P15: Critical Analytical Measurements for Fermentation Optimization

Most bioreactor fermentation processes share a basic principle; optimizing and controlling an organism’s chemical environment leads to consistent and enhanced product yield.  The required conditions do not remain constant throughout the various stages of cell growth, and therefore, must be closely monitored and controlled.

Among the critical analytical measurements are pH, dissolved oxygen (D.O.), dissolved carbon dioxide (CO₂), and cell density.  Maintaining ideal solution pH is critical for proper cell development and growth.  During aerobic fermentation, controlling dissolved oxygen concentration assures adequate supply of oxygen for respiration.  In keeping with the principles of the Process Analytical Technology (PAT) initiative, the addition of the measurement of dissolved carbon dioxide in solution provides a more complete picture of the respiratory cycle, and helps prevent CO₂ toxicity.  In this paper, emphasis is given to the use of this new CO₂ measurement device.

Measurement and control of the above parameters optimizes the likelihood of a successful fermentation.  Monitoring the resulting cell mass using optical density provides immediate feedback confirming the process progression.  Details of each measurement methodologies are presented.  Specific system demands of the biotechnology industry including hygienic and sterilizable designs and agency conformance are discussed.