Automated application of low energy electron irradiation enables inactivation of pathogen- and cell-containing liquids in biomedical research and production facilities

Abstract

Ionizing radiation is widely used to inactivate pathogens. It mainly acts by destroying nucleic acids but causes less damage to structural components like proteins. It is therefore highly suited for the sterilization of biological samples or the generation of inactivated vaccines. However, inactivation of viruses or bacteria requires relatively high doses and substantial amounts of radiation energy. Consequently, irradiation is restricted to shielded facilities—protecting personnel and the environment. We have previously shown that low energy electron irradiation (LEEI) has the same capacity to inactivate pathogens in liquids as current irradiation methods, but generates much less secondary X-ray radiation, which enables the use in normal laboratories by self-shielded irradiation equipment. Here, we present concepts for automated LEEI of liquids, in disposable bags or as a continuous process. As the electrons have a limited penetration depth, the liquid is transformed into a thin film. High concentrations of viruses (Influenza, Zika virus and Respiratory Syncytial Virus), bacteria (E. coli, B. cereus) and eukaryotic cells (NK-92 cell line) are efficiently inactivated by LEEI in a throughput suitable for various applications such as sterilization, vaccine manufacturing or cell therapy. Our results validate the premise that for pathogen and cell inactivation in liquids, LEEI represents a suitable and versatile irradiation method for standard biological research and production laboratories.

Monte Carlo Simulation of SARS-CoV-2 Radiation-Induced Inactivation for Vaccine Development

“…While it would currently be impossible to have mass production in large heavy ion accelerators, cheaper technologies might be an alternative solution to produce high-LET radiation beams, e.g., commercial cyclotrons working at high intensity, or even high-activity a-particle sources. To reach irradiation of large amounts of viral particles, it is possible to use disposable bags and continuous flow of viruses in a thin film, a method developed for virus inactivation using 200-keV electrons, which demonstrated an ability to effectively inactivate influenza and other viruses in a reasonably short time (63). If the calculation performed in the current work is supported by experimental data, we expect that great effort will be undertaken to develop simple methods for collecting large quantities of high-LET radiation-inactivated viruses.…”

Low Energy Electron Irradiation Is a Potent Alternative to Gamma Irradiation for the Inactivation of (CAR-)NK-92 Cells in ATMP Manufacturing

“…In addition to the conventional gamma irradiation, low energy electron irradiation (LEEI) has emerged as a novel method for NK-92 cell inactivation (18). Since the penetration depth of the accelerated low energy electrons is limited to < 1 mm in water (19), a thin film of liquid has to be generated to ensure complete irradiation (18). Compared to gamma irradiation, LEEI allows delivery of a high dose rate, which leads to a shorter treatment time (18,20).…”

“…Since the penetration depth of the accelerated low energy electrons is limited to < 1 mm in water (19), a thin film of liquid has to be generated to ensure complete irradiation (18). Compared to gamma irradiation, LEEI allows delivery of a high dose rate, which leads to a shorter treatment time (18,20). One of the greatest benefits of LEEI is the generation of only small amounts of secondary radiation (the Bremsstrahlung, X-rays) (18).…”

“…Compared to gamma irradiation, LEEI allows delivery of a high dose rate, which leads to a shorter treatment time (18,20). One of the greatest benefits of LEEI is the generation of only small amounts of secondary radiation (the Bremsstrahlung, X-rays) (18). This is the reason why LEEI facilities do not need to be equipped with complex shielding systems and therefore can easily be implemented in basic laboratories, even as an in-line tool in GMP environments (21).…”

“…This is the reason why LEEI facilities do not need to be equipped with complex shielding systems and therefore can easily be implemented in basic laboratories, even as an in-line tool in GMP environments (21). Furthermore, the applied LEEI doses can be adjusted by current intensity, resulting in a wellcontrollable on-off-process with a very good reproducibility, a great advantage over gamma radiation, which is caused by the spontaneous decay of radioactive material (18).…”