Single-pulse Gy-scale irradiation of biological cells at average dose-rates above $10^{13}$ Gy/s from a laser-wakefield accelerator

We report on the first experimental characterization of a laser-wakefield accelerator able to deliver, in a single pulse, doses in excess of 1 Gy on timescales of the order of tens of femtoseconds, reaching unprecedented average dose-rates above $10^{13}$ Gy/s. The irradiator is demonstrated to deliver doses tuneable up to 2.2 Gy in a cm$^2$ area and with a high degree of longitudinal and transverse uniformity in a single irradiation. In this regime, proof-of-principle irradiation of patient-derived glioblastoma stem-like cells and human skin fibroblast cells show indications of a differential cellular response, when compared to reference irradiations at conventional dose-rates. These include a statistically significant increase in relative biological effectiveness ($1.40\pm0.08$ at 50\% survival for both cell lines) and a significant reduction of the relative radioresistance of tumour cells. Data analysis provides preliminary indications that these effects might not be fully explained by induced oxygen depletion in the cells but may be instead linked to a higher complexity of the damages triggered by the ultra-high density of ionising tracks of femtosecond-scale radiation pulses. These results demonstrate an integrated platform for systematic radiobiological studies at unprecedented beam durations and dose-rates, a unique infrastructure for translational research in radiobiology at the femtosecond scale.