In the lighthouse project RNAuto, seven Fraunhofer Institutes are researching on automated production technologies for innovative mRNA-based therapeutics. This will facilitate the technological basis for access to novel vaccines or gene and cell therapeutics for numerous patients. The aim is to ensure a resource-saving and economical healthcare. 

Previous solutions do not sufficiently consider the complete process chain for scaled manufacturing under the high requirements of the good manufacturing practice (GMP). Due to a lack of interfaces, as well as a modular design and suitable sensor technology for online quality control, many manual steps are still required for semi-automated all-in-one devices. In addition, these devices are not usable for allogenic cell therapeutics.

Therefore, the consortium aims to develop an automated screening device for the process development of mRNA nanotransporters and a closed expansion module with an integrated quality control. By replicating all process steps in a digital twin, production can be continuously monitored and optimized. 

In the lighthouse project, Fraunhofer IMS is responsible for the development of the sensor technology for online quality control. In close cooperation with the Fraunhofer IMM, a miniaturized fluorescence-based flow cytometer module will be developed that uses microfluidic sample processing to monitor the state of cells in just a few hundred microliters. Fraunhofer IMS uses time-resolved photodetector arrays based on single photon avalanche diode (SPAD) technology. The integration will be done via microsystem 3D integration technologies with microfluidics to form a single measurement unit. Via sensor-related AI-based data analysis, multiparametric data will be extracted from the time course of the fluorescence signal and made available for process control.

The feasibility of the project is demonstrated by two drug candidates - an mRNA vaccine for prophylaxis against the viral disease West Nile fever and an mRNA-induced gene therapy against cancer based on natural killer cells (NK cells) derived from healthy donors.