ONLINE CHARACTERIZATION OF A HYBRIDOMA CELL-CULTURE PROCESS

The on-line determination of the physiological state of a cell culture process requires reliable on-line measurements of various parameters and calculations of specific rates from these measurements. The cell c oncentration of a hybridoma culture was estimated on-line by measuring optical density (OD) with a laser turbidity probe. The oxygen uptake rate (OUR) was determined by monitoring dynamically dissolved oxygen c oncentration profiles and closing oxygen balances in the culture. The base addition for neutralizing lactate produced by cells was also moni tored on-line via a balance. Using OD and OUR measurements, the specif ic growth and specific oxygen consumption rates were determined on-lin e. By combining predetermined stoichiometric relationships among oxyge n and glucose consumption, and lactate production, the specific glucos e consumption and lactate production rates were also calculated on-lin e. Using these on-line measurements and calculations, the hybridoma cu lture process was characterized on-line by identifying the physiologic al states. They will also facilitate the implementation of nutrient fe eding strategies for fed-batch and perfusion cultures, (C) 1994 John W iley & Sons, Inc.