An Integrated Acoustofluidic Device with Raman Spectroscopy for Process Analytical Technology for Continuous Manufacturing of Vaccines*

Viral epidemics and pandemics require rapid development and manufacturing of vaccines to limit the spread of the disease and minimize loss of life. Rapid production of vaccines requires standardized processes for controlling the quality of the product, demanding more innovative and reliable methods in process analytical technology (PAT). In this project, we use Raman spectroscopy as a PAT tool and combine it with machine learning algorithms to characterize viral particles for continuous in-process monitoring of vaccine contents. We use acoustofluidic methods to concentrate particles and improve the Raman signal and establish the basis for a standardized detection method. Different virus-like particles and vaccines were tested and characterized , showing our capability to identify the viral particles using the Raman spectra. Our spectro-acoustic PAT enables the real-time quantification of virus particles necessary for the continuous manufacturing of vaccines.