Level measurement in bioreactors is useful for fed-batch and continuous operation. Depending on reactor size, process requirements, and budget, several different systems are available. For media preparation and holding tanks, level measurement provides essential information on the filling status.
Conductive Level Probe (σ)
The conductive level probe is the simplest and most economical option for level control. It is primarily used for smaller scale reactors. The probe is mounted on the vessel lid and reacts to contact and non-contact only, according to the same principle as antifoam control. In continuous cultivation, the liquid level is maintained by removing medium with a harvest pump as soon as the probe is in contact with the medium. For fed batch applications, the maximum level must be reached for the probe to be able to take a measurement.
This method provides a purely volumetric information about the vessel content. If it is primarily important to limit a certain level in order to prevent overflow of vessel content in the exhaust line or in addition ports in vessel headspace, this probe is an ideal solution. If it is important to get continuous information about the level content from zero to maximal filling height or if the actual weight of the fermentor content has to be measured or kept constant, other measurement principles will be necessary such as those described below.
Platform Scale and Load cells (F)
For smaller to mid-sized pilot vessels, the entire fermentor can be placed on a platform scale to determine the liquid level within the vessel.
At larger scales – usually of 300L and higher volume – the vessel legs may be equipped with integrated load cells. The Tare must be carefully measured, considering among others, the filling of the heating jacket and dosing lines of the fermentors.
In larger and rigidly piped fermentors where not all peripheral piping is placed together with the vessel on a platform, all the connecting piping to the vessel standing on load cells must be especially considered during plant design and installation: shorter pipes, pipes with large diameters or potentially unsuitable angles must be avoided, usually by placing flexible inserts. If not, mechanical forces as the pipes expand or contract at different temperatures will result in an incorrect indicated weight value.
The measurement value for the fermentors contents is independent from the gas hold up of the liquid, meaning that the measurement always provides the real value for the mass of the liquid within the vessel. Hence, changing aeration rate or stirrer speed will not change the measurement value for weight of the fermentor content. On the other hand, the indirectly determined volumetric level can vary with different gas hold up.
The scale/load cells measure the weight of the fermentor contents and are calibrated for the density of the liquid at a particular volume. As this method measures the liquid level throughout the vessel, it is suitable for continuous monitoring of the fed batch process.
Platform scales or weight cells are solutions providing precise and unadulterated measurement values for weight of vessel content, independent of intensity of agitation. However, this comes at the cost of additional effort in the design and manufacturing of the plant.
“BioWeight” differential pressure (Δp)
Bioweight sensors are an alternative to the solutions above for continuous level monitoring at pilot or production scale. Two connected pressure sensors located in the vessel bottom and headspace of the vessel measure the differential pressure resulting from the weight of the liquid column between the two sensors. Thus, the total weight of liquid in a cylindrical vessel with known diameter can be precisely determined. The volume is calibrated based on the density of the medium. The probes are small, accurate and dead leg free as well as easy to install.
Furthermore, the differential pressure method is independent of any forces resulting from peripheral piping or other extraneous factors like operators leaning on the vessel while sampling for instance. No expensive and service intensive flexible pipe inserts are necessary, nor does the filling status of connecting pipes affect the measurement value. As it is the case for platform scales and loads cells, the measured weight value for the contents of the fermentor is independent from the gas hold up of the liquid.
The “BioWeight” measurement system provides precise measurement values for weight of vessel content with a minimum of installation complexity. It is especially suitable for large vessels with a tall geometry. However, intensive stirring may influence the measurement value.