Comparison of Time-Gated and Traditional Raman Spectroscopy in Upstream Bioprocess

Time-gated Raman Spectroscopy (TGRS) is an emerging analytical technique with the potential to transform real-time bioprocess monitoring by overcoming the fluorescence interference that limits Traditional Raman Spectroscopy (TRS). In this study, we compared the performance of TGRS and TRS for quantifying key analytes; glucose, and lactate in Chinese hamster ovary (CHO) cell cultures. Accurate and timely measurement of these metabolites is essential for maintaining optimal conditions in upstream biomanufacturing processes.

Partial Least Squares (PLS) regression models were developed to evaluate calibration, cross-validation, and external prediction performance. TGRS achieved significantly lower RMSEP values for glucose (0.33) and lactate (0.22) compared to TRS (1.43 and 0.89, respectively), along with higher R² prediction scores (0.98 and 0.99). TGRS also required fewer latent variables and showed minimal bias, indicating greater model robustness.
These findings establish TGRS as a viable Process Analytical Technology (PAT) tool for accurate, in-situ monitoring of analyte concentrations during biomanufacturing.