Optimizing Bioreactor Processes with Flow Control

In bioreactors delicate processes take place to multiply biological materials. These processes contain valuable substances, sometimes even beyond a price tag, and can be an important step in a new vaccine or treatment.

Our commitment to customers in the biotech industry is to quarantee a reliable and reproducible flow control in their bioreactors. For this we use mass flow controllers.

For this blog we interviewed Vincent Hengeveld, Product Manager at Bronkhorst, about the use of flow controllers to realise a realiable and reproducible gas flow control. ‘Reliability refers to the quality of being able to be trusted to do what somebody wants or needs’ (Definition Oxford dictionary). Vincent explains why our flow controllers can be referred to as ‘reliable’.

Why do we refer to our flow controllers as ‘reliable’?

Our mass flow instruments are using robust sensors and valves, have stable electronics and firmware, and are best in class regarding MTBF – Mean Time Between Failure – data (based on the IEC 61508 standard).

Additionally, material traceability and accuracy are assured by material and calibration certificates, which results in improved reliability for your biological process.

Could you explain what the high accuracy statement means and why this is an important selection criteria for our customers in the biotech industry?

Download here our Bronkhorst MTBF Statement

How is the gas flow controlled?

For these applications Bronkhorst offers mass flow controllers, based on reliable and accurate capillary bypass technology and valve technology. This allows you to achieve a dynamic flow range of up to 1 : 1000, providing the low and high flow rates required for the growth process. Mass flow controllers using capillary bypass technology, have a tube-shaped flow sensor inside that is positioned parallel – in bypass – with the main flow path. There is a split of gas flow into the flow sensor and the main flow path. This technology enables reliable and accurate flow measurement and control for all gases involved.

How is the gas flow controlled?

Flow sensor used in the capillary bypass technology

Why is an accurate gas flow control needed?

Optimal accuracy and ratios are required to allow the biological substance to grow in the right environmental conditions. During a bioreactor campaign, biological substance grows over time and requires an increasing flow rate during the growth process. Both low and high gas flow rates are needed.

The principle of bypass technology

Only a part of the gas stream flows through the sensor and is warmed up by two heater elements (RHT1 and RHT2). The gas flow through the flow sensor is a proportional measure for the total flow through the instrument. Due to the homogeneous nature of the temperature distribution within the sensor, only the flow rate, the density and the heat capacity of the gas determine the flow output signal (Q, ρ, Cp).

Reliability over time – MTBF rating

Mean Time Between Failures (MTBF) is used as a measure for availability and reliability of products. MTBF predicts the time that equipment is operating between breakdowns or stoppages. There are several methods of calculating the MTBF rating, with the IEC 61508 based on the Exida component database being the industry standard. With a MTBF rating of over 130 years for the major biotech industry product lines, we are best-in-class.

Onsite service technician

Easy field calibration

The conversion method and free software tools, make it is easy for you to calibrate the instruments in the field with Air and Nitrogen. This way, you can maintain the high accuracy of the instrument as documented in the calibration certificate. Which was provided to you together with the flow device.

Intelligent flow controllers for bioreactor processes

Especially for bioreactor processes, when working with valuable substances, it is very helpful if you can monitor the ‘health’ of your instruments. To ensure the continuity of your process. For this, several parameters & diagnostics are interesting:

Measuring the device internal temperature and detecting temperature variations to improve product quality
Response alarm to monitor if the flow controller reaches and maintains its setpoint within the specified limits. It it helpful to indicate if the inlet pressure is too low, if a gas bottle is almost depleted, or to detect obstructions in the system.
Power-up alarm message and function to return; after a power failure the process can continue directly returning to the last setpoint.
Measure & valve out; by comparing the values of these parameters over time, you can detect if something has changed in the setup. E.g. a variation in inlet pressure or if there is some clogging or wear of components in the setup. In this case maintenance is adviced.