. Instruments and techniques for bioprocess variables determination and monitoring

To achieve the biological potential of cells, the optimal environmental conditions must be maintained in the bioreactor for cell growth / product formation, at least with regard to the key parameters. Generally speaking, biological systems are influenced by different process variables, which have a direct influence on cell metabolism. Sensors for these variables are (typically) inserted into specially designed ports on the bioreactor. As bioreactors increase in size (i. e. in the industry field), the mixing problems become usual and probe location becomes problematic. To accurately outline large fermenters, probes may be collected from several locations.

A. Direct physical determinations

The existence of defined and optimal environmental conditions for biomass and product formation means that different physical and chemical parameters require to be kept constant or conforming to an optimal evolution trend during the process, i. e. any deviation from a specified optimum might be corrected by a control system.

The standard direct physical determinations are3: (1) temperature; (2) pressure (over pressure); (3) agitator shaft power and rate of stirring; (4) foam; (5) gas and liquid flow; (6) weight.

Temperature determination is important for bioprocess evolution as well as other process operations (i. e. sterilization, concentration, and purification). The temperature measurement is made in the range +20oC to +130oC through mercury-in-glass thermometers, bimetallic thermometers, pressure bulb thermometers, thermocouples, metal-resistance thermometers or thermistors; all of them must be steam-sterilizable at 120oC. The most popular are the Pt100 resistance thermometers.

Pressure measurements may be needed for several reasons; the most important of them is the safety. Industrial and laboratory equipment is designed to withstand a specified working pressure plus a factor of safety. Also, the measurement of pressure is important in media sterilization. Moreover, the pressure will influence the solubility of gases and contribute to the maintenance of sterility, when a positive pressure is present. The standard measuring sensor is the membrane pressure gauge based on strain or capacitance measurements.

The formation of foam can create serious problems in no controlled situations: loss of broth, clogging of gas analyzers, infections, etc. It is a common practice to add an antifoam agent when the culture starts foaming above a certain predetermined level. A standard foam sensing consists in an electrical conductivity / capacitance / heat conductivity probe.

A number of mechanical antifoam devices have been made, including discs, propellers, brushes attached to the agitator shaft above the surface of the broth. Unfortunately, most of the mechanical devices have to be used in conjunction with an antifoam agent, without negative influence on the bioprocess behavior.