Chemometric Solutions | Enhancing Mammalian Cell Culture Monitoring

Enhancing Mammalian Cell Culture Monitoring with Raman Spectroscopy

Project Overview

Within the framework of the ICONSENSUS Project, our primary objective was to elevate the monitoring of mammalian cell cultures—an integral component of modern pharmaceutical production. The sensitivity of these cultures necessitates precise monitoring and stringent process control. Traditional methods for real-time measurement of critical parameters like glucose, glutamine, glutamate, and lactic acid often suffer from drawbacks such as sluggishness, inaccuracy, or exorbitant costs.

Innovative Solution

To overcome these challenges, we embraced advanced spectroscopic techniques, specifically Raman and 2D Fluorescence Spectroscopy. This strategic choice was driven by the need for a solution that offers high-speed, accurate, and information-dense assessments of key parameters and the metabolic state of cell cultures. Despite not being the most cost-effective option, the use of these advanced spectroscopic methods justified the investment, especially considering their capacity to simultaneously measure multiple parameters.

Implementation

Our implementation strategy involved training machine learning models using spectra obtained from test cultivations. Prioritizing simpler regression models for their broad applicability, we aimed to maximize reliability and resilience. For continuous processes, we seamlessly integrated Just-in-Time Learning (JITL) to automatically adapt to subtle shifts in the process, eliminating the need for frequent recalibration.

Just-In-Time Learning

Results:

The project yielded notable outcomes, particularly through the implementation of Just In Time Learning (JITL) and the use of Raman hardware with exceptional detection limits. The estimated limit of detection was an impressive 0.1 mmol/L for various chemical compounds, with notable results for specific parameters:

Glucose concentration: Error margin of 0.3 g/L
Lactate concentration: Error margin of 0.2 g/L
Glutamine concentration: Error margin of 0.15 mmol/L
Glutamate concentration: Error margin of 0.2 mmol/L

These results underscore the transformative potential of Raman spectroscopy in revolutionizing mammalian cell culture monitoring. By enhancing both efficiency and accuracy, this innovative approach promises to elevate pharmaceutical production processes through tighter process control, ultimately contributing to the advancement of the pharmaceutical industry.