December 20, 2025 – A new study published in Bioprocess and Biosystems Engineering demonstrates how Time-Gated Raman Spectroscopy (TGRS) significantly improves analytical sensitivity for monitoring complex upstream bioprocesses — a development with strong implications for real-time process control in biopharmaceutical manufacturing.
Bioprocessing, especially mammalian cell culture like CHO (Chinese Hamster Ovary) systems, depends on accurate, real-time monitoring of key analytes (e.g., glucose, lactate, ammonia, glutamine, alanine). Conventional inline process analytical tools like standard Raman spectroscopy are valuable but limited by fluorescence interference, which reduces sensitivity and increases the limit of detection (LOD).
Time-Gated Raman Spectroscopy uses the time delay between Raman scattering and slower fluorescence emission to suppress background noise, enabling clearer detection of chemical signals even in complex media. By synchronizing laser pulses with detector timing, TGRS selectively captures Raman signal while minimizing fluorescence.
In this study, researchers applied a pure component modeling approach and Net Analyte Signal (NAS) analysis to evaluate how TGRS compares with traditional Raman in CHO cell culture samples.
This work highlights how TGRS can enhance Process Analytical Technology (PAT) by enabling more sensitive, accurate, and inline measurement of key variables in cell culture — a crucial capability for real-time monitoring, process control, and optimization. The improved analytical performance supports robust decision-making and could help advance automation and precision in biomanufacturing.
The authors note that future efforts will focus on developing chemometric models to translate TGRS signals into quantitative process insights within dynamic bioreactor environments, further unlocking the technology’s potential for industrial use.
👉 Read the original article:
https://link.springer.com/article/10.1007/s00449-025-03261-y