Cell culture monitoring: overcoming the “1 parameter = 1 probe” equation
Real-time is required to offer the capability to monitor the process by adjustment of the process parameters and feedings, namely automatic and real-time absolute quantitation of glucose, lactate, total and viable cell densities, without or with a minimal sampling. No sampling is required for use at R&D small-scale where frequent samplings would undermine cell growth. Besides, frequent samplings increase the risk of contamination.
The mentioned quantitation is the minimal information required for USP understanding.
A combination of two probes based on an enzymatic assay and two probes based on capacitance measurement would allow performing glucose, lactate, TCD and VCD monitoring in USP. But, four additional probes are almost impossible to implement on a bioreactor. Besides, such combination would be complex to implement in term of data alignment and calibration consistency.
Raman spectroscopy overcomes this problem and offers additional analytical capabilities, such as monitoring of glutamine, glutamate, other amino acids, protein conformation, etc., that no other solution can propose in-line.