CELL-DENSITY MEASUREMENTS IN HOLLOW FIBER BIOREACTORS

The cell density measurement technique described is based on the relationship between the electrical conductivity of a suspension of membrane-bound vesicles and the volume fraction enclosed by those membranes. This relationship was described mathematically by H. Fricke and has been proven to hold for suspensions of blood (human, dog and horse), yeast, and mouse lymphoma cells. A probe has been developed which has been shown to provide a stable, non-destructive measurement of cellular volume fraction within a hollow-fiber bioreactor. Although there is some uncertainty involved in calculating the volume fraction, the results of several experiments lead to the same conclusions. As the cells approach 0.3 volume fraction in the current reactors, oxygen limitation becomes apparent. Simultaneously, the cells lose tolerance for high lactate concentrations, and either consume lactate or produce it at lower rates. The combination of oxygen limitation and lactate inhibition seems to cause cell death.