On-line, real-time measurements of cellular biomass using dielectric spectroscopy.

Introduction All else being equal, the productivity of a biological process is determined by the quantity of biomass present. There is therefore a major requirement for the accurate measurement and control of the biomass within fermentors, at both laboratory and industrial scales. Presently the range of sensors available that can be used in situ and reliably for the monitoring and regulation of biotechnological processes in general is rather limited. These sensors normally rely upon physical (e.g. optical, mechanical and electrical) or chemical variables (e.g. pH and concentration) rather than biological ones per se (Sarra et al., 1996; Pons, 1991). However only physical methods allow the on-line, real-time estimation of biomass (Harris and Kell, 1985). As well as physical methods, any easily determinable chemical that is produced or consumed by cells at an essentially constant rate during cell growth may also be used to assess biomass, e.g. carbon dioxide evolution and oxygen consumption. In these indirect methods biomass is then calculated based upon mass balances, stoichiometric relationships or empirical constants. However, this type of approach has the great disadvantage that it does not generally discriminate between biomass and necromass (Kell et al., 1990). Even if biomass was easily measurable there is still the question of what is biologically relevant information for fermentation control and how can one define and quantify it (e.g. metabolism, viability, vitality, morphology) (Kell et al., 1987; Kell, 1987a;