Biosensor for deconvolution of individual cell fate in response to ion beam irradiation

• Published in: Cell reports methods Vol. 2; no. 2; p. 100169
• Main Authors: Niklas, Martin, Schlegel, Julian, Liew, Hans, Zimmermann, Ferdinand, Rein, Katrin, Walsh, Dietrich W.M., Dzyubachyk, Oleh, Holland-Letz, Tim, Rahmanian, Shirin, Greilich, Steffen, Runz, Armin, Jäkel, Oliver, Debus, Jürgen, Abdollahi, Amir
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.02.2022; Elsevier
• Subjects: biodosimetry; biosensor; Cell-Fit-HD; clinical ion beam irradiation; double strand breaks; fluorescent nuclear track detector; FNTD; ion beam cancer therapy; particle therapy; radiobiological effects; biosensor; fluorescent nuclear track detector; double strand breaks; biodosimetry; Cell-Fit-HD; FNTD; clinical ion beam irradiation; particle therapy; ion beam cancer therapy; radiobiological effects
• ISSN: 2667-2375; 2667-2375
• DOI: 10.1016/j.crmeth.2022.100169

Clonogenic survival assay constitutes the gold standard method for quantifying radiobiological effects. However, it neglects cellular radiation response variability and heterogeneous energy deposition by ion beams on the microscopic scale. We introduce “Cell-Fit-HD4D” a biosensor that enables a deconvolution of individual cell fate in response to the microscopic energy deposition as visualized by optical microscopy. Cell-Fit-HD4D enables single-cell dosimetry in clinically relevant complex radiation fields by correlating microscopic beam parameters with biological endpoints. Decrypting the ion beam’s energy deposition and molecular effects at the single-cell level has the potential to improve our understanding of radiobiological dose concepts as well as radiobiological study approaches in general. [Display omitted] •Cell-Fit HD4D is a biosensor that allows tracking of single irradiated cells•The sensor correlates single-cell radiation dose with biological endpoints•It also reveals variability in radiation responses in tumor cell population•Potential to enhance understanding of therapeutic radiation dose concepts Ion beam cancer therapy (IBCT) is transforming radiotherapy into a highly precise discipline within oncology. Despite its promising clinical success, there is still a lack of understanding around the molecular and physiological changes in an individual tumor cell in response to the heterogeneous physical energy deposition in the ion beam. We therefore developed the biosensor “Cell-Fit-HD4D”, enabling long-term monitoring of single tumor cells after clinical ion beam irradiation in combination with single-cell dosimetry. It enables correlation of physical beam parameters with biologically relevant endpoints in IBCT. Niklas et al. present Cell-Fit-HD4D, a biosensor that allows for microscopic tracking of fates and desired biological readouts in individual cells, in response to a therapeutically administered radiation dose. It has the potential to yield insights into the connection between dose deposition and cellular response in ion beam therapy.