Speaker
Description
Purpose:
Laser-driven acceleration of ionizing radiation has rapidly progressed from theoretical models to reproducible experimental demonstrations. Within the Extreme Light Infrastructure (ELI), recent developments now enable systematic biological studies using laser-accelerated electrons, protons, and neutrons. The aim of this work is to present key experimental achievements and corresponding biological results obtained in pioneering in vitro and in vivo models, highlighting the potential of laser-driven beams for radiobiology and preclinical research.
Methods:
Experiments were performed at the ELI Beamlines (ELI BL) and ELI ALPS facilities using human glioblastoma (U251) cells and zebrafish embryos (24 hpf) as biological models. Custom-designed sample holders were developed for each setup to accommodate the specific beam conditions. Dose distributions were calculated via Monte Carlo simulations, and beam size and sample positioning were optimized accordingly. For proton and electron irradiations, EBT3 and EBT4 Gafchromic film dosimetry was employed, while neutron delivery was monitored using bubble and scintillation detectors. The analyzed biological endpoints included DNA double-strand breaks (γH2AX), apoptosis (Acridine Orange staining), morphology, and survival. Conventional irradiations — i.e., LINAC-based photon and electron, and cyclotron-based proton and neutron exposures — served as reference standards.
A total of eleven laser-driven irradiation campaigns were completed: six with electrons, four with neutrons, and one with protons.
• Neutron beam (ELI ALPS): Generated via deuterium–deuterium fusion using laser-plasma technology. The source operated stably for several hours at 10–100 Hz. Doses between 0.05–1.5 Gy were delivered in vacuum over six repeated irradiations. Dose mapping and Monte Carlo simulations ensured uniform exposure.
• Proton beam (ELI Beamlines): A laser-accelerated beam operated stably for several hours, delivering 2–3 Gy in air at the plateau region. Three runs at six dose levels (2.2–2.8 Gy) were performed with precise dosimetry and verified beam parameters.
• Electron beams (ELI BL and ELI ALPS): Six experimental campaigns comprising 126 runs and 87 dose points (2–126 Gy) were conducted in air. Laser-wakefield acceleration produced reproducible dose delivery at ultra-high dose rates per pulse.
Results:
Laser-driven radiation sources have rapidly improved in alignment accuracy, beam quality, and stability, demonstrating suitability for biological experiments with good dose control and measurable biological effects.
• Neutron irradiation (ELI ALPS): Zebrafish embryos exhibited clear dose-dependent increases in γH2AX and apoptotic cell counts. Comparative analysis revealed similar biological effects for laser-based and conventional neutron (CN) exposures. The calculated RBE₍apoptosis₎ = 3.5 and RBE₍DNA-DSB₎ = 2.5, confirming high biological effectiveness of the 3.2 MeV laser-driven neutron beam.
• Proton irradiation (ELI Beamlines): Stable beam performance enabled precise biological characterization at the plateau region. Zebrafish embryos irradiated at 2.2–2.8 Gy showed significant apoptotic and DNA damage induction, yielding RBE₍apoptosis₎ = 1.3, consistent with conventional low-LET radiation expectations.
• Electron irradiation (ELI BL and ALPS): Across 126 runs, laser-driven electrons induced dose-dependent apoptosis, DNA damage, and morphological abnormalities (reduced body length, smaller eye diameter, pericardial and yolk sac edema). Preliminary data suggest promising normal-tissue sparing compared with LINAC-based electron irradiation.
Overall, the biological endpoints confirmed that laser-driven beams induce biologically relevant, dose-dependent effects and, at higher doses, exhibit healthy tissue–sparing properties compared to conventional accelerator sources.
Discussion:
These results represent a major step toward the integration of laser-driven radiation into radiobiology. High-power laser systems now routinely achieve stable multi-hour operation with sufficient energy and repetition rate to support systematic biological studies. The combination of ultra-high instantaneous dose rate and micrometer-scale focusing enables irradiation geometries relevant for investigating FLASH-like and microbeam effects, as well as highly localized tissue responses.
However, further refinement of beam transport, dosimetry calibration, and online monitoring remains essential. Establishing common standards for beam characterization and biological evaluation across ELI sites will be crucial to ensure comparability and reproducibility of results.
Conclusion:
Following extensive theoretical groundwork, experimental validation at ELI facilities has confirmed that laser-driven electrons, protons, and neutrons can elicit controlled, biologically meaningful effects in both cell and organism models. These findings demonstrate the feasibility of laser-based sources for radiobiology and preclinical research, bridging the gap between high-power laser physics and biomedical application.