In-Line Real-Time Monitoring Of CHO Cell Culture Process Parameters Using Raman Spectroscopy

Cell culture processes are complex and highly variable and yet only a handful of key parameters such as temperature, pH, and dissolved oxygen (DO) are typically controlled in real time. While measurement and control of these parameters are essential for a robust process, they do not provide a direct indication of the culture content itself; instead, they provide only broad assumptions on the culture’s true state and offer limited insights into the process and cell growth.

In contrast, critical process parameters (CPP) such as glucose, lactate, or ammonium and key performance indicators (KPI) such as total cell density (TCD) and viable cell density (VCD) provide direct indication of the culture’s content and state. These measurements are typically measured offline, however, and do not provide real-time information or effective process control. Another challenge of monitoring cultures is the requirement for daily, manual sampling which increases the risk of batch failures due to the increased risk of contamination.

This application note describes use of the ProCellics™ Raman Analyzer with Bio4C® PAT Raman Software (also known as Raman PAT Platform) to perform inline and real-time measurement of TCD, VCD and the concentration of glucose, lactate and ammonium in a bench-scale bioreactor.