Development of Next Generation Biomedical Sensor for Single Cell Four Dimensional Tracing of Cellular Response to Ion Beam Irradiation

Clonogenic survival of few colonies out of a population of cells that have received a defined amount of energy (J) per mass (kg) represented by the dose unit Gray (Gy) constitutes the gold standard method for quantifying radiobiological effects. We aimed to engineer the next generation biophysical hybrid detector technology using ion beam irradiation with clinical high linear energy transfer (LET) carbon ions combined with 4D single cell fate imaging. Development of a novel biomedical sensor (Cell-Fit-HD4D) and the first successful deconvolution of individual cell fate in response to microscopic ion beam deposition visualized by optical microscopy is reported. Cell-Fit-HD4D enabled single-cell dosimetry in clinically relevant complex radiation fields. A spectrum of experimentally derived physical parameter such as the quantity and the sum of LETs (ΣLET) of primary carbon ion particles traversing cell nuclei were correlated with biological endpoints i.e., DNA-Damage repair kinetic, chronic cell cycle arrest (senescence) and clonogenic survival. Decrypting the physical dose and molecular effects at single cell resolution via Cell-Fit-HD 4D has the potential to revolutionize our comprehension of radiobiological dose concept.