The internal composition of the living cell is vastly different from its environment, notably with respect to pH and ion concentrations (Na+, K+). In fact, the differences are essential for the maintenance of the proton-motive force, which is used by an organism to perform work, for instance to make ATP, to drive thermodynamic unfavourable reactions and to take up substrates from the medium.
Numerous methods have been developed to measure membrane potentials, ion concentrations and pH-differences across the cell membrane. Many of the methods are based on the use of radio-labelled compounds that can be measured with high sensitivity. More recent methods take advantage of the fluorescent properties of new-designed or natural substances. In our measurement of the intracellular pH in methanogens, for instance, we just use coenzyme F420 which is present in the cells in high amounts and serves as a very accurate pH probe. More convential methods, like atomic absorption spectroscopy, are applied for the determination of ion concentrations like Na+ and K+.