monitor Biopharma/Biotech or Brewing applications

This level of impact makes dissolved CO2 (dCO2) a critical process parameter (ie. pH, DO, and Viable Cell Density), that is necessary to be continuously monitored and automatically controlled to ensure high process productivity, scalability, and quality.

Dissolved CO2’s Role from R&D to Production

As a process is optimized, CO2 is relatively easy to maintain and control, given the smaller volumes of bench top reactors. But as the scale and design of reactors become larger, so does the challenge of maintaining an optimal CO2 range. With a smaller surface to volume ratio in larger vessels, it becomes harder to strip CO2 via surface aeration. The differences in CO2 between scales have a direct impact on titer production and quality.

It is important to establish a kLa profile as well as monitor dCO2 levels at the small scale, which can then be applied to a large process, to meet the challenge of increased accumulation of CO2 that develops at the bottom the reactor. Designing a thorough CO2 profile at the small scale can enable speedy scale up strategies, reducing the chance of having to scale a process back down to troubleshoot.

Real-time dissolved CO2 measurement enables exact replication from small to large scale, removing another variable that could require time consuming iterations between process development and manufacturing.

CO2 Real-time Measurement

Along with pH and DO, it is imperative to understand a culture’s optimal CO2 range at all times that may vary by cell line and vessel size. This calls for an in-situ measurement that can optimize visibility and reduce time-consuming grab samples.

Mettler Toledo’s InPro 5000i CO2 probe can accurately and continuously provide dissolved CO2 measurement at all process scales. The InPro 5000i utilizes the Severinghaus principle for measuring dCO2 in media, the same technology as a typical offline blood-gas analyzer. This introduces the opportunity to take an already proven technology from a slow manual process on the bench to a fast and easy in situ measurement.

Real-time measurement of dCO2 can deliver higher viable cell densities, improve growth profiles, and give larger product yields. The benefits of knowing more about dissolved CO2 measurement in bioprocess is outlined further in the new dCO2 Theory and Best Practice booklet from Mettler Toledo here. Please reach out to ProAnalytics to schedule a trial today!