Synthetic modeling: A cell‐free approach for faster implementation of Raman spectroscopy in cell culture

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, celllines, 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.