Monitoring of SARS-CoV-2 VLP production bioprocess by mid-infrared spectroscopy

• Grant number: 21/14451-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2022
• End date: February 29, 2024
• Field of knowledge: Engineering - Chemical Engineering
• Principal Investigator: Eutimio Gustavo Fernández Núñez
• Grantee: Felipe Moura Dias
• Host Institution: Escola de Artes, Ciências e Humanidades (EACH). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Classic off-line analytical techniques for biochemical monitoring of bioreactions are commonly used, however, they demand the acquisition of equipment, specialized labor and costly analysis time. Nevertheless, modern bioprocess monitoring requires techniques that can be applied to the simultaneous determination of critical process parameters, with minimal runtime and little or no sample preparation. In this sense, mid-infrared spectroscopy (MIR) combined with multivariate statistical or artificial intelligence techniques has been shown to be a viable alternative. MIR can be used to analyze critical process parameters such as nutrients, metabolites, denaturation, aggregation and product concentration, as well as quantification of biopharmaceutical phosphorylation and glycosylation levels. Given the above, the present work aims at the acquisition of MIR spectral data and the quantification by classical techniques of nutrients, metabolites, concentration of viable cells, viral titers and concentration of virus-like particles (VLP) of the samples generated in the process of developing SARS-CoV-2 VLP production in benchtop bioreactors. Correlation models between spectral data and previously defined parameters will be calibrated from multivariate analysis - principal component analysis, partial least squares and artificial neural networks. From this, it is expected the simultaneous determination of critical process parameters through spectral data in a quick and less expensive way for a better characterization, monitoring and control of the bioprocess in the different stages of development until the eventual commercial scale. This work will also make it possible to lay the foundations for the development of chymosensors in the near future.