Cell-fluorescent ion track hybrid detector: A novel hybrid technology for direct correlation of single ion tracks and subcellular damage sites in clinical ion beam

Despite a rapid development in ion beam cancer therapy there is still a great lack in understanding the fundamental mechanisms linking physical energy deposition and biological response on the subcellular scale. A cell-fluorescent ion track hybrid detector (Cell-Fit-HD) was thus developed for direct correlation of single ion tracks and subcellular damage sites in clinical ion beams. It is based on the fluorescent nuclear track detector (FNTD) read out by confocal laser scanning microscope (CLSM). The FNTD was coated with various cell lines to create the actual hybrid composite. Different cell compartment specific fluorescent stains were tested on the Cell-Fit-HD. A protocol was developed to read out the hybrid in-situ by a single CLSM. Single ion tracks detected were reconstructed in the biological compartment and correlated to radiation-induced DNA double strand break sequences as well as to cell survival kinetics. Cell-Fit-HD enables the investigation of radiation-related cellular events along single ion tracks on the subcellular scale. Microscopic physical parameters of each incident ion can be extracted and correlated to the cellular damage response pattern. The unique spatial resolution of Cell-Fit-HD could help to gain a deeper understanding between particle hits and resulting biological effects beyond the statistical relations we know today