Inline Raman spectroscopy as process analytical technology for SARS-CoV-2 VLP production

Area of Science:

• Biotechnology
• Process Analytical Technology (PAT)
• Spectroscopy

Background:

• Monitoring bioprocesses like SARS-CoV-2 VLP production is crucial for optimizing yield and quality.
• Traditional offline methods for monitoring biochemical parameters are time-consuming and labor-intensive.
• Inline process analytical technology offers real-time insights into bioprocess dynamics.

Purpose of the Study:

• To develop and validate inline Raman spectroscopy methods for real-time monitoring of SARS-CoV-2 VLP production.
• To compare the performance of chemometric models, including Partial Least Square (PLS) and Artificial Neural Network (ANN), for predicting biochemical parameters.
• To assess the applicability of these models across different culture media.

Main Methods:

• Inline Raman spectroscopy was employed for real-time data acquisition during SARS-CoV-2 VLP production.
• Chemometric models, including linear, PLS, and ANN, were developed to correlate spectral data with biochemical parameters.
• Key parameters monitored included viable cell density, cell viability, glucose, lactate, glutamine, glutamate, ammonium, and viral titer.

Main Results:

• ANN models generally provided better fitting for most biochemical parameters, while PLS models were more suitable for viable cell density and glucose.
• The developed models demonstrated good accuracy in predicting parameters within their quantified ranges, with low mean absolute errors.
• The models showed robust performance across two different culture media, indicating broad applicability.

Conclusions:

• Inline Raman spectroscopy, coupled with chemometric modeling, is a powerful tool for real-time monitoring of SARS-CoV-2 VLP production.
• ANN and PLS models offer effective strategies for predicting critical biochemical parameters, enabling better process control and optimization.
• This approach facilitates efficient bioprocess monitoring and can be adapted for various cell host systems and culture conditions.