Synthetic modeling: a cell-free approach for faster implementation of
Raman spectroscopy in cell culture
- Célia Sanchez,
- Hadi El Radi,
- Nathan Gay,
- Johan Cailletaud,
- Kévin Grollier,
- Fabrice Thomas,
- Thierry Gonthiez
Abstract
Monitoring cell culture is crucial for gaining a deeper understanding of
processes and ensuring the production of safe and high-quality products.
The capability to measure in real-time several parameters of interest
can be achieved with Raman spectroscopy. However, before using Raman
spectroscopy to monitor a specific process, a calibration phase is
required to develop chemometric models that correlate Raman spectra with
the target parameters. It is mandatory to conduct this phase with
multiple batches to build robust models that account for biological
variability. This model building phase can be time-consuming and require
a lot of resources. The industry is actively seeking solutions to
simplify and expedite this step without compromising accuracy. Moreover,
the current approach has limitations regarding changing cell culture
media, cell-line, or process scale. The novel synthetic model approach
provides a significant gain of time and resources for the calibration
phase which is reduced to just a few days. The methodology involves
using cell-free samples of cell culture media that are spiked with
various concentrations of target compounds. The results indicate that
the innovative approach enables accurate measurement for glucose and
lactate parameters in real process conditions comparable to a standard
modeling methodology.